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The chemistry of 3-methyl-3-nitro-1, 2-butanedicarboxylic acid

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The chemistry of 3-methyl-3-nitro-1, 2-butanedicarboxylic acid

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Content THE CHEMISTRY OF
3-METHYL-3-HITRO-1,2-BUTANEDICARBOXYLIC ACID
A Thesis
Presented to
the Faculty of the Department of Chemistry
University of Southern California
In Partial Fulfilment
of the Requirements for the Degree
Master of Science
by
Philip S. Magee
March, 1952
UMI Number: EP41598
All rights reserved
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Dissertation Publishsng
UMI EP41598
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1**
yuteA
C l SZ. MMI
This thesis, written by
is i
under the guidance of hX.3... Faculty Committee,
and approved by all its members, has been
presented to and accepted by the Council on
Graduate Study and Research in partial fu lfill
ment of the requirements for the degree of
Master of Science
In Chemistry
Faculty Committee
airman
ACKNOWLEDGMENT
The author wishes to thank Dr. Milton Kloetzel
for his guidance of the studies described herein.
TABLE GF CONTENTS
CHAPTER PACE
I. INTRODUCTION .......................... 1
II. DISCUSSION OF EXPERIMENTAL RESULTS ... 8
A. The Preparation of Dimethyl 3-Methyl-
3-nitro-l,2-butanediearboxylate ... 8
B. Studies in Esterification and
Hydrolysis ....................... 9
G. The Ring Closure of 3-Methyl-3-nitro-
1.2-butanediearboxylie Acid ..... 21
D. The Ammonolysis and Aleoholysis of
3-Methyl-3-nitro-l,2-butanedi-
carboxylic Anhydride .............. 23
E. The Reaction of Some N-Substituted
Monoamides of 3-Methyl-3-nitro-
1.2-butanedicarboxyllc Acid with
"Dehydrating" Reagents ............ 29
F. Attempted Frledel-Crafts Reactions
with 3-Methyl-3-nitro-l,2-butane-
dicarboxylic Anhydride ............ 33
G. The Attempted Preparation of Dimethyl
3-Nitro-l,2-propanedlearboxylate
and Dimethyl 3,3-Dimethy1-4-nltro-
1.2-butanedicarboxylate ............ 34
H. The Elimination of Nitrous Acid from
3-Methyl-3-nItro-l,2-butanedi-
earboxylic Acid and its Derivatives . 36
I. The Thermal Stability of 3-Methyl-
3-nitro-l,2-butanedicarboxylic Acid
and its Derivatives................ 40
III. EXPERIMENTAL.......................... 44
A. Reagents and Solvents............. 44
V
CHAPTER PAGE
B. The Michael Condensation Reaction
with 2-Nitropropane................... 47
(1) Dimethyl 3-Methyl-3-nltro-
1.2-butanedicarboxylat e ........... 4-7
C. Esterification and Hydrolysis
Reactions of 3-Methyl-3-nitro-
1,2-butanediearboxylic Acid and
its Esters......................... 47
(1) The Half Hydrolysis of Dimethyl
3-Methy1-3-nitro-l,2-butane-
dicarboxylate .................... 48
(2) The Complete Hydrolysis of
Dimethyl 3-Methyl-3-nitro-
1.2-butanedicarboxylate ........ 48
(3) The Sulfuric Acid Esterification
of 3-Methyl-3-nitro-l,2-butane-
dicarboxylle Acid................ 49
(4) The Sulfuric Acid Esterification
of 3-Carbomethoxy-4-methy1-4-nitro-
pentanoic Acid ................ 50
D. The Sulfuric Acid Esterification
of Various Aliphatic Acids.......... 50
(1) Succinic Acid .......... 50
(2) Glutarle Acid .............. 51
(3) Adipic Acid............. 51
(4) Sebacic Acid ........... 51
(5) Phenylacetic Acid................ 52
(6) Trimethy lace tic A c i d ............ 52
(7) o-Nitrobenaolc Acid ........ 53
(8) Phthalic Acid.................... 53
VI
CHAPTER
PAGE
. Ring Closing Reactions of 3-Methyl-
3-nitro-l,2-butanedicarboxylic Acid
and the N-Sabstituted Monoamides .... 53
(1) The Action of Aeetic Anhydride
on 3-Methy1-3-Ritro-l,2-butane
dicarboxylic A c i d ................ 53
(2) The Action of Thionyl Chloride on
3-Methyl-3-nltro-l,2-butane
dicarboxylic Acid . ........... 55
( 3) The Action of Acetyl Chloride on
3-Methyl-3-nitro-l,2-butane-
dicarboxylic Acid .............. 55
(k) The Action of Acetic Anhydride on
the o-Toluidide of 3-Methyl-
3-nitro-l,2-butanedlcarboxylic
Acid............... 56
(5) The Action of Acetyl Chloride on
the Anilide of 3-Methyl-3-nitro-
1.2-butanedicarboxylic Acid .... 56
(6) The Action of Thionyl Chloride on
the Anilide of 3-Methyl-3-nltro-
1.2-butanedicarboxylic Acid .... 56
(7) The Action of Thionyl Chloride on
the Phenylhydrazide of 3-Methyl-
3-nitro-l,2-butanedicarboxylic
Acid........... 57
(8) The Action of Phosphorus Pentoxide
on the Anilide of 3-Methyl-3-nitro-
1.2-butanedlcarboxylic Acid .... 57
(9) The Action of Sulfuric Acid on the
Anilide of 3-Methyl-3-nitro-
1.2-butanedlcarboxylic Acid .... 58 t
(10) The Action of Sulfuric Acid on the
Phenylhydrazide of 3-*Methyl-3-nitro-
1.2-butanedicarboxylie Acid .... 58
vll
• CHAPTER PACE
(11) The Action of Anhydrous Hydrogen
Fluoride on the Anilide of
3-Methyl-3-nitro-l,2-butane-
diearboxylic Acid........... 59
(12) The Preparation of N-Phenyl-
3-methyl-3-nitro-l,2-butane-
diearboximide ....................60
F, The Ammonolysis and Aleoholysis of
3-Methyl-3~nitro-l,2-butanedi
carboxylic Anhydride.................... 61
The Ammonolysis of 3-Methy1-3-nitro-
1,2-butanediearboxylic Anhydride .... 6l
(1) With o-Toluidine ................. 6l
(2) With Aniline ............ 62
(3) With Phenylhydrazine........62
(4) With n-Dodeeylamine.........63
(5) With n-Propylaaine ......... 6^
(6) With Piperidine.............6^
(7) With Aqueous n-Propylamine ..... 65
(8) Aleoholysis of 3-Methyl-3-nitro-
1,2-butanedicarboxylic Anhydride
■with Methanol......................65
(9) The Attempted Hydrolysis of N-Phenyl-
3-methyl-3-nitro-l,2-butanedi-
ea,rboxiiaide..........................66
G. The Relationship between 3-Garbomethoxy-
A-methyl-^-nltropentanoio Acid and the
o-Toluidide of 3-Hethyl-3-nitro-l,2-
butanedicarboxylic Acid .......... 67
Vlii
CHAPTER PAGE
(1) The Ammonolysis of 3-Garbomethoxy-
4-methyl-4—nitropentanoyl Chloride
with o-Toluidine .......... 67
(2) The Silver Salt Esterification of
the o-Toluidide of 3-Methyl-3-nitro-
1,2-butanediearboxylic Acid .... 68
H. Some Attempted Frledel-Grafts Reactions
of 3-Methyl-3-nltro-l,2-butanedicarboxylie
Anhydride on Aromatic Compounds .... 69
(1) Anisole..................... . 69
(2) p-Xylene ................ ..... 70
(3) Toluene .............. 71
I. Some Michael Condensations Involving
litromethane................. 72
(1) With Dimethyl Fumarate ....... 72
(2) With Dimethyl Teraconate......... 73
J. The Elimination of litrous Acid from
3-Methyl-3-nitro-l,2-butanedlcarboxylic
Acid in Ion-basic Media . . ........ 73
(1) The Prolonged Action of Acetic
Anhydride on 3-Methyl-3-nitro-l,2-
butanediearboxyllc Acid ...... 73
(2) The Prolonged Action of Acetic
Anhydride on Dimethyl 3-Methyl-3-
nitro-1,2-butanedicarboxylate ... ?b
(3) The Action of Aeide on 3-Methyl-3-
nltro-l,2-butanediearboxylle Acid. . 75
K. The Thermal Decomposition of 3-Methy1-
3-nitro-l,2-butanediearboxylic Acid
and its Derivatives . ................ 76
ix
CHAPTER PAGE
(1) The Decomposition of 3-Methyl-
3-nitro-l,2-butanedicarboxylic
Acid .......... 76
(2) The Decomposition of the Phenyl
hydrazide of 3-Methyl-3-nitro-l,2-
butanedicarboxylle Acid ....... 77
(3) The Decomposition of the Anilide of
3-Methyl-3-nltro-li2-butane-
dicarboxylic Acid . . ........ 78
(A) The Decomposition of the n-Propyl-
amide of 3-Methyl-3-nltro-l,2-
butanedlcarboxyllc Acid ....... 78
(5) The Thermal Stability of Dimethyl
3-Methy1-3-nitro-l, 2-butanedi-
carboxylate............... .... 78
(6) The Decomposition of 1-Carbomethoxy-
3-methyl-3-nitro-2-butanecarboxyllc
Acid................... 79
(7) The Partial Decomposition of 3-Garbo-
methoxy-4-methyl-A-nitropentanoic
Acid ............................. 79
(8) The Thermal Stability of the o-Toluidide
Ester of 3-Methy1-3-nitro-l,2-butane
dicarboxylic A c i d .................. 80
(9) Thermal Stability of 3-Methy1-3-
nitro-l, 2-butanedicarboxylie
Anhydride .................... 81
(10) Thermal Stability of N-Phenyl-3-
methyl-3-nltro-l,2-butanedi-
carboxiraide . 81
IV. SUMMARY................. 82
BIBLIOGRAPHY
85
LIST OP TABLES
TABLE PAGE
I. The Sulfuric Acid Esterification
of some Carboxylic Acids.................. 18
II. The Relative Rates of Esterifi
cation of Garboxylic Acids Under
Standard Conditions ............ ..... 19
III. The Ammonolysis of 3-Methyl-3-
nltro-1,2-butanedlcarboxylic Anhydride
with Aromatic and Aliphatic Amines ..... 25
IY. Some Friedel-Crafts Reactions ............ 33
CHAPTER I
INTRODUCTION
Compounds in which a nitro group is in a position
removed by two carbon atoms (beta position) from a carbox-
1 2
ylic group have been known for seventy years. * Before
the advent of readily available nitroalkanes, beta-nltro
carboxylic acids and their derivatives were rare entities
,and no chemical investigations were Initiated other than
. 2
one reported reduction to the corresponding amino acid.
The early methods of preparation consisted of the silver
nitrite metathesis with beta-iodoproplonie acid by
2
Lewkowltsch (equation 1) and the nitric acid oxidation of
branched aliphatic acids such as isovaleric acid by Bredt*'
(equation 2).
1 (1) ICH2CH2C00H +• AgN02 --- > €> 2NCH2CH2C00H - f - Agl
(2) (eH3)20H0H2C00H M 0 3 , (CHj UC-CH^COOH 4- f OH-j )oO(NOi)o
uo2
Some doubt has been cast on the validity of the nitration
;work by recent Investigators who were unable to repeat the
3
observation with isovaleric acid. However, the products
claimed by Bredt appear quite reasonable in light of what
is now known concerning the nitration of aliphatic
h ,
compounds.
Interest in the reactions of nitroaliphatic
compounds was considerably augmented by the availability
of simple nitroalkanes from the vapor phase nitration
for the preparation of beta-nitro carboxylic acids during
the last decade, none of which involve the introduction of
the nitro group per se. These methods may be summarized
as follows:
a. The Michael condensation of hydrogen cyanide with a
conjugated nitroolefin followed by hydrolysis of the beta-
nitropropionltrile. ^
b. The alkylation of malonic ester with 2-ehloro-2-nitro
6
propane.
h ,
process. Thus, a number of methods have been developed
(3) 02IGH=G HCH » QolGHoC-GN *2^ QoHCHoC-COOH
CH-j CH^ 0*2
(4) OpN-C-Cl -f <-*CH
^ I I
COOC2H5 0* 3^ 00021*5
COOG2H5
I
> 02N-G-CH
CH3 GOOG2H5
c. The ozonolysis of a 3-nitroalkene prepared by the
Michael condensation of a nitroalkane with 1-cyanobuta-
3
3
diene.
( 5) Qa^-G^H^GHCHgC^M °3 GgM-G-CHgCGQH
CHo
I *
GHo
I 3
d. The Michael condensation of 2-nitropropane with
Dimethyl J-methy1-3-nitro-l,2-butanedicarboxylate,
chosen for a fundamental study of the beta-nitro
carboxylic acid system. The choice of this compound for
such a study is a logical one for three reasons. It can
be readily prepared on a large scale from inexpensive
reagents. Secondly, it is uncomplicated by acidic
hydrogen alpha to the nltro group and lastly, more
preliminary work has been done on this system than on any
other.
Kloetzel demonstrated the lability of the nltro
group under basic conditions. Thus, if dimethyl 3-m©thyl
3-nitro-l,2-butanedlcarboxylate is allowed to stand with
one mole of diethylamine, the elements of nitrous acid
dimethyl fumarate
OHGOOCHo
(6) I! 3
CHGQOCH3
- I - (CH^JgOHNOg
Et2NH
CILjGOGGH.
> CHCOOCHo
I 3
C(CH3)2NG2
prepared by the method of Kloetzel^ (equation 6), was
*
are slowly eliminated. Dimethyl teraconate is obtained in
yields of 70-85 $ together with water and H-nitroso-
diethylamlne (equation 7).
gh2coogh3 gh2cooch3
(7) CHCOOCH3 +• (G2H5) 2HH >. C-COOCH3 - f - (C2H5) 2HH0
C(GH3 )2NQ2 CH3-G-CI3 +- h2g
It is interesting that dlethylamlne, in a lower molar ratio
(0.2 mole), functions as an excellent catalyst for the
preparation of the beta-nitro carboxylie ester
(equation 6). Under more drastic basic conditions
(refluxing aqueous potassium hydroxide), the elimination
7
is rapid and attended with hydrolysis of the ester groups.
It is noteworthy that with dlethylamlne the elimination
proceeds more rapidly than the ammonolysis of the ester
groups.
The work presented in this paper was carried out
with two principal objectives in view. It was desired,
first of all, to study the conditions under which the
carboxylic functions could be investigated without
incurring the elimination of the nitro group. Secondly,
a search for specific conditions under which the nitro
group can be caused to eliminate seemed desirable. These
two objectives were realized by an integration of the
results from the following studies:
(1) An investigation of the esterification and
hydrolysis of 3-me'fcky1-3-nitro-l,2-butamediear-
boxyllc acid and its methyl esters was undertaken.
This study was initiated by Kloetzel who isolated
•the two Isomeric monomethyl esters.? The
expansion of this work led indirectly to a new
procedure for the rapid esterification of
aliphatic acids.
(2) Ring closing reactions were studied in developing
the conditions necessary for the formation of the
cyclie compounds, 3-methy1-3-nitro-l,2-butane
dicarboxylic anhydride and B-phenyl-3-®ethyl-
3-nitro-l,2-butanediearboximlde. It was found
that some of the common ring closing reagents,
such as acetic anhydride, were also effective in
causing the elimination reaction, often
concurrently and sometimes predominantly.
(3) Ring opening reactions were studied in the
aleoholysis and ammonolysis of 3-methyl-3-nitro-
1,2-butanedicarboxylic anhydride. It was clearly
demonstrated that a single product is predominant
in the ammonolysis of the unsymmetrieal anhydride,
indicating preferential attack at one position.
Furthermore, it was shown by a relative structure
proof of the products that aleoholysis and
ammonolysis attack the same position. Ammonolysis
of the anhydride with some of the more basic
aliphatic amines caused considerable elimination,
the highest yields of amides being obtained with
the less basic aromatic amines.
(4) Some unsuccessful attempts were made to effect a
Friedel-Crafts reaction with 3-methyl-3-nitro-
1,2-butanedlcarboxylic anhydride and various
aromatic compounds. Under the conditions employed
only tarry products were obtained.
(5) Two attempts were made to prepare nitrocarboxylic
esters through Michael condensations involving
nltromethane. The condensation of nitromethane
with dimethyl fumarate in the presence of diethyl-
amine did not yield dimethyl 3-nitro-l,2-propane-
dlcarboxylate but rather the elimination product,
dimethyl itaeonate (dimethyl methylidenesuccinate)*
Apparently, nitrous acid was eliminated as rapidly
as the beta-nltro carboxylic ester was formed.
The condensation of nitromethane with dimethyl
teraconate was not effected in the presence of
triethylamine even after five months at room
7
temperature.
(6) The elimination of nitrous acid from 3-iaethyl-
3-nitro-l,2-butanediearboxylle acid was found to
occur slowly under acidic conditions or in the
presence of "dehydrating" agents such as acetie
anhydride. Thus, while the beta-nitro group
parallels the beta-halogen groups in its lability
toward weak bases, it more closely resembles the
beta-hydroxy group under acidic and "dehydration"
conditions.
(7) The thermal decomposition of 3-siethyl-3--nltro-
1,2-butanedicarboxylic acid and its derivatives was
carried out at 1^5 i 3°. 3?he primary process
proved to be the elimination of nitrous acid even
in those instances where ring closure might have
Q
been predicted. In spite of the qualitative
nature of this work, the rates of decomposition of
structurally dissimilar derivatives were so
markedly different that it was possible to place
several restrictions on the nature of the process.
CHAPTER II
DISCUSSION OF EXPERIMENTAL RESULTS
A. The Preparation of Dimethyl 3-Me thy1-3-n1 tr o-
112-butanedlcarboxylate.— Before the commercial
availability of the simple nitroalkanes, beta-nltro
carboxylic acids were prepared by methods involving the
1 2
direct substitution of the nitro group. » More recently,
these acids and their derivatives have been prepared by
3 ?
condensation reactions involving either a nitroalkane *
£
(equations 5 and 6), an alpha-chloronltroalkane
(equation * 0 , or a conjugated nitroolefin-* (equation 3).
Some of these methods require an additional step in order
to form the beta-nitro carboxylic aeid or ester (equations
3 and 5)» However, the fundamental structure is generated
in each case by a condensation reaction with a nitroalkane
or derivative thereof. The preparation of dimethyl
3-methyl-3-nitro-l,2-butanediearboxylate as developed by
Kloetzel? (equation 6) Involves the condensation of a weak
acid, 2-nitropropane, with a conjugated earbonyl system,
dimethyl fumarate, under the catalytic influence of a weak
base, dlethylamlne. The optimum conditions are realized
when the dlethylamlne concentration is 0.2 mole per mole
of ester in the presence of 3 moles of 2-nltropropane.
After standing at 30° for six days or at 20° for fourteen
days, the mixture affords 70-80 % yields of dimethyl
3-methyl-3-nitro-l,2-butanedicarboxylate accompanied by
only 10-15 % of the elimination product, dimethyl
teraeonate (equations 6 and 7). Under the same conditions
of time and temperature but in the presence of one mole of
diethylamine per mole of ester, the yields of these two
products are reversed. As this preparation proved to be
adaptable to runs of five hundred grams without technical
difficulties, no effort was made to improve the reaction
conditions. Chromatographic purification of the reaction
mixture, employing activated alumina (Alcoa F-20), proved
successful but was not superior to fractional distillation
under reduced pressure.
B. Studies in Esterification and Hydrolysis.— It
has been shown that if dimethyl 3-methyl-3-nitro-
1,2-butanediearboxylate is refluxed for two hours with 1 %
hydrochloric acid, a monomethyl ester is obtained in 91 $
7
yield. Prolonged refluxlng of this monomethyl ester with
1 % hydrochloric acid (three days) is necessary to convert
it to the dicarboxylic acid.? Thus, there is a marked
difference in the relative rates of hydrolysis of the two
carboxylic ester groups. As the obtainable yield of the
monomethyl ester is 91 the rates of hydrolysis must
10
differ by at least a factor of ten. Further, it was
demonstrated that a controlled esterlfieation of 3-®©'thyl-
3-nitro-l,2-butanedicarboxylic acid resulted in a 93 %
yield of a monomethyl ester isomeric with that formed in
the partial hydrolysis of the dimethyl ester.^
In accordance with the observations of Menschutkin^ on the
relative rates of esterification of primary and secondary
carboxylic acids, the results were interpreted as follows:
OH2COOCH3
(8) GHGOOGH3
G(CH3)2H02
1 % HC1
2 hrs. reflux
GH2CG0H
GHGOGGH3
C(CH3)2N02
C%GG0H
(9) GHCOQGH,
c(ch3.)2ng2
1 % HC1
3 days reflux
GH2COOH
GHC00H
c(gh3)2io2
(10)
GH2COOH
CHG00H
IT CH3OH
C(CH3)2H02
2 hrs. reflux
CH2C00CH5
CHGGOH
c(ch3)2no2
This work was repeated and verified, the only
extension feeing the direct hydrolysis of dimethyl
3-methy1-3-nitro-l,2-butanedicarboxylate to the die&rfe-
oxylic acid in yields of 85-90 %. Alkaline hydrolysis of
the dimethyl ester was reported to occur rapidly, with
concurrent loss of the nitro group, to yield teraeonic
acid (equation 11).^
The possibility that the wrong structures were
assigned to the isomeric monomethyl esters was carefully
considered. As the nitro group Is effectively buffered
from electronic interactions with the carboxyl groups
through the carbon chain, the only interaction possible
would be that of a neighboring group type in which the
nltro group itself could attack the secondary carboxyl
group and aid the esterification in some manner. The
anomalous behavior of o-benzoylbenzoic acid in 100 %
sulfuric acid is the only reported instance in which a
neighboring group interaction with the carboxyl function is
sufficient to change the mechanism of ionization.
(11)
C(CH3)2H02
GHoGOOGE
0.5 hr. reflux I I
aqueous KOI
GHoCQOH
CH3-C-CH3
Two major pieces of evidence are presented by Newman and
coworkers in support of the postulated resonance hybrid
ion (equation
(12)
The observed Yan*t Hoff i-factor agrees closely with the
predicted value of 4 based on the represented stoichiom
etry (equation la).12*1^ seconaiy, if the sulfuric acid
solution is allowed to react with pure methanol, two
products are obtained, the normal ester (56 %) and the
methyl ether-lactone which Newman calls the "pseudoester8
(40 These products correspond to attack by
methanol at the two most positive centers of the hybrid
ion (equation 13)*
13
s+
G~GcEt
(13)
6 5
V ^ e
V I I
0
t-
C— C^H
^V^GOOCH^
The"normalH Ionization of a carboxylic acid in 100 %
sulfuric acid appears to be the simple acceptance of a
proton to form a dihydroxycarbonium ion (equation 14).
^0 + ^ 0H _
(14) ECX -h HpSCh, > RCX + HSOi,
OH * * OH *
The stoichiometry of this ionization would predict a Van*t
Hoff 1-factor of 2 and this is indeed found to be true for
14
most carboxylic acids. This reaction (equation 14) is
considered to be the first reversible step in a normal
acid catalyzed esterification.
It has been demonstrated by Newman that solutions of
2,4,6-trimethylbenzoie acid in 100 % sulfuric acid are
rapidly esterlfied when added to pure methanol whereas
benzoic acid is recovered quantitatively under identical
conditions.1- *
The trimethylbenzoic acid displays an i-faetor of about 4,
indicating the formation of an oxoearbonium ion
(equation 15); on the other hand, the unsubstituted
yfi ¥ 4. _
(15) aG\QH 2H2S% ----^ RC-0 +- H30r +- 2HSO4
benzoic acid has an i-factor near 2, the carboxyl group
functioning as a Lewis base (equation l4).l2»^
The theoretical reasons for the formation of this
oxoearbonium ion are discussed by Mewman^ but are not
pertinent to the present studies. The Important point is
that the oxoearbonium ion esterifies more rapidly than the
1 dihydroxycarbonium ion. Hewman asserts that this is
positive evidence that the oxoearbonium ion is the more
16
reactive species. This, however, is not necessarily
true. Hewman overlooks the fact that two processes may
oceur to the dihydroxycarbonium ion in the presence of
methanol, one of which does not lead to esterification
(equations 16 and 17).
+/GH
(17) RCf + CH3OH
OH ^
. 0
+
OH
+- CH3QH2
Conversely, the oxocarbonium ion can function in only one
way under the same conditions (equation 18).
In view of the evidence presented by Newman, it was
considered possible that the secondary carboxyl group of
3-methyl-3-nitro-l,2-butanedie&rboxyllc acid could
esterify more rapidly than the primary group if an
oxocarbonium ion were formed. This ion might be formed
preferentially if the nitro group effected a stabilization
analogous to that of the carbonyl group in stabilizing the
oxocarbonium ion of o-benzoylbenzolc acid (equations 12
and 19). No direct evidence is available to indicate that
(18) EG — 0 - I - CH3OH
+■
CH2COOH
I ^ 0
CH2C00H
(19)
16
the nitro group Is capable of such a stabilization,
although it has been proposed to explain the complete
ionization of 2,ij~-dinitr©benzenesulfenyl chloride in 1©0 %
sulfuric acid (equation 20).^
SGI +- H2SC%
*02 ng2
+- HG1 +■ HSO"
It was shown, however, that the nitro group does not
provide enough stabilization to favor the formation of the
oxoearbonium ion of o-nitrobenzoic acid. Thus, no ester-
i
ifieatlon was observed after pouring the sulfuric acid
solution into methanol, the acid being recovered
unchanged.
The results obtained with 3-fflethyl-3-nltro-l,2-bu-
tanedicarboxyli© acid and 3-carbomethoxy-i}—methyl-4-nltro-
pentanoic acid are of considerable interest. It was found
that a solution of the dicarboxyllc acid in 96 % sulfuric
aeid is esterifled when poured into methanol to yield 52 %
of the same monoester obtained in the controlled Fischer
esterifieatlon (equations 10 and 21)
17
CH«C00H
I
(21) GHG00H
2) GH3OH
1) h2sok
jJHgGOOCl^
CHG00H
c(GKj)2m z C(GH3)2If 02
Similarly, the secondary beta-nitr© carboxylic ester was
converted to the dimethyl ester in 72 % yield (equation 22).
The possibility that this was unambiguous evidence
for an oxocarbonium ion was completely eliminated by
demonstrating that this method of esterifieatlon was
general for aliphatic acids. Thus, several dicarboxylic
acids were found to yield 70-82 % of the dimethyl ester
when subjected to these conditions (Table I). The actual
percentage of esterifieatlon is probably higher in these
eases as only the dimethyl ester was isolated. The
primary phenylacetic acid was esterifled in 90 % yield
whereas the maximum obtainable yield of methyl trimethyl
acetate was only 60 %,
CH2 C00H
1) EgSO^
2) CH3OH
OH2 COQCH3
CHCOOCHo (22) CHGOOCH3
G(GEj)zm z
CHCOOCHo
I *
G(GH3)2S02
Table I*
18
ACID % YIELD OF ESTER
Succinic 76
Glutaric 77.5
Adiplc 70
Sebacic 82
Phenylaeetle 90
Trimethylacetie 60
o-Sitrobenzoic O
' Phthalle 0
BenzoiclS 0
2,k,^-Trimethylbenzoie^(equation 15) 78
•»
This method may have considerable value as a chemical
means of separating aliphatic and aromatic acids.
Although Yan't Hoff lrfactors are unavailable
Ik
exeept for trimethylacetlc acid (1 = 1.99) and benzoic
acid1^ (1= 1.76-2.07), there is little doubt that the
remainder ionize in sulfuric acid by a proton transfer.
It is probable, therefore, that the mechanism Involved is
identical with that of the Fischer esterifieatlon in which
the catalyst concentration is many times smaller,
necessitating higher temperatures and longer reaction
times. If this is true, the explanation for the
nonreactivity of benzoic acid under the conditions of high
catalyst concentration, moderate temperature, and short
reaction times (1-2 minutes) should appear in the specific
rates of esterifieatlon. A comparison of the relative
19
rates of acid catalyzed esterifieatlon shows the specific
rate constant of benzoic acid to be lower than that of
trimethylacetie acid by a factor of eight (Table II).
The relatively low yield of methyl trimethylacetate
(Table I) is indicative of an approaching limit in the
scope of this method and thus, it is not surprising that
benzoic acid fails to react under these conditions.
Table II18
Relative Rates of Esterifieatlon
of RCOOH Under Standard Conditions
ACID k(relative)
Acetic 1.00
Propionic 0.83
2-Methylproplonlc 0.5^
Phenylacetic 0.56
Trimethylacetie 0.025
Benzoic 0.0030
The explanation for the large increase in the
observed velocity of esterifieatlon is found in the rate
expression for this process (equation 23). The first term
(23) Al|8ter)=ki(RCG0H)(H+)(CH30H) - k2(RC00CH3)(H+)(H20)
of this expression will greatly Increase in magnitude as it
Is dependent on the catalyst concentration. Conversely,
the second term will be suppressed by the excess of
catalyst due to a decrease in the effective water
concentration by proton acceptance. The net result is a
considerable augmentation of the esterifieatlon rate over
that observed under ordinary reaction conditions, thus
permitting lower temperatures and relatively short reaction
times.
Hone of these results or conclusions derived
therefrom lend support to the possibility of a different
mechanism functioning in the esterifieatlon of beta-nitro
carboxyllc acids. The oxocarbonium ion species of
o-benzoylbenzoic acid and 2,^,6-trimethylbenzoic acid do
not form under normal esterifieatlon conditions. Thus,
o-benzoylbenzolc acid yields only the normal ester and
2,if,6-trimethylbenzoiG acid esterifies much more slowly
than benzoic acid, in direct contrast to the results
obtained with solutions in sulfuric acid. There seems
little justification, therefore, to assume any mechanism
other than that involving the dihydroxycarbonlum ion in
the esterifieatlon of beta-nitro earboxylic aelds. The
structures assigned to the isomeric monoesters of 3-niethyl-
3-nitro-l,2-butanediearboxylic acid are probably correct.
21
It Is interesting to note that the only reported
instance of ionization to form an aliphatic oxocarbonium
ion is due to a sterle effect and not to a neighboring
group interaction. It was reported by Jacobs and
Florshelm that ethyl cis-meso-2,4-dlmethylcyclopentane-
carboxylate was rapidly hydrolyzed in 100 % sulfuric acid
(equation 2^).^ The Van*t Hoff i-factor of the carboxylic
G. The Ring Closure of 3-Methyl-3-nitro-l,2-butane-
\
diearboxyllc Acid.— The desirability of studying the
conditions under which 3-saethyl-3-nitro-l,2-butanedlcarb-
oxylic acid could be eyelized to the anhydride was twofold.
If the reaction were accomplished with retention of the
nitro group, the number of conditions to which this system
could be subjected would be increased. Secondly, the
cyclic anhydride would be a valuable Intermediate for
studies of the Frledel-Grafts reaction (succinoylation)
and certain unsymmetrieal ring opening reactions.
Ihen 3-niethyl-3-nitro-l,2-butanediearboxylic acid
was heated with acetic anhydride at 90-100° for 0.5 hour.
CHo\e00G2H5
GOGH
acid was found to be greater than 3
20
22
the cyclic anhydride was readily formed In yields of
80-90 % (equation 25). When the heating was allowed to
oh2gooh CH20s
I (CH3 CO)20 | /0
(25) GHGOGH -----2- ------ 5- CH-CT
I I ^0
G(GH3)2N02 G(CH3)2H02
proceed for one hour the solution became yellow and
nitrogen dioxide was slowly evolved. The yield of the
cyclic anhydride was somewhat lowered (77 %), and a careful
processing of the hydrolyzed filtrate permitted the
isolation of pure teraconic acid (6 %), verifying the
elimination reaction. This interesting result parallels
the elimination of water from beta-hydroxycarboxylic acids
under similar conditions. The formation of the cyclic
anhydride in essentially quantitative yield was effected
by the use of thionyl chloride or acetyl chloride at
relatively low temperatures and short reaction times. The
anhydride was formed in 99 % yield when the diearboxyllc
acid was refluxed with thionyl chloride (77°) for 0.5 hour
and in 98 % yield when refluxed with acetyl chloride (51°)
for 0.25 hour. The ease of anhydride formation is not
surprising as it is known that alkyl substituents markedly
increase the rate of such ring-closing reactions.^
23
The anhydride ie readily hydrolyzed to the diearboxylic
acid under acidic catalysis at 100°, but may be recovered
unchanged from a solution in 96 % sulfuric acid when this
solution is poured onto ice*
D. The Ammonoiysis and Alcoholysis of 3-Methyl-
3-nltro-l,2-butanedicarboxylie Anhydride.— The
ammonoiysis of 3-aethyl-3-nitro-l,2-butanedicarboxylic
anhydride was studied in order to further the knowledge of
the sterie effect of the 2-nitropropyl group and to
determine the behavior of the system with amines of
varying basicity. There are very few instances in which
the direction of cleavage of an unsymraetrieal cyclic
anhydride has been demonstrated unequivocally. Anschutz
showed by alternate synthesis that the principle product
obtained when ammonia cleaved phenylsuecinic anhydride
was the primary amide (equation 26).^
CHC00H
c6h5
Others have simply determined that only one amide was
obtained in the ammonoiysis reaction and have logically
assumed that the less hindered carboxyl group was attacked
(equation 2?).®
(27) (CH.
CH3CHC
: ^ (CH3)2CCOOH
GH^CHCONHG^H^
(assumed structure)
It is probably safe to follow this rule in most Instances,
especially when the attacking amine in large and highly
prone to steric factors.
The cleavage of 3-iaethyl-3’ '-mitro-l,2-butane-
diearboxyllc anhydride was carried out in benzene at
60-70° by addition of a benzene solution of the desired
amine. The weaker amines, such as aniline, o-toluidlne,
and phenylhydrazine, cleaved the anhydride smoothly under
these conditions in high yield with no observable heat
being liberated. Conversely, the cleavage by the
stronger aliphatic amines was vigorously exothermic,
nitrogen dioxide being evolved with a marked reduction
in the isolable yields. Only one amide was Isolated
in each Instance (equation 28), the assumption being that
25
CH2C^o ch2conhr
(28) GH-cC + RKH2 ^ CHGGGH
1 , 0 I
G(CH3)2HG2 C(GH^)2N02
the primary carboxyl group was attacked preferentially.
The results of this Investigation are summarized in
Table III*
Table III
Ammonoiysis of 3-Methyl-3-nitro-l,2-butanedicarboxyllc
Anhydride with Aromatic and Aliphatic Amines in Benzene
at 6©-?0©
Amine % Yield Melting Point
o-Toluidine 96 148-149° d.
Aniline* 8? 123-124° d.
Phenylhydrazine 82.5 149-150° d.
n-Dodecylamlne2 34 131-131.5° d,
n-Propylamine2,3 28 148-149° d.
Piperidine2 16.5 162-163° d!
1) Melting point depends on rate of heating; decomposition
begins at approximately 110°. 2) Exothermic with
evolution of nitrogen dioxide. 3) Yield Increased to 6l %
by effecting reaction of the anhydride with n-propylamine
in water.
26
The methanolysls of 3-aie thyl-3-nl tro-l,2-butane-
diearboxylic anhydride proceeded without catalysis yielding
63 % ©f the primary ester after refluxlng for one hour
(equation 29).
gh2c<^ gh2cooch3
I /Q -H GKLOH — ^ I
(29) GH-C<^ ? CHCOOH
C(GH3)2N02 C(CH3)2N02
The ester was difficult to purify, possibly due to the
presence of some secondary ester. The monoester obtained
in the alcoholysis reaction is the same as that obtained
by the controlled esterifieatlon of 3-niethyl-3-nltro-
1,2-butanedicarboxyllc acid (equation 10). The relatively
low yield of the primary ester parallels the results
obtained by Anschutz when phenylsucclnic anhydride was
21
subjected to methanolysls. Anschutz found that, although
the major product was the expected primary ester, a
significant quantity of the secondary ester (25 %) was also
present (equation 30). There are two competing factors in
ch2c' ch2cqoch3 ch2cooh
(30) 0H-<° 4-OH3OH --------0HC0GH + kc00CH3
°6H5 ° °6H5 ?s % <**5 25 J8
the basic cleavage of phenylsuceinlc anhydride. The size
of the phenyl ring lowers the probability factor for attack
at the secondary carboxyl group but its potential
electronegativity could increase the suseptibility of
attack at this position. As the 2-nitropropyl group is
known to be relatively electronegative compared to hydrogen
(2-nitropropane is a weak acid), it was considered
possible that the same situation would govern the eleavage
of 3-iaethyl~3-nitro-l,2-butanedlearboxylic anhydride.
When the attacking group is large, as in the ammonoiysis
reaction with an aromatic amine, the sterlc effect is
large enough to overcome the inductive effect resulting in
high yields of a single product. When the attacking group
is relatively small, as in the methanolysls reaction, the
1sterlc effect may not be large enough to completely
'overcome the activation of the secondary carboxyl group by
the electronegative substituent, resulting in a lower yield
of the primary ester.
It was desired to establish the structure of the
monomethyl esters with respect to one of the monoamides.
For this purpose the o-toluidlde was chosen. There are two
reasons for this choice. o-Toluldine cleaves the anhydride
unsymmetrically to give a 96 % yield of a single amide.
Secondly, the bulky structure of this hindered amine
28
(o-methyl group) makes the reaction at the primary carboxyl
group a virtual certainty. The relation of the primary and
secondary methyl esters to the o-toluidide will thus prove
the direction of cleavage in the methanolysls reaction and
will essentially establish the structures of these esters.
The o-toluldlde was converted to the sodium salt by
titration and then precipitated as the silver salt. The
silver salt was dried and refluxed in benzene with methyl
iodide for six hours (equation 31). The methyl ester of
GH3 CH3
oh2cqhh<^~~^ cn2v o m ^ y
(31) GHGQOAg OH3X ^ CHCOOCH3
| benzene I
G(CH^NO;? C(GH3)2N02
the o-toluidide was obtained in 31 % yield. 3-Garbomethoxy-
methyl-4-nitropentanolc acid was then converted to the
acid chloride by means of thionyl chloride. This was not
Isolated, due to thermal instability, but was obtained in
benzene solution, the thionyl chloride being removed by
repeated benzene distillations. The acid chloride
solution was allowed to react with o-toluidlne to form the
o-toluidide ester in an overall yield of 35 % (equation 32).
29
GH3
CHgCQOH CHgGOGl GHgCOHH^"^
(32) GHGOGGH3 ®QGXZ p CHCOOCH3 > GHGQQGH3
g(ch3)2ho2 c(ch3)2no2 c(ch3)2no2
The two o-toluidlde esters were shown to be identical, thus
supporting the postulated structures of the primary and
secondary methyl esters and demonstrating the direction of
methanolysls relative to ammonoiysis.
E* The Reaction of Some N-Substltuted Monoamides of
3-Methyl-3-nitro-l,2-batanedlcarboxylio Acid with
“Dehydrating" Reagents.— The ring closure of the anllide
to H-phenyl-3-methyl-3-nltro-l,2-butanedlearboxlmlde
(equation 33) was successfully carried out in 62 % yield
by employing acetyl chloride diluted with benzene. A red
color slowly developed during the 0.5 hour reflux period
indicating that more than one reaction was proceeding.
eH2ooNH , Q A-A
(33) CHGOOH ----------^ eH-0^ \=/
I I G
c(ch3)2hg2 c(ch3)2no2
30
A number of other unsuccessful attempts were made to
form the cyclic Imides from the H-substituted monoamides.
These amides (anilide, o-toluidide, and phenylhydrazine)
reacted rapidly with thionyl chloride at temperatures of
0-50° to form highly colored products of unknown
constitution. These products resisted purification by
:reerystalllzatlon and chromatography and were apparently
■ unchanged when heated with 40 % hydrochloric acid at 100°
for thirty hours. No solid material was found in the
hydrolysate liquor.
The anilide and o-toluldide were converted to
unworkable red oils by undiluted acetic anhydride (90-100°)
and acetyl chloride (51°) after ten minutes of heating.
These conditions are sufficient for the ring closure of
i 22
;suceinanilic acid (equation 3^). If the reaction mixture
is worked up before the red color develops, the amides are
recovered unchanged.
The anilide and o-toluidide were recovered unchanged
from their solutions in 96 % sulfuric acid after standing
ch2cooh
CH-C0C1
0
31
for one hour at room temperature. Pouring the solution
onto ice caused the precipitation of the amides. The
phenylhydrazlile, however, was partially hydrolyzed under
these conditions, the liberated phenylhydrazine being
identified as the phenylthiourea (reagent; phenyl isothio-
23
cyanate). J The treatment of the anilide with phosphorus
pentoxide under refluxing benzene (80°) for one hour was
without effect, the material being recovered in a state
of high purity. Finally, no ring closure was observed
when the anilide was dissolved in liquid hydrogen fluoride
and allowed to stand at room temperature for two hours.
Again, the anilide was recovered.
It is Interesting to consider a possible explanation
for the decomposition of the anilide under ring closing
conditions (acetyl chloride, thionyl chloride, or acetic
anhydride). If nitrous acid is eliminated, it is probable
that some H-nitroso-N~phenylamlde will be formed
(equation 35). These compounds are thermally unstable and
0H2C0HH^~^ CH2G0HH GH2C0N (HO)
(35) CHC00H G-CGQH
II
GH^-C-CH^
^ C-C00H
C(GH3)2N02
have "been shown by Grieve and Hey to decompose by a free
radical mechanism (equation 36). Polymerization and
GH2C0N(N0) GH2C<^
I v==/ I 0* r_,
(36) G-G0OH ________ ^ G-C00H -f H£ ^
GH3-G-GH3 CH3-iGH3
coupling reactions would be expected of these radicals
and the formation of a colored mixture resisting
purification would not be unusual.
An attempt was made to open H-phenyl-3-methyl-
3-nitro-l,2-butanedicarboxlaide by acid hydrolysis to form
the secondary anilide (equation 37). The N-phenylimide,
:0
+ f 2000H
(37) CH-C<^ v=/ H3° ^ CH-CONH^A
| ^ 0 | \ = /
G(CH3)2N02 C(CH3)2N02
however, proved resistant to hydrolysis and was recovered
unchanged after eleven hours of reflux with 5 % hydro
chloric acid. This reaction may be of use x*ith other
unsyrametrieal succinlmides where the more efficient basic
33
hydrolysis can be employed. Thus, the ammonoiysis of the
anhydride would yield the unhindered amide and the ring
closure followed by selective hydrolysis would afford the
isomeric, hindered amide.
F. Attempted Friedel-Crafts Reactions with 3-Hethyl-
3-nltro-l.2-butanedlcarboxyllc Anhydride.— Several
unsuccessful attempts were made to effect a Friedel-Crafts
reaction of 3-®s'fchyl-3-mitro-l,2-butanedicarboxylie
anhydride with an aromatic system. Anisole and p-xylene
were chosen for their known reactivity in this reaction,
aluminum chloride being used as the catalyst. Bark colors
formed Immediately on the addition of the aromatic compound
to the reaction mixture and tarry products were obtained
in each instance. The conditions employed are summarized
1 in Table IV.
I
Table IV
Friedel-Crafts conditions; Aluminum chloride catalyst
Aromatic System Solvent Temperature Time
Anisole Ethylene chloride ©o 2 hours
p-Xylene Nitrobenzene 2$° 1A.5 hours
p-Xylene Ethylene chloride o° 19 hours
A single effort was made to sucelnoylate toluene,
employing 3-iaethyl-3“nitro-l,2-butanediearboxyllc anhydride
3k
dissolved in 96 % sulfuric acid. The two phase system was
stirred for 0.5 hour at room temperature, the anhydride
(62 %) being recovered when the solution was hydrolysed
with ice. Further variations of catalyst, solvent, or
conditions were not tried.
©. The Attempted Preparation of Dimethyl 3-Hltro-
1.2-propanedlearboxylate and Dimethyl 3»3-Dlmethyl-4-nitro-
1.2-butanedicarboxylate.— Two attempts were made to
extend the use of amines as catalysts in the Michael
condensation.7 The condensation of nitromethane with
dimethyl fumarate was selected since the expected product,
dimethyl 3-nitro-l,2-propanedicarboxylate, would be of
interest for further worh in this field (equation 38).
The conditions employed were exactly those used in the
proceed steadily for about two days, when solution of the
dimethyl fumarate ceased. Continued standing for thirty
days did not effect further solution and the majority of
the ester (?0 %) was recovered by filtration.
CHC00CEU
(38) GHCOOCH3
— CH3HO2
CH2C00CH3
GHCOQCEU
1 3
CH0NO0
2-nitropropane condensation.? The reaction was observed to
Fractionation of the nitromethane solution yielded some
I-nitrosodiethylamine and dimethyl Itaconate (8 %).
Apparently the elimination reaction is more rapid in this
instance than is the condensation. This would explain the
observation that the reaction proceeded only about 25 %
to completion, as the diethylamine was converted to the
N-nitroso compound which is not an effective catalyst.
The attempted condensation of nitromethane with
dimethyl teraconate (equation 39) was earried out in the
CH2OOOCH3 CH2COOCH3
(39) G-GOOCH3 -1-CH3NQ2 Et3K ^ GHGGOCH3
CH3-C-GH3 CH3-C-CH3
ch2no2
presence of one mole of triethylamine per mole of ester.
The reaction mixture was allowed to stand at room
temperature for five months. Fractionation of the mixture
permitted an 85 % recovery of the dimethyl teraconate,
indicating that essentially no condensation had occurred.
This is not surprising in view of the reported
suseptibility of the Michael reaction to sterlc inter
ference when groups are substituted in the alpha or beta
positions.^-*
Elimination of nitrous Acid from 3-Methyl-
3-nitro-l,2-batanedtcarboxyllo Acid and its Derivatives.—
Previous work on these compounds by Kloetzel? and on
similar compounds by van Tamelen and Zyl^ has shown that
the elements of nitrous acid are readily eliminated under
basic conditions (equations 7, 11» and 40). In this sense
GH-a
I 3
OgN-C-CH(COQC2H5)g +- c->GH(C0002H5)2 — ____ ^
(40) CH3
GH3n ^cgoc2h3
g=g +- CH2(C00G2H5)2 4- ho2
CH3 C00C2H3
the beta-nitro earboxyllc acids resemble the beta-halo
earboxylic acids in which hydrogen chloride is eliminated
under basic conditions. Some work has been done with
elimination reactions of nitroalkanes and their derivatives
to show certain qualitative relationships. For example,
1,2-dlnitro alkanes eliminate nitrous acid under basic
1 conditions to yield the conjugated nitro olefin.2^ fhe
nitro olefins are also formed by the dehydration of
37
2-nltro alcohols with phosphorus pentoxide.2? More
informative are the results obtained with the acetates of
2-nitro alcohols and with halogen derivatives of nitro
alkanes. It has been shown in a number of instances that
the acetates of 2-nitro alcohols eliminate the elements of
acetic acid under basic conditions.That the acetate
group is much more readily eliminated than the nitro group
is shown by the 95 % yields of nitroolefins obtainable
through this reaction.2^ Furthermore, the elimination of
hydrogen bromide has been demonstrated to be the preferred
process in systems where both groups are in favorable
positions.30*31 prom -^freee observations it can be
concluded that beta-nitro earboxylic acids will undergo
*
basic elimination less readily than beta-bromo earboxylic
or beta-acetoxy earboxylic acids of the same carbon
skeleton.
The first nonbasic elimination reaction studied was
that occurring under the Influence of acetic anhydride.
It will be recalled that 6 % teraconic acid was isolated
after one hour of heating the dicarboxylic acid In acetic
anhydride at 90-100° (section G). That this was not simply
a slow thermal decomposition was shown by refluxing the
dicarboxylic acid in acetic acid (b.p. 118°) for three
hours. Mo discoloration or evolution of nitrogen dioxide
38
•was observed. However, the gas was evolved shortly after
the addition of aeetie anhydride (25 % by volume). The
evolution was slow and the refluxing was continued for
forty hours. From this solution it was possible to isolate
pure teraconic acid in 5^ % yield. The elimination of
nitrous acid under these conditions finds its counterpart
in the action of acetic anhydride on beta-hydroxy earboxylic
•acids. It is interesting to note that the dimethyl ester
.proved to be completely stable under similar conditions.
On the basis of this parallelism with beta-hydroxy
earboxylic acids it was considered possible that the beta-
nitro earboxylic acids would conform in another fundamental
reaction; that is, the elimination under acidic conditions.
It was realized immediately that if this reaction were
effected it would, of necessity, be very slow. This
conclusion follows from the observed stability of the system
in acidic hydrolysis reactions (section B), It was found
that a rapid evolution of nitrogen dioxide occurred if
3-methyl-3-nitro-l,2-butanedicarboxylic acid were heated in
96 % sulfuric acid for ten minutes at 80-90°. On dilution
and prolonged cooling it was possible to Isolate the gamma-
lactone, terebinic acid,^2 in 30 % yield (equation 41).
39
|H2 G00H OHoOOOH GOGH
(41) GHG0OH ■> CHCOOH
0(CH3)2 H02 CH3 -C-CH3
It was demonstrated by Kloetzel that teraconic acid would
the product is not surprising. The difficulty involved in
separating this water soluble product from a sulfuric acid
solution is such as to suggest the presence of a much
greater quantity than was isolated. That this elimination
proceeds only very slowly in aqueous solution was verified
by refluxing the dicarboxylic acid in 10 % hydrochloric
acid for 15© hours. A low melting mixture was obtained
from which the lactone was separated by fractional
crystallization in 12 % yield. Again, the means of
separation suggests the presence of more than was isolated,
possibly 30-40 % more. It has thus been demonstrated that
the beta-nitro group can be eliminated under at least two
conditions that are effective with beta-hydroxy earboxylic
acids.
It is worth noting that decarboxylation has not been
observed in conjunction with the elimination of the nitro
lactonize in the presence of 50 % sulfuric acid.^ Thus,
40
group. This reaction occurs with certain beta-halo
carboxylic acids under basie conditions and involves a
concurrent elimination and decarboxylation to yield an
olefln.^
I. The Thermal Stability of 3-Methyl--3-altro-l,2-
butanedlcarboxyllc Acid and its Derivatives.— Various
substituted succinic acid monoamides melt with
decomposition to form the cyclic lmides (equation 42).®
H H
1 I
CHo C-CONHo CH-sG~0v
^ I ^ melting ^ I
(42) CHoG-COOH CH-aG-G^
* * 1 *1 ^
CH3 ch3
0
This reaction occurs so readily in some instances that it
is difficult to obtain the true melting point of the
O
monoamide. As it was known that the beta-nitrodlcarbox-
ylic acid and the monoamides melted with decomposition
(Table III), it was considered important to study the
course of these reactions.
Very little work has been done on the pyrolysis of
nitro aliphatic compounds. One example, however, is very
interesting and again gives a qualitative picture of the
relative ease of elimination (equation 43). This reaction
was effected by Blomquist ejb the nitroolefin being
obtained In 8& % yield (compare section G; relative ease
of elimination).
The choice of conditions for the pyrolysis study was
partially dictated by the melting points of the derivatives
studied. As all of the compounds melted below 150° a
decomposition temperature of 145° was employed. The
reactions were carried out in an open tube immersed in an
oil bath, the temperature control being no poorer than £ 3°.
With the exception of the monoamides, which were found to
decompose rapidly, the melts were heated for a period of
two hours.
In each instance where decomposition occurred, the
process was one of nitrous acid elimination, even when ring
closure would have been predicted. Thus, 3-niethyl-3-nltro-
1,2-butanediearboxylic acid did not yield the anhydride,
but rather underwent a slow decomposition resulting in a
58 % isolable yield of teraconic acid. Similarly, the
phenylhydrazide, anilide, and n-propylamide rapidly
decomposed (5*~20 minutes) at their melting points with
,elimination of nitrous acid. The melts were hydrolyzed to
42
teraconie acid In yields of 14 %, 31 %% and 65 %
respectively. It should be stressed that these yields are
meaningless comparatively a,s considerable polymerization
and other side reactions occurred simultaneously. The
major objectives were to demonstrate that elimination had
occurred by the isolation of teraconie acid and to obtain
a qualitative idea of the relative rates of decomposition.
A study of the methyl esters provided additional
information. The dimethyl ester and the secondary
monomethyl ester were found to be relatively stable at 145°
!for two hours, whereas the primary monomethyl ester
decomposed at about the same rate as the dicarboxylie acid.
Teraeonlc acid was obtained in 50 % yield from the
hydrolyzed melt. A comparison of the structures shows that
the beta-nitro carboxylic acid structure appears necessary
for the decomposition under these conditions. That the
esterifieation of this system retards the decomposition was
strikingly demonstrated by showing that the methyl ester
of the o-toluldide (equation 36) was completely stable to
the prolonged heating. The o-toluidide itself decomposes
rapidly at itB melting point. Ho satisfactory explanation
has been realized for the rapid decomposition of the
monoamides. Possibly a different mechanism is Involved
(equations 28 and 29).
If cyelization were the first step in the
decomposition, then the anhydride and the N-pheny1imide
would necessarily decompose at least as rapidly as the
dicarboxylie acid and the corresponding anilide
respectively. This was found not to be true, the anhydride
and N-phenylimide being stable under the pyrolysis
conditions. This indicates that the thermal elimination
of the nitrous acid, whatever the nature of the mechanism,
is a primary process in each Instance and cannot pass
through these cyclic intermediates.
EXPERIMENTAL*
Reagents and Solvents
(1) Acetic acid: Bakers CP reagent
(2) Acetic anhydride: Mallinckrodt reagent grade
(99.5 %)•
(3) Acetone: b.p. 55-56.5°, redistilled commercial
product.
(4) Acetyl chloride: Mallinckrodt reagent grade.
(5) Adipie acid: m.p. 151-153°, Eastman Kodak Company
(6) Alumina, activated: Alcoa F-2G, Aluminum Company
of America.
(7) Aluminum chloride: Baker and Adamson Company,
anhydrous sublimed reagent.
(8) Aniline: b.p. 182-185°, Baker and Adamson reagent
redistilled from zinc dust.
(9) Anisole: b.p. 152-15^°, Eastman Kodak Company,
redistilled.
(10) Benzene: Bakers CP reagent, dried over sodium
wire.
(11) Diethylamlne: b.p. 55-56°, Eastman Kodak Company,
redistilled.
(12) Dimethyl fumarate: m.p. 101-102.5°, Fischer
esterificatlon of fumarle acid.
(13) n-Dodeeylamine: f.p. 25°, Armour and Company.
(14) Ether, absolute: Bakers CP reagent, dried over
sodium wire.
All melting points and boiling points are uncorrected
45
(15) Ethylene chloride: b.p. 82-83°, Mefford Chemical
Company, dried by codistillation and redistilled,
courtesy of R. Swidler.
(16) Glutarie acid: m.p. 94-96°, student preparation,
courtesy of N. Kharasch.
(17) Hydrochloric acid: Du Pont reagent grade.
(18) Hydrogen fluoride, liquid: Matheson Company.
(19) Methanol, absolute: b.p. 55-56°, distilled from
magnesium methylate.
(20) Methyl iodide: Paragon Division of the Matheson
Company.
(21) Nitrobenzene: b.p. 208-210°, redistilled student
preparation, courtesy of L. Cameron.
(22) o-Nitrobenzoic acid: m.p. 145-147°, by aqueous
permanganate oxidation of o-nltrotoluene.
(23) Nitromethane: Eastman Kodak Company.
(24) 2-Nitropropane: b.p. 119-121°r Commercial
Solvents Corporation, redistilled.
(25) Phenylaeetie acid: m.p. 76-77°, Eastman Kodak
Company.
(26) Phenylhydrazine: b.p. 239-243°, redistilled
product, source unknown.
(27) Phenyl isothiocyanate: Eastman Kodak Company.
(28) Phosphorus pentoxide: Assay 98 Baker and
Adamson reagent.
(29) Phthalic acid: m.p. 188-19©° d. (sealed tube),
Eastman Kodak Company.
(30) Piperidine: Eastman Kodak Company.
(31) n-Propylamine: Paragon Division of the Matheson
Company*
46
(32) Sebacic acid: m.p. 131-133°, Paragon Division
of the Matheson Company.
(33) Succinic acids m.p. 185-187°, Bakers CP reagent.
(34) Sulfuric acid: 96 Dm Pont reagent grade.
(35) Thionyl chloride: Hooker Electrochemical
Company, 8 High-Grade M.
(3^) Toluene: Bakers CP reagent.
(37) o-Toluidlne: b.p. 198-200°, Eastman Kodak
Company, redistilled, eourtesy of H. Swidler.
(38) Triethylamine: Paragon Division of the Matheson
Company.
(39) Trimethylacetie acid: m.p. 33-35°, student
preparation, courtesy of C. Kezarian.
(40) p-Xylene: b.p. 137-137.5°, redistilled product,
courtesy of H. Swidler.
4?
B. The Michael Condensation Reaction with 2-Hitropropane.
(1) Dimethyl 3-Methyl-3-nitro-lt2-butanedlcarboxy-
late.— Dlethylamine, 3,65 g. (0.05 mole), was added to a
slurry of 36 g. of dimethyl fumarate (0.25 mole) in 66.8 g.
of 2-nltropropane (0.?5 mole). The mixture was allowed to
stand at room temperature for fourteen days. The solution
of the ester was complete after three days with the
development of a green color. The excess 2-nitropropane
was removed on the steam bath under aspirator pressure, the
residual oil becoming dark brown. The oil was then
dissolved in a minimum volume of 1:1 benzene and petroleum
ether (b.r. 45-60°) and passed slowly through a ten inch
column (20 mm. diameter) of activated alumina (Alcoa F-20).
The dark impurities were absorbed strongly, a clear yellow
eluent being obtained. The solvents were removed on the
steam bath and the residual oil crystallized on cooling.
The solid was recrystallized from ether and petroleum ether
(b.r. 45-60°); yield, 40.5 g. (70 %)t m.p. 35-36°.
This method of purification is not superior to the
fractionation under pressure, which results in yields of
70-80 % J *
C. Esterlfication and Hydrolysis Reactions of 3-Methyl-
3-nitro-l,2-butanedlcarboxyllc Acid and its Esters.
(1) The Half Hydrolysis of Bimethyl 3-Methyl-
3-nitro-l,2-butanedjearboxylate.— Dimethyl 3-methyl-
3-nitro-l,2-butanedicarboxylate, 65 g. (0.279 mole), was
refluxed with 500 ml. of 3 % hydrochloric acid for three
hours. On cooling, an oil separated which crystallized
while standing at 0G for eight hours. The white solid
;was collected on a Buchner funnel and allowed to dry in
air: yield, 55 g* (90 %), m.p. 102-105°. a single
crystallization of the material from ether and petroleum
ether (b.r. ^5-60°) yields the pure 3-carbomethoxy-ty-
methyl-4-nitropentanoic acid, m.p. 108-110°.
This procedure is an improvement over that
presented by Kloetzel? in that it is not necessary to
concentrate the solution in order to realize a 90 % yield.
(2) The Complete Hydrolysis of Dimethyl 3-Methyl-
3-nitro-l,2-butanedlcarboxylate.— Dimethyl 3-methyl-
3-nitro-l,2-butanedicarboxylate, 30 g. (0.128 mole), was
added to 300 ml. of 10 % hydrochloric acid and heated on
the steam bath for thirty hours. The ester went into
solution after twenty hours. The volume of the solution
was reduced to about 30 ml. by distillation at aspirator
pressure on the steam bath* The solution was seeded with
the dicarboxylie acid and cooled to 0°. Crystallization
was rapid and the solid was separated and allowed to dry
49
In air; yield, 23.5 g. An additional 0.5 g. was obtained
by concentrating the mother liquor; total yield, 24.0 g.
(91 fa), m.p. 135-140° d. A single crystallization from
water yielded pure 3-aiethyl-3-nitro-l, 2-butanedicarboxylic
acid, m.p. 144-145° d.
(3) The Sulfuric Acid Esterlflcation of 3-Methyl-
3-nitro-i,2-butanedlcarboxyllc Acid.— 3-Methyl-3-nitro-
1,2-butanedicarboxylie acid, 10 g. (0.04-88 mole), was
powdered and dissolved in 4-0 ml. of 96 % sulfuric acid. The
rate of solution is slow at room temperature. This solution
was poured slowly, with stirring, into 150 ml. of methanol
cooled in an ice bath. The resulting solution was then
poured on 200 g. of iee and seeded with 1-carbomethoxy-
3-methyl-3-nitro-2-butaneearbQxylle acid. A white,
;crystalline solid separated and was collected on a sintered
glass funnel, being washed with a few milliliters of cold
water. The solid was allowed to dry in air; weight,
6.80 g., m.p. 43-49°. The material was found to be soluble
in 1M sodium carbonate. Only a minor residue was
insoluble, indicating the presence of small amounts of the
dimethyl ester. The material was crystallized from ether
and petroleum ether (b.r. 45-60°); yield, 5.52 g. (52 fa) t
m.p. 60-65°. Recrystallization Increased the range to
69-73°. A mixed melting point with an authentic sample of
50
the primary monoester showed no depression.
(4) The Sulfuric Acid Esterlfieatlon of 3-Carbo-
methoxy-4-methyl-4-nltropentanolc Aeld.— 3-Garbomethoxy-
4-methyl-*J~nitropentanoic aeld, 3 g* (0.0137 mole), was
dissolved In 10 ml. of 96 % sulfuric acid. This solution
was poured slowly, with stirring, into 15 ml. of methanol
cooled in an ice bath. The solution was then poured onto
100 g. of ice. A seed crystal of the dimethyl ester was
added to induce crystallization. The material was collected
in a sintered glass funnel and washed with a small amount
of water. The solid was allowed to dry in air; yield
2.30 g* (72 %), m-p. 31-33°. Crystallization from ether
and petroleum ether (b.r. ^5-60°) raised the melting point
to 35-36°.
B. The Sulfuric Aeld Esterlficatlon of Various Aliphatic
Acids.
(!) Succinic Acid.— A solution of succinic acid,
20 g. (0.1? mole), was prepared in 50 ml. of 96 % sulfuric
acid and poured slowly, with stirring, into 70 ml. of
methanol cooled in an ice bath. This solution was poured
on 200 g. of ice. The mixture was extracted with one
,200 ml. and two 100 ml. portions of benzene. The combined
extracts were washed with water, sodium carbonate solution,
and water again. The wet benzene was pumped down on the
51
steam bath, the water eodistilling In the process. The
residual ester was distilled at normal pressure; yield,
18.75 g* (76 %)> b.p. 189-190°, f.p. 18.0°. The literature
values are: b.p. 195*3°, f.p. 18.5° and 18.7°.55,36
(2) G-lutarlc Acid.— Glutarlc acid, 10 g.
(0.0758 mole), was dissolved in 96 % sulfuric acid and
poured slowly, with stirring, into 50 ml. of methanol
cooled in an ice bath. This solution was processed as in
the, esterlficatlon of succinic acid, the ester being
distilled at normal pressure; yield, 9.4 g. (77*5 %)*
b.p. 204—208°. The literature value is: b.p. 213.5-214'°.3?
(3) Adiplc Acid.— A solution of adlpic acid, 20 g.
(0.137 mole), was prepared in 5® ml* of 96 % sulfuric aeid
and poured slowly, with stirring, into 5® ml. of methanol
cooled in an ice bath. This solution was processed as in
the esterlficatlon of succinic acid, the ester being
distilled at normal pressure; yield, 16.6 g. (70 %),
b.p. 224—225°, f.p. 9*5°. The literature values are:
b.p. 10?.6°/11 mm., f.p. 10.3°.36
(4. ) Sebacic Acid.— Ten grams of sebaeic acid
(0.04-95 mole) was dissolved in 4-0 ml. of 96 % sulfuric acid
and poured slowly, with stirring, into 4-0 ml. of methanol
cooled in an ice bath. This solution was processed as in
52
the esterlfication of succinic acid, the ester being
distilled under reduced pressure; yield, 9.4 g. (82 %),
b.p. 109-111°/*!'.0 mm., f.p. 24.9°. The literature values
are: b.p. 175°/20 mm,, f.p. 26.4° and 26.6°.36,38
A sample of dimethyl sebacate was prepared by a
Fischer esterifIcation, f.p. 25.5°. A mixed freezing point
determination showed no depression, f.p. 25.2°.
(5) Phenylaeetlc Aeld.— Phenylacetic acid, 20 g.
(0.147 mole), was dissolved in 50 ml* of 96 % sulfuric acid
and poured, with stirring, into 50 ml. of methanol cooled
in an ice bath. This solution was processed as In the
esterlficatlon of suceinie acid, the ester being distilled
at normal pressure; yield 19.8 g. (90 %), b.p. 214-218°.
The literature value is: b.p. 220°.
(6) Trlmethylacetlc Acid.— Twenty grams of tri-
methylaeetic aeid (0.196 mole), was dissolved in 50 ml. of
96 % sulfurle acid and poured slowly, with stirring, into
50 ml, of methanol cooled in an ice bath. This solution
was processed as in the esterlficatlon of succinic acid,
ether being used in place of benzene as an extracting
solvent. The ether solution was dried over ealcium sulfate
(Drlerite) and fractionally distilled; yield, 13.6 g.
(60 %), b.p. 97-100°. The literature value is:
99.5-100°.
53
(7) o-Nitrobenzolc Aeld.— o-Hitrobenzoic aeld,
1.0 g., was dissolved In 10 ml. of 96 % sulfuric acid and
slowly added, with stirring, to 15 ml. of methanol cooled
in an iee bath. This solution was poured on 40 g. of ice.
A pale-yellow, crystalline solid separated on standing.
.This was collected in a sintered glass funnel and washed
with a small quantity of water. The solid was allowed to
dry in air; weight, 0.?2 g. (72 % recovery), m.p. 143-145°.
A mixed melting point with the starting material showed no
depression.
(8) Phthalic Acid.— Two grams of phthalic acid was
dissolved in 20 ml, of 96 % sulfuric aeld and poured
slowly, with stirring, into 20 ml. of methanol cooled in an
ice bath. This solution was poured on 50 g. of ice,
'causing a white solid to precipitate. The solid was
collected in a sintered glass funnel and washed with a
small quantity of cold water. The material was allowed to
dry in air; weight, 1.80 g. (90 % recovery),
m.p. 187-188° d. (sealed tube). A mixed melting point
with the starting material showed no depression .
E. Ring Closing Reactions of 3-Methyl-3-nitro-l,2-butane-
dlearboxylic Acid and the N-Substituted Monoamides.
(1) The Action of Acetic Anhydride on 3-Methyl-
3-nltro-l,2-butanedlcarboxylic Acid.— Five grams of
54
3-methyl-3-nitr©-l,2-butanedicarboxylie acid (0,0244 mole)
was added to 8 ml. of acetic anhydride. The mixture was
heated for one hour on the steam bath, the solid going into
solution after a few minutes of heating. The dicarboxylie
anhydride crystallised readily when the solution was cooled.
The solid was collected on a Buchner funnel and washed with
petroleum ether (b.r. 45-60°); yield 3.50 g. (77 %) $
m.p. 110-112°. Crystallization from acetone and petroleum
ether (b.r. 45-60°) yielded pure 3-methyl-3-nltro-
1,2-butanediearboxylic anhydride as white scales,
m.p. 112-112.5°.
. Anal. Calcd. for G?H^©5 : C, 44.92 » H, 4.84.
Found: G, 45.06 ; H, 4.6l.
The filtrate was hydrolyzed by heating with 10 ml.
of water for one hour. The volume of the solution was
reduced to about 6 ml. oh the hot plate and then cooled to
0°. Transparent needles separated slowly in dusters over
a period of three days. The crystals were separated and
identified as teraconic acid by a mixed melting point with
an authentic sample; yield, 0.30 g. (6 %), m.p. l67-l69°d.
Yields of the dicarboxylie anhydride as high as
91 % are possible if the heating period is reduced to
0.5 hour and the ratio of acetic anhydride to the
dicarboxylie acid is reduced (I.25 g. acid/ml. acetic
55
anhydride). The anhydride was readily hydrolyzed by
refluxing two hours with 10 % hydrochloric acid yielding
the pure dicarboxylie acid, m.p. 145-146° d.
Action of Thionyl Chloride on 3-Methyl-
3-nltro-l,2-butanediearboxylle Acid.— 3-Methyl-3-nitro-
1,2-butanedlcarboxylic acid, 2.05 g. (0.01 mole), was
refluxed with 8 ml. of thionyl chloride for 0.5 hour. A
white solid began to separate on cooling. Five milliliters
of petroleum ether (b.r. 45-60°) was added and the contents
were cooled to 0° to complete the crystallization. The
solid (white scales) was collected in a sintered glass
funnel and washed with petroleum ether (b.r. 45-60°). The
solid proved to be 3-siethyl-3-nltr©-l,2-butanedIearboxylie
anhydride; yield, 1.86 g, (99 %), m.p. 102-107°.
Crystallization from acetone and petroleum ether raised the
melting point to 110-112°.
(3) The Action of Acetyl Chloride on 3-Methyl-
3-nltro-l,2-butanedloarboxyllc Acid.— 3-Methyl-3-nitro-
'1,2-butanediearboxylic acid, 2.05 g. (0.01 mole), was
refluxed with 8 ml. of acetyl chloride until the solid
went into solution (15 minutes). On cooling, a white solid
precipitated. Petroleum ether (b.r. 45-60°), 5 ml., was
added and the mixture cooled to 0° to complete the
separation. The white solid was collected and washed with
56
.petroleum ether (b.r. 45-60°). A mixed melting point with
an authentic sample identified the solid as the dicarboxylie
anhydride; yield, 1.83 §• (98$), a.p. 104-108°.
Recrystallization raised the melting point to 110-112°,
Action of Acetic Anhydride on the o-Toluidide
of 3-Methyl-3-nltro-l,2-butanediearboxylle Acid.— One gram
of the o-toluidlde was heated on the steam bath with 5 al«
of acetic anhydride for ten minutes. A cherry red color
developed rapidly and on hydrolysis of the solution, a red
oil separated which resisted efforts to cause
crystallization. If the solution was hydrolyzed before the
red color developed, the starting material was recovered.
(5) Action of Acetyl Chloride on the Anlllde of
3-Methy1-3-nltro-l,2-butanediearboxylle Acid.— One gram
of the anilide was heated with 5 al. of acetyl ehloride
on the steam bath for ten minutes. A dark red color
rapidly developed and a red, viscous oil separated on
cooling which could not be crystallized.
These are the conditions under which succinanilic
acid is closed to N-phenylsuecinimlde.2^
(6) The Aetlon of Thionyl Chloride on the Anlllde of
3-Methyl-3-nitro-l,2-butanedlearboxylle Acid.— Two grams
of the anilide was allowed to react with 10 ml. of thionyl
chloride at room temperature for one hour. The solution
57
was hydrolyzed hy pouring on ice, a red oil separating as
the hydrolysis proceeded. The oil was extracted with 5©
of benzene and the solution was dried over calcium sulfate
(Prierite). The red solution was passed through a ten inch
column of activated alumina (Alcoa F-20), the colorless
s
eluent being collected. On evaporation, however, it was
i
found that the eluent contained no solid material.
Fractional elution of the column yielded only colored oils.
(7) The Action of Thionyl Chloride on the Phenyl-
hydrazide of 3-&e'fchyl-3-nltro-l,2-butanediearboxylle Acid.—
One gram of the phenylhydrazlde was allowed to react with
5 ml, of thionyl chloride in 10 ml. of benzene at room
temperature. The material went into solution, turning first
green and then nearly blacK in color. After standing for
0.5 hour, the solution was hydrolyzed with 3© g. of ice.
Evaporation of the benzene left an orange-red solid which
resisted efforts to effect purification. This material
was heated on the steam bath with 40 % hydrochloric acid
for thirty hours. The substance did not go into solution
or undergo hydrolysis as the filtrate was shown to contain
no solid material.
(8) The Action of Phosphorus Pentoxide on the Anlllde
of 3-Methy1-3-nltro-l,2-butanedlcarboxylle Acid.— One gram
of the anilide was refluxed with 2 g. of phosphorus
pentoxide in 15 ml. of benzene for one hour. The mixture
was cooled and hydrolyzed by the addition of 10 g. of ice.
The benzene was then evaporated on the steam bath. On
cooling, a white solid separated which was collected and
washed with a small quantity of water. The material was
crystallized from acetone and petroleum ether (b.r. 45-60°)
weight, 0.75 g* (75 % recovery), m.p. 119.5-121° d. A
mixed melting point with the anilide showed no depression.
(9^ Action of Sulfuric Acid on the Anilide of
3-Hethyl-3-nitro-l,2-butanediearbQxylie Acid.— One gram
of the anilide was dissolved in 5 ml. ®f 96 % sulfuric
,acid. The solution was maintained at 50° on the steam bath
for five minutes and then hydrolyzed by pouring on 30 g. of
ice. A sticky, white material separated and slowly
solidified. The solid was collected and crystallized twice
from acetone and petroleum ether (b.r. 45-60°); weight,
0.45 g. (^5 % recovery), m.p. 117-118° d. A mixed melting
point with the anilide showed no depression.
(10) The Action of Sulfuric Acid on the Phenyl-
hydrazide of 3-Methyl-3-nltro-l,2-butanedlcarboxylie Acid.-
Three grams of the phenylhydrazide was dissolved in 10 ml.
of 96 % sulfurie acid. A strawberry red color developed
and darkened to a purple-red after a few minutes at room
temperature.^ After standing for fifteen minutes the dark
59
red solution was poured onto 50 g, of ice. The color was
discharged instantly but no solid material separated. The
solution was carefully neutralized to a phenolphth&lein
endpoint with concentrated sodium hydroxide. A small amount
r
of oil separated at the endpoint. Phenyl lsothiocyanate,
0.5 ml., was added with shaking. After a few minutes of
shaking a small amount of a gummy, brown solid separated.
The solid was removed and crystallized from 95 $ ethanol
after a single treatment with activated carbon (Nuehar C);
very light, colorless needles formed, m.p. 173-17^° d.
An authentic sample of the phenyl thiourea of phenyl-
hydrazine was prepared and crystallized from 95 % ethanol,
m.p. 172-173° d. A mixed melting point showed no
depression. It may be concluded then, that one of the
processes occurring in this reaction was hydrolysis. It is
interesting that this was not observed with the anilide.
(11) The Action of Anhydrous Hydrogen Fluoride on the
Anlllde of 3-Methyl-3-hltro-l,2-butanedlearboxyllc Acid.—
Two grams of the anilide was placed in a copper flask with
one inlet attached to a tank of anhydrous hydrogen fluoride.
The copper flask was placed in an ice bath and approximately
25 ml. of hydrogen fluoride was allowed to condense. The
flask was sealed and permitted to stand at room temperature
for two hours. After cooling and venting the flask, the
hydrogen fluoride solution was poured into a copper beaker
and allowed to evaporate. The brown residue was dissolved
in acetone and treated with activated earbon (Huehar C).
The solution was evaporated to about 5 ol. and 5 ml* of
petroleum ether (b.r. 45-60°) was added. On cooling to 0°
and seeding with the anilide a slow crystallization occurred.
The crystals were oily and were recrystallized from the
same solvent pair; weight 1.02 g. (51 % recovery),
m.p. 116-117° d. A mixed melting point with the anilide
showed no depression. Evaporation of the mother liquor
yielded an oil which could not be crystallized.
(12) The Preparation of H-phenyl-3-methyl-3-nltro-
1,2-butanedlearboxlmlde.— Benzene, 40 ml. , and acetyl
chloride, 20 ml., was added t© 16.80 g. (0.06 mole) of the
anilide. The mixture was refluxed on the steam bath for
ten minutes, hydrogen chloride being evolved. An additional
15 ml. of acetyi chloride was added and the refluxlng was
continued until all of the solid was in solution; total
reflux time, 0.5 hour. The cherry red solution was reduced
in volume on the steam bath to about 4© ml. to eliminate
the excess acetyl chloride. Benzene, 2© ml., was added and
the solution was eooled to 5°» ©rystallization was induced
by scratching and the white solid was collected and washed
with 20 mi. of benzene; yield, 9.80 g. (62 %)t
61
m.p. 131-133°. Two crystallizations from acetone and
petroleum ether (b.r. 45-60°) did not change the melting
point. The material separated as white needles and was
insoluble in sodium bicarbonate solution.
Anal. Caled. for : N, 10.68*
Found: N, 10.36, 10.4?.
F. The Ammonolysis and Aleoholysis of 3-Methyl-3-nitro~
1,2-butanediearboxylic Anhydride.
(1) The Ammonolysis of 3-Methyl-3-nltro-l,2-butane-
dlcarboxyllc Anhydride with o-Toluldlne.—- 3-Methyl-
3-nitro-l,2-butanedicarboxylic anhydride, 5 g. (0.026? mole)
was dissolved in 100 ml. of benzene on the steam bath. To
this solution was slowly added 2.86 g. (0.026? mole) of
o-toluidine in 20 ml. of benzene. A white solid separated
1 and the solution became yellow. The contents were heated
on the steam bath for ten minutes and allowed to cool. The
solid was collected and washed with 20 ml. of benzene;
yield, 7.55 g. (96 %)t m.p. 143-145° d. Two crystalli
zations from acetone and petroleum ether (b.r. 45-60°)
raised the melting point to 148-149° d. The o-toluldide
separated as white needles.
Anal. Calcd. for : C, 57.15 » H, 6.16.
Found: C, 57-41 J H, 6.36.
(2) The Ammonolysis of 3-Methyl-3-nitro-l,2-butane-
dicarboxylie Anhydride with Aniline,— 3-Methyl-3-nitro-
1,2-butanediearboxylle anhydride, 10 g. (0.0535 mole), was
dissolved in 100 ml, of hot benzene. To this soltition was
slowly added 5 g* of aniline (0.054 mole) in 30 ml. of
benzene. The solution was heated on the steam bath for
twenty minutes, becoming yellow and depositing a white
solid. The contents were allowed to cool and the solid was
collected in a Buchner funnel. After washing with 40 ml.
of benzene and allowing to dry, the solid weighed 13.0 g.
(87 %), m.p. 121-122° d. The anilide separated from the
acetone and petroleum ether (b.r. 45-60°) as white needleB,
m.p. 123-124° d. The melting point of this compound
varied considerably, depending on the rate of heating.
Anal. Galcd. for » G, 55*69 » H, 5*75*
Found: C, 55*64 ; H, 5*71.
(3) The Ammonolysis of 3-Methyl*-3-nltro-l,2-butane-
dlearboxyllc Anhydride with Phenylhydrazlne♦— Phenyl-
hydrazine, 5*8 g. (0.054 mole), in 40 ml. of benzene was
added slowly to 10 g. of 3-methyl-3-nitro-l,2-butane-
dicarboxyllc anhydride (0.0537 mole) dissolved in 100 ml.
of hot benzene. The solution was heated on the steam bath
for ten minutes, a white solid separating in the process.
The contents were cooled and the solid was collected and
washed with 20 ml. of benzene; yield, 13.9 g. (82.5 %),
m.p. 146-147° d. The phenylhydrazlde separated from
acetone and petroleum ether (b.r. 45-60°) as small, white
scales, m.p. 149-150° d.
Anal. Caled. for : 0, 52.88 ; H, 5-81.
Found : C, 52.?6 ; H, 5.88.
(4) The Ammonolysis of 3-Methyl-3-nltro-l,2-butane-
dlcarboxyllc Anhydride with n-Dodecylamlne.— n-Dodeeyi-
amine, 5 g. (0.027 mole), was added slowly to 5 g* ©*
3-methyl-3-nitro-l,2-butanedicarboxylic anhydride
(0.0268 mole) in 100 ml. of hot benzene. The reaction was
exothermic and nitrogen dioxide was visibly evolved
(probably due to a local concentration effect). The
solution was heated on the steam bath for five minutes and
allowed to cool. Only a small amount of solid separated
and the solution was again raised to boiling on the steam
bath. Petroleum ether (b.r. 45-60°), 80 ml., was added
and the solution cooled. The solid which separated was
soapy in consistency and appearance. After collecting
and drying, the dodecylamide was crystallized from acetone,
separating in small silvery scales; yield, 3.4 g. (3^ %)$
m.p. 128-130° d. Recrystallization from acetone raised
the melting point to 131-131.5° d.
Anal. Calcd. for O19H36N2O5 : 0, 61.26 ; 1, 9.74.
64
Found: C, 61.12 ; H, 9*53*
(5) The Ammonolysis of 3-Methyl-3-nltro-l,2-butane-
dlcarboxylic Anhydride with n-Propylamlne.— Ten grams
of 3-siet;hyl-3-nltro-l, 2-butanediearboxylic anhydride
(0.0537 mole), was dissolved In 100 ml. of hot benzene.
To this solution was slowly added 3*2 g* of n-propylamine
(0.054 mole) In 30 ml* of benzene. The reaction was
exothermic and caused the benzene to reflux. A white
solid separated from the solution on cooling and was
collected on a Buchner funnel. The solid was very gummy
and had to be crystallized twice from acetone and petroleum
ether (b.r. 45-60°); yield, 3.70 g. (28 %),
m.p. 148-149° d. The n-propylamlde separated from acetone
as white flakes, m.p. 148-149° d.
Anal. Galcd. for * N, 11.37*
Found: H, II.25.
(6) The Ammonolysis of 3-Methyl-3-nitro-l,2-butane-
dlearboxyllc Anhydride with Piperidine.— Piperidine,
2.3 g* (0.02? mole), in 40 ml. of benzene was added
slowly to 5 g* of 3-methyl-3-nitro-l,2-butanedicarboxylic
anhydride (0.0268 mole) dissolved in 200 ml. of hot
benzene. A small amount of gummy solid separated. The
volume was reduced to about 50 ml. on the steam bath.
On cooling, an oil separated. The solvent was allowed to
evaporate In an open dish, leaving the oil behind. After
several days of standing, partial crystallization occurred.
The material was crystallized three times from acetone
and petroleum ether (b.r. 45-60°), separating as white
needles; yield, 1.2 g. (16.5 %), ®.p. l6l-l63° d.
Anal. Calcd. for Ci2H20N2°5 :
Found: H, 10.42.
(7) The Aqueous Ammonolysls of 3-Methyl-3-nitro-
1,2-butanedlcarboxylle Anhydride with n-Propylamlne.—
Five grams of 3-®ethyl-3-nitro-l,2-butanedicarboxyllc
anhydride (0.026? mole) was dissolved In 40 ml. of water
containing 3*54 g. of n-propylamine (0.06 mole) with
warming. The solution was cooled and acidified with
hydrochloric acid. A white solid separated and was
collected and washed with 10 ml. of water. The material
was dried in a vacuum desiccator over calcium chloride
and crystallized from acetone and petroleum ether (b.r.45-
60°); yield, 4.0 g. (61 %), m.p. 141-142° d. A mixed
melting point with an authentic sample of the n-propyl-
amide showed no depression.
This method Is applicable to all of the water
soluble amines and is a superior method of preparation.
(8) The Alcoholysls of 3-Methyl-3-nitro-l,2-butane-
dlcarboxyllc Anhydride with Methanol.— Four grams of
3-methyl-3-nltro-l,2-butanedicarboxylie anhydride
(0.0214 mole) was dissolved in $0 ml. of methanol and
refluxed for one hour. The methanol was pumped off on the
steam hath leaving a colorless oil. The oil was dissolved
in 10 ml. of 1:1 ether and petroleum ether (b.r. 45-60°),
the solution being cooled to 0° and seeded with 1-carbo-
raethoxy-3-methyl-3-nitro-2-butaneearboxylie acid. A very
slow crystallization occurred, requiring several days for
completion. The colorless crystals were separated and
o
washed with petroleum ether (b.r. 45-6© ); yield, 2.95 g*
(63 %), m.p. 66-73°. ®ke monoester was recrystallized
from the same solvent pair, m.p. 71-74°. A mixed melting
point with an authentic sample of l-carbomethoxy-3-methyl-
3-nitro-2-butanecarboxylic acid showed no depression.
(9) The Attempted Hydrolysis of H-Phenyl-3-methyl-
3-nltro-l,2-butanedlcarboxlmide.— Four grams of N-phenyl-
3-methyl-3-nitro-l,2-butanedlcarboximide was refluxed for
eleven hours with 150 ml. of 5 % hydrochloric acid. Some
of the H-phenylimide went into solution. The solution was
filtered hot to separate the water soluble fraction from
the unreacted N-phenylimide. After drying, the unreacted
material weighed 2.80 g., m.p. 131-133°. The filtrate, on
eooling, deposited white, fluffy needles. This
crystalline material was collected and dried; weight,
O.kO g., m.p. 127-132°. A mixed melting point with an
authentic sample of I-phenyl-3-*methyl-3-nitro-l, 2-butane-
diearboximide showed no depression; total weight, 3.20 g.
(80 % recovery).
G. The Relationship Between 3-Cax*b©fflethoxy-Ji~-methyl-
^-nltropentanoic Acid and the o-Toluidlde of 3-Methyl-
3-nltro-l,2-butanediearboxylle Acid.
(1) The Ammonolysis of 3-Garbomethoxy-4-methyl-
If-nitropentanoyi Chloride with o-Toluldine.— 3-Carbo-
methoxy-4-methy1-4-nitropentanolc acid, 10 g. (0.0^57 mole),
was refluxed with 60 ml. of thlonyl chloride for 0.5 hour.
To the orange solution was added 300 ml. of benzene. The
solution was then pumped down to about 100 ml. in volume.
This process was repeated three times with 250 ml.
portions of benzene. A previous attempt to remove the
thionyl chloride by a simple distillation on the steam
bath resulted in extensive decomposition; this method
was thus necessary. To the cooled benzene solution of the
acid chloride was added 9.8 g. of o-toluidlne (0.092 mole)
in 30 nil. of benzene. A fluffy white precipitate formed.
After standing for one hour at room temperature the solid
was collected and washed with benzene. The material was
soluble in water and was assumed to be the o-toluidlne
hydrochloride; yield, 6.35 g. (97 %)• The filtrate,
which had become dark red, was washed once with 50 %
hydrochloric aeid and once with water. The solution was
dried by codistillation, the volume being reduced to about
100 ml. The solution was treated three times with
activated carbon (Uuchar C) to effect decolorizatlon and
was then reduced to about 50 ml. in volume. On eooling,
a white crystalline material separated which was collected
and washed with petroleum ether (b.r. 45-60°). The crude
solid was recrystallized from methanol, separating as
small,; white needles; yield, 4.94 g. (35 i>),
m.p. 121.5-125°. The melting point of the methyl ester of
the o-toluidide was raised to 124-126° by a final
crystallization from methanol.
Anal. Galcd. for
^15^20^2^5 • * ^^ *
Found: N, 9.20.
(2) The Silver Salt Bsterlfleatlon of the o-Tolui-
dlde of 3-Methyl-3-nitro-l,2-butanedlcarboxyllc Acid.—
The o-toluidide, 3.6 g. (0.0122 mole), was suspended in
80 ml. of water and titrated to the phenolphthalein
end-point with 10 % sodium hydroxide. The silver salt was
then precipitated by adding 2.5 g. of silver nitrate
(0.0147 mole) in 50 ml. of water. The white solid was
collected and washed with a small quantity of water (it is
very soluble in methanol and somewhat soluble in water).
The wet silver salt was placed in 200 ml. of benzene and
the water was removed by codistillation. The silver salt
was now yellowish-green due to the action of light. To
the benzene (about 100 ml.) and silver salt was added 5 ml.
of methyl iodide (0.08 mole), the mixture then being
refluxed for six hours. Activated carbon (Nuehar G) was
added and the solution was filtered. The colorless
filtrate was pumped down to about 30 ml* and then allowed
to evaporate in an open dish. A mass of white needles
remained; yield 1.15 g. (90.6'ft), m.p. 122-125°. The
material was crystallized from methanol, separating as
small, white needles, m.p. 124-126°. A mixed melting
point with the compound prepared by the ammonolysls of
3-carbometh©xy-ty-methyl-4-nitropentanoyl chloride with
o-toluidine showed no depression.
H. Some Attempted Friedel-Crafts Reactions of 3-^ethyl-
3-nitro-l,2-butanedicarboxylie Anhydride on Aromatic
Compounds.
(1) The Attempted Succinoylatlon of Anlsole with
3-Hethyl-3-nltro-l,2-butanediearboxylie Anhydride.—
3-Methyl-3'-nitro-l,2-butanediearboxylie anhydride, 0.38 g.
(0.0020 mole), was dissolved in 10 ml. of ethylene
chloride and cooled to 0° in an Ice bath. To this solution
was added 0.60 g. of aluminum chloride (0.0045 mole) with
shaking. Anisole, 0.43 g. (0.004 mole), was then added
dropwise with shaking. A dark red color developed
immediately and the mixture was allowed to stand at 0°
for two hours. Fifteen milliliters of 30 % hydrochloric
acid was added slowly with shaking followed by 25 ml. of
water. The excess anisole was then removed by steam
distillation. A black, tarry residue remained which could
not be purified.
(2) The Attempted Succlnoylation of p-Xylene with
3-Hethyl-3-nltro-l,2-butanediearboxyllc Anhydride.—
3-Methyl-3-nitro-l,2-bmtanedlcarboxylic anhydride, 0.50 g.
(0.002? mole), was dissolved in 10 ml. of nitrobenzene at
room temperature. Aluminum chloride, 0.82 g. (0.0062
mole), was added with shaking causing the formation of an
orange color. The p-xylene, 0.50 g. (0.004? mole), was
added dropwise, the color changing instantly to a dark red
and becoming almost black as the addition proceeded. The
solution was allowed to stand at room temperature for
14.5 hours. The mixture was hydrolyzed by adding ice and
hydrochloric acid and was .then submitted to steam
distillation to remove the nitrobenzene. A black solid
separated as the distillation proceeded. Efforts to
purify this material were unsuccessful.
This reaction was repeated with the same stoichi
ometry, employing 15 ml. of ethylene chloride in place of
10 ml. of nitrobenzene. The reaction was allowed to
proceed at room temperature for nineteen hours. The black
solution was hydrolyzed with ice and hydrochloric acid in
a separatory funnel. The acid layer was drained off and
the ethylene chloride solution was washed twice with water.
The ethylene chloride was then extracted with sodium
carbonate solution. Mo precipitate was formed when the
extract was acidified while the ethylene chloride solution
yielded an unworkable tar on evaporation,
(3) The Attempted Succinoylatlon of Toluene with
3-Methyl-3-nitro-l,2-butanedicarboxylic Anhydride.—
3-Methyl-3-nitro-l,2-butanedicarboxylie anhydride, g.
(0.920 mole), was dissolved in 25 ml. of 96 % sulfuric
acid. To this solution was added 2.0 g. of toluene
(0.022 mole) with stirring. A dark, red color rapidly
developed and the solution was allowed to stand at room
temperature for 0.5 hour. The sulfuric acid solution was
then poured on 150 g. of ice. The color disappeared and
a white solid separated. The solid was collected and
washed with 10 ml. of cold water and then allowed to dry
in air. The material was identified as the recovered
72
. anhydride by means of a mixed melting point; weight,
2.30 g. (61.5 % recovery), m.p. 104-107°.
It is interesting that the anhydride was not
hydrolyzed by this procedure.
I. Some Michael Condensations Involving Nitromethane.
(1) The Michael Condensation of Nitromethane on
Dimethyl Fumarate.— To 150 g. of dimethyl fumarate
(1.04 mole) was added 180 ml. of nltromethane (3.35 mole)
and 24 ml. of diethylamine (0.25 mole). The mixture
slowly turned dark, first orange and then brown. The ester
went into solution steadily at room temperature for about
two days and then apparently stopped. No more ester
appeared to react even after standing for thirty days.
' The unreacted ester was collected and crystallized from
methanol after treatment of the solution with activated
: carbon (Nuehar C); weight, 105 g. (70 % recovery),
m.p. 100-101°. The mother liquor was pumped down on the
steam bath and the residual oil was fractionated under
reduced pressure. The yellow N-nltrosodlethylamine came
over in the expected range (b.r. 75-85°/l4 mm.) and was
discarded. The pressure was then reduced to 4 mm. and a
colorless oil was collected, b.p. 64-68°/4 mm. This oil
gave a negative sodium fuson test for nitrogen and is
73
undoubtedly dimethyl itaeonate; yield, 13.0 g. (8 %).
The boiling point reported in the literature is
56-58°/l.3 mm.?
(2) The Attempted Michael Condensation of Nitro-
methane on Dimethyl Teraoonate.— Dimethyl teraconate was
prepared by the method of Kloetzel? in 70 % yield. The
dimethyl teraconate, 10 g. (0.05^ mole), was mixed with
nitromethane, 3^ g. (0.56 mole), and trlethylamine, 7.2 g.
(0.07 mole). The mixture was allowed to stand at room
temperature for a period of five months. Ho color change
characteristic of the reaction occurred. The nitromethane
and triethylamine were pumped off and the residual oil was
distilled under reduced pressure; weight, 8.5 g. (85 %
recovery), b.p. 97-102°/5.5 Jam. A sodium fusion analysis
for nitrogen was negative and it was concluded that
essentially no reaction had occurred.
J. The Elimination of Nitrous Acid from 3-Methyl-
3-nitro-l,2-butanediearboxylie Acid in Non-basie Media.
ProlongAction of Acetic Anhydride on
3-Methyl-3-nltro-l,2--butanedlcarboxyllc Acid.— Two grams
of 3-aethyl-3-nltro-l,2-butanediearboxylic acid
(0.0098 mole) was dissolved in 30 ml. of glacial acetic
acid and refluxed for 2.5 hours. There was no evidence of
elimination such as discoloration or actual evolution of
nitrogen dioxide. Acetic anhydride, 10 ml., was then
added. Brown fumes of nitrogen dioxide were evolved
almost immediately. The evolution of gas was slow and
the refluxlng was continued for forty hours. The solution
was nearly black at the termination of the reflux,
probably due to polymerization. Water, 20 ml., was added
to hydrolyse the anhydride and the solution was evaporated
to dryness in the hood. The dark brown solid was
dissolved in 20 ml. of water and treated twice with
activated carbon (Nuchar G). The solution was evaporated
to dryness, leaving a light brown solid. This material
was crystallized from acetone and petroleum ether; weight,
0.80 g., m.p. 153-156° d. Recrystallization from water
yielded white, needle clusters, m.p. 162-163° d. A mixed
melting point with an authentic sample of teraconic acid
showed no depression; yield, 5^ %•
(2) The Prolonged Action of Acetic Anhydride on
Dimethyl 3-Methyl-3-nitro~l,2-butanedlcarboxylate.— Ten
grams of dimethyl 3-methyl-3-nltro-l,2-butanedlcarboxylate
(0.043 mole) was dissolved in a mixture of 40 ml. of
acetic acid and 20 ml. of acetic anhydride. The solution
was refluxed for fourteen hours. There was no evidence
of decomposition such as a color change or the evolution
75
of nitrogen dioxide. Fifty milliliters of water was added
and the solution was evaporated to about 15 ml. on the
steam bath, The colorless oil was dissolved in 10 ml. of
ether. Petroleum ether (b.r. 45-60°) was added until
cloudiness occurred at room temperature. The solution was
cooled to 0° and seeded with dimethyl ester. The material
which separated was again crystallized from the same
solvent pair to yield colorless crystals of dimethyl
3-methyl-3-nitro-*l,2-butanedicarboxylate; weight, 7*5 §•
(75 % recovery), m.p. 35-36°.
(3) The Action of Acids on 3-Methyl-3-nltro-l,2-bu-
tanedlcarboxylle Acid.— Two grams of 3-methyl-3-aitro-
1,2-butanedicarboxylle acid (0.0098 mole) was dissolved
in 10 ml. of 96 % sulfuric acid. The solution was heated
on the steam bath (about 900) for ten minutes. A rapid
evolution of nitrogen dioxide occurred, the solution
turning dark in the process. The solution was cooled and
poured on 20 g. of iee. More nitrogen dioxide was evolved
and the solution was heated on the steam bath for ten
minutes to eliminate the excess gas. On cooling to 0° and
seeding with a crystal of terebinic acid, white crystals
slowly separated. The material was collected, washed with
a small quantity of water, and allowed to dry in air;
yield, 0.45 g. (29 %), m.p. 170-171° d. Crystallization
from water raised the melting point to 171-173° d. A
mixed melting point with an authentic sample of the
y1 -lactone, terebinic acid showed no depression.
Three grams of 3-methyl-3-nltro-l,2-butanedicarboxy-
lic acid (0.0146 mole) was refluxed with 100 ml. of 10 %
hydrochloric acid for one hundred and fifty hours. The
solution turned somewhat dark and was treated with
activated carbon (SJuehar G) and then evaporated to dryness.
A yellowish-white solid remained; weight, 2.57 g.,
m.r. 90-115° (obviously a mixture). The solid was dissolved
in the minimum amount of hot water and seeded with
terebinic acid. A small amount of crystalline material
separated; weight, 0.3 g., m.p. 167-170° d. This material
was recrystallized from water and identified as terebinic
acid by a mixed melting point (13 % yield), m.p. 170-172° d.
It is probable from the great difference in the velocities
of this reaction under the two conditions that the rate
expression is dependant on the hydrogen ion concentration.
K. The Thermal Decomposition of 3-Methyl-3-nitro-
1.2-butanedicarboxylic Acid and Its Derivatives.
(1) The Decomposition of 3-Methy1-3-nitro-l,2-butane-
dlcarboxyllc Acid.— One gram of 3-methyl-3-nitro-
1.2-butanedlearboxylic acid (0.004-9 mole) was heated by an
77
oil bath In an open tube at 145 dz 3° for two hours. The
melt slowly turned yellow and then dark red, steadily
evolving nitrogen dioxide. The red melt was oooled and
dissolved in a minimum of hot water. The solution was
cooled and seeded with teraconic acid. White, needle
clusters formed, which were separated and dried; yield,
0.45 g. (58 $), m.p. 151-156° d. Recrystallization from
water raised the melting point to 160-162° d. A mixed
melting point with authentic teraconic acid showed no
depression.
The Decomposition of the Phenylhydrazide of
3-Hethy1-3-nltro-l,2~butanedicarboxylic Acid.— Two grams
of the phenylhydrazide (0.0068 mole) was melted at 147°
in an open tube in an oil bath. A rapid decomposition
occurred which was essentially complete in twenty minutes
at 145 dz 3°. The black oil did not solidify on cooling
and was hydrolyzed by heating with 10 ml. of 10 %
hydrochloric acid for four hours on the steam bath. The
solution was treated with activated carbon (Kuchar C) and
filtered. White needles separated on cooling. This
material was collected and dried; yield, 0.15 g* (14 ^),
m.p. 154-156° d. Recrystallizatlon from water raised the
melting point to 160-162° d. A mixed melting point with
teraconic acid showed no depression.
(3) The Decomposition of the Anilide of 3-Methyl-
3-nitro-l,2-butanedlearboxyllc Acid.— Two grams of the
anilide (0.0072 mole) was melted at 125° in an open tube
heated by an oil bath. An immediate, rapid decomposition
occurred at 125 dt 3° with a vigorous evolution of gas.
The melt became dark red and the decomposition was
essentially complete in five minutes. The melt was
processed as in the case of the phenylhydrazlde, the solid
obtained being identified as teraconic acid; yield, 0.35 g«
(31 %)> m.p. 158-160° d.
Decomposition of the n-Propylamide of
3-Methyi-3~nltro-l,2-butanedicarboxylic Acid.— Two grams
of the n-propylamide (0.0081 mole) was melted at 147° in
an open tube as before. Again, a rapid decomposition
proceeded essentially to completion at 145 rt 3° in five
minutes, the melt turning dark in the process. The melt
was processed as in the ease of the phenylhydrazlde, the
isolated solid again proving to be teraconic acid; yield,
0.83 g. (65 %)y m.p. 163-166° d.
(5) The Thermal Stability of Dimethyl 3-Methyl-
3-nltro-l,2-butanedlcarboxylate.— Three grams of dimethyl
3-methyl-3-nitro-l,2-butanedlcarboxylate was heated in an
open tube by an oil bath at 145 i 3° for two hours. No
evolution of nitrogen dioxide was observed although the
79
melt slowly assumed a light brown color. On cooling the
: melt solidified, m.p. 29-31°. This slight decrease in the
melting point from the original 35-36° indicates that only
a few percent of the total dimethyl ester decomposed under
the conditions.
(6) The Decomposition of 1-Carbomethoxy-3-methy1-
3-nltro-2-butanecarboxylic Acid.— l-Carbomethoxy-3-®ethyl-
3-nitro-2-butanecarboxylic acid, 2.1 g. (0.0096 mole), was
heated at 1A5 ii 3° in an open tube for 2.5 hours. After
a short induction period of five minutes, the evolution of
gas became evident. The decomposition was steady but a
little slower than that of the dicarboxylic acid. The
dark, red melt was hydrolyzed by heating with 10 ml. of
10 % hydrochloric acid on the steam bath for four hours.
The solution was treated with activated carbon (Nuehar C)
and allowed to cool. White needles separated and were
identified as teraconic acid by a mixed melting point;
yield, 0.40 g. (59 %), m.p* 160-163° d.
(7) The Partial Decomposition of 3-Carbomethoxy-
4-methyl-4-nltropentanoic Acid.— ■ Two grams of
3-carbomethoxy-4-methyl-4-nitropentanoic acid was heated at
145 dz 3° in an open tube for two hours. A very slow
elimination of gas occurred accompanied by a gradual
change in eolor to dark red. The melt solidified on
80
cooling and was crystallized from acetone and petroleum
ether (b.r. 45-60°) after treatment of the solution with
activated carbon (Huchar C); weight, 1.20 g., m.p. 100-
103°. A mixed melting point with the starting material
showed no depression; recovery, 60 %.
It is possible that the apparent slow decomposition
of this ester was due to an ester interchange process, the
isomeric l-carbomethoxy-3-methyl-3-nitro-2-butanecarboxylle
acid being the species undergoing elimination.
(8) The Thermal Stability of the o-Toluldide Kster
of 3-Methyl-3-nitro-l,2~butanedlcarboxyllc Acid.— The
methyl ester of the o-toluldlde, 0.5 g., was heated in an
open tube at 145 dz 3° for two hours. The melt slowly
turned a light brown but no gas was evolved. The contents
of the tube solidified on cooling, m.p. 120-125°. This
lowering from the initial melting point of 124-126°
indicated that only a few percent of the compound underwent
decomposition. A mixed melting point verified the fact
that no rearrangement had occurred. This result is
remarkable when compared with the very rapid decomposition
of the unesterlfied monoamides. The o-toluidide, itself,
although not studied in this series, melts with rapid
decomposition.
(9) The Thermal Stability of 3-Methyl-3-ni'k*,Q-
1,2-butanedlcarboxyllc Anhydride.— Two grams of 3-methyl-
3-nltro-l,2-butanedicarboxylic anhydride was heated in an
open tube at 145 d= 3° for two hours. A very slow
elimination of gas occurred, the melt turning light yellow
by the end of the period. The melt solidified on cooling,
m.p. 105-110°. This lowering of the melting point
indicated that only a few percent of the anhydride could
have undergone decomposition. A mixed melting point
verified the identity of the anhydride.
(10) The Thermal Stability of N-Pheny1-3-methy1-
3-nltro-l,2-butanedlcarboxlmlde.— One gram of N-pheny1-
3-methyl-3-nitro-l,2-butanedicarboximide was heated in an
open tube at 145 dr 3° for one hour. Decomposition was
very slow, the melt turning red but not evolving any
appreciable amount of gas. The melt solidified to a glass
on cooling and was crystallised from acetone and petroleum
ether (b.r. 45-60°); weight, 0.90 g. (90 % recovery),
m.p. 131.5-132°. A mixed melting point with the H-phenyl-
lmide showed no depression.
SUMMARY
(1) Esterlfication and hydrolysis reactions of
3-methyl-3-nitro-l,2-butanediearboxylie acid and its
derivatives were investigated. In the course of this work,
a new procedure for the rapid esterifieation of aliphatic
acids was developed.
(2) Ring closing reactions of 3-*aethyl-3-nitro-
1.2-butanedicarboxylic acid and its N-substltuted
monoamides were investigated under various conditions. The
formation of the cyclic anhydride was readily accomplished
but the monoamides were rapidly decomposed under similar
conditions. The nature of the decomposition was not
determined but probably involved the elimination of
nitrous acid. By a proper modification of conditions the
monoanillde was closed to N-pheny1-3-methy1-3-nltro-
1.2-butanedlcarboximide.
(3) The ammonolysis and alcoholysis of 3-siethyl-
3-nitro-l,2-butanedicarboxylic anhydride demonstrated that
the ring opens predominantly in one direction. The
monoester obtained in the alcoholysis reaction proved to be
identical with the monoester obtained by a controlled
esterlfication of the dicarboxylic acid. A relative
structure proof was effected to show that methanolysls and
ammonolysis proceed by attack at the same position.
83
(4) Several unsuccessful attempts were made to
carry out a Friedel-Crafts reaction of 3-methyl-3-nltro- .
1.2-butanecarboxyllc anhydride with toluene, p-xylene,
. and anisole. Only tarry products or recovered starting
materials were obtained.
(5) An attempt to extend the series of beta-nitro
carboxylic esters by condensing nitromethane with dimethyl
fumarate was unsuccessful. The expected product, dimethyl
3-nitro-l,2-propanedlcarboxylate, was not obtained as it
apparently lost nitrous acid as rapidly as it was formed.
The only produets observed were H-nitrosodiethylamlne and
dimethyl itaconate. A single attempt to condense nitro
methane with dimethyl teraconate in the presence of
triethylamine was unsuccessful. The reactants were
unchanged after a period of five months.
(6) The elimination of nitrous acid from 3-methyl-
3-nitro-l,2-butanedicarboxylic acid was found to proceed
slowly in the presence of acetic anhydride and also under
the influence of strong acids. These elimination reactions
in nonbaslc media parallel the dehydration of beta-hydroxy
carboxylic acids under similar conditions.
(7) The thermal decomposition of 3-niethyl-3-nitro-
1.2-butanedicarboxyllc acid and all of its known
derivatives at 145 rt 3° was studied in the hope of
effecting ring closures pyrolytieally as has been observed
Q
with certain succinic acid derivatives. In each instance
in whieh decomposition occurred, the primary process
proved to be the elimination of nitrous acid rather than
eyelization. That ring closure was not Involved in the
intermediate steps was demonstrated by the stability of
3-methyl-3-nitro-l,2-butanedicarboxylic anhydride and the
N-phenylimide under pyrolytie conditions. It was also
found that esterlfication of the secondary carboxylic
group greatly retarded the decomposition.
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Creator Magee, Philip Stewart (author)

Core Title The chemistry of 3-methyl-3-nitro-1, 2-butanedicarboxylic acid

Degree Master of Science

Degree Program Chemistry

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