The synthesis of certain derivatives of adamantane: The synthesis of certain substituted naphthalenes.

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Content TEE SYNTHESIS OF CERTAIN DERIVATIVES OE ADAMANTANE y THE SYNTHESIS OF CERTAIN SUBSTITUTED NAPHTHALENES A T hesis P re se n te d to th e F a c u lty of th e Department o f Chem istry The U n iv e r s ity o f Southern C a l i f o r n i a In P a r t i a l F u l f i ll m e n t o f th e Requirem ents f o r th e Degree M aster of Science Herman I . Enos, **r. May, 1943 UMI Number: EP41542 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. Published by ProQuest LLC (2014). Copyright in the Dissertation held by the Author. D is s a rts to PaWte!*ig UMI EP41542 Microform Edition © ProQuest LLC. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 D ean Secretary D fl^ ...M a y ..l5 .* ...1 9 4 3............. Faculty Com m ittee ..... Chairman This thesis, written by Herman I . Enos j r . ; v ;.... / | 3 under the direction of M s. Faculty Committee, C T ^ e 0 and a p p ro ved by all its members, has been presented to and accepted by the Council on Graduate Study and Research in partial fulfill ment of the requirements for the degree of J .Mastex..of...|cienGe................... PART ONE TABLE uF CONTENTS CHAPTER PAGE I . HISTORICAL..........................................-........................................ 1 Review of th e l i t e r a t u r e ............................................. 1 I I . LISCUSSION . . ...................................................... 6 C onclusions ............................................................ 11 I I I . EXPERIMENTAL . ................................................................. 13 P r e p a r a tio n o f 4-hydroxy-3-carbo:K:y- h e n z a ld e h y d e ................................................................... 13 The, p r e p a r a t i o n o f 4 -h y d ro x y -3 -ca rb o x y - cinnam ie a e i d . . . .......................... 15 The d i e t h y l e s t e r o f 4 -h y d ro xy-3 earbo xy- cinnam ic a c i d ...................................................................... 17 BIBLIOGRAPHY........................................................... 18 PAST OEE LIST OP TABLES TABLE PAGE I . Data on th e P r e p a r a tio n of 4 -hydro 2 cy-3-c a rh o x y - henzaldehyde ......................... ..... .. ... 15 I I . Data on the P re p af& tio n of 4 -h y d ro x y -3 -o arh o x y - cinnaraic acid* . ............................................................ 17 PART O il THE SYHTHESIS OR CERTAII DERIVATIVES OP ADAMA1TAHE HISTORICAL 3 ,7 , f t i e y c l o ( 3 ,3 ,1 ,1 , ) decane, adam antane, Gio h16» was d isc o v e re d i n 1933 by Landa and Machacek i n th e a r o m atic f r a c t i o n of Hodonin p e tro leu m b o i l i n g between 190° and 195°C* (4 ). H | h i s compound,, i s of i n t e r e s t f o r s e v e r a l r e a s o n s . I t has a h ig h d e g re e of symmetry and s t a b i l i t y , the carbon atoms having th e space l a t t i c e of carb o n i n diamonds. The normal t e t r a h e d r a l v a le n c i e s of carbon atoms £ and 6 , and 4 and 8 , and 9 and 10, l i e i n p e r p e n d ic u la r p la n e s and hen@e a p p ro p r i a t e s u b s t i t u t i o n may make an asym metric m olecule (6 ). I t has f o u r of 'i t s carbon atoms a t b rid g e h e ad s. S u b s t i t u t i e n t s a t such carbon atoms have been found t o be v e ry s t a b l e . (4 ). T his s t a b i l i t y may be due to die i n a b i l i t y of such a system to undergo .talden i n v e r s io n , or to form a carbonium • > M \ io n . Back s id e approach of a n u c le o p h il i c group i s p r e vented' by th e cage formed by the o th e r carbon atoms about a b r id g e head carbon atom. A carbonium io n and the t h r e e 2 atoms bonded to i t must be c o p la n a r (4) (5 ). Mven though adamantane was n o t d isc o v e re d u n t i l 1933, s e v e r a l i n v e s t i g a t o r s have t r i e d to p re p a re such a t r i c y c l i c s t r u c t u r e w ith poor s u c c e s s . Meerwein and c o -w o rk ers, e x p e r- t o p re p a re a d e r i v a t i v e of adamantane by t h e fo llo w in g r e a c t i o n (14) (1 5 ). Meerwein was n o t a b le to i s o l a t e any of th e p r o d u c t. He d id , however, p o in t out the h ig h s t a b i l i t y to be expected i n such a s t r u c t u r e because of t h e p o s s ib l e s t r a i n l e s s bonds and th e s i m i l a r i t y of such a s t r u c t u r e to the; c o n f ig u r a tio n of h e x a m e th y le n e te tra -a m in e . K l e i n f e l l e r and F re rc k s were u n s u c c e s s f u l i n t h e i r a tte m p ts to condense 2 - c h l o r o m e t h y l - 2 - n i t r o - l ,3 - d i c h l o r o - propane w ith 1 , 3 ,5 ,- t r i k e t o c y c l o h e x a n e i n m ethanol and sodium m e th y la te (1 )* im en tin g w ith s u b s t i t u t e d b ic y c lo ( 3 , 3 , 1 , ) nonames, attem p ted CH3 0gCU C0gCH3 uu i r ✓ / CHg 0 60gGH3 u C0gCH33 3 S:$ t t g e r succeeded in p re p a r in g th e t e t r a methyl e s t e r o f a d a m a n t s n e - 2 , 6 - d i o n e - l , 3 , 5 , ? - t e t r a c a rb o x la te by the method o f Meerwein by u sin g GHgBrgin m ethanol and sodium m e th y la te i n a s e a le d tube a t 120°, showing the c o n d e n sa tio n does not tak e p la c e r e a d i l y . He was u n a b le to p re p a re the h y drocarbon from t h i s d e r i v a t i v e . Clemensen re d u c tio n of t h e compound gave o nly the c o r r e sponding d i o l . S tro n g e r tr e a tm e n t fp and H i),g av e no i s o l a t a b l e p r o d u c ts , f o r a b e ta keto_ e s t e r i t was rem ark- < • a b ly s ta b le toward d e c a r b o x y la tio n . I t was s ta b le i n a c i d , and to h e a t , d i s t i l l a t i o n from m etal s a l t s y ie ld e d no d e f i n i t e p ro d u c ts . P re lo |f a tte m p te d to condense the t r i e t h y l e s t e r of m e th a n e tr ip r o p io n ic a c id i n th e p resen c e of sodium i n •b o ilin g to lu e n e as f o llo w s (16). However only- one c o n d e n s a tio n to ok p la c e and th e p ro d u ct i s o l a t e d , i n sm all ;y i e l d , was 3 - c a r b e th y - 4 - k e to cycohexane p ro p io n ic a c i d . H e=c2h5 Toluene ^ 4 R=C2H5 Using th e method o f Meerwein and B o t ti n g e r , P re lo g succeeded i n t h e fo llo w in g c o n d e n sa tio n (1 7 ). R e d u ctio n of t h e k e to groups was accom plished by th e STolfif-Kishner method. D ecarbo nox ylation was c a r r i e d out i n sm a ll yi& ld by p a s s in g the v a p o r over h e a te d copper b r o n z e , (from 650 mg. o f the a c id was o b ta in e d 9.7 mg. adam antane)• S im u lta n eo u sly and in d e p e n d a n tly o f P r e lo g , Brown and lo la n d developed a method of s y n t h e s i s w hich in v o lv e s th e compound, 3~ oarbethoxy-4-keto-eyclohexane p r o p io n ic a c id a s an i n te r m e d i a t e . Roland a tte m p te d a Dieckmann i n tr a m o l e c u l a r condent- CO2 CH3 2 s a t i o n of 3 -c a rb e th o x y -4 -k e to -c y e lo h e x a n e p ro p io n ic a c id He was unable to i s o l a t e any of th e d e s ir e d p r o d u c t, f h i s s t a r t i n g m a t e r i a l i s th e same a s t h a t i s o l a t e d as th e p ro d u c t of Dieekmann c o n d e n sa tio n of the t r im e t h y l e s t e r oF methane t r i p r o p i o n i c a c i d o f P re lo g . However, m etallic sodium i s a r e l a t i v e l y poor condensing agent when compared to th e s tr o n g p ro to n a c c e p to r sodium tr ip h e n y lm e th y l em p loyed by Hauser to e f f e c t o th e r d i f f i c u l t c o n d e n sa tio n s (1 0 ). io la n d was u n able to d e term in e th e p ro p e r c o n d itio n s fo r t h i s c o n d e n s a tio n due to la c k of m a t e r i a l . DISCUSSIOH. •"{('■{ i r I I t i s th e o b je c t of t h i s r e s e a r c h t o co n tin u e the stu d y of th e c o n d itio n s n e c e s s a ry to b r in g a b o u t the con d e n s a tio n of e th y l e s t e r 3 - c a r b e th o x y - 4 -k e to - o e ta -h y d r o cinnamic a c id to 2 ,4 ,9 t r i keto-adam antaae begun by fo la n d , In o rd e r t o do so i t was n e c e ssa ry t o a tte m p t t o improve th e y i e l d s i n th e v a r i o u s s t e p s le a d in g to th e s y n th e s is of th e d i e t h y l e s t e r of 3 -carb eth o x y -4 -k eto -o c ta h y d ro cin n co n ic a c id and to s e p a r a te and i d e n t i f y i t s c i s and t r a n s form s. Cr03 HSG HC00QgH5 HAc } h2^ h2 gCHgCOOCgHg I t i s p o s s ib l e f o r th e p ro d u ct to e x i s t i n two iso m e ric forms i f c h a i r and bed forms o f t h e cyclohexane r in g a r e assumed to e x i s t i n m obile e q u ilib r iu m . Ih e s te p s i n its . s y n th e s is a r e : 01 OH OH ICOOH (CHgCO)gO^ H i IH CHgbbbfe y -H< COOH CHCI COOH UaOH !H=CHCOOH OH HC00CgH5 CgHgOH H ~1T— » H (H^CHCOOCgHg CCbOCgHs CH . (H) v Hg /Haney W Hg HgCHgCOOCgHg Ors, c h a i r T rans, c h a i r I t was a t f i r s t th o u g h t t h a t only the c i s isom er would be capable of condensing because of t he p ro x im ity of th e a lp h a hydrogen of t h e 2- c a r b e th o x y - e th y l s id e c h a i n 't o th e carb o x y l group of t h e o t h e r t h a t i s p o s s ib le only i n th e one iso m er. However i n th e p resen c e o f the. b a s ic con densing agent e n o l i z a t i o n may p o s s ib l y occur a t th e 2- k e to group c a u sin g p a r t of th e r i n g c o n ta in in g th e clouble bond and t h e s u b s t i t u e n t groups to become o o p la n a r. I n the f o rm a tio n o f t h e ta n to m e ric k e to form th e r e i s e q u al chance of th e c i s and t r a n s forms of th e compound form ing sin c e th e c a rb eth o x y sid e c h ain is p a r t of the p la n a r e n o l system . A s.the c i s form condenses the e q u ilib riu m would be s h i f t e d i to th e r i g h t u n t i l a l l of th e t r a n s form i s , is o m e r iz e d . E s t e r c o n d e n sa tio n s , a c c o rd in g to t h e mechanism advanced by H auser (1) (10), in v o lv e s the back s id e a p p roach of a n u c le o p h il i c group a t the carboxy e s t e r group w ith su b sequent e x p u ls io n of t h e a lc o h o la t e a n io n as i l l u s t r a t e d by the fo llo w in g g e n e r a l e q u a tio n . R$CH2COOB + j320 l a ether^ (E?CHCOOEf A _jR<L=GHCOOcf ) Z 5 3 G H 4 - E a + Then r e p r e s e n t i n g th e resonance form o f th e anion by Cl) Space, models show t h a t i t i s s t e r i c l y p o s s ib l e f o r the c o n d e n sa tio n of the t r a n s , c h a i r iso m er of 3 -c a rh e th o x y - 4-ketoeyeohexane p ro p io n ic a c id to take p la c e . I f th e c o n d e n sa tio n t a k e s p la c e ste p w ise , th e fo llo w in g fo rm u las r e p r e s e n t t h e p o s s ib l e - c o n f ig u r a tio n o f the a n io n s f o r th e f i r s t s t e p , and of the p ro d u c ts which t h e i r c o n d e n sa tio n would g i v e . (OR) •9 There should he l e s s tenden cy f o r fo rm a tio n of a n io n (B) th a n f o r e i t h e r (A) o r (C) because th e system in v o lv e d i s -COCHRCO- i n which th e re i s o f te n l e s s tenden cy t o con dense th a n in , th e u n s u b s t i t u t e d system -COCHgOO-. The. p ro d u ct from (B), e th y l b i c y c l o - ( 3 , 3 , 1 , )-n o n an e -2 , 8- d i o n e - l - e a r b o x y l a t e , would not be c a p a b le of f u r t h e r c o n d e n sa tio n . The product from (A), i s i d e n t i c a l to the p ro d u ct from (C), e th y l b i c y c l o - ( 3 , 3 , 1 , ) -non an e-2 , 8 - d io n e - 3 - c a r b o x y l a t e . I t s f u r t h e r c o n d e n sa tio n would be e f f e c t e d by th e fo llo w in g c o n d it i o n s . I f th e trip h e n y lr a e th y lio n prom otes th e form ation of th e e s t e r a n io n by e l e c t r o p h i l i c a t t a c k follo w ed by tb s e x p u ls io n of th e trip h e n y lm e th a n e m olecule we would e x p e c t, because of th e h in d e ra n c e to th e approach o f th e jZ 5gC +gro u p , th e form of t h e an io n to be th e fo llo w ip g : I f t h i s carb o n io n r e t a i n s i t s c o n f i g u r a ti o n the hydrogen atom w i l l h in d e r th e approach to th e e a rb eth o x y gro u p . 10 However, I f th e tr ip h e n y lm e th y lio n prom otes th e fo rm a tio n of th e e s t e r anio n by th e more p l a u s i b l e mechanism of d i s p l a c i n g the i o n i z a t i o n e q u ii i b r i m by removal of th e p r o to n through th e i r r e v e r s i b l e fo rm a tio n of trip h e n y lm e th a n e , th e fo llo w in g form s o f the e s t e r a n io n are -no ssible. Resonance betw een th e two forms o f t h i s would n o t be e x p e c te d to e x i s t because form (D) would not be cop a n ar a t carb on atoms 1 , 6 , 7 ,8 a s form (1 ) must b e . T his i s f o r t u n a t e because th e form (E) could not condense due to th e g r e a t l y in c r e a s e d d is ta n c e betw een t h e a n io n and ■ carboxy g ro u p s, The form (D) should be c a p a b le of conden s a t i o n . The n a tu re of the tau tom erism , and th e r e l a t i v e s t a b i l i t i e s of th e s e two forms o f th e e s t e r a n io n w i l l c e r t a i n l y in f lu e n c e the f i n a l c o n d e n s a tio n to 2 ,4 ,9 trik e to a d a m a n ta n e . C ondensation of chlo ro fo rm and s a l i c y l i c i n sodium hyd ro xide s o l u t i o n have been in c r e a s e d . The tim e o f r e a c t i o n h as been d e c re a se d from over n ig h t to ab o u t th re e h o urs by th e i n t r o d u c t i o n of p o tassiu m o l e a t e as an emul s i f y i n g a g en t w hich in c r e a s e s th e s u r fa c e of th e ch lo ro fo rm The c o n v e rsio n and y i e l d i n th e Hiemer iiem ann Id 11 a v a i la b l e t o the sodium s a l i c y l a t e and sodium hydroxyde s o l u t io n i n t h i s h e te r o geneous r e a c t i o n . The p ro d u e t has been o b ta in e d i n p u r e r form th an p r e v io u s ly r e p o r te d as evidenced by th e c o l o r l e s s n e e d le s o b tain ed of M. P.. o o„ 257.8 -2 5 8 .2 C; The m a t e r i a l was p r e v io u s ly d e s c r ib e d o as p a le y e llo w n e e d le s M. P. 248 C. The y i e l d i n the P e rk in c o n d e n sa tio n o f th e 4- h ydroxy -3 -carbox y-benzaldehyd e w ith sodium a c e t a t e i n b o i l i n g a c e t i c anhy dride has been in c r e a s e d and t h e p ro d u ct f r e e d from aldehyde m a t e r i a l f o r the f i r s t tim e . Solvent r e c r y s t a l l i z a t i o n i s n o t s u f f i c i e n t to perform t h i s s e p a r a t io n , because aldehyde m a t e r i a l was e x tr a c te d by b i s u l f i t e s o l u t i o n from m a t e r i a l tw ice r e c r y s t a l l i z e d from a c e t i c a c id and is o p ro p y l a le o h o l. f h e .a ld e ly d e f r e e acid i s of a pronounced y ello w c o lo r and does not m elt below o 400 a t which te m p e ra tu re i t i s only d arken ed . At red h e a t on a s p a t u la i t slo w ly sub lim es and burns le a v in g a dark r e s i d u e , which upon a d d i t i o n of w a te r, g iv e s a n e u t r a l s o l u t i o n . The e s t e r i f i c a t i o n of the 4-hydroxy-A carboxy-cinnam ic a c id had j u s t been s t a r t e d when i t became n e c e s s a ry to d i s c o n tin u e the work on t h i s problem . However th e e s t e r i s a s o l i d of low m e ltin g p o in t which i s p a le yellow a f t e r two c r y s t a l l i z a t i o n , from e th a n o l." 12 Work on t h i s problem was i n t e r r u p t e d by the n e c e s s i t y of g iv in g our u n d iv id e d a t t e n t i o n t o an o th er problem , c o n f i d e n t i a l i n n a tu r e , and d i r e c t e d toward / ' a more e f f i c i e n t p u r s u i t o f t h e c u r r e n t w ar. I t has r e c e n t l y come to our a t t e n t i o n t h a t P relo g and S eiw erth (B e r. 74B 1769 (1941)) have succeeded i n the d e c a rb o x y la tio n of th e e s t e r d e s c r ib e d on page 4 by o th e r methods which g iv e b e t t e r y i e l d s . The adam antane-1 ,5 - d i - e a rb o x y lic a c id p re p a re d by W olff-K ishner r e d u c tio n o f th e dim eth yl e s t e r 2 , 6-d ik e to ^ a d a m a n ta n e -1 , 5 - d ic a r b o x y lic acid was c o n v erted to th e d i a c id c h lo r id e which i n t u r n was c o n v erted t o th e diam ide. Hofmann rearrangem ent' o f the diam ide y ie ld e d th e diam ine. The ben zo y l d e r i v a t i v e of th e diam ine gave the dibrom ide when t r e a t e d w ith phosphorus p en tab ro m ide. R ed uction o f th e dibrom ide w ith sodium m e th y la te ard Kaney n i c k e l g iv e s adamantane i n good y i e l d . The dibrom ide was made i n even b e t t e r y i e l d s by t r e a t i n g th e d i s i l v e r s a l t of th e d i a c i d w ith bromide in c a r b o n t e t r a c h l o r i d e . EXPERIMEMTAL P r e p a r a tio n o f 4 -h y d ro x y -5 -ca rb o x y -b en z ald eh y d e . OH OH H H O 0OH +. HCCI3 + 4 Ha OH !C00Ia+3 la C I + 3H0H ! h ®he method of feeimer and (Eiemann (18) (19) was i * fo llo w e d . 396 grams o f U. s . P. s a l i c y l i c a c id was d i s so lv e d i n a s o l u t i o n of 700 grams of U. a . P. laOH i n 2000 m l. of H2O. 2!he s o lu tio n was cooled to 55°G and 283 Ml. of CHCI3 were added c a u t i o u s l y and the m ix tu re was r e f lu x e d o v e r n ig h t, (The r e s u l t i n g m ix tu re was poured i n to s i x to e ig h t tim e s i t s volume of H2O and n e u t r a l i z e d w ith c o n c e n tra te d HC1 to p r e c i p i t a t e the p ro d u c t and th e u n re a c te d s a l i c y l i c a c i d . On th e f i r s t t r i a l , s e p a r a t i o n o f t h e p ro d u c t was a tte m p te d by th e method of (Poland (2 0 ). ih e magma was ex t r a c t e d w ith e t h e r . 'The marked d i f f e r e n t i a l s o l u b i l i t y betw een s a l i c y l i c a c id and th e p a ra and o rth o aldehyde iso m ers was n o t rep ro d u c ed . 'Therefore ths s o l i d r e s id u e * o b ta in e d upon e v a p o r a tio n of th e e t h e r was e x tr a c t e d w ith s a t u r a t e d sodium b i s u l f i t e s o l u t i o n and th e m ixture d e composed a t the b o i l i n g p o in t w ith 6H. H2SO4 and the p a ra isom er f i l t e r e d o f f a f t e r c o o lin g to 60° a s d i r e c t e d by H o te-A ll m e ltin g p o i n ts a r e u n c o rr e c te d . Reimer and Piemann (1 ?). / On a l l subsequent t r i a l s th e method of Cohen and Wayne (6 ) was u s e d . She r e a c t i o n m ix tu re a f t e r p r e c i p i t a t i o n was f i l t e r e d and the mixed c r y s t a l s d r ie d and ta k e n up i n b o i l i n g 95% e th a n o l. Upon c o o lin g , t h e f i r s t crop o f o c r y s t a l s was p a le y e llo w , M. P. £52-254 G. Shree to f i v e r e c r y s t a l i z a t i o n s from e th a n o l, u s in g n o r i t e , gave long w h ite n e e d le s o f c o n s ta n t m e ltin g p o in t 2 5 7 .8 - 2 5 8 .2°G. F u r th e r c ro p s of s a l i c y l i c a c id were o b ta in e d by c o n c e n tra t i o n o f t h e m other l i q u o r which c o n ta in e d a y ello w im p u r ity . Upon u s in g t h i s re c o v ere d s a l i c y l i c a c id i t was noted t h a t the r e a c t i o n s t a r t e d more q u ic k ly and r e f lu x e d s tr o n g l y w ith l e s s a p p lie d h e a t . Assuming t h i s to be due t o e m u ls i fy in g e f f e c t o f th e b ip ro d u c t s e v e r a l e m u ls ify in g a g e n ts were t e s t e d . fD r e ft, sodium s t e a r a t e , A e ro so l 0. i '., Po tassiu m O l e a t e ) . Potassium o le a te was found to be the b e s t on th e 8t h t r i a l s 0.25 gram of p otassiu m o l e a te was added i n 50 ml. warm H2O j u s t a f t e r th e a d d i t i o n of th e c h lo r o form . She r e a c t i o n s t a r t e d im m ediately and re flu x e d spon ta n e o u s ly f o r one h o u r, and th en w ith i n t e r m i t t e n t h e a tin g f o r t h r e e h o u r s . She co n v ersio n was in c r e a s e d c o n s id e r a b ly . TABLE I Weight ' of s a l i c y l i c a c id g r a m s Conversion °/ /o Y ield M elting p o in t deg. 0 Remarks grams f A 1 A 6 .1 45 9.7 248-251 393 10.7 50 17.5 254.5-256 393 12.04 57 17.6 254-255 2 2 6 g .rec o v ere d s a l i c y l i c a c id uss l 393 13.95 66 30.1 130g. recovered, s a l i c y l i c a c id use 392 9.50 45 15.9 259 393 14.3 68 259 398 . 14.3 67 251-252 l . h g . Rcuassiuin O leate used 393 17.8 84.3 249 U.2bg. ro ta s siu m O leate used T he,p r e p a r a t i o n o f 4-hydroxy-3-carboxy-cinnafflic a c i d . (?H OH HO^^COOH (0H3 G0)20 v HC^^COOH H Q ^ C H 6JE^JdbK >. H \ i H CHO CH=OHOOOH The method used was t h a t o f Oohen and Wayne. .. One p a r t o f 4 -h y d ro x y -3 -ca rb o x y -b en z ald eh y d e , one p a r t of anhydrouss sodium a c e t a t e , and 2 .5 p a r t s o f a c e t i c anhy dride „ were r e f lu x e d a t 180° 2° f o r f i v e h o u rs . The r e q u ire d amount of 50^ KOH was added and th e m ix tu re r e flu x e d f o r < $ a l f an h o u r. A f te r c o o lin g th e deep red s o l u t i o n was made d i s t i n c t l y a c id by th e a d d it i o n of e x cess c o n c e n tra te d 16 h y d r o c h lo ric a c i d which caused a l i g h t y ello w m a t e r i a l t t o p r e c i p i t a t e . This, was washed w ith b o i l i n g w a te r and d r i e d . o The crude p ro d u ct m elted a t 227.2 G. A wide v a r i e t y of s o l v e n ts {methanol, e th a n o l, is o p ro p a n o l, g l a c i a l a c e t i c a c i d , e th y l a c e t a t e , m ethyl c e l l o s o l v e , a c e to n e , d io x a n e , benzene,and th e fo llo w in g s o lv e n t p a i r s : a lc o h o l- w a te r , d io x a n e -w a te r, m ethyl c e l lo s o lv e - w a te r , a c e to n e - w a te r ) were found to be u n - s a t i s f a c t ory. C r y s ta ls from g l a c i a l a c e t i c acid had M. P. 2 3 7 .4 °0 . C r y s t a ls from is o p ro p a n o l had M. P. 2 3 9 .2 °0 .g 3 9 .2 °C . T his i n d ic a t e d the c r y s t a l s o b ta in e d were a ls o a m ix tu re . Bach tim e a s o lv e n t c r y s t a l l i z a t i o n was a ttem p ted a sm all r e s i d u e rem ained which would n o t m elt belcw red h e a t on a s p a t u la b u t which d id n o t le a v e an in o rg a n ic r e s id u e on i g n i t i o n . When th e c r y s t a l s from g l a c i a l a c e t i c a c id and is o p ro p a n o l were e x tr a c t e d w ith s a t u r a t e d sodium b i s u l f i t e and washed th o ro u g h ly w ith b o i l i n g w a te r, p a le y e llo w powder rem ained which d id n o t m elt below 400°. (was s l i g h t l y darkened i n c o lo r ) Prom 100 grams of aldehyde was o b ta in e d 3 9 .8 grams o f c i n n a m i c 'a c i d . (39.8%) The m a te r ia l was p u r i f i e d by e x t r a c t i o n w ith s a t u r a t e d sodium b i s u l f i t e s o l u t i o n (tw ice) and washed c o p io u s ly w ith b o i l i n g w a te r. The a c id d id n o t m e lt below 400°.C,, TABLE I I 17 Weight of Aldehyde grams Y ield ‘ 1 ' ...................................... .... . l_ ! grams fo .......1 0 — sodium s a l t of t h e aldehyde used only an o i l re c o v e re d . . . . . . TO 9.9 —- a l l of pro d u ct u sed i n a tte m p t t o f in d a s u i t a b l e s o lv e n t 3 9 .8 .3 9 .8 _ TOO 69.2 67.7 TOO 56.5 67.4 100 _ 5.7.. 5. 65.1 52g. rec o v ere d aldehyde used ...............- 87 ................... ~ £ L - o . 64.9 55g. re c o v e re d aldehyde used The d i e t h y l e s t e r of 4 -h ydroxy~ 5-carboxy-elnnam ic a c id . OH OH H d ^ o c o o H Q£H5oh H$fJ ^ JG O 2O 2H5 HgSO^ CH=CHCOOH CH=CHC0 0 C2H5 The e s t e r i f i c a t i o n was c a r r i e d out hy th e f i s h e r method. The, a c id (116.4 grams) was d i s s o lv e d i n 3 l i t e r s a b s o lu te e th a n o l to which 50ml. of c o n c e n tr a te d HgSO^ was added and th e e h e r r y red s o l u t io n r e lfu x e d f o r E8 h o u rs . The e x ce ss a lc o h o l was removed by d i s t i l l a t i o n and the r e s id u e tak e n up in e t h e r . The e t h e r ,s o l u t i o n was e x tr a c te d w ith s a t u r a t e d sodium b ic a r b o n a te s o l u t i o n u n t i l no f u r t h e r a c id was removed. The e t h e r la y e r was d r ie d over HagSO^ and c o n c e n tra te d u n t i l a mass of y ello w c r y s t a l s form ed. ' BIBLIOGRAPHY A. BOOKS 1. Adams, S o ger, B d ito r-in -c h ie iff, Organic R e a c tio n s . Vol.- I , lew York: John Wiley and s o n s ,’ 1942. ^91 pp. 2. A dkins, Homer,, R e a c tio n s o f Hydrogen. P i r s t E d itio n ; Madison, W isconsin: fhe U n iv e r s ity o f W isconsin p r e s s , 1937. 178 pp. “* 3 . G atterm an, and ,W & e la n d , L a b o rto ry Methods i n Organic C hem istry, 1932. 435 pp. B. PERIODICAL ARTICLES 4 . B a r t l e t t , and Cohen. J . Am.ehem. Soc. 62: 1183-89. 1.940. ~ 5. B a r t l e t t , and Knox, J . Am. Chem. so c . 61: 3184-92, 1939. “ — 6. B o ttg e r , Oskar, B er. 70B: 315-25, 1937. 7. Cohen, and wayne, J . Ohem. S o c ., London, 121: 1022-29, 1922. 8. Connor, and A dkins, J . Am. Ohem. Soc. 54: 4678-90,1932. 9. G rigsby, Hind, Chanley, and W estheimer, J . Am. Chem.Soc. ' 54j_ 2606-10, 1942. ! --------------- 10. H auser, 0. R. J . Am. Chem. so c . 63: 3256, 1941. 11. K l e i n f e l l e r , Hans, and P r e rc k s , J . P r a k t. Chem. 138: 184-206, 1933. " 12. Landa, and Machacek, C o lle c tio n Szechoslavac Chem. Gommun. 5: 1-5 , 1933^ 13. Landa, Machacek, M jourek, and Landa, Chimie e t I n d u s t r i a . S p e c ia l number 506-10, June, 1933. j 14. Meerwein, Hans, and Schurmann. Ann. 398: 196-242, 1913. 15. Meerwein, K ie l, K losgen, and schoeh, J . P r a k t. ohem. 104: 161-206, 1922. 16. P re lo g , and B a le n o v ic , B er. 75B: 875-77, 1940. 17. P re lo g , and S e iw e rth , Ber 74B: 1644-48, 1941. 18. Beimer, and liem ann, B er. 9; 1271., 1876. 19. Beimer, and fiem ann, B er. 9: 1285, 1876. G. UNPUBLISHED MATERIALS 20. fo la n d , W., A ttem pted S y n th e sis of Adamantane, M asters J IL'hesi's, Purdue tJ h iv e rs ity ,' i/y ’ e s t l L aifayette, In d ia n a . 1942. p a r t two TABLE OE 0OUTSITS CHAPTER PAGE I . , HISTORICAL.............................................. ■ .................... 1 Review, of th e l i t e r a t u r e . . . . . . . 1 Benzene d e r i v a t i v e s . . ....... 1 N aphthalene d e r i v a t i v e s . . . . .. 5 Phenanthrene d e r i v a t i v e s ... .. . 7 I I . .DISCUSSION ..................................... 9 Purpose o f t h e p r o b l e m ......... 9 Method, I .................................. 9 Method I I ................................................. . . IB A l t e r n a t i v e methods . . . . . . . . . 16 C onclusions ........................................ El I I I . EXPERIMENTAL ................................... 22 P r e p a r a tio n of th e e th y l e s t e r o f 2 - c h l o r o a c e ti c a c id . . . . . . . . . 22 P r e p a r a t io n of 2 -c h lo ro -a c e ta m id e . . 23 P r e p a r a tio n of 2 - c h l o r o - a c e t o n i t r i l e . .24 P r e p a r a tio n o f 4 - h y d r o x y - c h lo ro - a c e to - n a p h th a le n e ............................................. 25 P r e p a r a tio n of 4 -h y d ro x y -l-(2 ,'-h y d ro x y - a c e 'to ) - n a p h t h a l e n e ....................................... . 26 P r e p a r a tio n of 4 - h y d r o x y - l - ( 1 '-h y d ro x y s ’ - d i e t h y l amino e th y l) - n a p h th a le n e 27 / ‘ iy .i CHAPTER PAGE P r e p a r a t io n of c h lo r o a c e ty l c h lo r i d e . 28 P r e p a r a t io n of 4 -m e th o x y -l-c h lo ro - a e e to -n a p h th a le n e ........................................ 30 P r e p a r a tio n of 4 - m e th o x y -l-fw -d ih u ty l a m in o -a c e to )-n ap h th a le n e . . . . . . . 33 P r e p a r a tio n o f 4 -h y d ro x y -l-n a p h th o ic a c id . . ............................. 35 BIBLIOGRAPHY ............................. 37 PART TW O LIST OP TABLES TABLE PAGE I . , L a ta on th e P r e p a r a tio n o f th e e th y l e s t e r of 2 - c h l o r o - a c e ti c a c id . . . * .22 I I , L ata on th e P r e p a ra tio n of 2 - c h lo r o - acetam ide ........................................ . . . . . 23 I I I . Lata, on the P r e p a r a tio n of 2 - c h lo r o - a c e t o n i t r i l e ....................................................... 25 17. L ata on th e P r e p a r a tio n o f c h lo r o a c e t y l c h l o r i d e .................................................. 30 PART T W O THE SYNTHESIS OE CERTAIN SUBSTITUTED NAPHTHALENES HISTORICAL S u b s t it u t e d a m in o -a lc o h o ls of th e ty p e , f l ^ 1 Eg — two open c h ain a l k y l groups o r one c y c l ic a l k y l group a re u n re p o rte d i n the l i t e r a t u r e . .Compounds w ith th e s t r u c t u r e K r-L irsU /'L J a/ R z “ H, OH, OMe, QEt, halogen Xy E - H,Me , E t , e t c . are known ( 1 ,3 ,6 ,1 8 ,2 3 ,2 4 ) which a re p h y s i o l o g i c a l l y a c t i v e . T u tin , Oaten, and Hann, i n 1909, (23) s y n th e s iz e d 2- Q c H O H c H ^ A /H ^ a H t o compare i t s p r o p e r t i e s w ith th o s e of th e n a t u r a l p ro d u ct .HOHc ^ /V H C ^ 3 e p in e p h rin e , >// C h lo ro a c e ty l c h lo r id e was condensed w ith a n is o le by a P rie d e l- G ra ft s y n t h e s i s w ith aluminum c h lo r id e i n c a r b o n d is u lf id e to g iv e p -h y d ro x y -w -c h lo ro a ce to p h e n o n e , a c c o rd in g to a m o d if i c a t io n o f th e method of Kunckel (10) C « , o < 3 + c / c m c < 3 c / - 4 H O < ( Z ^ c o c ^ c i C? They were u n a b le t o condense t h i s p ro d u ct w ith ammonia i n a lc o h o lic s o l u t i o n , so th e y a c y la te d th e p h e n o lic hydroxyl group w ith a c e t i c anhydride and condensed w ith p o tassiu m 2 p h th a lim id e . H x ! O c o c ^ o J j> c- v ^ V OCOC/4j O c Hx 1 2 0 -f. f ^ C J O \ i* e ~ f> I I i • u a / c / ^ c o C D ^ ^ c ^ - c - / / C / * Ha,CC > 3 AJbcdb£~ X k J U -* H o 0- 3 U * ~ C O C H ^ J V H ^ H C ! OH This p-hydroxy-w -am ino-acetophenone could n o t be reduced w ith aluminum amalgam. The h y d ro c h lo rid e was reduced by th e Blanc- B ouveault-B lanc method to th e d e s ir e d 2 - (p -h y d ro x y -p h e n y l)- 2-hy droxy -eth ylam in e which i s u n s ta b le b o th d ry and in aqueous s o l u t i o n . A/a. Q zH sO H c H O H G H i A / t b j H c t o H H. T osw inckel, i n 1912 s y n th e s iz e d h o rd e n in e , 3 H ^an amine f i r s t i s o l a t e d from w heat germ ( 6 ,2 4 ) . p-M ethoxy-w -ehloroacetophenone p rep ared hy th e method of Kunckdl (10) was eondensed w ith dim eth yl amine a lc o h o li c s o l u t i o n . \ocN x a ' J < c h '3. -f I h i H I O C & 3 'ihe methoxy group was c o n v erted t o a h y d ro x y l group by r e f l u x i n g w ith red phosphorus and hydrogen io d id e , and the r e d u c t io n was c a r r i e d out by h e a tin g w ith re d phosphorus and hydrogen io d id e i n a s e a le d tu b e . cocHJ^HX ■ H I P M X P / O o % HX OH ! ° ^ JJlXaCOj EZO OH - Spath and Gohring, i n 19EO, accom plished th e s y n t h e s i s o f d l- e p h e d r in e , J ^ j j j by th e fo llo w in g s e r i e s o f r e a c t i o n s (1 9 ). The s id e ch ain i s f i r s t f i t t e d w ith a p p r o p r ia te f u n c t i o n a l groups and a tta c h e d to th e r i n g th ro u g h a g r ig n a rd s y n t h e s i s , a f t e r which c o n d e n sa tio n w ith th e amine i s c a r r i e d out and th e hydroxyl group f r e e d , CH3CHgCH0 + Br2 CHgCHBrCHO + HBr CH3CHBr0H0 + HBr + CHgOH _______^ OHgCHBrCHBrOCHg + HOH 0H30HBrGHBr0CH34 0MgBr _________ '0CHOCH3GHGH3Br 4 MgBr2 cH O C //3 C H c tf3A /K .r f3 H & l CH-octf, c tt C/A &L cttocH, C/VcV, /vM-c^ 3 H O H C H C H 2 f f H C t f 3 H & t. -+C//3 8 a . 5 liphedrine was a ls o s y n th e s iz e d "by Manske and Johnson (12) and S k ita and K e il (17) in a v e ry d i f f e r e n t manner which h as a g e n e r a l a p p l i c a t i o n a s p o in te d out "by Manske an d Johnson (1 3 ). 1 1, 2 ’- d ik e to - p r o p y l benzene i s condensed w ith th e a p p r o p r ia te amine i n a b s o lu te a lc o h o l and reduced w ith hydrogen and p latin u m oxide c a t a l y s t to g iv e d i r e c t l y dl-epfy(riLne i n y i e l d s up to 50%. Analogues i n th e n a p h th a le n e s e r i e s a re u n re p o rte d i n th e l i t e r a t u r e . However Houben (17) (18) has s y n th e s iz e d 4 - h y d r o x y - l- c h lo ro a c e to -n a p h t.h a le n e ; by a g e n e ra l type r e a c t i o n which b e a rs h i s name. A n i t r i l e o r s u b s t i t u t e d n i t r i l e i s condensed w ith a p h e n o l, n s p h th o l, o r a r y l e th e r i n th e p resen c e of f r e s h l y fu se d z in c c h l o r i d e , a b s o lu te e t h e r , and d ry h y d ro g e n c h lo rid e . c / > c o c o o s / 3 £ M < ^ (j> C H 0HCfKti3N CH3 $ 2 ^ ^ c o 6 - a / c / / 3 O H Z a/C L Ha OH h o h \ 1 O C / t x c / ffihis compound a f f o r d s a s t a r t l i n g m a t e r i a l f o r a s y n t h e s i s s i m i l a r t o t h a t of f u t i n , Gatoh, and Hann, (23)., Bey and B ajagopalan (2.) r e p o r t th e s y n t h e s i s of an am ino-ketone hy th e c o n d e n sa tio n of 4 -m eth o x y -l-w -io d o a ee to n ap h thalene w ith p o tassiu m p h th a lim id e and subsequ en t h y d r o ly s is w ith HBr to g iv e 4 -h y d ro x y -l-(w -a m in o -a c e to ) n a p h th a le n e hydrobrom ide. c o c o c H x Ny & c H 3 O C J43 S ' 7 Dey and R ajagoplan i n th e same p a p er a ls o d e s c rib e a n o th e r method of p r e p a r in g w -am ino-acetonaphthones by F r i e d e l and G ra ft r e a c t i o n of a n a p h th y l e t h e r and a c e t y l g ly c y l c h lo r i d e . C O C / ^ A / U C O C ^ OR The p h y s i o lo g ic a l a c t i o n o f an analogue i n the ) p h e n an th ren e s e r i e s was d e s c rib e d i n 1934 by Edmunds, Eddy, and Small (3 ). The 3 - { £ '- d i e t h y l a m in o - l- h y d r o x y - e th y l} - ‘ ;-.n p h enanthren e E ric h M o settig and Jacob van de Kamp (1 4 ). Phenanthrene was a c y la te d i n presen ce of aluminum c h lo r id e w ith a c e t y l c h l o r i d e . The 3-iso m er was t r e a t e d w ith brom ine i n c o ld a b s o lu te e t h e r s o l u t i o n t o g iv e 3 - (w -brom o-aceto)- p h e n a n th re n e . This was condensed w ith th e secondare amine i n a b s o lu te e th e r s o l u t i o n to g iv e the 3 - (w -d ie th y l-sm in o - a c e t o }?p h e n an th ren e which was reduced ivith hydrogen i n ab so l u te e th a n o l s o l u t i o n to g iv e th e 3 - ( I '- h y d r o x y - E ' - d i e t h y l - a m in o -e th y l)-p h e n a n th re n e as r e p r e s e n te d below . was s y n th e s iz e d by ^ + ciC ccH x /vH co cti3 8 < f a - 2 . f B T A o c o c h ^ 2 ^ ~ O U L ^ s r z - . - - - - s . < H x - 0 - 0 . C O C H Q ^ E T ^ p _______ , n 'COCHz N R -,. F t P jC iJdt. a b cs. H a. ’ tH OH CH 2fi/R v 3- {1' -hydroxy-£ ' - d im e th y la m in o -e th y i) -p h en an th ren e was a ls o p re p a re d i n t h i s manner. i)ISCUSSIOI The o b je c t of t h i s re s e a r c h i s to s y n th e s iz e th e .fo llo w in g s e r i e s of s u b s t i t u t e d amino a lc o h o ls , decahydro q u in o lin e , The f i r s t method a tte m p te d c o n s is te d i n th e a tte m p t to condense 4 -h y d ro x y -l-c h lo ro a e e to n a p h th a le n e w ith d i e t h y l amine. I t was f i r s t n e c e s s a r y to p re p a re e h l o r o a c e t o n i t r i l e . This was p rep a red by th e method of S c h o ll (8) a s m o dified by S te in k o f f (1 1 ). I t was condensed w ith a lp h a n a p h th o l i n a b s o lu te e th e r s o l u t i o n i n the presen ce of anhydrous zin c c h lo r i d e and d ry hydrogen c h lo r i d e , by the proceedure de s c r i b e d by Houben (16) (17), t o g iv e the 4 -h y d ro x y - l- e h lo ro a c e to n a p h th a le n e . This s e r i e s of r e a c t i o n s i s r e p r e s e n te d by th e fo llo w in g e q u a tio n s . C H O H C H ^ /V ^ i n which DHg » dim ethyl th ro u g h d i - n - o c t y l , and p ip e r d in e , t e t r a hydro q u in o lin e , 6 -m e th o x y -te tra -h y d ro q u in o lin e , and c c i c^ ca/ CL-CM^C/ 10 C)C H XC N < - Ha 7 } ^ H s ) j o H C g c tia .t/O C ? . f j - t i g ^ H ^ N H - H a O H The c o n d e n s a tio n s te p was c a r r i e d out by r e f l u x i n g th e eh lo ro k eto n e and d ie th y la m in e i n a b s o lu te e t h e r s o l u t i o n f o r t e n h o u rs . The m ix tu re p r e c i p i t a t e d a re d sem i c r y s t a l l i n e m a t e r i a l alm ost im m ediately which stu c k t o the w a l ls of the f l a s k . T his s o l i d m a te r ia l i s i n s o lu b le in w a te r and has a m e ltin g p o in t of 106°-107°C. I t cannot be th e expected d i e t h y l amine h y d r o c h lo r id e . T his m a t e r i a l would not be expected t o be th e h y d ro c h lo rid e of th e amino- k eto n e which i s p ro b a b ly a weaker base th an d ie th y la m in e because o f t h e e l e c t r o n e g a t i v i t y of th e caro bon yl g ro up. I t could .however ,be a q u a te n a ry ammonium s a l t of the p h e n o lic hydroxyl group o f e i t h e r th e amino-ketone o r the u n re a c te d eh lo ro k e to n e of t h e fo llo w in g ty p e : coc/^A/R- 11 HJhen th e e t h e r i a l s o l u t i o n which rem ains a f t e r f i l t r a t i o n i s e x tr a c te d w ith w a te r and aqueous sodium h y d ro x id e, th e aqueous la y e r s were red c o lo re d and gave a red r e s id u e upon e v a p o ra tio n . R e c r y s ta l'iz a tio n from e th a n o l- w a te r m ix tu re gave pure u n re a c te d c h lo ro h y d ro x y - k e to n e , Upon e v a p o ra tio n of the e t h e r i a l s o lu tio n a t a r r y re d r e s id u e was o b ta in e d . These r e s u l t s p a r a l l e l th o se of T u tin , Gaton, and Hann on t h e i r a ttem p ted c o n d e n s a tio n of p -h y d ro x y -w -c h lo ro - If acetophenone w ith ammonia and w ith methA lam ine. (1 3 ). Even though th e s e r e s u l t s i n d ic a te d t h a t th e conden s a t i o n had ta k e n p la c e only to a l im i te d e x te n t, a r e d u c t io n o f th e m a t e r i a l i s o l a t e d from e t h e r s o l u t i o n was a tte m p te d . The m a t e r i a l was ta k e n up i n a b s o lu te is o p ro p y l a lc o h o l and an e x c e ss o f 3 E. aluminum is o p r o p y la te s o l u t io n was added. This m ix tu re was allow ed to r e f l u x f i v e h o u rs d u rin g which tim e no a c e to n e was o b ta in e d . That no acetone was o b ta in e d i s a t t r i b u t e d t o th e f a c t t h a t th e r e f l u x column of th e a p p a r a tu s was to o long f o r the volume of s o l u t i o n and hence th e h o t v ap o r d id n o t re a c h th e to p . The d ark red s o l u t i o n was c o n c e n tr a te d by d i s t i l l a t i o n u n d e r reduced p r e s s u r e and th e aluminum is o p r o p y la te was decomposed w ith w a te r , from an e t h e r e x t r a c t o f t h i s m a t e r i a l was o b ta in e d a c o l o r l e s s o l i q u i d of b o i l i n g p o in t 139- 142 G having a d e f i n i t e e s t e r o d or. Because o f la c k of tim e t h i s i n t e r e s t i n g s id e r e a c t i o n p ro d u ct could n o t be i d e n t i f i e d . (The b o i l i n g p o in t o f is o p ro p y l c h lo r o a c e ta t e i s 1498 (E 5 ).) Prom th e aqueous l a y e r o r from th e a l k a l i and a c id s o l u t i o n s of th e s o l i d s no i s o l a t a b l e p ro d u ct could be ob t a i n e d . This method of s y n th e s is was th e® efo re abandoned. Because th e p r e v io u s r e a c t i o n s seemed t o i n d i c a t e t h a t th e d i f f i c u l t y was due t o th e p h e n o lic hydroxyl group i t was d ecided to a tte m p t th e s y n t h e s i s by form ing a' m ethoxyl group from th e p h e n o lic hydrox yl group and remove i t a f t e r th e c o n d e n sa tio n had been accom plished. The fo llo w in g e q u a tio n s r e p r e s e n t t h i s approach: N ^ c f l O H O C H i C f iC j ^ c s ^ + b i c I J o c / ^ c / c o c H ^ n Ri, c>H fll(iOPr\ i f f O H C O C /^ H ^ H I n •4 ? ' h i OH ____ II J 1-ftiN H o c H 3 H c i 13 The m e th y la tio n o f f r e s h l y d i s t i l l e d a lp h a n a p h th o l was c a r r i e d out i n good y i e l d hy a l t e r n a t e a d d i t i o n s of sodium hydroxide and d im eth y l s u l f a t e "both by numerous sm all a d d it i o n s and "by only two a d d i t i o n s . The a jp h a n a p h th y l m ethyl e th e r i s v e ry pure having o nly a h a l f d eg ree b o i l i n g range a t 25 mm p r e s s u r e (14 3°-143 .5 °C ). y i e l d s up t o 93fo of t h e o r e t i c a l were o b ta in e d . T his m ethyl e t h e r was d is s o lv e d i n n itr o b e n z e n e , an e q u iv a le n t of aluminum c h lo r id e added, follow ed by slow a d d i t i o n o f c h l o r o a c e ty l c h lo r i d e p re p a re d from c h l o r o a c e t i c a c id and t h i o n y l c h l o r i d e . Uo hydrogen c h lo r id e was e v o lv e d . A f t e r s ta n d in g over n i g h t th e m ix tu re was poured in to ..ic e and h y d ro c h lo ric a c i d . The n itro b e n z e n e l a y e r was s e p a r a te d , o d r ie d and as much n itro b e n z e n e removed a s p o s s ib le a t 150 C and 25 mm p r e s s u r e . The d i f f i c u l t l y c r y s t a l l i z a b l e m a t e r i a l was f i n a l l y c r y s t a l l i z e d by co n tin u ed e x t r a c t i o n w ith l i g r o i n and d i e t h y l e th e r and was r e c r y s t a l l i z e d from b e n ze n e-p e tro leu m e t h e r m ix tu re . I t was n o t th e d e s ir e d p ro d u ct b u t p ro b a b ly a dilcetone a s evidenced by i t s h ig h m e ltin g p o in t of. 256°C. The I’r i e d e l - O r a f t r e a c t i o n was f i n a l l y s u c c e s s f u l l y c a r r i e d out to g iv e t h e d e s ir e d 1 ,4 compound by d i s s o l v i n g the a lp h a n a p h th y l m ethyl e t h e r and tbs c h lo r o a c e ty l c h lo r i d e , t h i s tim e p re p a re d from phopharus t r i c h l o r i d e and c h l o r o a c e t i c a c i d , i n G. P. d ry carbon d i s u l f i d e and a d d in g t h e aluminum c h lo r id e slo w ly . A f t e r d eco m p o sitio n o f th e complex by a d d i t i o n of ic e and w a ter any f r e e p h e n o lic m a t e r i a l was removed by ex- i t r a c t i n g w ith sodium hydroxide and the carbon d i s u l f i d e e v a p o ra te d , The p ro d u ct was r e c r y s t a l l i z e d from e th a n o l o o u n t i l p u re , w h ite n e e d le s , m e ltin g p o in t 70.7 -7 1 .4 0* The c o n d e n sa tio n of th e 4 - m e th o x y -l- e h lo ro a c e to - n a p h th a le n e w ith d ib u ty la m in e was a tte m p te d as b e fo re t h i s tim e w h ite c r y s t a l s p r e c i p i t a t e d alm o st im m ediately a f t e r h e a t in g was begun. The amine h y d ro c h lo rid e was f i l t e r e d o f f and th e e th e r c o n c e n tr a te d to a t h i c k amber m a t e r i a l which s o l i d i f i e d on s ta n d in g . From a lc o h o l- w a te r m ix tu re s only an o i l was o b ta in e d . A p o r t i o n of t h i s o i l was d is s o lv e d i n benzene and t h e t r a c e s o f a lc o h o l and w a te r d i s t i l l e d o u t. An o i l was o b ta in e d by adding p etroleu m e t h e r o r hep tan e to th e c o n c e n tr a te d benzene s o l u t i o n . This o i l was c r y s t a l l i z e d by e x t r a c t i o n w ith h o t p e tro leu m e th e r and co n tin u o u s s c r a t c h in g f o r a p ro lon ged p e rio d . The r e s i d u e , r e c r y s t a l l i z e d from b e n z e n p -h e p ta n e , was a deep orange c o lo re d powder M. P .238°0. That t h i s i s th e d e s i r e d p roduct i s u n l i k e l y because of th e h ig h m e ltin g p o i n t . I f th e am ino-ketone however, was o x id iz e d by th e a i r d u rin g th e long p e rio d o f h e a t in g i t would giv e 4 -m eth O x y -l-n ap h th o ic a c i d . 15 The m e ltin g p o in t of 4 -m e th o x y -l-n a p h th o ic a c id re c o rd e d by Gatterm an and Hess (26) i s 232°C, One gram of m a te r ia l re c o v e re d from -the p e tro leu m e t h e r e x t r a c t s was h e ated two h ours w ith 7.0 ml h y d rio d ie a c id (d. - 1 . 7 ) and 0 .4 grams red p h o sp h o ru s. A sm all amount of o o y ello w c r y s t a l s were o b tain ed which m elted a t 150 -167 0 . r a p id h e a t i n g . T his i s p ro b ab ly a m ix tu re which may c o n ta in 4 - h y d ro x y -l-n a p h th o ic a c id .(M . P. 1 8 3 ,4°C) (5)* Prom th e same r e a c t i o n a dark o i l was a ls o o b ta in e d . I t was e x tr a c t e d w ith h o t sodium c a rb o n a te s o l u t io n ; T he.w ashings n e u t r a l i z e d w ith /■material Q 0 h y d r o c h lo r ic a c i d , gave a w h ite c r y s t a l l i n g / m e l t i n g a t 90-93 G. I t steam d i s t i l l s and has the c h a r a c t e r i s t i c odor of a lp h a i n a p h th o l. Mixed m e ltin g p o in t of th e r e c r y s t a l l i ^ e d m a t e r i a l w ith known sample o f a lp h a n a p h th o l, 9 5 .6 ° - 9 6 .7 ° C ., proves t h a t i t i s a lp h a - n a p h th o l. A nother c o n d e n sa tio n (.12 m oles) i n e th e r was begun b e fo re th e i d e n t i t y of th e s e p ro d u c ts was e s t a b l i s h e d . I t was h e a te d i n t e r m i t t e n t l y f o r 19§ h o u r s . Recovery o f 16.0 gms of th e d ib u ty la m in e h y d ro e lo rid e i n d ic a t e d a 75fo r e a c t i o n . The e t h e r s o l u t i o n was t r e a t e d w ith n o r i t e , e x tr a c t e d w ith h y d rio d ie acid (d. = 1 ,7 ) , d r ie d over sodium s u l f a t e , and c o n c e n tra te d ; upon a d d i t i o n of p e t - e t h e r an o i l s e p a r a te d . At t h i s w r i t i n g t h i s o i l has n o t c r y s t a l l i z e d . The h y d rio d ie a c i d e x t r a c t s o l i d i f i e d on s ta n d in g . The s o l i d s were e x tr a c te d w ith b o i l i n g w a te r. The s o l u t i o n upon c o o lin g , d e p o s ite d som e-yellow 16 c r y s t a l s which a re p ro b a b ly d ib u ty lam in e h y d ro io d id e . The rem ainin g o i l was d is s o lv e d i n h o t 95fo e th a n o l and c o o le d . I t d e p o s ite d y ello w c r y s t a l s which m elt w ith o o o d e co m p o sitio n a t 110 - H E G a f t e r s i n t e r i n g a t 90 G t h i s i s p ro b a b ly th e d e s ir e d amine s a l t b u t r e p r e s e n t s only a v e ry sm all amount of th e s t a r t i n g m a t e r i a l . These r e s u l t s se em .to i n d ic a t e t h a t d u r in g th e conden s a t i o n th e s id e c h ain i s e a s i l y o x id ized by c o n ta c t w ith a ir * The c o n d e n sa tio n cou ld p ro b a b ly be s u c c e s s f u l l y c a r r i e d out by e x c lu s io n of oxygen w ith an atm osphere of n i t r o g e n . Also th e r e a c t i o n could p ro b a b ly be speeded up by u s in g a s o lv e n t such as benzene which b o i l s about f i f t y d e g re e s h i g h e r th a n e t h e r . I t i s a ls o * p ro b a b le t h a t th e am ino-ketone may be i s o l a t e d from th e m ix tu re by p a s s in g i n dry hydrogen c h l o r i d e . I t may be n e c e s s a ry to add hexane to d e c re a s e th e s o l u b i l i t y o f th e .amino-ketone h y d ro c h lo rid e in the benzene s in c e the p o l a r i t y of t h e s o lv e n t would p ro b a b ly be in c r e a s e d due to th e s o l u b i l i t y of hydrogen c h lo r id e i n benzene. I f the r e d u c tio n and, s p l i t t i n g of t h e e t h e r cannot be accom plished s t i l l a n o th e r method o f s y n t h e s i s is a v a i l a b l e based upon th e Spath and Gohring s y n th e s is of e p h e d rin e , B rom ination of a c e ta ld e h y d e should give' a lp h a b ro m o ac etald e - hyde which when t r e a t e d w ith hydrobrom ic-a e i d in m ethyl a lc o h o l would g iv e 1 ,2 -dib ro m o-l-m eth oxy e th a n e . I f t h i s were th en allow ed t o r e a c t w ith th e g r ig n a rd re a g e n t from 4 -b ro m o -l- 17 methoxy n a p h th a le n e , th e pro d u ct would he 4 - m e t h o x y - l - d 1- m eth o x y -2 ’-b ro m o -e th y l^ -n a p h th a le n e . Upon c o n d en satio n w ith a second ary amine t h i s would g iv e th e c o rresp o n d in g t e r i a r y amine which c o u ld he t r e a t e d w i t h h y d rih d ie a c id to s p l i t th e m ethoxyl gro u p s and give the d e s i r e d 4-?hydroxy-l- (1 ’-hydroxy- 2 ' - d i a l k y l a m i n o - e t h y l ) n a p h th a le n e . T his i s r e p r e s e n te d by th e fo llo w in g r e a c t i o n s . CH3 CHO -f- O C / L /VUftu ~ h C . H 6 i \ , O C : O O f ottf3 a! cftoHCf/^ a/ r ■ 18 The p o s s i b i l i t y o f a d a p tin g Manske and J o h n s o n 's •d ik e to n e c o n d e n s a tio n w ith a second ary amine and s u b s e quent c a t a l y t i c r e d u c tio n i s remote because o f th e observed d i f f i c u l t i e s i n p r e p a r in g hydroxy and methoxy s u b s t i t u t e d phenyl a lp h a d ik e to n e s . Also the c o n d e n s a tio n w ith a seco ndary amine would le a d t o d i f f i c u l t i e s because t h e r e i s no a v a i l a b l e hydrogen atom on the amine n i t r o g e n atom to e f f e c t th e d e h y d ra tio n n e c e s s a ry to d i s p la c e th e e q u i l i brium t o th e r i g h t through h y d ro g e n a tio n of the u n s a t u r a t e d i n t e r m e d i a t e • R C O C O c H 3 + r ^ H z y $ \ C o Q ^ - o H ____ c H 3 R C O C 'fl/'R m i D/i cfio R O K h H JJiU m o H C H C ^ N U R x N H R I f t h i s r e a c t i o n were a tte m p te d i n th e s y n t h e s i s o f th e s e r i e s of compounds u n d e r i n v e s t i g a t i o n a k e to ald ehyd e would be r e q u i r e d . I t i s c o n c e iv a b le t h a t by e n o l i z a t i o n o f th e k eto n e hydroxy amine, a r e d u c tio n m ight o c c u r. RC.0CI40 Or* / N R \ ^ R t o o C o f l - 19 V H ,PM / ? d = < NR? m > 1/ o H - oH H H 'fhis in te r m e d ia te c o u ld d e h y d ra te i n one of two ways depending upon w h e th er th e a r y l r a d i c a l or th e KgU group i s th e b e s t donor of e l e c t r o n s , b u t o nly one of which could g iv e t h e d e s ir e d p r o d u c t. I t a ls o could d i s s o c i a t e to- g iv e a hydroxy a ld e h y d e . o t t N R \ _ *— A < r ~ c ^ H + H M R Z H H u O R H ~/VR z. H Q H R - t ^ k - N R - >y - i H h R C M £ H O 20 Even i f t h i s in te r m e d ia te co u ld form th e lik e ly h o o d o f i t s g iv in g th e d e s ir e d pro d u ct i s s m a ll. The, p o s s i b i l i t y of p re p a rin g an i n t e m e d i a t e of th e type by h e a tin g w ith aluminum c h lo r id e i s rem ote. E. ¥?. S tro u g h to n (1935) (12.) r e p o r t s t h a t a lp h a n a p h th y l a c e ta te r e a r r a n g e s to th e 4 -iso m e r to th e e x te n t of only 4$ a n d ,t h a t th e 4 -iso m e r on c o n tin u e d h e a tin g w ith aluminum c h lo r i d e g iv e s 60% c o n v e rsio n t o th e 2 -iso m er. ¥ % £ / ? 0 21 ■v C onclusion, D aring th e f o u r months of work on t h i s problem a prom ising approach to th e s y n th e s is of th e d e s ir e d compounds has been d e v e lo p e d . A lthough none of th e compounds have been s y n th e s iz e d , o nly one o p e ra tio n i s s t i l l t o be i n v e s t i g a t e d ( i . e . th e r e d u c t i o n ) .. I f . i t should be found t h a t th e r e d u c tio n cannot be c a r r i e d o u t, an a l t e r n a t i v e method which in v o lv e s no r e d u c tio n has been su g g e ste d . EXPERIMENTAL P r e p a r a tio n o f th e e th y l e s t e r of 2 - c h l o r o - a c e t i c a c i d . C1CH2C00H + C2H50H h2s£4^ 010H2C00@2H5 + HOH Pour hundred gms. of 2 -c h lo ro a c e t i c acid was d is s o lv e d i n 240 gms o f a b s o lu te e th a n o l,a n d 50 gms conc. s u l f u r i c a c id and was r e flu x e d f o r seven hours ( P is h e r Method). The m ix tu re was c o o le d and ta k e n up i n 400 ml of e t h e r and e x tr a c t e d f i r s t w ith w a te r, and th e n s a t u r a t e d sodium b ic a r b o n a te s o l u t i o n u n t i l th e w ashings remained b a s i c , and f i n a l l y w ith w a te r . The e t h e r s o l u t i o n was d r ie d o v e r sodium s u l f a t e . The e th ^ r was removed on a w a te r b a th and. t h e e s t e r d i s t i l l e d w ith f r e e flam e. The f o r e - r u n of 20 ml. (13Q°-140°) w as( d is c a rd e d and th e f r a c t i o n b o i l i n g between 140°-142°C was c o l l e c t e d . Y ield 335 gms, 64.7% TABLE L CICHgCOOE Yj.e ld B. P., Remarks I gms gms $ °0 400 336 64.7 140°-142° 400 285 54.9 140°-142° m ecan ical l o s s d u rin g washing 400 247 4 7 .7 140°-142° A ll m elting' p o i n t s ’ a r e u ncorrectecl. 23- P r e p a r a tio n o f 2 - c h lo r o - a c e ta m id e . 1 ^ - - - — T 1 - 1 | | - 7 ' 1 1 ~ ' 1 | | 1 ~ - ~ > i i l l .. .... .... CICH2COOC2H5 + EH4OH ______ ^ GICH2COM2+ C2H5OH * h20 > Two hundred and f i f t e e n grams of the e th y l c h lo r o - a c e t a t e was p lac ed i n a 2 -1 , 3-n eck , K. B. f l a s k f i t t e d w ith a H ershberg s t i r r e r and cooled e x t e r n a l l y i n an i c e - s a l t b a th . Two hundred ml of c o ld conc. C. P. ammonium hydroxide fd, = 0 .9 ) was added. White c r y s t a l s o f t h e amide began t o form im m ediately. In f i f t e e n m inu tes 200 ml more ammonium h y d ro x id e was added and th e m ix tu re s t i r r e d f o r f i f t e e n m in u te s. I t was th e n allow ed to s ta n d i n th e i c e b a th f o r o n e -h a lf hour and th e n im m ediately f i l t e r e d by s u c tio n and washed w ith 60 ml c o ld w a te r . A fte r p u l l i n g out a s much w a te r a s p o s s i b l e by th e s u c t i o n pump th e w h ite n e e d le l i k e c r y s t a l s were d r i e d i n th e a i f over n i g h t , and th e n i n a vacuum d e s i c c a t o r f o r two days; y i e l d 147 gms. 88.6%. M. P. 9 3 .5 °-1 0 1 ° c . This i n d ic a t e d p rod uct was s t i l l wet and t h e r e f o r e a p o r t io n was d r ie d over a hot a i r d r i e r f o r t h r e e hours and washed w ith d ry e t h e r M. P. 1 2 0 .0 ° - 1 2 0 .4 ° C .. However most of th e m oist p ro d u ct was used i n th e n e x t s te p d i r e c t l y , TABLE I I C1 CH2 COOC2 H5 Y ield hemarks gms. gms. % 2 1 5 1 4 7 8 8 . 6 M. P. wet 9 3 .5 ° - 101°C nure d rv 1 2 0 . 0 - 1 2 0 . 4 0 2 1 5 1 1 6 7 0 . 7 d r ie d over h o t a i r d r i e r 2 8 5 1 6 5 7 5 . 7 n a n ri 2 6 5 1 5 0 7 4 . 3 u n it n h -_____ _____ _. ............... ...................... 24 P r e p a r a tio n of 2 -c h io rp a c e to n i t r i l e . C10H2C0M2 p2°5 ) CICHgCI + ( % 0 ) x - P205 f i f t y - s i x gms of 2 -c h lo ro a c e ta m id e was added w ith 86 grams phosphorus p en to x id e (10% e x c e ss) to a 1-1 , E. B .' f l a s h and th o ro u g h ly m ixed. The f l a s k was a rra n g e d fo r reduced p r e s s u r e d i s t i l l a t i o n in c lu d in g a stop co ck open t o th e a i r i n o rd e r t o c o n tr o l th e p ressu re , as d e s i r e d . H eating was begun a t a p re s s u re of 200 mm p re s s u re w ith a sm all luminous flam e. The m ix tu re began t o ch ar b e fo re an y th in g d i s t i l l e d . The f i r s t m a t e r i a l d i s t i l l e d a t 94°Q a t 204 mm p r e s s u r e . H e atin g was c o n tin u ed and th e p re s su re w a s.slo w ly lowered t o o 13 mm a t w hich p re s s u re the B. P. was 80 0. The h e a t c o n d u ct ance was -very poor and g r e a t d i f f i c u l t y was en cou ntered in h e a t in g th e c e n t e r p a r t of the m ix tu re hence a sm all amount of amide d i s t i l l e d , i n a n o th e r run w ith 60 gms of amide and 102 gms phosphorus p en to x id e d i f f i c u l t y was en countered a g a in i n h e a tin g th e m ix tu re p r o p e r ly a lth o u g h l e s s amide d i s t i l l e d because h e a t in g was begun a t 250 mm. These two runs were. J J combined and r e d i s t i l l e d o v e r phosphorus p e n to x id e a t a t m ospheric p r e s s u r e £ . P. 123°-129°0; y i e l d 68.5 gms, 74.7%. f o r a l l subsequ en t ru n s 40 gms of amide and 90 gms of phosphorus p en to x id e were mixed i n a 2 1 f l a s k and h e a tin g began a t 250 mm. In t h i s manner a l l d i f f i c u l t y w ith the d i s t i l l a t i o n o f th e u n re a c te d amide was e lim in a te d . 35 'i'ABIE I I I ClOHgCGMg . P2°5 Y ield , B. P. ----------------- --------- ■ Remarks 1 gms gms gms 1 o °C 56 86 . 68.£ 74. 0 0 1E3 -1E9 ( 60 103 40 90 f t' Crude p ro d u ct from 4 t r i a l s 40 90 9 9 .C 75. ( 0 0 1E3 -129 was r e d i s t i l l e d to g e t h e r from P2°5 40 90* ‘ 40 90 P r e p a r a tio n of 4 -h y d ro x y -c h lo ro a c e to -n a p h th a le n e 6 c O c h f ^ C ! O H E \ o I h i s p r e p a r a t i o n was c a r r i e d out by th e method of Houben, B er, 60B, 1759. (1927). 31.6 gms r e c r y s t a l l i z e d (from) w a te r) a lp h a n a p h th o l and 13,3 gms c h l o r o a c e t o n i t r i l e was d is s o lv e d i n 60 ml p ure dry e t h e r and a p p ro x im a te ly 10 gms of f r e s h l y fused powder zin c c h lo r id e was added. Dry hydrcpgen c h lo r id e g e n e r a te d by dropping c o n c e n tra te d hydro- c l o r i c a c id i n t o c o n c e n tra te d s u l f u r i c acid i n a s p e c ia l a l l g l a s s a p p a ra tu s was p assed f i r s t through a s u l f u r i c a c id 26 b u b b le r , th e n th ro u g h a phosphorus p e n to x id e g l a s s wool sp ray t r a p , th e n thro u g h a tube o f dry e t h e r and f i n a l l y i n t o th e r e a c t i o n m ix tu re . In t h r e e h o u rs th e s o l u t i o n had become g re e n c o lo re d and i n two h o u rs more the yellow k e t a - mine complex' had d e p o s ite d . The y e llo w complex was removed i n t o a b e a k e r and h y d ro liz e d w ith 300 ml 20% a c e t i c a c i d . T he.crude p ro d u ct (28.2 gms) was ta k e n up i n b o i l i n g benzene, th e s o l u t i o n t r e a t e d w ith n o r i t e and cooled to room te m p e ra tu re . The p ro d u c t, was snowy w hite powder w ith some l a r g e r , f a i n t l y c o lo r e d , c r y s t a l s M.P. 183*8-184.0°0; Y ield 19.9 gms, 60.2%. In subsequent r e a c t i o n s i t was found t h a t e th a n o l was a b e t t e r s o lv e n t f o r th e r e c r y s t a l l i z a t i o n . P r e p a r a tio n of 4 -h y d ro x y -l-,(2 T -h .y d ro x y ac eto )-n ap h th a le n e. d is s o lv e d i n 25 ml o f a s o l u t i o n of e th a n o l and 0.36 gm sodium hydroxide (100% ex ce ss) and was r e f lu x e d f o r one h o u r. The red c r y s t a l s which d e p o s ite d on sta n d in g o v e rn ig h t were washed w ith e th a n o l and t h e o rg an ic pro d u ct d is s o lv e d i n b o i li n g e th a n o l and t r e a t e d w ith n o r i t e and f i l t e r e d . The p u r i f i e d p ro duct was i n form of y ellow p l a t e s M. P. -299°-300°C. ZOc H ^ O H -t M o l OH OH OH One,gram o f 4 - h y d r o x y - l-c h lo ro a c e to n a p h th a le n e was 27 P r e p a r a tio n of 4-hydroxy 1- ( 1 1-hydroxy-2 '-d ie th y la m in o - e t h y l )-n ap hth alen e* C O C //jA ( C y .M s \ c H - 0 /- lC tf a / 1 / f e ' n \ U o p r \ 1 (c U 3)x Z H O H The crude pro d u ct from th e c o n d e n sa tio n o f 0.02 m oles of 4 - h y d ro x y - l-c h lo ro a c e to n a p h th a le n e w ith d i e t h y l amine,. £ . e . s e p a ra te d from a s o l i d m a te r ia l supposed a t th e time to he d i e t h y l amine h y d ro c h lo rid e hy f i l t r a t i o n and th e e t h e r e v a p o ra te d ) p re p a re d hy Dr. Brown was d is s o lv e d i n 25 ml is o p ro p y l a lc o h o l, 50 ml 3 I aluminum is o p r o p y l a t e was added, and the m ix tu re r e f lu x e d f o r f i v e h o u rs i n a 200 ml B. B. f l a s k a tta c h e d t o a 575 mm v ig re a u x column to f r a c t i o n a t e a c e to n e from th e is o p ro p y l a lc o h o l. However the r e f l u x was n o t g r e a t enough t o h e a t th e column and no ace to n e was o b ta in e d . Upon c o o lin g th e m a te r ia l a l l remained in s o l u t i o n and was d a rk red i n c o lo r . D i f f i c u l t y was en co u n tered i n removing th e is o p ro p y l a lc o h o l. The is o p ro p y l a lc o h o l was f i n a l l y removed hy reduced p r e s s u r e d i s t i l l a t i o n a t 100-120 mm w ith a l a r g e c a p i l l a r y a i r opening and c o n t r o l l i n g the p r e s s u r e hy a hand o p e ra te d p in c h clamp to minimumize humping. 28 Water was added and th e b lu e s o l i d was broken up w ith a g l a s s r o d . She S o l i d s and th e s o l u t i o n was t r a n s f e r r e d to a s e p a r a to ry fu n n e l and e x tr a c te d w ith e t h e r . The b r i l l i a n t p u rp le e t h e r e x t r a c t was d r ie d over sodium su lfa te ; and d e c o lo r iz e d w ith n o r i t e . Upon removal of the e t h e r about 3 ml o f a c o l o r l e s s l i q u i d o f B.P. 139°-142° was o b ta in e d . I t had t a d e f i n i t e e s t e r odor b u t i t was follo w ed by a sh a rp se n s a t i o n s i m i l a r t o t h a t of hydrogen c h lo r id e and gave a t e s t f o r h a lo g e n . The m a t e r i a l was not f u r t h e r i n v e s t i g a t e d . The s o l i d m a t e r i a l w hich was not s o l u b l e i n w a te r or e t h e r was d is s o lv e d i n c o n c e n tra te d sodium h y d ro x id e, t h i s was a c i d i f i e d w ith h y d ro c h lo ric a c id and brought t o n e u t r a l p o in t w ith sodium b i c a r b o n a t e . P his was f i l t e r e d but th e f i l t r a t e c o n ta in e d only sodium c h lo r i d e . The .p r e c i p i t a t e was washed w ith b o i l i n g w a te r b u t a g a in th e w ashings p r e c i p i t a t e d only sodium c h lo r id e when s a t u r a t e d w ith hydrogen c h l o r i d e . The experim ent was abandoned. The p r e p a r a t i o n o f o h lo r o a c e ty l c h l o r i d e . A. From t h io n y l c h lo r id e and c h lo r o a c e ti c a c i d . GlOHgOOOH + S O C lg ___________ClCHgCOCl 4 SOg + HOI Thionyl c h lo r id e was p u r i f i e d by th e method sugg ested by F i e s e r (19) one hundred ml t h io n y l c h lo r id e was d i s t i l l e d from 20 ml q u in o lin e and th e n from 40 ml b o ile d l in s e e d o i l ; 29 B. P. 7 5 .6°-76°C; y i e l d 47$. f o r t y seven and t h r e e - t e n t h s grams o f c h lo r o a c e tie a c id was p laced i n a 500 m l-3-neck f l a s k f i t t e d w ith dropping fu n n e l, a r e f l u x con denser p r o t e c te d by a calcium c h lo rid e tu b e , and, a m ercury se a le d s t i r r e r , and 77.2 g of t h io n y l c h lo r id e was added slo w ly w ith s t i r r i n g . .When about h a l f of th e t h i o n y l c h lo r id e had been added th e m ix tu re was warmed b u t t h e r e was s t i l l no evid ence o f r e a c t i o n . The rem aining t h i o n y l c h lo r id e was added r a p i d l y anl th e c o n te n ts of th e f l a s k h e a te d on a w a te r b a th t o 60°C. S t i r r i n g was stopped when g a s began t o be g iv en o f f . The m ixture was f i n a l l y o r e flu x e d a t 70*80 C u n t i l no more g as was evo lved. The m a t e r i a l was d i s t i l l e d and th e f r a c t i o n b o i l i n g a t 1 0 l2 i0 4 .5 ° 0 was c o l l e c t e d ; y i e l d 52 gms, 78.3$. J5o more pure q u in o lin e was a v a i l a b l e on s h o r t n o t ic e and hence f u r t h e r p ro d u c tio n of c h lo r o a c e ty l c h lo r id e had t o be made by a n o th e r method. B. from phosphorus t r i c h l o r i d e and c h lo r o a c e ti e a c i d . PC13 + 3C1CH2C00H _________ ■ 301CH2C0C1 + P (0H)3 Three hundred f i f t y seven grams of c h lo r o a c e ti e a c id and 115 ml phosphorus t r i c h l o r i d e (p r o p o rtio n s 3 moles to 1.05 m oles) were mixed t o g e th e r and h e a te d on a w ater b a th one and o n e -h a lf h o u r s . The m a t e r i a l was d i s t i l l e d w ith a fre e flam e and th e d i s t i l l a t e f r a c t i o n a t e d th ro u g h a v ig re a u x 30 o o column. B o ilin g range c o l l e c t e d , 99 -106 ; y i e l d 108.8 gms, 2 5 .5 fo TABLE IT ClOH COOH y i e l d B. P. Remarks gms gms fo °C 357 108.8 25,5 b b 99 -106 M S & l i g t F S k f H ? l o s s h r P G l.g 179 89.7 42 .1 b o 103 -107 R efluxed 2 h ours stood 2 days. The p r e p a r a t i o n c >f 4 -m e th o x y -l-c h lo ro a c e to n a p h th a le n e . A. P r i e d e l and G ra ft r e a c t i o n i n n itr o - b e n z e n e . The expected r e a c t i o n : + c i c t i c c c i f i l £ t ± f Y ] + H C -I <phf°x ■ ■ octf3 Seventeen and o n e h a lf grams of a lp h a n a p h th y l m ethyl e t h e r was d is s o lv e d i n 140 ml of n itro b e n z e n e in a 500 ml 3-neck f l a s k f i t t e d w ith a dropping f u n n e l, a m ercury s e a le d s t i r r e r , and a t r a p to c a tc h hydrogen c h l o r i d e . A f te r c o o lin g th e s o l u t i o n i n a s a l t - i e e b a th , thenaluminum c h lo r id e was added slow ly over a p e rio d of t h r e e - f o u r t h hour ( f a s t e r a d d it i o n r e s u l t s in t a r s ) . Then the c h lo r o a c e ty l c h lo r id e was added drop by drop from th e dro ppin g fu n n e l as a 31 25fo s o l u t i o n in n itr o b e n z e n e . When no hydrogen c h lo r id e was g iv e n o f f th e c h lo r o a c e ty l c h lo r id e s o l u t i o n was added f a s t e r , and s t i r r i n g was c o n tin u ed one hour a f t e r th e l a s t was added. The m ix tu re was then allow ed to warm up to room te m p e ra tu re . The s o l i d s a l l d is s o lv e d and th e s o l u t io n became d a rk e r and warmer b ut no hydrogen c h lo r id e was l i b e r a t e d . The m ix tu re was s t i r r e d over n i g h t . The r e a c t i o n m ix tu re was d i l u t e d w ith e th e r (4 volum es), e x tr a c t e d w ith w a te r, and th e n w ith 10fo sodium c a rb o n a te u n t i l th e aqueous la y e r gave no p r e c i p i t a t e upon a c i d i f i c a t i o n . The e t h e r la y e r was washed a g a in w ith w a te r and d r ie d over sodium s u l f a t e . A fte r tre a tm e n t w ith n o r i t e and removal o f th e e t h e r , th e n i t r o benzene was removed by d i s t i l l a t i o n a t 25 mm p r e s s u r e up t o i a te m p e ra tu re of 150°G.. The o i l which rem ained was e x tr a c t e d w ith p etro leu m e t h e r tw ice a f t e r w hich e t h e r was added causing th e m a t e r i a l to c r y s t a l l i z e . The pro d u ct was r e c r y s t a l l i z e d from b en zen e-p etro leu m e t h e r r e s u l t i n g i n a l i g h t brown powder which had a m e ltin g p o in t of 256°C. The m a t e r i a l e x tr a c t e d by th e petroleum e t h e r a l s o c r y s t a l l i z e d to a p a le y ellow powder which m elted above 230°. Y ield o f c r y s t a l l i n e m a t e r i a l , 1 gm. F u rth e r i d e n t i f i c a t i o n was n o t a ttem p ted sin c e t h i s m a t e r i a l was o b v io u sly n o t th e d e s ir e d mono s u b s t i t u t i o n p ro d u c t. B. F r i e d e l and C ra ft r e a c t i o n i n carbon d i s u l f i d e . 22 MM + c i c H j C O C / M | Z s ^ |^J 0 1 -t- # c / ^ ^ o c H3 Z ° c H 3 k one mole ru n was a tte m p te d a cc o rd in g t o th e method used hy U.G.L.A. 1 5 8 .E grams 1-m ethoxy-naphthalene was d is s o lv e d i n 800 ml carbon d i s u l f i d e w ith 11S.9 gms .chloro- a c e t y l c h lo r id e and p la c e d i n a 2-1 , 3-neck f l a s k f i t t e d w ith an aluminum c h lo r id e a d d i t i o n tu b e , a r e f l u x cond en ser con n e c te d thro u g h a calcium c h lo r id e tube to a gas t r a p , and a m ercury se a le d s t i r r e r . To th e v ig o r o u s ly s t i r r e d s o l u t i o n 133.3 gms o f aluminum c h lo r id e was added ov er a p e rio d o f one and o n e -h a lf h o u rs. The m ix tu re was allow ed t o r e f l u x f o r th r e e h o u rs u n t i l th e e v o lu tio n of hydrogen c h lo r i d e had p r a c t i c a l l y c e a se d . The m ixtu re was cooled i n an i e e - b a t h and crack ed i c e was added follo w ed by 400 ml of w a te r i n s e v e r a l p o r t i o n s . P a rt of the g re e n magma was e x tr a c t e d d i r e c t l y w ith 10u /o sodium hydroxide but s e p a r a tio n of la y e r s was d i f f i c u l t so th e rem aining m a t e r i a l was e x tr a c t e d w ith w a te r . She carbon d i s u l f i d e l a y e r was p laced i n a b e ak e r and th e carbon d i s u l f i d e was allow ed to e v a p o ra te by sta n d in g in th e hood. The 'c r y s t a l s were d is s o lv e d i n h o t e th a n o l and t r e a t e d w ith n o r i t e , and allow ed to ..c r y s t a l li z e i n s e v e r a l 33 c ro p s . White n e e d le s , M. P. 7 0 .7°-71.4°C ;, Yield. 85.9 gms. The. m other l i q u o r was trea te d , w ith n o r i t e and f u r t h e r c o n c e n tr a te d to y i e l d 21.5 gms of m a t e r i a l s l i g h t l y d is c o lo r e d M. P. 69.4°-69.7°C *. T o ta l y i e l d 107.4 gms; 54.6% The p r e p a r a t i o n of 4 - m e th o x y - l- ( w -d jb u ty la m in o - a c e to )- n a p h th a le n e . c o c ^ c / ^ c o c H ^ i C t U l J + ^ ^ - ^ 0 0 o c /43 O c U 3 Ten grams of 4-m ethoxy 1 - (W rc h lo ro a c eto) n a p h th a le n e ‘was d is s o lv e d i n th e minimum amount o f a b s o lu te e t h y l e th e r and 15.8 ml d ib u ty la m in e was added. The m ix tu re was allow ed to r e f l u x f o u r te e n and o n e -h a lf h o u rs. Becovery of 6.2 grams of d ib u ty la m in e h y d ro c h lo rid e i n d ic a te d 87.7% r e a c t i o n . The. o i l o b ta in e d by e v a p o r a tio n o f th e e t h e r cou ld n o t be c r y s t a l l i z e d from e th a n o l w a te r m ix tu re s . The o i l re c o v ere d i from th e a lc o h o l w a te r m ix tu re by d e c a n tin g t h e m other liq u o r w ith o u t c o n c e n tr a tin g was d is s o lv e d i n e x c e ss benzene and th e t r a c e s of a lc o h o l and w a te r d i s t i l l e d o u t. Upon a d d itio n of petro leu m e th e r t o th e c o n c e n tr a te d benzene s o l u t i o n an o i l was obtained* T his o i l was e x tr a c te d fo u r tim es w ith h o t pe tro leu m e t h e r and s c ra tc h e d c o n tin u o u sly u n t i l th e resid u e c r y s t a l l i z e d . The g o lid r e s id u e was th en d is s o lv e d i n hot 34 benzene and h e p tan e was added u n t i l th e m ix tu re was j u s t c lo u d y . One drop o f benzene was th en added to put e v e ry th in g i n s o l u t i o n and th e m ixture allow ed to cool t o room te m p e ra tu re . A deep orange powder was o b ta in e d m e ltin g o o p o in t 238 C. a f t e r s i n t e r i n g a t 224 0* (* § - gram was o b ta in e d ) . The p e tro leu m e th e r e x t r a c t s were c o n c e n tra te d and th e m a t e r i a l o b ta in e d was r e c r y s t a l l i z e d from a b en zen e-hep tan e m ix tu re . (1 gm of m a t e r i a l was o b ta in e d ) . Since th e s e p ro d u c ts d id n o t ap p ea r t o be th e exp ected am ino-ketone th e rem aind er of th e o i l was n o t c r y s t a l l i z e d . A second c o n d e n sa tio n i n e t h e r had been s t a r t e d b e fo re th e s e p ro d u c ts were o b ta in e d . T w enty-eight grams of the V c h lo ro k e to n e (.12.m oles) and 34.1 gms d i b u t y l amine (.26 m oles) i n 300 ml a b so lu te e th e r were h e a te d i n t e r m i t t e n t l y f o r 19§ h o u rs, and allo w ed to sta n d o v e r- n ig h t tw ic e . Recovery of 16 .0 grams o f d i b u t y l amine h y d ro c h lo rid e i n d i c a t e d 75% r e a c t i o n . The e th e r was t r e a t e d w ith n o r i t e w ith no a p p a re n t e f f e c t . I t was e x tr a c te d tw ice w ith 30 ml h y d rio d ic a c id (d. =1.7) to e x t r a c t th e amines and d r ie d over sodium s u l f a t e . C oncentra t i o n and a d d i t i o n of petro leum e t h e r gave a c o n s id e r a b le amount of o i l y m a t e r i a l which upon sta n d in g two days d id n o t c r y s t a l l i z e . Upon c o o lin g th e hydrogen io d id e e x t r a c t s o l i d i f i e d . I t was e x tr a c t e d w ith 1 l i t e r b o i l i n g w a ter in which i t was v e ry i n s o l u b l e . The w a te r e x t r a c t gave a sm all amount of a ye llo w s e m i - c r y s t a l l i n e m a t e r i a l which i s p ro b a b ly d i b u t y l amine h y d ro io d id e . The rem aining o i l was d is s o lv e d i n h o t 95% e th a n o l and upon c o o lin g i t . d e p o s ite d about 2 grams of an orange o o c r y s t a l l i n e powder o f M. P. 110 -112 C w ith deco m p o sitio n , a f t e r s i n t e r i n g a t 90°. This i s p ro b ab ly th e hydrogen io d id e s a l t of th e d e s i r e d 4 -m eth o x y -l-(w -d ib u ty lam in o a ce 'to )- n a p h th a le n e . C o n c e n tra tio n of th e m other l i q u o r t o o b ta in more m a t e r i a l gave o nly o i l s . P r e p a r a t io n of 4 -h y d ro x y -l-n a p h th o io a c i d . One gram of th e m a t e r i a l i s o l a t e d from the f i r s t c o n d e n s a tio n and t e n t i t a t i v e l y i d e n t i f i e d a s 4 -m e th o x y -l- n a p h th o ic a c id was b o ile d i n an open f l a s k w ith 7 ml h y d r io d ic a c i d (d, - 1 .7 ) and 0 .4 gms red phosphorus fo r two h o u rs . The m a t e r i a l d id not d is s o lv e b u t a f t e r a b o u t o n e -h a lf h o u r formed an o i l y l a y e r which f l o a t e d on to p o f th e h y d rio d ic a c i d . The m ix ture d e p o s ite d two d i f f e r e n t s o l i d m a t e r i a l s upon c o o l i n g v The y ellow c r y s t a l l i n e coo/-/ c o o H 36 m a te r ia l was s e p a r a te d m e c h a n ic a lly from th e dark brown o o s e m i - c r y s t a l l i n e m ass, i t m elted a t 150 -167 0 w ith ra p id h e a t in g . .It was a p p a r a n tly impure b u t th e sm all amount o b tain ed was l o s t i n an a ttem p t t o r e c r y s t a l l i x e i t from a lc o h o l- w a te r . The dark brown m a te r ia l, d is s o lv e d i n hot 10% sodium carb o n ate s o l u t i o n which p r e c i p i t a t e d a w h ite c r y s t a l l i n e m a t e r i a l upon a c i d i f i c a t i o n w ith h y d r o c h lo r ic a c i d . I f f . P. o o 90 -93 C . , r a p id h e a t in g . T h e ‘m a te r ia l i s v o l a t i l e w ith steam and h as th e c h a r a c t e r i s t i c odor o f a lp h a n a p h th o l. The m a t e r i a l r e e r y s t a l l i z e d from a b en ze n e-h e p ta n e m ixture gave a mixed m e ltin g p o in t w ith a known pure sample of a lp h a n a p h th o l of 9 5 .6 °-9 6 .2 °C . The pure a lp h a n a p h th o l m elted 9 6 .2 °-9 6 .8 °C . The p r i n c i p l e p rodu ct from th e attem p ted s p l i t t i n g o f th e methoxy group w ith h y d rio d ic a c i d i s t h e r e f o r e a lp h a n a p h th o l. 1 . 2 . 3. 4. 5. 6» 7. 8 . i 9. 1 0. 11. 1 2 . 13. 14. 15. 16. 17. 18. 19. BIBLIOGRAPHY Chen and S chm idt, Bphedrine and R elated S u b sta n c e s. B a ltim o re ; W illiam s and W ilkin s, 1930,121 pp. Dey and R ajagop lan, Arch. Bharm. 277. 359, 377, 1939. A. 34, 5085, 1940.) Edmunds, Eddy and Sm all, J . AM. Med. A ssn . 103. 1417, 1934. E ie s e r , Louis G, E xperim ents i n Organic C hem istry. I I E d itio n ; lew'York'; !D . C'.‘ Heath' and Co.',1941,p . 381. G atterm an and H ess, Am (1888) 244 73. ( H e ilb r o n 's D ic tio n a r y o f Organic Compounds V o l .I I p . 3 0 1 .) (B eil X p. 329) Henry, The P la n t A l k a lo i d s . T hird E d itio n , P h ila d e lp h ia ; P. B l a k i s t o n 's Sons and Co. I n c . , 1939, 689 pp. Houhen, J . , B er. 59. 2878. 1926. Houhen, J . , and B is h e r, W., B e r. 60B. 1759, 1927. Jacobs and H e id e b e rg e r, Organic S y n t h e s i s , c o l l e c t i v e Volume I ; Hew York; John Wiley' & 'Sons, p. 153. K unckel, B e r. 30. 1718, 1897. Lund, H., B er. 70B. 1520, 1937. Manske and Johnson, J . Am. Chem. Soc. 5 1 . 580, 1929. Manske and Johnson, J . Am. Chem. Soc. 5 1 . 1906, 1929. M o se ttig and van de Kamp, J . Am. Chem. Soc. 5 5 . 3448-53, Rabcwicz-Zubkowski, R oczniki Chem. 9. 538, 1929. (C. A. 24 106, 1950.) S c h o ll, R ., B e r. 29. 2415, 1896. S k ita and K e i l, B e r. 62 B 1142, 1929. Sm all, L. A ., p r i v a t e comm unication. Spath and Gohring, M onats. 4 1 . 319, 1920, (C.A. 15 38 20. S te in k o p f, W., B e r. CU 2540, 1908. 21. S t e ln t e n , Chemisehe Zent. 1879 I I 659 (B e il I I p . ’ 1 ' 9 & ,) " ' 22. S tro u g h to n , J . Am. Ghem. Soc. 5 7 . 202* 1935. 23. T u tin , Gaton, Hann, J . Am. Soc. 95. £113, 1909, 24. Voswinckel, H ., B er. 45. 1004, 1912.

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Creator Enos, H. I. (author)

Core Title The synthesis of certain derivatives of adamantane: The synthesis of certain substituted naphthalenes.

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Degree Master of Science

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

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Permanent Link (DOI) https://doi.org/10.25549/usctheses-c17-789530

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University of Southern California Dissertations and Theses