This 13 page thesis investigates the cyclization of w-tertiary butyl uramido benaoic acid and establishes the equation for the resulting reaction

Lovett, John R.

English

Ursinus College

Ursinus College Digital Commons @ Ursinus College Chemistry Honors Papers Student Research 5-8-1953 Cyclization of W-tertiary Butyl Uramido Benzoic Acid John R. Lovett Follow this and additional works at: https://digitalcommons.ursinus.edu/chem_hon  Part of the Chemistry Commons Click here to let us know how access to this document benefits you. Urs inus College L i b r a r y , URSINUSIANA COLLECTION C lass 0 Box (Sfcwr\r^ QYCLIZAnON OF CO-TBRn,ARY BUTYL URAMIDO BEt^ZOIC AOID Th is paper i s submitted to the f a c u l t y o f Urs inus Col lege i n p a r t i a l f u l f i l l m e n t o f requirements f o r departmental honors i n Ohemietry. Submitted: Approved: Urs inus Col lege May 8 t h , 1955 Acknowl edgemsnt I w ish to express n̂ ^ g r a t i t u d e to those who helped me i n the formation of t h i s paper; p a r t i c u l a r l y to Dr . Roger P . S ta i g e r f o r h i s e f f o r t i n prov id ing me w i th the problem and f o r h i s he lp i n the s o l v i n g of i t ; to Dr . R u s a e l l D. S t u r g i s f o r h i s v a luab l e adv ice and c r i t i c i s m ; to Dr . Harm d 0 . Beache l l and Mr. Thrygve R. Meeker of the U n i v e r s i t y of Delaware f o r t h e i r a id i n ob ta in ing and i n t e r p r e t i n g the i n f r a - r e d spectrographs; and to Miss Kath leen J . Aecker le f o r her help-i n the preparat ion o f t h i s paper. Contents I . I n t r o d u c t i o n I I . Syn thes i s o f w - T e r t i a r y B u t y l Uraraidn Benzoic Acid A. The P repara t i on o f T e r t i a r y Bu ty l Amine B . The P r epara t i on of I s a t o i c Anhydride C. Tne React ion o f the Amine w i th I s a t o i c Anhydride D. I s o l a t i o n and P u r i f i c a t i o n o f u ) -Te r t i a r y B u t y l Uramido Benzoic Acid I I I . O y c l i z a t i o n of the Synthes ized Product A. Procedure B . Apparatus 0 , Treatment D. I s o l a t i o n , P u r i f i c a t i o n , and I d e n t i f i c a t i o n 1 . S o l i d i n the F l a s k 2 . L i q u i d - D e r i v a t i v e i n the Reac t i on Tubes I V . Conclusions I . I n t r o d u c t i o n I n most cases , w - s u b s t i t u t e d uramido benzoic a c i d s , when r e f luxed w i t h mi ld dehydrat ing agents , undergo r i n g c l o -sure to form 5 - subs t i tu t ed benzoylene ureas^ Equat ion: 0 0 / ^ ' i i D B) M u j > t>EHVPl2ATlNJ6 | V . i i I 7 I 4- U. 0 H O I H When w - t e r t i a r y buty l uramido benzoic ac id i s t rea ted i n the same manner, however, the products o f the r e a c t i o n are a f i n e white c r y s t a l l i n e p r e c i p i t a t e and an u n i d e n t i f i e d gas. I f the s o l i d were the expected 5 - t e r t i a r y bu ty l benzoylene u r e a , p u r i f i c a t i o n would have y i e l d ed a compound w i th a me l t ing po in t o f approximately l 6 0 G. - the p u r i f i e d c r y s t a l l i n e product me l t -ed a t 555*0. The ob jec t o f t h i s paper i s to i n v e s t i g a t e the o y c l i z a -t i o n o f u - t e r t i a r y bu ty l uramido benaoic ac id and to e s t a b l i s h the equation for the r e s u l t i n g r e a c t i o n . 1 1 . Syn thes i s o f u ) - T e r t i a r y B u t y l Uramido Benzoic Acid Th i s syn thes i s was accomplished i n three s t eps . The f i r s t step invo l ved the prepara t i on o f t e r t i a r y buty l amine; the second, the prepara t ion o f the i s a t o i c anhydride; and the t h i r d . 1 . Doctoral d i s s e r t a t i o n , Roger P . S t a i g e r , U n i v e r s i t y o f Pennsy l van ia , 1955. - 2 -the r e a c t i o n o f the amine w i th i s a t o i c anhydride to fonn the t u - t e r t i a r y bu ty l uramido benzoic a c i d . 2 A. The p repara t i on o f T e r t i a r y B u t y l Amine This amine was prepared by the h y d r o l y s i s o f t e r t i a r y b u t y l u r e a . Equat ion : Apparatus: F i g . A r A- * 2 . Adams, Roger, _et. a ] _ . , Organic Syntheses , V o l . , 2 9 , p. 21 Procedure: : A one l i t e r round bottom f l a s k was charged w i th 60 grams ( 1 . 5 moles ) of sodium hydroxide p e l l e t s and 75 c . c . o f water . A f t e r the sodium hydroxide was completely d i sso l ved i n the water , 70 grama o f t e r t i a r y bu ty l u rea and 225 c . c . o f ethylene g l y c o l were added. A r e f l u x apparatus as descr ibed i n F i gu r e A was s e t up. The m ix tu r e was r e f l uxed gent ly f o r four hours . The t e r t i a r y bu t y l u r e a g radua l l y d i s so l v ed and a ge l a t inous mass o f sodium carbonate appeared i n the f l a s k . Any ammonia evolved was d i s -solved i n the water contained i n the beaker shown. At the end o f four hours , heat ing was d iscont inued and the m ix tu re was al lowed to cool to room temperature or l ower . The r e f l u x apparatus was rep laced by the arrangement shown i n F i gure B . and the contents o f the f l a s k '-ere d i s t i l l e d . The f r a c t i o n d i s t i l l i n g i n the temperature range 40 to 60*C . was c o l l e c t ed i n an i ce -coo l ed r e c e i v e r to prevent l o s s o f product . The y i e l d o f crude amine was 5 5 - 59 grams. The impure product was then dr i ed by a l l ow ing 5 - 7 grams o f sodium hydroxide p e l l e t s to remain i n con tac t w i th i t f o r two hours . Fur the r p u r i f i c a t i o n was accomplished by r e d i s t i l l i n g the amine from an apparatus s i m i l a r to tha t shown i n F i gure C, The f r a c t i o n d i s t i l l i n g between 44 ' -46*0. was c o l l e c t e d , again i n an i c e - coo l ed r e c e i v e r . The y i e l d weighed from 51 to 5^ grams. The purs product was a c o l o r l e s s l i c u i d having the c h a r a c t e r i s t i c - 5 -araine odor o f dead f i s h . T e r t i a r y buty l amine has a dens i t y 0 0 of 0.699 (20 0 . ) and an index o f r e f r a c t i o n o f 1 .5800 (20 0 . ) . Since three molar amine i s used i n the r e a c t i o n , the pure amine was d i l u t e d to t h i s m o l a r i t y by adding the r eau i r ed amount o f water , 5^.5 c . c . o f water f o r every 15 . 5 c . c . o f pure amine. B . The P r epa ra t i on o f I s a t o i c ;lnhydride^ Eauat ion : Procedure: ' One mole o f a n t h r a n i l i o ac id ( l 5 7 grams) was d i s so l v ed i n a m ix ture of 150 grams (125 c . c . ) o f concentrated hydroch lo r i c ac id and one l i t e r o f water . The s o l u t i o n was f i l t e r e d in to a 5 . C l a r k , R o b e r t o . , " i s a t o i c Anhydride. 1 . React ion With Pr imary and Secondary Amine and With Some .Amides," The J o u r n a l o f Organic Chemistry . Volume 9 , N-̂ ^ , Jetnuary, 19^^ . - 6 -t h r e e - l i t e r , three-necked f l a s k f i t t e d w i th a sea led mechanical s t i m w , an i n l e t tube reaching to the bottom o f the f l a s k , and an o u t l e t tube connected to a sa f e t y f l a s k , fo l lowed by a Drech-s e l absorber charged w i th ammonium hydrox ide . The mix ture was s t i r r e d mechanica l ly and phosgene was passed through an empty sa f e t y b o t t l e and then in to the s o l u t i o n o f a n t h r a n i l i o aoid a t such a r a t e (about two bubbles per second) t h a t bubbles o f gas escaped only s lowly a t the sur face o f the l i a u i d (hood) . The temperature rose , but was r e a d i l y maintained near SO 'c . by r e g -u l a t i o n o f the r a t e a t which the phosgene was in t roduced . The r a t e o f absorpt ion o f phosgene was found to be inc reased as the r a t e o f s t i r r i n g was i n c r e a s e d . Separa t ion o f i s a t o i c anhydride be-gan soon a f t e r the stream o f phosgene was s t a r t e d . The process wss continued during s e v e ra l ( 2 to 4 ) hours or u n t i l the absorp-t i o n o f phosgene was much decreased. The f l a s k was disconnected and a stream o f a i r bubbled through i t s contents to remove the phosgene. The white s o l i d was c o l l e c t e d , washed seve ra l times w i th co ld water , and dr ied a t 110 0 . Y i e l d s from a number o f runs ranged from 115 grams to 125 grams ( 7 1 - 11%) o f m a t e r i a l me l t -i n g a t 240- 245 C , pure enough f o r u s e . F u r t h e r p u r i f i c a t i o n may be e f f ec ted by c r y s t a l l i z a t i o n s from 95% ethanol (50 c . c per gram) or from hot dioxane ( lO c . c . per gram). 4 0, Reac t ion o f the ^Amine w i th I s a t o i c .Anhydride The r e a c t i o n invo l ved the d i s s o l v i n g o f a s u f -4 . S t a i g e r R. P . , o£. c i t . , pg. 2 6 -28. - 7 -f i c i e n t amount of i s a t o i c anhydride i n the three molar t e r t i a r y bu t y l amine and the a c i d i f y i n g o f the c l e a r s o l u t i o n w i t h co ld d i l u t e s u l f u r i c a c i d . The r e a c t i o n or molar r a t i o i s : 0.815 grams o f i s a t o i c anhydride _ 1 mole 12„5 c c . o f 5M t e r t i a r y bu ty l amine 7 . 5 moles Equat ion: O C \^ Apparatus: The apparatus requi red i n t h i s step cons is ted o f on ly a 500 c . c . beaker and two i c e ba ths . Procedure: Using the above r e a c t i o n r a t i o the appropr iate amount o f i s a t o i c anhydride was added to the three molar t e r t i a r y bu ty l amine. When the anhydride was completely d i s s o l v e d , the s o l u t i o n was d i l u t e d to four times i t s volume. Any p r e c i p i t a t e was f i l t e r -ed o f f and the s o l u t i o n was placed i n an i c e - b a t h . Gold d i l u t e s u l -f u r i c ac id was then added s lowly and the s o l u t i o n w i s s t i r r e d con-s t a n t l y . D. I s o l a t i o n and P u r i f i c a t i o n o f w - T e r t i a r y B u t y l U r a -mido Benzoic Acid A whi te p r i c i p i t a t e formed when the s o l u t i o n was - 4 * a c i d to i n d i c a t o r . The p r e c i p i t a t e was separated by suc t i on f i l t r a t i o n . P u r i f i c a t i o n was accomplished by d i s s o l v i n g the product i n hot e thy l a lcoho l and adding a smal l amount o f no r i t e . The f i l t e r e d s o l u t i o n was then r e p r e c i p i t a t e d by the slow add i t i on o f i c e co ld water . The p r e c i p i t a t e was again i s o l a t e d by suc t i on f i l t r a t i o n . The p u r i f i e d product was a snow-white compound having a me l t ing po int o f l65* 'c . I I I . O y c l i z a t i o n o f the Synthes ized Product A. Procedure I t was noted tha t a s o l i d and a gas were produced when t e r t i a r y bu t y l uramido benzoic ac id was r e f luxed i n d i l u t e s u l f u r i c a c i d . The composition o f the s o l i d was e a s i l y proven. Some problems arose i n the i d e n t i f i c a t i o n o f the gas. The major problem was to produce enough gas to make i d e n t i f i c a t i o n p o s s i b l e . The p r i n c i p l e d i f f i c u l t y was the f a c t t ha t on ly smal l amounts o f the w - t e r t i a r y buty l uramido benzoic ac id could be prepared. The second problem of i d e n t i f y i n g t h i s gas had to be looked at i n an-other l i g h t . I n dec id ing what reagent to use i n conver t ing the gas in to an i d e n t i f i a b l e d e r i v a t i v e , some assumption had to be made concerning the nature o f t h i s gas. Af ter cons ide ra t i on of the p o s s i b i l i t i e s provided by the r e a c t i o n i n ques t ion , i t was de-cided tha t the gas was probably an unsaturated hydrocarbon. I n view o f the f a c t t ha t r e l a t i v e l y heavy, n o n - v o l a t i l e l i q u i d s are - 9 -producsd when bromine i s used to s a tu ra t e the double bond i n 5 gaseous a lkenes , the method used here was to pass the gas in to a bromine-water m i x t u r e . B . Apparatus For reasons a l ready noted, the apparatus had to be kept as smal l as p o s s i b l e . I t cons is ted o f a 200 c . c . s t a n -dard tapered round bottom f l a s k ( l ) f i t t e d w i t h a r e f l u x con-denser ( 2 ) . I n the top of the condenser, a two holed rubber stopper was placed conta in ing two p ieces o f g l ass tubing which protruded s l i g h t l y in to the condenser. One o f the two p ieces was shor t and was pro-v ided w i th a p iece o f rubber tubing which could be clamped t i g h t l y s h u t . Th is acted as a pressure equa l i z e r ( 5 ) to p r e -vent the backing up o f the con-ten ts o f the r e a c t i o n tubes when the f lame was removed from beneath the f l a s k . The other p iece o f tub ing l ed to the bottom o f the f i r s t r e a c t i o n tube (4V, A second r e a c t i o n tube ( 5 ) 5 . Wertheim, fi.. Textbook o f Organic Chemis t ry , New York , The B l a k i s t o n Company, 1951 , p. 62^ - 1 0 -was connected to the f i r s t and a f i n a l p iece o f tubing served as an o u t l e t f o r the system. The r e a c t i o n tubes were smal l t e s t tubee. An i c e bath ( 6 ) surrounded the r e a c t i o n tubes to avoid l o s s o f product , ~ C. Treatment About four grams o f u - t e r t i a r y bu t y l uramido benzoic a c i d were placed i n the round bottom f l a s k . Approximately 100 c . c . o f 20% s u l f u r i c ac id were added. .he r e a c t i o n tubes were charged by the add i t i on o f 2 c . c . o f bromine and 10 c . c . of water to each. The apparatus was then arranged as p r e v i ous l y descr ibed , and the pressure v a l v e was c l o s ed . The mix ture was r e f l uxed about s i x hours . The r e a c t i o n could be assumed completed when the s o l i d present i n the f l a s k became d ispersed throughout the mix ture r a t h e r than remaining on the sur face of the d i l u t e s u l f u r i c a c i d . F u r t h e r , unon coo l ing , the s o l i d i n the f l a s k had a c r y s t a l l i n e form d i f f e r e n t from the o r i g i n a l w - t e r t i a r y bu t y l uramido benzoic a c i d . D. I s o l a t i o n , P u r i f i c a t i o n , and I d e n t i f i c a t i o n 1 . S o l i d i n the F l a s k The contents o f the f l a s k were cooled and the c r y s t a l l i n e s o l i d present was separated by auct ion f i l t r a t i o n . The substance was p u r i f i e d by repeated r e c r y s t a l l i z a t i o n s from an a lcoho l -water m i x t u r e . The d r i e d , p u r i f i e d s o l i d had a mel t ing o • po int o f 555 C . The me l t ing po in t o f benzoylene u r e a i s 555 G. - 1 1 -Mors conc lus i v e croof was obtained when i n f r a - r e d spectrographs o f por t i ons o f the compound prepared i n the above manner and tha t o f s epara t e l y prepared benzoylene urea were found to be i d e n t i c a l . i . 6 3.6 M.b 5,6 X.X> ' i . C i 16.0 \l.o \l.o O - O m . 6 \S.o \(,.^ Wave Length i n Microns F i gure P . I n f r a - r e d Spectrograph o f Benzoylene Urea J * . , » 1 J , j i 1 * i i 1 1 . 6 3 '0 5-0 t - 6 ^.t « . 0 ^ . 6 ^••« U .6 M.p \3.6 \j.6 \ 4 . o Wave Length i n Microns F i gure G. I n f r a - r e d Spectrograph o f the S o l i d i n the F l a s k The graphs i l l u s t r a t e d i n f i g u r e P and G o f benzoylene - 1 2 -u r e a and the s o l i d i n the f l a s k were determined w i th a B a i r d Assoc ia tes Double Beam I n f r a - r e d Spectrophotometer us ing a mul l o f the sample i n Nu j o l . . . 2 . L i q u i d - D e r i v i t i v e i n the Reac t i on Tubes l i f t e r the r e a c t i o n had been c a r r i e d to complet ion, the unreacted bromine i n the r e a c t i o n tubes was r e -duced by the add i t i on o f a sa tura ted sodium b i s u l f i t e s o l u t i o n . The s o l u t i o n was then n e u t r a l i z e d by the add i t i on o f sodium hy-drox ide . The heavy l i q u i d i n the bottom o f the r e a c t i o n tubes was the compound to be i d e n t i f i e d . Because o f the smal l amount o f product (about 0 . 5 c . c ) , p u r i f i o a t i o n was d i f f i c u l t . The l i o u i d was dr i ed by p l a c i n g i t i n a smal l t e a t tube conta in ing a chip o f anhydrous ca lc ium c h l o r i d e . Repeated dry ings were necessary . A m i c r o - d i s t i l l a t i o n was performed on the dr i ed l i q u i d . The r e d i s t i l l e d compound was c o l o r l e s s and f a i r l y dense. Three micro b o i l i n g po in t s were taken on both the p u r i -f i e d l i q u i d md a cont ro l (benzene ) . The average reading fo r benzene was 81 C. or one degree greater than the recorded b o i l i n g 0 p o i n t . The average reading fo r the unknown compound was 151 C. or two degrees g rea te r than the recorded b o i l i n g po int o f i s o -butylene dibromide (B. P . ihg^G.), Tne r e f r a c t i v e index o f the remainder of the p u r i f i e d l i o u i d was 1.5110 ( 2 5 * 0 . ) . The r e f r a c t i v e index o f i sobuty l ene dibromide i s 1.5119 (20*'o. ) . - 1 > I V . Conclus ions From the foregoing r e s u l t s , the f o l l ow ing conc lus ions have been reached: ( 1 ) tha t the s o l i d product o f the r e a c t i o n i n nues t i on was benzoylene u r e a . Comparison o f the me l t ing -po in ts and i n f r a -red spectrographs o f the product i n the f l a s k and benzoylene u r ea show t h a t these two compounds are i d e n t i c a l . • ( 2 ) t ha t the l i q u i d d e r i v a t i v e produced i n the r e a c t i o n tubes was i sobuty l ene dibromide and tha t there fore the gas evolved i n the r e a c t i o n i n nues t ion was i s obu ty l ene . To support t h i s conc lus i on , the s i m i l a r i t y o f the p h y s i c a l constants o f the un -known l i o u i d and those o f i s obu ty l ene dibromide i s c i t e d . No other poss ib l e brorao d e r i v a t i v e has p h y s i c a l c h a r a c t o r i s t i c s which compare favorab ly w i th these c ons t an t s . I n view o f these conclusions,©--tertiary buty l uramido benzoic a c i d , when r e f l uxed w i th d i l u t e s u l f u r i c a c i d , r eac t s i n the f o l l ow ing manner: o H o H C U , I n s t ead o f r i n g c l osure o c cu r r ing to y i e l d 5 - t e r t i a r y bu t y l benzoylene u r e a , i sobuty l ene i s c leaved and r i n g c l o sure occurs w i t h the format ion o f unsubs t i tu t ed benzoylene u r e a . 

Cyclization of W-tertiary Butyl Uramido Benzoic Acid

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Cyclization of W-tertiary Butyl Uramido Benzoic Acid

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