•V THE PREPARATION OF THE ACETYL DERIVATIVE OF ETHYL ACETONE DICARBOXYLATE fJY HELEN MILLAR HOPKINS THESIS FOR THE D E G K E O BACHELOR O F S C I N G E IN CHEMISTRY COLLEGE OF LIBERAL ARTS AND SCIENCES UNIVERSITY OF ILLINOIS 1922 UNIVERSITY OF ILLINOIS ^■5 C ___iLun0 ig£ THIS IS TO CERTIFY THAT THE THESIS PREPARED UNDER MY SUPERVISION BY HJELM_JiILIJlRJiOP_KXIlS- ENTITLED_JTiiK_RREEARAXIOiI-UF-Tti£-^AU.ET-^L-Deaj.VA-?iVE-OF-ET-MY-L A_CETON£_I!iriARB.QXILATiI IS APPROVED BY ME AS FULFILLING THIS PART OF THE REQUIREMENTS FOR THE DEGREE OF ?AQii?kQ?__Qll_SCXEN_CE Instructor in Charge Ac Tu^q HEAD OF DEPARTMENT OF 51 ""'1 Digitized by the Internet Archive in 2015 https://archive.org/details/preparationofaceOOhopk Table of Contents Acknowl edgement The Ileohanism of the isodehydraoetio Ester Condensation I Introduction — 1 ±1 jiixperiraental 1. ihe isodBiiy^i'acetic ester condensation 3 2. The condensation of malonic ester and acetoacetic ester 4 3. The condensation of malonic ester with itself 5 III Conclusion 6 IV bibliography 7 The Preparation of the Acetyl Derivative of Ethyl Acetone Dicarboxylate . I introduction — 3 II Experimental 13 1. Preparation of ethyl acetone dicarboxylate— 13 2. The action of crignard's reagent on ethyl acetone dicarboxylate — 17 3. The action of benzoyl chloride on the magnesium compound of ethyl acetone dicarboxylate- 18 4. The action of benzoyl chloride on ethyl acetone dicarboxylate in pyridine solution 19 5. The preparation of the acetyl derivative of ethyl acetone dicarboxylate 19 III Conclusion — — — — — — 20 IV Bibliography 22 Introduction The purpose of this investigation is to discover the mechanism of the isodel:iydracetiG ester condensation. In the isodehydracetic ester condensation two molec- ules of acetoacetic ester combine breahing out, first, a molecule of v/ater and second, a molecule of ethyl alcohol. The follov;ini_, explanation has been given. The question that arose is whether the hydrogen atom connected with the carbon atom would be reactive enough to combine with the h;^droxyl group. Acetoacetic ester exists in two forms, the enol If acetoacetic ester in the enol form v.ould react with the keto acetoacetic ester which had the assumed structure U CF_G— OH OH u. CE^irCHO -OG2E5 and the keto form the mechan.ism of the reaction a - 2 - would be: .0 CH.-G=GH-3- ® \ 7 ^-G=GH=G C^HgO CH„-C-0ii- CzO 3 , ^ 0 / U-Gii GOOG2K5 3 the water brealciiig out first and then the alcohol - I'.'Ialonic ester enolized in this way only ,G-0H / ^OCoEk C-H “ C-OC2H5 so if rnalonic ester can be ester the second mechaniS;:: inade to unite \7ith acatoacetic is probably correct. aKPSEiiiEaiTij. !The Acetoacetic ester Oondensation T?ie acetoacetic ester condensation has been carried out in the following manner'**: 100 g. of acetoacetic ester and 250 g. of concentrated siilphuric acid v;ere mixed to- getlier (no internal heating being allowed). Then the mixture v/as kept at room temperature for 10 to 14 days. The mixture gradually thickened and assumed a brown color. At the end of the period of standing the mixture was poured in 500 g. ice and 500 g. of water. m/liite crystals probably a complex of unknown constitution may be repres- £ ented by the formula Gi8S-££09. These needle-like crystals were filtered off and washed with water to remove the acid. Then the filtrate v/as extracted with ether. The crystals were dissolved in the same solvent and the solutions vmshed with 'water and then extracted with 10 c.c. of sat- urated potassium carbonate solution. The carbonate broke up the complex and the potassium salt of isodehydracetic acid dissolved in the water and was separated from the ether. The solvent now contained the pure ester. It was dried with calcium chloride, the ether distilled off and the ester vacuum distilled. The portion boiling from 173°-180° at 23 mm. was collected. . i '■ ■ .’tf 'i , t V',. jSSr&u.,' ' , ■ ,4 '*i4^ «<'V ■ i«-*^' ikjil^B ^ ^ - t • « M I ,, • r '/..f X i.-<- , ,vtf^: •' -s t> v-«n.‘«£V».Tr> jJri . ;,!»!■, 5 »■ ■ '’a “)>l\ ^ I : ‘l-i '.■#•' ' ‘ ^ ^ ' , -..VV If rT !.. .’» .. t>i 't, •? , ' ’ % ’ ■.<4' . ’ ♦ %• Ojc* in ‘t, V.,) :'’J n t »■ ■># -■'■ ■' ') ' - ,1- ■ .'i‘':r : "^4^'' CI'*'^ ^i'A: ‘ „ ;■ ; )itM T ,^o| . !^K ' ' ■'■4MO . '’- • i ■ifr.'T (,.,0 1'^’:^. if-; l.l «v' ' ■■';^(' ':■ ■ ■* ' ’ ’■ ■ ! ‘'*' .' 'v% '4' i' : \ .1' ,!'^ , . 'J T"^ r I ' ; 1. r ;' •' ,f f'V.' ■** . ''iM rr-’j :/^v "XtJ. , :| ^ ‘ ^]|5 k iiaMiJ*. t,d^ .:* ? : ..v\ '».v i * ",l, j f ' I'.’jy . .0^'' .'*1' .1'^* 'fc^V . ty-’ * ’ r 1 . ' V .•^' , ■ . Y *- '“ • » “ ^ , . , ' ■ ■ ’■* »!•',. •'■;J I *iH !tU'<:' <'& , 'fl I" X' .,^, '‘ii0 • I " , .': ' » ' ' ' :^ fi*Jv' - f ' i»n “^ni rt l «* f I 4 . k . /d -4- rz A The ester may be brominated * , using 2 c*c. bromine to 6 g. oi the isodehydracetio ester v/hich had been dissolved in 15 G.c. of chloroform. After the action was complete the solution was washed with sodiuin sulphite and sodirmi bicarbonate solutions, dried, and the product recrystallized from alcohol, after evaporating the chloroform. These crystals of monobromo-isodehydracetic ester melted at 870 0 . 9OOC2H5 QCOG2H5 p r C - GHr. G = G - GH 05 / V ^ / \ Hc^GG ^0 ^ Bro-^H..G -0 0 + H'Br. ^11 / " \ / ‘(JH 0=0 GBr-G = 0 The condensation of acetoacetic ester was carried out in order to understand the manipulation better. It was found that the reaction could be completed in nine hours if the temperature was kept between 35® and 40®. Ivlalonic ester and Acetoacetic Ester Gondensation 250 g. of sulphuric acid were added to 62 g. of malonic ester and 50 g. of acetoacetic ester, and the mixture v;as cooled v/i th ice. This solution was allowed to stand thirteen days. At the end of that time it was thich and brown. This solution was pOured on 370 g. of ice and 370 g. of v;ater. No precipitate was obtained. To separate out the ester the solution was extracted three times v/ith ether. This solution -o- was treated similarly to the solution obtained by the condensing of acetoacetic ester* During the vacuuin distillation three portions were collected* Dirst portion 108° at 27 mm. - 120° mm. at 27 mm. Second ’ ’ 117° at 40 mm. - 177° mm. at 30 mm. Third ’ ’ 179° at 39 mm. ~ 202° mm. at 35 mm. This third portion v/as yellow. On refractionating it the liquid boiling between 185° - 192° at 35 mm. was saved. Six grams v;ere dissolved in pure dry chloroform and 2 c.c. of I bromine v;ere added, ^he solution v;as allowed stand vd th shading. Brown glubiiles separate out, but standing disappeared These glubules v/ere insoluble in chloroform but dissolved in alcohol, vfnen the latter v/as evaporated, no crystals separ- ated out. This residue had a purple color. After being allov/ed to stand for about three months it solidified to v/hite crystals that melted at 81° C. The mixed melting point of this compound and the monobromo-isodehydracetic ester previously prepared v/as 83° C. This then was ethyl- monobromo-isodeliydracetate. The chloroform soluble portion was washed vdth sodium sulphite and sodium bicarbonate solutions and then dried with calcium chloride and the bromo- compound crystallized from alcohol. By tahing mixed melting points this also was found to be etliyl-monobromo-isodehydr- acetate. The melting point of the third portion was between 15° !«• ^ I i - 6 - and £5^. vVhen allowed to stand in a mixture of ice and salt for a considerable length of time { for about 2 cc* to solidify it took about 2 hours) the ester was of a light yellov; color and was waxy. Various other proportions were used and experiments carri- ed out but no new facts were discovered. Condensation of I.Ialonio Ester v/ith Itself To determine ?;hether malonic ester reacts with itself in the presence of sulfuric acid, 50 g. of malonic ester v/ere treated with 125 g. of concentrated sulphuric acid. The reaction mixture was worked up as has been described. After purification a product boiling at 199° C. was obtained. This is the boiling point of malonic ester. To obtain further evidence 2 c.c. of the product were treated \Yith 10 c.c. of concentrated ammonium hydroxide and allov/ed to stand. \j'hite crystals melting at 170° G. separated out. This is the melting point of raalonamide and shows that malonic ester is unchanged by the action of concentrated sulphuric acid in the cold. CONCLUSION 1. I'.Ialonic ester vail not react with acetoacetic ester using concentrated sulphuric acid as the condensing agent. 2. ilalonic ester does not condense -with itself in the presence of concentrated sulphuric acid. 1 **^ *- f V' .' ■ r/ * ijO iAfi ■-. t' ■ 5 ^':V^i''-i%s’''‘W’' ' ■< ■>{, V . >^ 1 . ■* 'L'.T'-’ j I t\i} "P ; 4 •' ' — ■ ( ^ ^ •c>u ' - / ;V*^' <\ ■ '■;, ■ '>:'■.*! Vf*. S'IiTj..' .» . V. vn'i'-' '« ; .. .- t- :»j I ‘ f.-tli ' ■ • ■• 1. r.:- [fc^'■ y>. ';r » %-':. >■ ■*' %p ,r vv'mJ ,. -■-• ^....C'’'.. - v.’i ' ;* ■y I .'i ; '' ■‘J y' ' frt: ’r; jfi. r ^ f ’^4 ' I -.. . :• a.; iS I V-f' ■,•■■■ ,.y|v.‘; 5'M?# y j ' V ' — "r^ ?*apSS5i#t5£;J»^ .....r -7- BIBLIOGRAPHY 1. Ann. 222, 4 ( 1883) 2. Ann. 259, 152 (1890) 3. Ann. 222, 25 (1883) 4. Ber. 745 (1893), s,* r T’ j , 1 t o>‘- t ) u. ._' , * ‘J! .' ■}i .:&»•. i* •Jii^ *X ' " ‘•■r *.rUtit ' 4^ J, r,j ..'1 / l> t 4 >,. -\U( . « - 7-, ■\. \jf ■' . ,r tr •1 --.J™ - • • *x* .11 > ■ ,, I *> \ ' ’ 1 .b •1 ,. ■'’ * ■' J ■ V . i ■ ,iS ' i - 8 - Ihe Preparation of tlie Aceta^l Derivative of Ethyl Acetone DicarlPOi^-late Intro dn ctlon The beta alkyl and aiyl glutaconio acids have been made by tv/o general reactions- Esters of certain acetylenic 1 2 acids add malonic ester in the follov/ing manner; * On treatment of this ester vd. th potash the potassium salt of the desired acid is obtained. Acidification then yields the acid. GOOGgHg GHg G5H5G5GGOOG2H5 GOOG2H5 GH( GOOGgHg)^ GHOOZ G H -S GHOOG2H5 IT KDE GH( GOOGgHs)^ GH GOOIC GHGOOxi IT GH^GOOH E 2 The hydrolysis by alkalies of alpha pyrones also yields the potassium salts of these acids. p^' » . . .> ' • V . M * V iff \v ■>■ : _ : f;S «^ 0 .gilij^ V ; tr' t>6xgbf ^y p:X . f • i i-i.' vij.' ,-•. .'Af : Jt.* Ijl. I v-Ja *■!■<'?■ > < •s, M ; .c^Xo'i 5,f l. aJ ’ :i c::r.pZ^:fr I if' it> -, . . ., I . i / j' Jl. - M -s- GE-G=0 \ GEGOOiC n GE 0 iCOE GEa-G b , \ * y GrC-GEg GOOII GEgGOOE -h GHgCOOIC 4- GgHgOH If the CQitral keto group of ethyl acetone dicarboxylate would react with Grignard’s reagent, a compound would he obtained which on dehydration and hydrolysis should yield a beta substitution product of glutaconic acid* GKgCOOGgHs G=0 j GHgGOOGgHg HOE^ G^HglilgBr GH2G00G2H5 CgHg-C-OMgBr GHgGOOGgEg G.Hp--G-OE o 0 , GHgGOOCgHg G-OE GE2GOOG2E5 GH2GOOG2E5 -EOE P O b, GHGOOGgEg GE..GOOE I ^ C,H,-C 6 5 „ GEGOOE Other tautomeric esters, aceio-acetic ester^ and malonic ester^ react in the enolic form when treated with Grigiiard's reagait, giving metallic derivatives which on liydro lysis yield the original ester. The amount of enolization is dependant u^on the concentration, tempeiature, and solvent,^ -10- Slmilarly to acetoacetic ester vLi ch is the mono-carboxylio ester of acetone, the dicarhoxyli c ester is stron.ly acid. It dissolves in sodium cerbonate solution probably because 17^ of it exists in the enol form in solution.*^ After it was found that ethyl acetone dicarboxyla te acted as an alcohol the use of Grignard’s reagent on the ester itself was abandoned. OHgGOOGgHg GOH IT GHGOOGgHg CHgGOOGgHg G,H IlgBr G-0I.IgBr p ^ If GHgGOOGgHg t- ^6^6 HOH G-OH IT GHGOOG^H. £ 0 The difficulty with the hydroxyl group could possibly be remedied by replacing the hydrogen atoms witha benzoyl or an acetyl group and treating the resultifig compound vd.th Grignard’s reagent. GHgGOOGgHg ’ ^ G-OG-G^H^ G^H^.ivlgBr GHGOOGgHg ^ GHpGOOGpH. C H_-G-0G-G.Er, GHzG '•OCgHg Uli HGl GH^GOOGgh^ GeHg-G-O-GOC.H, ’ xOH Gh=C \ GHgGOOG^Hg r earran.^ e G^Hj^-G-O-GOGgH^ ' 1 CKgCOOCgK, ^ ‘C I. . • i )jTr I i:v ••r K '1 1 I u i ■<* ■ J T ^ - * c.y JU4.?i r :o .‘’3^-'sa A* .1. i i\ -11- CKCQOH IT acid- C^Hr--G -- — ^ 6 5 , CH COOH There v/as the possibility also of getting GH.COOGoH;; ' ^ .of ^ C-O-G^G.H. GHGOOGgig^ by the action of Grignard’s reagait on the carbonyl gronp o^ the benzojrl radical. An attempt was made to make the benzoyl derivative by Q the action of benzoyl chloride on the organic magnesium compound GH2GOOG2K5 G-OilgBr G1-G0G .Hp- TT GHGOOG2H5 CHpGOOG^H. I ^ ^ o G-O-GOG^Hg -V I-IgBrGl GECOOG^H^ S 5 Ano tiler method that was tried was a general one for tbe making of 0 - compounds from enolic esters and ketones by the action of the acid chloride on the ester in pyridine solution. The: compound with the structure^^ GKgGOOGgKg G-OGOG„H. IT C 0 GHGOOOgHg has a melting point of 57°. This substance has such a similar I - 12 - s tra c tLir e to that of the desired corr - ril the,t ii ;,as lope.. t>u-t ti' e latter wo-. 1.1 be a solid. In the prt.paration oriy a hig ^.1 boiling nr^terial v/as obtained which was decouposed on distilling so the acetyl derivative was prepared by the action of acetyl chloride on the beng.ene solution of ethyl acetone dicarboxylate in the presence of pyridine. Ihe active agent in this reaction is The resulting cornpouiid has the formula: GEgCOOGgEg /P I ^ GHOQuO E 2 5 k simple tvjst to distinguish ett.yl acetone dicarboxylate from the beta derivatives of glataccnlc ester can be made by adding a dilute solution of copper acetate to an ether solution of the ester. In the presence of a snail anount of the etbpl acetone dicarboip"la te the ether ia^ er is a bluish^ green and in the presence of a larger amicunt of ester^^ blue bushp crystals separate and can be reerps ta llized from alcohol. The crys uals .elt at 14.a° G. aad have the . ormula GEpGOOGpE^ Gn GOOG.rl. ’ I S 2 t) 0-0 Gu-O-G ’ IT Gir:G0UG£E5 GhG00G„E^ o -is- 12 The Preparation of Ethyl Acetone Dicar'box.ylate* Three preparation of this ester were niade using the following directions: "In a 5 1. glass jar eq.uipped v;i th a mechanical stirrer and coo led v/ith ice and salt, place 9 Ih. of fuming sulphuil c acid (20^;. Add slowly in small portions 1000 g. of citric acid so that the temperature of Hie reaction does not rise above 0° until about l/S of the acid has been added, and not above 10*^ until aboLit 2/3 of the citric acid has been added, the final temperature should be about 20°. After the greater part of the citric acid has been added (about 4/5) and the temper- ature has risfen nearly to 20° there will be a vigorous evolution of gas and much foaming. After this vigorous evolution has subsided the temperature will have fallen to 15°, the remainder of the acid ms^y be added at one time, and the mixture stirred until foaming has ceased. The jar should then be remolded from the cooling mixture and the temperature allov/ed to rise to 30° and kept at this temperature until all evolution of gas. has ceased, as will be seen by interrupting the stirring, when after a minute or so the mixture will appear as a clear, brown liquid vdth veiy fevv gas bubbles. The jar is now placed in a cooling mixtui-e and the teraperetare allowed to sink to 10%^. oVd then 2400 g, of finely ground ice added in small portions so that the temperatur w ^ <5 w 1 Vi I (, ■ / "v‘ f \ <.iA 3 ^* -14- of the mixture never rises above 40°. The first portions of ice must be added slowly but after the acid is somewhat diluted it may be added more rapidly. After all the ice has been added the mixture is cooled to 10° or 0*^, then filtered as rapidly as possible oit a funnel fitted with a filtrose plate sealed with sodium silicate, pressed down hard and suched as diy as possible. The acetone dicarboxylic acid should now appear as a slight- ly pinkish- v;hite flaky material. After being well pressed and sucked dry, it is washed with ethyl acetate by stirring with sufficient of the acetate to wet the whole of the precip- itate in a beaker and again filter. The process is repeated v/ith more acetate. The yield is 430-460 grams. The acid is mixed with an equal weight of absolute alcohol v;hich has previously been saturated with dry hydrogen chloride and the mixture unarmed gently on the water bath to 40° with frequent shaking until all of the acid is dissolved. The flask is then closed v/ith a stop, er bearing a GaCl, tube and allov/ed to stan-d over night. The contents of the flask are now oil an equal v/eight of ice and the ester layer separated. The alcohol-v/ater layer is extracted several times with ether. The ether layer is added to the ester layer and the ether solution washed with 10/3 ITagCO^ solution until free from acid -15- then with dilute and finally twice v/ith water* The ester layer is heated on the water Data under diminished pressure as long as anything distils over. This process removed the watei", alcohol and ether* Tre es-ter is then vacuum distilled, collecting the fraction from 120®- 180° at 50 mm. The fraction is again vacu^nm distilled collecting the fraction "boiling from 155*^ - 162° at ^50 mm. The yield is 70 - 75^ of the weight of the acid”. The reaction is as follows: CH,,000H GH GOOH , C I c GOHGOOE H SO G=0 + GO -+• EOK GEgGOOE GEgGOOE Poliowing these directions it was found that the tempefature did not rise as rapidly as vas indicated. ."nen the jar v;as removed from the freezing mixture it took almost two nours for the temperature to rise to 30°, "but if the jar ’was sur- rounded with warm water much time was saved. ifiien the acid was washed v/ith ethyl acetate just enough was added to mcisten the acid, the yield of product v/as inc_eased and there v/as no noticeable decrease in the amount of ester obtained. It v/as possible to keep the acid without decompositior if the temperature was kept at about 10°. After the ester was prepared the separation of the ether layer became increasingly difficult because of tarry material p y : '■>■ fra u'^ ,r ‘4tu :^iJ^ '..ii « « • ;0“ V'’ ■‘^-' »• x/i' u V * 4* , - . - ‘ >1/. ^:^•' T- ■ i !i^: - -i6- arui emulsions. The ester- ether layer v/as filtered and ammonium sulphate added to the soliition and no farther difficulty was expert enced- In fractionating the ester its boiling point was found to be: 135° - 137° at 10 -12 mm. 175° - 180° at 75 mm 142° at 17 mm. Decomposition took place above 180° and the pressure rose ^0 100 mm. 5 lb. fuming suifuric acid (20fo) Prepe^ration I 3 lb. fuming sulfuric acid { 20'/o) 330 g. citric acid. 1800 g. ice. Yield of acid 173 g. 173 g. alcohol and hydrogen chloride. Yield of ester 65 grams. Preparation II 6 3/4 lbs. fuming sulphuric acid ( 20;b) 750 g. citric acid 1800 g. ice Yield of acid 232g. 255 g. alcohol and hydrogen chloride Yield of ester number of grams not Imov/n. -17- Preparation III 6 3/4 It), fuming sulphuric acid ( 20;4) 750 g. citric acid 1800 g. ice yield of damp acid 550 g. prohabUy 460 dryfacid 520 g. alcohol and hydrogen chloride Yield of ester 200 g. The theoretical yield of the acid using 750 g. of citric acid is 618 g., and the ester 855g. Action of Orignard*s reagent on Ethyl Acetone Dicarhos^/late The ratio of >9 mols of phenyl magnesium bromide to one mole of ethyl acetone dicarboxyla te was used to see if Grignard’s reagent would attach the middle heto group. 15 g. of ester in 15 c.c. of anhydrous ether, v.hich has stood in the cold to decrease the enolizaticn, was treated v.ith. the organic magnesium halide, 'ilien the latter bit the ester a white precipitate formed. Shortly afterwara.s the solution became brovn. The mixtare was refluxed tv.o hours and on standing v;hite crystals separated out. The mixture was poured on 50 g. of ice and 50 g. of water and 10 c.c. (l:l) sulfuric acid. The ester and water Inyers were separated and the ester layer was v/ashed with 5'fo sulphuric acid and then with water. The water layers were extracted with ether ,,V'- - ^ !fc' a.:^Aw4fi«25^'^;Sl!fe>^^ •'■.ijritSiaiWMjW" y . T a C'^V i w fe. .. .■T_pr :aifK?^jM^^^‘wwwKTria!gwgg>^-L-.^^ Lfru ^Ti^YrTffMWr •> «#MiiPi|l| IrlK f! ■- J ’ ' ■'■* U‘v ; / .> : /i. ■ 'Hi: *’-' * ‘ ,'■ • \.!i.'.'.'> i> ,'>iC'i\ '-S S'j, - ■■ ui —;xs$jm. * ; '"ik ’ ^ yj>. ■t .»■■'■, ■■ b J. ' '..'A'ltlW.' ^ •V i <. ■ f ■ i ■‘i- I* lii'i' tX / 'stVl J'i'» •iV*" lu*>I : ', > ■ ■ , • . ' 'V t. ^ . ^ I '.•• ■ ' '" I • ..'.4 ;;: 7.?,' i j ' ■■ ^ M"/ V,, *1 • m ' '! - ■ .', ; '^'c, ru^'VM . -i .u . ' iku\. •■-f. • ,m>‘ ‘in ■ i^r.. ■^ rf ■ t 'i ■ ■'' r -I' - A/''/; 's*« ■ np.i^p, II ' Iiiiii;iii"-^1 7 r-t # -18- After mixing the ester and ether portions the solution was dried v,l th anhydrous sodium sulfate and the solvent distilled off. Distilling in a vacuum 9 g. of ester and about 3 g. of residue were obtained. Tr.e latter was proved b;^ saponification to be decomposition priducts. The ester Vt/as fractionated and a colored portion of 3 g. was collected that boiled, giving off violet vapors, over a vade range of temperature (up to 160^) under 60 mm. pressure. From 160^ to 180° at 70 mm. a 5 l/£ g. portion of clear liquid distilled. The first frac tion was shown by the copper acetate test to contain a very small a’“::ount of ethyl acetone dicarbox- ylate and the second portion to be almost wholly this ester. The Action of Benzoyl Chloride on the I.la, :nesiurn Compound of Ethyl Acetone Di carb o x;;:late _ One equivalent of the Grignard reagent v;as dropped on an equivalent of ethyl acetone dicarboxylat e in solution in anhydrous ether which v/as srjrrounded by ice. Then one equivalent of benzoyl chloride in ether solution v/as added. After standing for half an hour the contents of the flesh were emptied into ice and a small amount of acid. The precipitate that was present dissolved. The water and ether layers v/ere separated and the latter v/ashed with v/ater, sodium carbonate solution, and again Mth water. A v/hite oily emulsion in the ether resulted. On evaporation of the solvent and recrystal- lizatioii of the product from water the substance was found to <* 4 'M # * 1 . i'.'. 4'^', * j'ij iti^' ^ ~lat e. Several attempts were made to make the acetyl derivative. In the most successful preparation the materials rsed v/ere: 25 g. etliyl acetone dicarboxylate. 83 cc. dry benzene . -niwSr* S' :f'~ ■'• ■lrM>~»»i'rr>t<^ i a#laM«c ; :. '_ lit*.' J J ,.\ •■I : y 'S'Ti '■ ■ ' *l iZ ^ * '■> -^t. '1 I i* - 20 - 10.5 g. acelyl clilorid^ 11 S* Pyridine The ester was dissolved in the benzene and the acet^^l chloride added. The mixture was kept cool but not cold enough to freeze the benzene. The pyridine was added drop by drop. The solution v;as allov/ed to stand laalf an hour and then was poured into 250 c.c. of v;ater v;hich contained the calculated amount of hydrochloric acid to react with tie pyridine. After separating tie benzene la.yer from the water, the latter v/as v/ashed ^vith very dilute hydrochloric acid solution, v/ith sodium carbonate solution, and finally dried with anhydrous sodium sulphate. The benzene was evaporated off and 'the remaining liquid was vacuum distilled. i^irst fraction 55® - 132® at 7 mm. Second Fraction 127® - 136.5® at 7 mm. Third fraction residue The second portion was redistilled and the constant boiling portion, 129® - 132® at 5 l/2 mm. pressure, was collected, and a carbon and hydrogen determination made. 17eight of sample .1635 g. Weight of v;ater .1035 g. V/eight of carbon dioxide .3289 g. Theoretical Sample 54.86^ 54.09/O Carbon Hydrog en 7.03 6.56^ The product was proved not to be ethyl acetone dicarboxylate - 21 - by the copper acetate test. This compound is then the acetyl derivative of ethyl acetone dicarhoxylate. CH^GOOC^Hp. I P xi O C-O-O-GH, It o GHGOOGgHg GQhGLUSIQITS 1. Ethyl acetone dicarhoxylate as is the case v/ith other tautomeric esters; reacts in the presence of Grignard’s reagent as an alcohol. 2. The acetyl derivative of the enol form of the ethyl acetone dicarhoxylate has been prepared. .7:^1 X^-.vfc," ~"VJty »»*■'■!*• <^ ^ .fc '?b^!'M' '00 fefr ''*•■; “T# *^**J BiblioKraphy 1 . J.pr.U) 490# 22,U894; 2. J.C.S. 73, 1015 U898) 3. Ann. 222, 31 (1884) 4. 0.73 (1), 1197 (1902) 5. J.A.C. 115, 1208-9 (1919) 6. Ann. 380, 212-42 (3911) 7. Meyer and Jacobson, Lehrbuch der Organischen Chemie, 1217 8. A.C.J. 31, 653 (1904) 9. Ber. 37, 3929 (1905) 10 . Ann. 363,35, (19u8) 11 . Ann. 261, 176 (1891) 12. Marvel and Chiles, unpublished work.