[CONTRIBUTION FROM TEE LABORATORIES OF THE UNIVERSITY OF BUFFALO]
T H E REACTIONS OF ORTHO ESTERS WITH CERTAIN ACID ANHYDRIDES* HOWARD W. POST
AND
EDWIN R. ERICKSON
Received June 89, 1937
Years ago Sawitsch reported that ethyl orthoformate had reacted with acetic anhydride' to give, not methylidene acetate (CH(OOCCHs)s) as had been expected, but instead formic acid and ethyl acetate. Undoubtedly ethyl formate was formed at the same time. Later Claisen made use of acetic anhydride in the reaction between ethyl orthoformate and ethyl acetoacetate.*. In this reaction the product w m ethyl a-ethoxymethyleneacetoacetate and it has been tacitly assumed that the function of the acetic anhydride was to remove ethyl alcohol, thus permitstingthe reaction to proceed. This type of reaction works equally well with acetylacetone2or with diethyl malonate12although in the latter case Claisen used zinc bromide as a catalyst. More recently Sah extended this type of condensation to prepare the corresponding products using, instead of the orthoformate the orthoacetate and the orth~benzoate.~These reactions were also carried out in the presence of acetic anhydride. Similar products were formed as a result of the action of ethyl orthoformate on diethyl acetonedicarboxylate,6on ethyl cyanoacetate6-', and on ethyl benzoylacetate. However, the action of acetic anhydride might not be as simple in these reactions as had been supposed. It might, for example, react first with the orthoester since previous work has shown that orthoesters undergo spontaneous, reversible decomposition to a slight extent even at room temperatures.l0 Many reactions of acid anhydrides can be readily ex-
* Abstracted from the thesis presented by the second author to the faculty of the University of Buffalo in partial fulfillment of the requirements for the degree of Doctor of Philosophy. 1 SAWITSCR, Jahresberichte, 1860, 391. * CLAISEN, Ber., 26,2729 (1893). a CLAISEN, Ann., 279, 19 (1897). SAH,J . A m . Chem. Soc., 63, 1836 (1931). 6 ERRERA, Ber., 31, 1682 (1898). e DE BOLLEMONT, Compt. rend., 128, 1338 (1899). DE BOLLEWONT, Bull. SOC. chim., [3],26, 18 (1901). DE BOLLEMONT, ibid., [3],26, 1828 (1901). 9 WEIS AND WOIDICH, Monatsh., 47,427 (1926). lo POST AND ERICKSON, J . Ana. Chem. Soc., 66,3851 (1933). 260
REACTIONS OF ORTHO ESTERS WITH ACID ANBYDRIDES
261
plained on the basis of a similar reversible, spontaneous decomposition, and, combining the two concepts, it was easy to predict a possible interaction between orthoester and acid anhydride, thus :
11.
(CH&0)20
111.
(CH3COO)-
IV.
(CH3CO)+
$ (CH3COO)-
+ (CH3CO)f
+ (HC(OCZH&)+ + CH&OOCH(OCzHa)z + (0CzHs)- + CH&OOCzHb
This reaction would have to be carried out at room temperatures or at least with very moderate heating, as Sawitsch reported nothing but esters and acids as the final products when ethyl orthoformate and acetic anhydride were heated.' If the above assumptions could be proven correct it might even be possible to show that these dialkoxyalkyl esters were intermediates in Snwitsch's reaction. It was a t first thought advisable to determine whether or not ethyl orthoformate would react with ketene, inasmuch as this compound, in a sense is an anhydride of acetic acid. But all attempts in this direction failed. True, diphenylketene reacts with ethyl orthoformate" but apparently ketene itself is unreactive. However, ethyl orthoformate was found to react with acetic anhydride at room temperature, according to the equation: V. (cH&0)20
+ HC(OC2Hs)s $ CH3COOCzH5 + CH3COOCH(OCsHs),
The main product of this reaction, diethoxymethyl acetate, is a clear, colorless liquid, formed in 41 per cent. yield on mixing the two reactants. The reaction is slow in the attainment of equilibrium. As the second step in the development of the concept, diethoxymethyl acetate was allowed to react with ethyl acetoacetate, also at room temperature, as a result of which ethyl a-ethoxymethyleneacetoacetate wm formed, probably according to the following series of equations:
+ +
VI
CH&OOCH(OC2Hs)z CHaCOCH&OOCzH5 e CHsCOOH CH~COCH(CH(OCIH~)~)COOCB~
VI1
CHsCOCH(CH(OCzHb)z)COOCzHs CZHbOH + CHzCOC( =CHOC~H~)COOCIH~
VI11
CHSCOOH
+
+ CzH60H
HOH
+ CH~COOC~HG,
and was isolated in 40 per cent. yield, together with ethyl acetate. The 11
BERT,Bull. soc. chim., [4], 37,1408 (1925).
262
HOWARD W. POST AND EDWIN R. EBICKSON
water formed may have reacted to decompose some of the complex acetate according to the equation: IX CH&OOCH(OC2H&
+ HOH * c H & o o c a 6 + HCOOGHs + C2H60H
Ethyl orthoformate also reacts with propionic anhydride in like manner, giving a 32 per cent. yield of diethoxymethyl propionate. Indecisive results were obtained with butyric anhydride. If the expected butyrate was obtained at all it had a boiling point so close to that of butyric anhydride that separation of the two was practically impossible. Furthermore, an approximately 34 per cent. yield of ethyl butyrate was obtained together with 20 per cent. of ethyl formate. Hence it seemed that in all probability diethoxymethyl butyrate was formed, and decomposed thus: X
CaH~COOCH(OQHs)2--+ Ca.rCOOCgH5
+ HCOOCzHs
Finally the reaction between ethyl orthoacetate and acetic anhydride was studied under the same conditions. Here, however, evidence was obtained leading to the conclusion that the reaction does not stop at a stage analogous to that reached in each of the preceding reactions but rather that alcohol is almost immediately lost from the complex acetate to produce a-ethoxyvinyl acetate and that this compound reacts to a certain extent with the original aa-diethoxyethyl acetate to produce 1,3,3triethoxy-1-butenyl acetate according to the equations: XI
(CHaC0)20
+ CHaC(OC2Hs)a C CHsCOOCzHs
XI1 XIII
+ CH~COOC(CH,)(0GHs)r
CHsCOOC(CHs)(OC2Hs)2 S GHsOH
+ CHaCOOC(OC2Hr)=CHs CHaCOOC(CHJ (OGHs)2 + CHaCOOC(OCas)=CH* + CHsCOOH + CH~COOC(OC~HS)=CHC(CH~)(OC~H& EXPERIMENTAL
Ketene, CHFCO, was prepared by the well-known method consisting of the pyrolysis of acetone. It was not liquefied. Acetone, CHsCOCHa, was purchased and purified. Crystalline potassium permanganate was added with intermittent shaking over a period of twenty-four hours, after which the acetone was directly distilled, then dried over calcium chloride. The second distillation then yielded a water-white acetone with a boiling point of 56.6" at 741 mm. Ethyl orthoformate, HC(OC1H&, was purchased from the Eastman Kodak Co. Constants found: b.p. 60°/30 mm.; n: 1.3900. Literature constants: b.p. 60°/30 mm.; n! 1.3915.lO
REACTIONS OF ORTHO ESTERS WITH ACID ANHYDRIDES
263
Ethyl orthoacetate, CH$(OCzH6)a, was purchased from the Eastman Kodak Co. and redistilled. Constants found: b.p. 66.5"/41 mm.; n: 1.3980. Acetic anhydride, (CHaCO)zO,was a commercial product, redistilled; b.p. 139". Propionic anhydride, (CZH~CO)ZO, was purchased from the Eastman Kodak Co., redistilled; b.p. 63"/13 mm.; n: 1.4048. , Butyric anhydride, (CaH,CO),O, was purchased from the Eastman Kodak Co., redistilled; n: 1.4070. Dzethozymethyl acetate, CHaCOOCH( O C Z H ~ )was ~ , first prepared in one of the attempts to induce a reaction between ketene and an orthoformate when the use of catalysts was tried, among others, acetic anhydride. But instead of the expected product from the ketene the substituted methyl acetate was obtained. Then on subsequent runs the new ester was prepared on a much larger scale. The two compounds, ethyl orthoformate and acetic anhydride were simply mixed in 0.5 molar amount each and allowed to stand a t 22" for four days in the dark. The reaction mixture was then distilled through a Widmer column. The properties of the compound were then determined; b.p. 79-80"/24 mm., 85-87"/30 mm., 170-172"/743 mm.; n: 1.:3959; d i 0 0.9919. Anal. Calc'd for C?HlcO4:C, 51.8; H, 8.7. Found: C, 52.2; H, 8.9. N (assuming molecular weight) = 39.28 (found), 39.46 (calc'd). The saponification equivalent was determined as the equivalent weight of the ester in its reaction with sodium hydroxide according to the equation,
x IV
CHaCOOCH(0CzHS)z
+ 2NaOH = CHaCOONa + HCOONa + ~ C Z H K O H $
and was found to be 82.60 as against the theoretical 81.05. The maximum yield was 41%, obtained, however, on a subsequent run by doubling the amount of acetic anhydride with respect to orthoformate, and making use of gentle heating, which distilled off the ethyl acetate as fast as it was formed. The chemical properties of the cclmpound were determined and can best be represented by the use of equations. The rieaction with water has already been mentioned (Equation X) and others follow.
+
XV
CHsCOOCH(OC2Hs)~ NaOH(5%, cold) = CHsCOONa HCOOCzH6
+
+
+ C Z H ~ O H(exothermic)
XVI CH~COOCH(OCZHK)ZNaHCOa(5% cold) = CHsCOONa HCOOCzHs
+
+ CZHSOH+ COS
The ester is readily soluble in dilute acids, reacts with cold neutral potassium permanganate, but does not react with bromine in carbon tetrachloride. It is easily and quickly hydrolyzed by cold dilute acids, which is to be expected as i t is really an orthoester. With aniline i t reacts as does the orthoformate: XVII
CHaCOOCH(0CzHs)z
+ 3CsHsNH2 = HC(NHCsH6)s
+ CHaCOOH + 2CzHsOH
This derivative melted at 137"-138" (corr.), and its identity was shown by determination of the melting point of a mixture with the product from the reaction of ethyl orthoformate with aniline.I2 XVIII[
HC(OC2Hs)a
+ 3CsHsNHz = 3CzHsOH + HC(NHCsHs)s
The mixture also melted a t 137"-138" (corr.).
GRACOLONE,Gazz. chirn. itaZ., 62,577 (1932).
264
HOWARD
W. POST AND EDWIN R. ERICKSON
Ethyl a-ethozymethyleneacetoacetate, CHaCOC (=CHOC&.)COOC2H~, waa prepared by the action of diethoxymethyl acetate on ethyl acetoacetate. The latter was purchased from the Eastman Kodak Co., and after drying over sodium sulfate and distillation through a Widmer column had a boiling point of 75" a t 15 mm. The esters were mixed in the proportion of 0.33moles of ethyl acetoacetate to 0.25molea of diethoxymethyl acetate, and slowly heated under reflux to gentle boiling. The solution rapidly turned yellow, then brown, to dark coffee-brown at which point the reaction mixture was distilled. The product, ethyl a-ethoxymethyleneacetoacetate corresponded to Claisen's product.13." It was a colorless oil, rather thick and heavy. Constants found: b.p. 146"/11 mm.; n: 1.4730;dy 1.0669. Literature constants: b.p. 149-151"/15mm.; dl6 1.0737.13s14 Anal. Calc'd for CpHlaO,: C, 58.0;H, 7.6. Found: C, 57.8;H, 7.6. The product reacted with 2,4-dinitrophenylhydrazinein alcoholic solution with a trace of hydrochloric acid to give a crystalline derivative, probably a pyrazolone. Ethyl a-ethoxymethyleneacetoacetate turns brown on standing, perhaps with polymerization. Diethozymethyl propionate, C2H6COOCH(OCzHt.)2,was prepared in the same manner as was the preceding acetate, Le., by the mixing of ethyl orthoformate (0.6mole) with propionic anhydride (0.5mole). The product was a colorless, oily liquid with a rather sharp odor in addition to the typical odor of an ester. Properties were deter0.9857;ng 1.4052. Saponification mined: b.p. 70-72'/10 mm., 177-179"/751 mm.; equivalent 87.15 (found), 88.56 (calc'd). N (assuming molecular weight) = 43.80 (found), 44.08 (calc'd). Anal. Calc'd for CsHleO,: C, 54.5;H, 9.2. Found: C, 54.2; H, 9.2. The compound hydrolyzes readily in water but not as rapidly as does the corresponding acetate. Trianilidomethane resulted from the action of aniline, it8 identity demonstrated by the method of mixture melting points. Diethozymelhyl butyrate, C3HtCOOCH(OC2H&, was assumed to be present in the reaction mixture when 0.5 mole of butyric anhydride and 0.5 mole of ethyl orthoformate were mixed and allowed to react exactly as above. The ester was not isolated but certain other compounds were isolated which could be assumed t o be decomposition products of the expected compound. In this reaction there were isolated 0.1mole of ethyl formate and 0.17mole of ethyl butyrate. a ,a-Diethozyethyl acetate, CH3COOC(CH3)(OCZHK)~, was prepared but not isolated, by the same method, namely, the interaction of 0.5 mole each of acetic anhydride and ethyl orthoacetate. On distillation large quantities of ethyl acetate were obtained. Another fraction, probably the desired product, boiled from 65" to 80" at 16 mm. It condensed as a colorless liquid but on standing turned a distinct violet in 15 minutes, the color deepening later to reddish-brown. a-Ethoxyvinyl acetate, CH3COOC(OCzHK)=CHp,was isolated from the fraction mentioned above which boiled from 65" to 80" at 16 mm. On redistillation, this fraction gave ethyl acetate, a trace of acetic acid and a fraction (7 CC. of a total 31 cc.) which boiled a t 130-133"and which reacted very rapidly with bromine in carbon tetrachloride. The saponification number of this material was found to be 64.46 as compared with the value calculated for a-ethoxyvinyl acetate of 65.04.
e
__
CLAISEN,Ann., 296,303 (1897). l4 CLAISEN,Ber., 28, 39 (1893). 13
REACTIONS OF ORTHO EBTERS WITH ACID ANHYDRIDES
265
I ,J,J-Triethoxy-f -bulenyZ acetate, CHICOOC(OCtHs)=CHC(OC2H&CHs, was isolated from the distillation process described in the preceding paragraph, boiling at 87-88' a t 13 mm. Other properties determined were n: 1.4462; 0.9817. Anal. Calc'd for Cl~HlzOr:C, 58.5; H, 9.0. Found: C, 58.2, 58.4; H, 9.2, 9.0. I t crystallized a t 20-21" t o large rectangular plates. I t was insoluble in water but soluble in the usual organic solvents, decolorized bromine in carbon tetrachloride very rapidly. The values for C and H check only for the formula C11H220~hence it acetate. is assumed the compound is 1,3,3-triethoxy-l-butenyl CONCLUSIONS
The experimental work herein presented indicates that in the reaction between an alkyl orthoformate and an aliphatic acid anhydride there is first formed a dialkoxyalkyl ester (Equation V), and that the formation of this compound is the first of a series of two consecutive reactions leading to the final group of simple esters. This statement has been verified for the reaction of ethyl orthoformate with acetic anhydride and with propionic anhydride and is probably true with butyric anhydride. In the reaction between ethyl orthoformate and ethyl acetoacetate in the presence of acetic anhydride, the function of the anhydride is not, as may be supposed, to remove ethyl alcohol. The present results show that the anhydride reacts with the orthoester to produce the dialkoxyalkyl ester and that this compound then reacts with ethyl acetoacetate to produce the alkoxymethylene derivative. Diethoxymethyl acetate was found to react with ethyl acetoacetate, yielding ethyl a-ethoxymethyleneacetoacetate (Equations VI, VII, VIII). The reaction between ethyl orthoacetate and acetic anhydride could not be made to yield the expected ester, corresponding in structure to those previously isolated. Instead, another compound, a-ethoxyvinyl acetate was found and it is assumed that a,a-diethoxyethyl acetate lost ethyl alcohol to form this compound (Equations XI, XII). A higher-boiling fraction was obtained which was probably formed by the interaction of apdiethoxyethyl acetate and a-ethoxyvinyl acetate with loss of acetic acid, namely, 1,3,3-triethoxy-l-butenylacetate (Equation XIII). SUMMARY
1. A new type of compound is presented as the product of the action of ethyl orthoformate on both acetic and propionic anhydrides. Evidence is also presented for the existence of a similar compound resulting from the action of ethyl orthoformate on butyric anhydride. 2. Diethoxymethyl acetate reacts with ethyl acetoacetate to give ethyl
266
HOWARD W. POST AND EDWIN R. ERICKSON
u-ethoxymethleneacetoacetate,the same product as is formed by the interaction of ethyl orthoformate and ethyl acetoacetate in the presence of acetic anhydride. It is proposed that d i e t h o w e t h y l acetate is the intermediate in this reaction. 3. The reaction of ethyl orthoacetate with acetic anhydride gives an unstable product which later loses alcohol to form a-ethoxyvinyl acetate, this product later reacting with the original compound, &,a-diethoxyethyl acetate to give 1,3,3-triethoxy-l-butenylacetate.
