ON T H E COURSE OF T H E ADDITION OF MALONIC ENOLATES TO a,b-UNSATURATED ESTERS ARTHUR MICHAEL Received July 17, 1957
Michael and Ross1 found that crot,onic and methylmalonic ethyl esters, catalysed by a small amount of alcoholic sodium ethylate, form the 1,2 addition product (I) with migration of the malonic a-hydrogen; while the crotonic ester and the methylmalonic ester enolate yield, by 1,2 addition with migration of the malonic methyl group, the dicarbethoxy enolate (11). CH3CHCHzCOOEt
CHaCHCH(CHs)COOEt
I
I
CHaC(C00Et)z
C(COOEt)=C(ONa)OEt (11)
(1)
In enolate additions to a,B-A-esters the reaction follows the course leading to the possible maximum neutralization of the sodium.2 I n compound (11) this condition is realized by the formation of a dicarbethoxy enolate; the migration of the malonic methyl group to the a-Acarbon of the crotonic ester being facilitated by the loosening influence of the poorly neutralized, strongly positive sodium upon the affinity of the methyl group for the carbon to which it is attached in the original methylmalonic en01ate.~ Recently* it was shown that the sodium enolates of malonic and methylmalonic esters “in non-polar solvents” react with a,8-acetylenic esters to form, with migration of the sodium to the monocarbethoxy group, the relatively inert, colored, monocarbethoxy enolates I11 and IV. The mechRC=C=C(ONa)OEt
RC=C=C(ONa) OEt
€€A
(COOEt)2 (111)
CHaC(CO0Et)r (IV)
* MICHAELAND Ross, J . Am. Chem. SOC.,(a) 62, 4598 (1930); ( b ) 63, 1150 (1931); (c) 66, 1632 (1933). 2 MICHAEL.See la and l b for literature. * MICHAEL,Ber., 39,2142 (1906);J . A m . Chem. SOC.,32, 997 (1910). 4 (a) GIDVANI, KON, WRIGHT,J . Chem. SOC.,1932, 10%’; (5) GIDVANIAND KON, ibid., 1932,2443;( c ) FARMER, GHOSAL, AND KON,ibid., 1936, 1804. 303 TEE JOURNAL OF ORQANIC CHEMISTRY,
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anism of these 1,4 additions is similar to that of the addition of potassium cyanide to c~,@-A-esters.~ No theoretical explanation has been advanced for this anomalous behavior of the acetylenic esters in forming monocarbethoxy enolates; nor, for the singular properties of the addition products. The English chemi s t ~believe ~ that a,P-ethylenic and a ,P-acetylenic esters should react similarly from a valence viewpoint. However, an acetylenic group exerts a far greater negative influence than an ethylenic upon an attached carbonyl. This shows itself in the enormously greater K values of the acetylenic than of the corresponding ethylenic acids (e.g., 2 X and 246 X for crotonic ttnd tetrolic acids, respectively), in the formation of monocarbethoxy enolates from acetylenic esters, while ethylenic esters yield malonic enolate derivatives, and in that the sodium in the acetylenic addition products is far less reactive, Le., intramolecularly better neutrallized, than in the corresponding ethylenic, malonic ester enolates.6 It is evident that the apparently abnormal enolate addition to a,@acetylenic esters is due to better neutralization, in the addition products, of the sodium in the mono- than in the dicarbethoxy enolate grouping. This conclusion is confirmed by the normal synthesis, through the catalytic process, of 1 ,2-addition products from malonic and methylmalonic esters with both CY ,P-acetylenic and CY ,P-ethylenic esters: the a-hydrogen and the residual radicals of the malonic esters function as addenda in the reactions. Furthermore, the course of addition of methylmalonic ester enolate to cr,P-acetylenic esters cannot afford a valid deduction with regard to the mechanism of the entirely different mode of enolate addition to the corresponding ethylenic esters. Unexplained, also, is the observation*' that sodium acts upon an ether solution of the free ester, isolated from IV, to yield the colorless, reactive malonic enolate (VII). An ethylenic ester of the type produced by CH&=C==C (OH)OEt
I
CH&=CHCOOEt
I
CH,C( COOEt) 2 ('VI (VI) CH3C=C (CH3)COOEt
CH3C(COOEt)z
I
C (COOEt)=C(ONa) OEt
(VI11 h h C H A E L AND WEINEW,J . Am. Chem. soc., ( a ) 69, 744 (1937); ( b ) ibid., 69, 749 (1937). 6 ( a ) MICHAEL, Ber., 98, 3222 (1905); (b) MICHAEL AND Ross, J . Am. Chem. Soc., 63, 2394 (1931).
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change of the labile monocarbethoxy enol (V) to the stable ketonic form’, (VI), does not react with sodium to yield the corresponding monocarbethoxy eno1ate5*’*,but the above chemical system can attain the maximum energy degradation by formation of dicarbethoxy enolate (VII). Expulsion of the a-hydrogen of VI, with migration of the ymethyl to the a-A-carbon occurs; the latter, a forced positional change, is analogous to that observed in the formation of I1 from crotonic and sodium enol methylmalonic esters’”. Anamalous, also, is the behavior of monocarbethoxy enolate (111) towards ethyl iodide in boiling alcohol4“;y-alkylation results with migration of y-hydrogen to the a-A-carbon. The sodium in I11 is so neutralized that a mineral acid is required to liberate the mother-substance easily4c; a-alkylation under the experimental conditions is, therefore, impossible6. However, an alkylation may take place indirectly, i.e., by union of the enolate sodium with the iodine of the iodide, intramolecular shifting of the reactive, malonic y-hydrogen of I11 to the a-A-carbon, and attachment of the ethyl group in the liberated y-position. Such a rearrangement-substitution does not occur in the action of ethyl iodide upon enolate IV; in this reaction, rn in alkylacetoacetic ester syntheses, the ethyl group assumes the a-position. Obviously, far more energy is required to overcome the chemical hindrance to the separation of the y-methyl of IV, than the reactive y-hydrogen of 111, from the attached carbon. The first fission may be effected in a suitably constituted compound by metallic sodium, through its great chemical potential for unsaturated oxygen, but not under mild conditions by the relatively weak affinity of the iodine of the iodide for the comparatively well-neutralized sodium of enolate IV. Attention was also called4cto the isomerization of I to I1 by sodium ethylate, but, since I is thus retrograded to methylmalonic ester enolate and crotonic esterg, the conversion follows inevitably from the interaction of these cornpoundsla. Although no reasons are adduced to support the opinion, Farmer, Ghosal, and K o believe, ~ ~ with ~ Holden and Lapworthlo, that in the methylmalonic ester addition reactions, “the a ,p-dimethyl ester is in all cases produced by the rearrangement of the ,y-esters primarily formed” and that “unless an equivalent of sodium ethoxide is present”, the 6 ,y7 MICHAEL [ J . prakt. Chem., 49, 20 (18!)4)] and FEIST [Ann., 346,82 (1906)l had previously examined the action of sodium malonic ester upon a,B-acetylenic esters and concluded that the esters liberated from the addition products have normal structures. 8 MICHAEL, Ber., 33, 3766 (1900). 0 MICHAEL, Ber., 33, 3749 (1900); INGOLD, J . Chem. Soc., 119, 1976 (1921). 1 0 HOLDEN AXD LAPWORTH, J . Chem. Soc., 1931, 2368.
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dimethyl ester, EtOOCCH2CH(CH3)C(CH3)(COOEt)2 (VIII) is formed. The latter statement is not probable; when more ethylate is present than is essential for catalysis, an amount of enolate corresponding to the excess of ethylate should be formed. Indeed, a small amount of enolate should appear under the usual catalytic conditions of the addition and undoubtedly it is this, not the ethylate, that really serves as the catalystll. The assumption that the p ,r-tlimethyl ester is always the primary product is also improbable. The addition was carried out with methylmalonic ester enolate and crotonic ester in ether solutionla and, from their viewpoint, as the enolate contains no a-hydrogen, the monocarbethoxy enolate corresponding to VI11 should be mainly the primary product. This course of addition would proceed with migration of the sodium from a dicarbethoxy enolate group to form a much less neutralized, monocarbethoxy enolate derivative. This supposition is as probable as to assume that an aqueous solution of equivalent amounts of crotonic acid ( K = 2 X low5)and sodium methylmalonate contains mainly sodium crotonate and free methylmalonic acid ( K = 87 X It may be assumed that a small proportion of the monocarbethoxy enolate of VIII, existing in balanced equilibrium with the dicarbethoxy eno1ateI2,undergoes the series of chemical changes postulated by Holden and Lapworth'O to explain the 7-methyl migration. Accordingly, the mono-carbethoxy enolate of VI11 would undergo alcohol elimination spontaneously, forming a 4-membered ring derivative, which would then add alcohol, with ring-fission occurring in such a manner that the dicarbethoxy enolate of the desired a ,p-dimethyl derivative would appear. Although it has been shownlc that these assumptions are chemically impossible, it may now be rnentioned that the reactions were carried out in dilute ethereal solution and ring fission by the theoretical amount of alcohol in very dilute ether solution at room temperature is too improbable to accept; especially, as rings in cyclic enolates are quite stable towards pure alcohol under far more drastic conditions. Further, the implied assumptionlo that the supposed intermediate, cyclic monocarbethoxy enolate would not rearrange mainly to the much better neutralized enolate, containing the sodium at the oxygen of the keto group, is parallel to assuming that the unknown, labile CH&OCH=C(ONa)OEt would not, spontaneously, largely change to the known keto-enolate. The labile cyclic enolate in Lapworth's scheme could rearrange by migration of sodium to a carbonyl of the dicarbethoxy group, the shift of the 7-methyl to the a-&carbon being followed by a series of successive reformations 11 12
MICHAEL, J. prakt. Chem., 60,475 (1899). For literature see reference 6b.
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and rearrangements. This speculation, however, would be merely a complicated and very improbable Inodification of the interpretation advanced by Michael and Ross1=. The course of most addition reactions involving enolates is so dependent upon the energy and chemical affinity relationships, ie., the chemical potential, exerted intermolecularly between certain atoms in the original chemical systems, that they cannot be explained rationally solely from valence viewpoints.
