4661
DEHYDRATION OF S O M E ~,/~-DIHYDROXY ESTERS
Sept. 5 , 1955
[CONTRIBUTION NO. 1155 FROM
THE
STERLING CHEMISTRY LABORATORY, YALE UNIVERSITY]
The Dehydration of Some a#-Dihydroxy Esters1j2 B Y
JAMES
ENGLISH, JR.,
AND
DONALD L. E I E Y W O O D
RECEIVED MARCH24, 1955 Several or,@-dihydroxyesters were prepared and dehydrated. With potassium bisulfate the dehydration leads to a mixture of products including p-keto acid derivatives; no evidence of a-keto acid formation was obtained.
In the course of his work on the structure of auxin a K0g13 reported that this substance, ana, pdihydroxylactone, was dehydrated to form a p-keto acid derivative, auxin b. In view of the reported discrepancies* between the properties of auxin b and synthetic analogs and considering the meager information in the literatures on acid-catalyzed dehydrations of a,@-dihydroxyacids, esters or lactones, it seemed desirable to examine the behavior of some model compounds under dehydration conditions. I t seems reasonable to expect dehydration either to a-keto acids or @-ketoacids or products derived from them. z
RCHpCOCOOR’
R-CHOHCHOHCOOR< RCOCHzCOOR’
On account of the known ease of dehydration of @hydroxy acids one might be tempted to predict that loss of the p-hydroxyl group would predominate. The preparation of simple a,@-dihydroxyesters was carried out either by oxidation of the corresponding unsaturated acids6 and subsequent esterification or by hydrolysis of glycidic esters from DarZen’s condensations. The former route was generally more convenient. The stereochemistry of the products has been assumed from the method of preparation.6 I t is of interest that ethyl a,@-dihydroxycaproateprepared by way of the corresponding glycidic ester was found to have the erythro configuration.6 Assuming the usual inversion on opening an epoxide ring in alkali, we may tentatively assign the trans configuration to the main product of the Darzen’s condensation of butyraldehyde and ethyl chloroacetate. The dehydration of erythro a,&dihydroxypelargonate, erythro-ethyl a$-dihydroxycaproate and erythro-methyl a$-dihydroxybutyrate over potassium hydrogen sulfate a t 1IC-1 15’ gave similar results. In all cases water and ethanol (or methanol) were evolved, condensed in a Dry Ice trap and identified. Fractionation of the neutral components of the mixtures gave in each case some starting material and a higher boiling ester mixture in addition to non-volatile decomposition products. These high boiling fractions were refractionated and obtained as thick liquids; they had infrared (1) Taken from a thesis submitted by D. L. Heywood in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Yale University, 1954. (2) We are indebted t o t h e Research Corporation for a grant in support of this work. ( 3 ) F. Kogl, Bcr., 688, 16 (1935). (4) J. B. Brown, H. B. Henbest a n d E . R . H. Jones, J. Chcm. Soc., 3634 (1950). ( 5 ) W. Kiosh, Bcv., S a , 337 (1922); J. W. Howard and W. A. Fraser, O U ~Synlh one) has been investigated in the hope that pharmaI1 151 0-152.3 Iti 66 35 66 56 3 11 5 13 cological tests on representative examples of the re3'4' A7 32 ti7 64 5 67 5 57 111 131 0-135 0 sulting products will furnish clues as to the most 91 5-92.5 44 7 2 91 72 77 8 26 8 01 IV promising types of derivatives for further studies. 1203.8-206.0" K' 66 02 65 25 1 47 4 -The alkylation of I with diacyl peroxides was car138.0-139.0 1 3 66 35 86 59 5 11 1 8 8 1.1 ried out according to the method of Fieser, Leffler 72 35 i2 27 7 9'4 8 0 1 VI1 110.0-111 .I) fi8 and co-workers2b except that a 10% excess of the 61 60 (54 47 6 20 A 2.5 VI11 167.0-168, 5'2 81 ( 1 ) This investigation was supported by a research grant ( P H S B-665) from t h e National Microbiological Institute of t h e National Institutes of Health, Public Health Service. ( 2 ) ( a ) I , . F . Fieser and A. E. Oxford, THISJ O U R N A L , 64, 2060 (194'2); i b ) 1. F . Fieser, M. T. Leffler, et o l . , ibid., 70, 8174 (19481. ,':+) ( a ) S. C Hooker. i b i d . , 68, 1163-1179 ( 1 9 3 8 ) : (h) I.. F. Fieser a n d X I . Fieser, ibid., 70, 3215 ( 1 9 4 8 ) . (1: 11.T Lemer and R. J. Hathaway. ibid.. 70, ,3222 (19481; X I . T . 1.efiIer. U. 5 Patent 2,541,473 (1951) [C. A , , 46, 7149f (1'25l)l. Y 'I. Pratt with X L. Drake, T H I S JOURNAL, 77, 37 (195.5) I n related studies of t h e mode of addition of various reagents tu i.8-riuinolinequinone, we have found t h a t 5.6.8-triacetoxyquinoline may he isolated in 47% yield after t h e addition of acetic anhydride fThiele reaction; J. Thiele and E. Winter, An?i., 311, 347 (1900); L . F. Fieser, THISJ O U R N A L , 70, 3165 (1948)). This triacetoxyquinoline may be converted t o I by methods used for t h e analogous conversion in t h e naphthoquinone series (L. F . Fieser, loc. L i t . ) . Since 5,Equinolinequinone i \ obtained from t h e readily available &-hydroxy v > d e \ suitahle altrr1iatii.r Y \ t i l hr5i.: f l > - b e
