Mercaptals

Mercaptals, CH2CH(SR)2, are formed in a like manner by the addition of mercaptans. The formation of acetals by noncatalytic vapor-phase reactions of acetaldehyde and various alcohols at 35°C has been reported (67). Butadiene [106-99-0] can be made by the reaction of acetaldehyde and ethyl alcohol at temperatures above 300°C over a tantala—siUca catalyst (68). Aldol and crotonaldehyde are beheved to be intermediates. Butyl acetate [123-86-4] has been prepared by the catalytic reaction of acetaldehyde with 1-butanol [71-36-3] at 300°C (69). 

Several kinds of products can be obtained by reaction of thioglycolic acid and its esters with aldehydes to form mercaptals, RCH(SCH2COOH)2, or with ketones to form thiolketals, RR C(SCH2COOH)2. Reaction with formaldehyde (qv) yields di- -butyhnethylene-bisthioglycolate [1433882-0] (MET ester) ... 

Two techniques, electrochemical reduction (section IIl-C) and Clem-mensen reduction (section ITI-D), have previously been recommended for the direct reduction of isolated ketones to hydrocarbons. Since the applicability of these methods is limited to compounds which can withstand strongly acidic reaction conditions or to cases where isotope scrambling is not a problem, it is desirable to provide milder alternative procedures. Two of the methods discussed in this section, desulfurization of mercaptal derivatives with deuterated Raney nickel (section IV-A) and metal deuteride reduction of tosylhydrazone derivatives (section IV-B), permit the replacement of a carbonyl oxygen by deuterium under neutral or alkaline conditions. 

The preparation of 7,7-d2-cholesterol in 1950 was the first example of deuterium incorporation into steroids via desulfurization of mercaptals with deuterated Raney nickel. A substantially modified version of this reaction subsequently became the first widely used method for site-specific insertion of two deuteriums in place of a carbonyl oxygen. This conversion consists of the preparation of a mercapto derivative (84 85), which usually... 

The mercaptal often crystallizes in high yield upon trituration of the reaction mixture. The crystalline product can then be collected by filtration and purified as above. 

Three different methods have been discussed previously (sections III-C,III-D and IV-A) for the replacement of a carbonyl oxygen by two deuteriums. However, in the conversion of a 3-keto steroid into the corresponding 3,3-d2 labeled analog, two of the three methods, electrochemical reduction (section ni-C) and Raney nickel desulfurization of mercaptal derivatives (section IV-A), lead to extensive deuterium scrambling and the third method, Clemmensen reduction (section III-D), yields a 2,2,3,3,4,4-dg derivative. 

Thioketals are readily formed by acid-catalyzed reaction with ethane-dithiol. Selective thioketal formation is achieved at C-3 in the presence of a 6-ketone by carrying out the boron trifluoride catalyzed reaction in diluted medium. Selective protection of the 3-carbonyl group as a thioketal has been effected in high yield with A" -3,17-diketones, A" -3,20-diketones and A" -3,l 1,17-triones in acetic acid at room temperature in the presence of p-toluenesulfonic acid. In the case of thioketals the double bond remains in the 4,5-position. This result is attributed to the greater nucleophilicity of sulfur as compared to oxygen, which promotes closure of intermediate (66) to the protonated cyclic mercaptal (67) rather than elimination to the 3,5-diene [cf. ketal (70) via intermediates (68) and (69)]." " ... 

Deuteration at C-12 by desulfurization of 12-thioketals with Raney Nickel preparation of the ethylene thioketal, 172 desulfurization of the mercaptal, 173... 

This ester is converted in high yield to the y -ketosulfoxide by means of the dimethyl sulfoxide anion. Heating in acetic acid then produces a hemi-mercaptal acetate, which on treatment with Raney nickel gives the desired 21-acetoxy-20-ketone in a 50-70% overall yield from the -ketosulfoxide. A 17a-hydroxyl may also be present during the sequence. 

The mercaptals obtained by the acid catalyzed reaction of J3-ketoesters, e.g., ethyl acetoacetate, with methyl thioglycolate (73) undergo the Dieckmann cyclization with alcoholic potassium hydroxide at lower temperatures to give ethyl 3-hydroxy-5-methyl-2-thiophenecarboxylate (74) in 75% yield. ° Besides ethyl acetoacetate, ethyl a-ethylacetoacetate, ethyl benzoyl acetate, and ethyl cyclopentanonecarboxylate were also used in this reaction/ It is claimed that /8-diketones, hydroxy- or alkoxy-methyleneketones, or /8-ketoaldehyde acetals also can be used in this reaction. From acetylacetone and thioglycolic acid, 3,5-dimethyl-2-thiophenecarboxyl-ic acid is obtained. ... 

Further evidence for a pseudooxazolone intermediate is the fragmentation of 72 by ethyl mercaptan in hydrobromic acid-acetic acid [Eq. (33)]. The mercaptal 74 hydrolyzes readily in acetic acid to give the 2-0X0 acid. 

Success finally resulted when the inosose ether (20) was converted to its ethylene mercaptal. The crude mercaptal was reduced with nickel, and the crude pentol pentamethyl ether cleaved in the usual manner. 

The Action of Lead Tetraacetate on Sugar mercaptals, E. J. Boume, W. M. Corbett, M. Stacey, and... 

Mepiquat chloride, 13 43t, 54-55 Mepiquat dichloride, 21 127 Mercaptals, production from acetaldehyde, 1105... 

In order to ascertain whether sufficient nickel to complete a given reaction has been used, the liquid phase may be tested for starting material before an attempt is made to isolate a product. In general the sodium fusion test for sulfur is satisfactory for this purpose but in certain individual cases a specific test may be more convenient. Thus, in the desulfurization of thioacetals (mercaptals), unreacted material... 

Kristallisierte Mercaptale von D-Ribose, von D-Lyxose und Derivate des Galactose-und Glucose-dibenzyl-mercaptals, by E. Hardegger, E. Schreier, and Z. El Heweihi, Helv. Chim. Acta, 33 (1950) 1159-1164. 

The occurrence of an intermediate A,A-h/s(thiol-S -yl)-arylamine (full mercaptal) has been repeatedly surmised to be involved in the semimercaptal reduction25,29,33,37... 

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