Hydrogen sulfide diketones

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

The parent hexathiaadamantane (185) is obtained preparatively when a solution of formic acid and hydrochloric acid in nitrobenzene is allowed to stand for several weeks in a hydrogen sulfide atmosphere the product which separated is almost insoluble in all common solvents and purification presents a problem. Only large volumes of dimethyl sulfoxide at reflux serve for recrystallization.224 The reaction of thioacetic acid with formic acid in the presence of zinc chloride gives tetramethyl-(186), monomethyl-, dimethyl-and trimethylhexathiaadamantane derivatives (187).225 Other variations include the reaction of thioacetic acid with a /i-diketone,226 and the use of boron trifluoride227 or aluminum chloride as a catalyst.228... 

Ketones are obtained from a-diketones by reduction with hydrogen sulfide in a pyridine-methanol solution [237], by refluxing with 47% hydriodic acid in acetic acid (yield 80%) [916], and by decomposition of monohydrazones with alkali [923]. Reduction of a-diketones to hydrocarbons is achieved by decomposition of bis-hydrazones by alkali [923]. 

Hydrogen sulfide is introduced into an ice-cooled solution of 0.2 mol of a 1,2-diketone and 0.02 mol of piperidine in 30 ml of dimethylformamide for 1 -4 hours. Elemental sulfur is precipitated during the introduction of hydrogen sulfide. The mixture is acidified with dilute hydrochloric acid the sediment is filtered with suction and dissolved in warm methanol the undissolved sulfur is separated, and the product is isolated by evaporation of the methanol and purified by crystallization. If the product after the acidification is liquid it is isolated by ether extraction and distillation after drying of the ether extract with sodium sulfate. Yield of benzoin from benzil after 1 hour of treatment with hydrogen sulfide is quantitative. 

If hydrogen sulfide is introduced for 4 hours into a solution of 0.2 mol of an a-diketone in methanol and 0.02 mol of pyridine, a monoketone is obtained. The yield of deoxybenzoin from benzoin is quantitative. 

Oxazinium perchlorates (267) are obtained by reactions of 1,3-diketones and benzonitrile in the presence of perchloric acid and acetic anhydride (88ZOR1561, 88ZOR2232, 91ZOR1986). 1,3-Thiazinium perchlorates are synthesized by treating oxazinium salts with hydrogen sulfide in absolute acetonitrile and then with perchloric acid (72S333). 

The treatment of 1,4-diketones with hydrogen sulfide and acid catalysts at low temperatures generally leads to the formation of the expected thiophenes in much better yields than has been observed for the Paal synthesis with the same diketones. For example, 1,2-dibenzoylethane (160 X = H) was converted to 2,5-diphenylthiophene (161) in only 25% yield under Paal conditions, but gave (161) in better than 45% yield when treated with hydrogen sulfide and dry HC1 in chloroform containing anhydrous zinc chloride at room temperature (52JOC1405). Yields were even better when the benzene rings of (160) were substituted. When X = Br in (160), a 69% yield of pure crystalline (161 X = Br) was obtained, and when X = OMe, the yield of (161) was 60%. 

The first recorded attempt to prepare a thio derivative of a /1-diketone resulted in the isolation of the colourless dimer (57 R = R = Me) from the reaction of acetylacetone and hydrogen sulfide in hydrochloric acid.243 Similar dimers with various R and R groups have been reported244 and the structure (57) has been confirmed from NMR and MS data.245 Other attempts to prepare dithio-/ -diketones (58) yielded 1,2-dithiolium salts (59).246... 

Diketone 388 and monoketone 389, which are depicted in the scheme as intermediates, have been obtained independently and have also been converted into compounds 390 by all the previously listed methods. Two more examples of naphtho[crf]thiapyrans are thionaphthalic anhydride 391, which is formed on interaction between naphthaloyl dichloride 367 and hydrogen sulfide (30RC657), and 2-oxo-9-thiononaphtho[cd]thiapyran 399, obtained on base-catalyzed recyclization of dithione 392 (84JA6084). 

Figure 3-20. The reaction of a 1,3-diketone with hydrogen sulfide only gives a monothio derivative, 3.11, rather than a 1,3-dithioketone.

Probably the most important reactant in the formation of volatile meat flavor compounds is hydrogen sulfide. It can be formed by several pathways during meat cookery, but one mechanism is Strecker degradation of cysteine in the presence of a diketone as established by Kobayashi and Fujimaki (29). The cysteine condenses with the diketone and the product in turn decarboxylates to amino carbonyl compounds that can be degraded to hydrogen sulfide, ammonia and acetaldehyde. These become very reactive volatiles for the formation of many flavor compounds in meat and other foods. 

Probably the most important reactant in the formation of volatile meat flavor compounds is hydrogen sulfide. It can be formed as a Strecker degradation product of cysteine in the presence of a diketone (37). 

Thiazoles and Thiazolines. Thiazoles and thiazolines provide nutty, roasted notes to meat flavors. These compounds can be formed by combining a diketone, such as 2,3-butanedione (diacetyl), with acetaldehyde, hydrogen sulfide, and ammonia (39). 2-Acetyl-2-... 

The disproportionation of thiopyrans into tetrahydrothiins and thiopyrylium salts has been described earlier, and the condensation of hydrogen sulfide with 1,5-diketones in the presence of acids such as perchloric acid presumably proceeds via such a disproportionation step to generate thianes (75MI22501). 

Monothio -diketones can be prepared by the action of hydrogen sulfide and hydrogen chloride on the appropriate -diketone in alcohol solution. Nevertheless the conditions are rather critical. At room temperature -dike-tones are in tautomeric equilibrium between the diketo form (I) and the chelated hydrogen-bonded form (II), and in polar solvents the concentration of the diketo form (I) is increased. Reaction with hydrogen sulfide occurs only with the diketo tautomer (I). Consequently, higher concentrations of hydrogen chloride are required for those -diketones which exist predominantly in the... 

In the case of a )ff-diketone (I) where R R, it has been shown by mass spectrometry that the nucleophilic attack by hydrogen sulfide takes place at the ketonic group attached to R if the electron-withdrawing power of R is less than that of R. > Consequently, 4,4,4-trifluoro-l-(2-thienyl)-l,3-butane-dione yields the monothio jff-diketone (III) as the only isomer. 

In the presence of hydrogen chloride, a-acetylenic ketones react with thioacetic acid to give a monothio-)S-diketone which is converted to a 1,2-dithiolium ion by phosphorus pentasulfide or hydrogen sulfide. These reactions, which involve some sort of oxidation, are discussed in the next paragraph. 

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