Thioacetic acid

Thioacetyl derivatives (155) are obtained by direct heterocyclization reactions (365. 378, 563) and by a sulfur-oxygen exchange" reaction involving thioacetic acid and A-2-oxazoline-5-one (154) or A-2-thiazoline-5-one (156) (Scheme 81) (365, 378, 379). Ra-Ni reduction of 155 affords the 5-unsubstituted thiazole (379). 

A-2-Oxazoline-5-one (2091 when treated with thioacetic acid yields the corresponding thiazoline-5-one (210) (Scheme 107) (458. 461). These results have been questioned recently (365) however, it appears in the later report that a large excess of thioacetic acid was used instead o-f the stoichiometric amount previously used. 

Phenyl-4-methyl-A-2-thiazoline-5-one (220) treated with excess SOjClj in dichloroethane and the crude product treated with thioacetic acid yields the 4-thioacetyl derivative (221) (Scheme 111) (446). 

The condensation of thioacetic acid with amino acids under drastic conditions provides a useful new synthesis of thiazoles (Scheme 146) (668, 669). Instead of the amino acid, Af-acyl <279) or N-thioacylamino acids (278) are used. 

The addition of aromatic and aUphatic thiols, RSH and ArSH, and a thioacetic acid to isoprene yields mainly the trans-l,4-adduct (56). The aromatic thiyl radicals, ArS , add almost entirely to the first carbon atom however, aUphatic thiyl radicals, RS, also add to the fourth C atom in significant amounts. 

Pharmaceuticals and Agrochemicals. Thioglycohc acid and its esters are useful as a raw material to obtain biologically active molecules. In cephalosporine syntheses, (4-pyridyl)thioacetic acid [10351 -19-8] (65) and trifluoromethane (ethyl) thioglycolate [75-92-9] (66) are used as intermediates. Methyl-3-ainino-2-thiophene carboxylate can be used as intermediate for herbicidal sulfonylureas (67) and various thiophenic stmctures (68). 

The preparation of quinazoline-2(and 4)-thiones follows those of the corresponding pyrimidines (67HC(24-1)270) but there is at least one special primary synthesis for quinazoline-4(3H)-thiones, illustrated by the reaction of o-aminobenzonitrile with thioacetic acid at 110 °C to give 2-methylquinazoline-4(3H)-thione in 90% yield (53JA675). 

CH3CL CHLOROMETHANE -86.903 7.5722E-02 1.4823E-05 -62.89 70 C2H40S THIOACETIC-ACID -178.876 6.9466E-02 4.6167E-05 -154.01... 

At low temperature a 1 1 adduct of thioacetic acid and an enamine could be prepared (709). The previously described reaction of aminomethylene ketones with hydrogen peroxide was extended to bisaminomethylene compounds. However, acylated cyclohexenamines led to cyclopentane-carboxamides (770), Trichloromethyl adducts of enamines and the rearranged amine derivatives were described in a further study (777). 

Another example of resort to heteroatoms to obtain both oral potency and a split between androgenic and anabolic activities Ls tiomestrone (99). Trienone, 98, prepared in much the same way as 23, undergoes sequential 1,6 and 1,4 conjugate addition of thioacetic acid under either irradiation or free radical catalysis to afford the compound containing two sulfur atoms. 

A mixture of approximately 11 parts of 17o-(2-carboxyethyl)-17(3-hydroxyandrosta-4,6-dien-3-one lactone and 10 parts of thioacetic acid is heated at 85° to 95°C for h hour. Excess thioacetic acid is removed by vacuum distillation at this point, and the residue is twice recrystallized from methanol, affording 7o-acetylthio-17o-(2-carboxyethyl)-17(3-hy-droxyandrost-4-en-3-one lactone, melting at approximately 134° to 135°C. Heated above this melting point, the product solidifies and melts again at approximately 201° to 202°C (with decomposition). 

The chloroacetylurea derivative (A = C1CH2) obtained from the above addition (Eq. 1), on treatment first with thioacetic acid and Et3N and then with cysteamine, afforded the corresponding thiol (A = HSCH2) (Eq. 3)l5). 

The 2- and 3-halogenoquinoxalines may be converted into the corresponding quinoxalinethiones by treatment with sodium hydrogen sulfide, sodium thiosulfate, thioacetic acid (with concomitant decarboxylation), or (indirectly) by treatment with thiourea followed by alkaline hydrolysis of the thiouronio intermediate (usually as a one-pot procedure). The same substrates furnish corresponding alkylthio-, arylthio-, or arylsulfonylquinoxalines by treatment with a salt of the appropriate alkanethiol, thiophenol, or benzenesulfinic acid. The following classified examples illustrate such processes. 

The "smelly shoe" of the elements. The oxidation product S02 has an acrid, burning smell, the reduction product H2S stinks like rotten eggs and is very toxic. Sulfur is, nevertheless, a most useful element. It occurs in elemental form and has therefore been known for a long time is mentioned in the Old Testament. Its main application today is in the production of fertilizers. Considerable amounts of sulfur are used in tire production for vulcanization. Sulfur is also a component of gunpowder. Physiologically indispensable as thioacetic acid and especially the S-S bridges that fix proteins in their shapes (e.g. insulin, but also in perms). A 70-kg human being contains 140 g of sulfur. 

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