Phosphorus pentasulfide

The reaction of phosphorus pentasulfide with a-acylamino carbonyl compounds of type Ilia also yields thiazoles. Even more commonly, a mercaptoketone is condensed with a nitrile of type IVa or a-mercaptoacids or their esters with Schiff bases. This ring closure is limited to the thiazolidines. In the Va ring-closure type, /3-mercaptoalkylamines serve as the principal starting materials, and ethylformate is the reactant that supplies the carbon at the 2-position of the ring. These syntheses constitute the most important route for the preparation of many thiazolidines and 2-thiazohnes. In the Vb t3fpe of synthesis, one of the reactant supplies only the carbon at the 5-position of the resultant thiazole. Then in these latter years new modern synthetic methods of thiazole ring have been developed (see Section 7 also Refs. 515, 758, 807, 812, 822). 

This reaction is explosive and proceeds in low yield (—21%) because of the instability of the thioformamide that is destroyed as soon as it is cyclized with 1 (113,491). The thioformamide is better prepared directly in the reaction mixture by condensing phosphorus pentasulfide and for-mamide at room temperature, in dioxane solution, according to reaction 1 (491,492),... 

When chloroacetaldehyde is condensed with higher thioamides prepared from amides and phosphorus pentasulfide according to Schwarz s method (222), 2-substituted thiazoles are obtained (4, 10,"22, 175). 

Aromatic thioamides can be prepared as described in the literature by different ways, either by S -> O exchange between the corresponding benzamides and phosphorus pentasulfide in pyridine solution in the presence of triethylamine (65, 646) as strong base, or by action of H2S on the appropriate nitrile with pyridine and triethylamine solvents using the method of Fairfull et al. (34, 374, 503). In this reaction, thioacetamide in acidic medium can also be used as a H2S generator with dimethylform-amide as the solvent (485). 

The reaction can be carried out in two steps (641). First, equimolar amounts of amide and phosphorus pentasulfide are mixed under stirring in dioxane, the temperature being kept below 45°C. After 20 minutes, the a-halocarbonyl compounds (in dioxane solution) are added in small portions. At the end of the addition the temperature reaches 80 to 100°C, and the reaction mixture is kept at this temperature for another hour. 

Thiazolium salts with alkyl (103, 722), arylalkyl (116), aryl (305), or heteroaryl (96) substituents on the nitrogen have been also prepared by this procedure. As in the thiazole series, N-substituted thioamides can be formed directly in the reaction mixture from phosphorus pentasulfide and N-substituted amides (127). These methods are important in the synthesis of thiamine 102 (vitamin Bj) (Scheme 45). 

This reaction was first described by Gabriel in 1910 (40), when he warmed an acylaminoketone (197a) with an equimolecular amount of phosphorus pentasulfide. The reaction (Scheme 103) is similar to the preparation of other five-membered oxygen- and sulfur-containing rings from 1,4-dicarbonyl compounds. 

Arylthiazoles were prepared either from w-formaminoaceto-phenones and phosphorus pentasulfide in 70% yield (47, 641) or by treating thioformaminoketones with concentrated sulfuric acid in water (344). Thioformaminoacetophenone itself was obtained by the action of potassium dithioformate on aminoacetophenone (251). 

The Gabriel s synthesis is also applicable when a polysubstituted thiazole is required (381, 550). Thus 2,4,5-trisubstituted thiazoles are obtained by treating the corresponding a-acylaminoketones with phosphorus pentasulfide for a few minutes at 100°C (550) or at higher temperature for heavier substituents (381). (Table 11-31). 

TABLE 11-31. THIAZOLES FROM -ACYLAMINOKETONES AND PHOSPHORUS PENTASULFIDE (Gabriel s synthesis)... 

Tliiazoles were usually obtained by treating the corresponding a-acylaminnketones with phosphorus pentasulfide for a few minutes at 10O°C... 

Alkoxythiazole derivatives (202) are formed in a similar manner by the action of phosphorus pentasulfide on a-acylamino esters (201) (64, 334, 711). 

Oxazoles (283) heated with phosphorus pentasulfide can be converted to thiazoles. In this manner, Keyer and Brooker obtained 2-methyl-5-phenylthiazoles (10), Ri = Me, R2 = H, R3 = Ph in 85% yield (Scheme 152) (389). 

Phosphorus pentasulfide in pyridine can be used also for simultaneous substitution of oxygen and chlorine in polysubstituted pyridazinones. For example, 4,5-dichloro- and... 

In some cases oxo compounds have been converted directly to the corresponding thiones with phosphorus pentasulfide. 

In addition to conversion to chloro compounds, -ones and diones have given thiones with phosphorus pentasulfide, whilst in some cases replacement by amine of alkoxy groups in preference to a chloro group has been observed (68JHC13). 

These a-acylaminoketones also provided a convenient synthesis of thiazoles on treatment with phosphorus pentasulfide (Gabriel s method). Although yields range from 45 to 80%, substituents are usually restricted to alkyl, aryl and alkoxy derivatives. Thus, reaction of the a-acylaminoketone (4) with P4S1Q gave the thiazole (5), and thiazole (7) itself was prepared in this manner in 62% yield from formylaminoacetal (6) (14CB3163). The corresponding 5-ethoxy compound was obtained from the a-formamidoester and phosphorus pentasulfide in an inert solvent. 

Several variations of this general procedure have been described. The functionalized dithiocarbamate (23) on heating with a mixture of phosphorus pentasulfide and tetrafluoroboric acid gave the 2-amino-substituted 1,3-dithiolylium tetrafluoroborate (24) in moderate to good yield (69CPB1924). 

Isoxazole compounds can be converted into the corresponding isothiazoles by successive catalytic hydrogenation, sulfuration with phosphorus pentasulfide and oxidation with chloranil (72AHC(14)l, 75SST(3)541). 2,1-Benzisoxazoles give the 2,1-benzisothiazoles directly, by the action of phosphorus pentasulfide in either pyridine or molten imidazole (73SST(2)556, 77SST(4)339). (See also Chapter 4.16 for further discussion of these topics.)... 

Reaction of /3-lactams with phosphorus pentasulfide affords the corresponding azetidine-2-thiones (c/. Section 5.09.4.3.1) (68JHC433). 

O-Alkylation of the readily available iV-unsubstituted azetidin-2-ones (/3-lactams) constitutes a versatile route to 2-alkoxy-l-azetines (cf. Section 5.09.3.2.3). Thus treatment of the /3-lactams (266) with trialkyloxonium tetrafluoroborates followed by basification affords the 2-alkoxy-l-azetines (267) in moderate yields (67JHC619,69LA(725)124). Similar treatment of the azetidine-2-thiones (268) (available from thiation of the corresponding /3-lactams with phosphorus pentasulfide) affords the analogous 2-ethylthio-1-azetines (269) (67JHC619), which are generally more stable than their 2-alkoxy analogues. 

Phosphorus pentasulfide [1314-80-3] M 444.5, m 277-283 . Purified by extraction and crystallisation with CS2, using a Soxhlet extractor. Liberates H2S in moist air. HARMFUL VAPOURS. 

Triazole has been prepared by the oxidation of substituted 1,2,4-triazoles, by the treatment of urazole with phosphorus pentasulfide, by heating equimolar quantities of formyl-hydrazine and formamide, by removal of the amino function of 4-amino-l,2,4-triazole, by oxidation of l,2,4-triazole-3(5)-thiol with hydrogen peroxide, by decarboxylation of 1,2,4-triazole-3(5)-carboxylic acid, by heating hydrazine salts with form-amide,by rapidly distilling hydrazine hydrate mixed with two molar equivalents of formamide, i by heating N,N -diformyl-hydrazine with excess ammonia in an autoclave at 200° for 24 hours, and by the reaction of 1,3,5-triazine and hydrazine monohydrochloride. ... 

The first N-thiosulfinylamine 4-Me2NC6H4N=S=S (10.2) was obtained as a deep violet solid (/Inmx 510 nm) in low yield by the reaction of phosphorus pentasulfide with N,N-dimethyl-4-nitrosoaniline. Compound 10.2 (M.p. 113-115°C) has much higher thermal stability than the corresponding thionitrosoarenes, but it decomposes to the corresponding azobenzene and sulfur on heating to 200°C. 

The Paal thiophene synthesis involves the addition of a sulfur atom, typically from phosphorus pentasulfide, to 1,4-dicarbonyl compounds and subsequent dehydration. 

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