Phosphorus pentasulfide, reaction with

Compounds of this type are readily prepared from the pyrido[l,2-f>]-cinnolinium-11-olates (338) (Section III,D,1) by reaction with phosphorus pentasulfide. Alkylation with ethyl bromoacetate gives the 11-ethoxycar-boxylmethylthio salts (349) which are useful intermediates for preparing other derivatives (Sections III,D,2 and 3). Hydrolysis of 349 regenerates the betaines 348. °... 

This reaction was originally designated by Gabriel [53] in 1910 phosphorus pentasulfide reacted with acylaminoketone (showed in below reaction) an equimolecular quantity to yield 2-phenyl-5-alkyl-thiazole. The reaction is analogous to the synthesis of additional five-membered oxygen and sulfur holding rings from 1,4-dicarbonyl compounds. 

Transformation of carbon-oxygen to carbon-sulfur bonds can be carried out with phosphorus pentasulfide. Amides are converted to thio-amides by sonication at 30-40°C for 1-2 h (Eq. 79). In comparison with conventional methods, less reagent can be used, and the reaction proceeds faster at a lower temperature.236 A similar reaction using the Lawesson reagent was reported.237 Phosphorus pentasulfide reacts with disulfides to give a thiophosphorylated product (Eq. 80).238... 

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),... 

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). 

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. 

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. 

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

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 reaction of 78 with phosphorus pentasulfide in xylene gives the corresponding 2-oxazolethione, which also forms the iV -methyl product with dimethyl sulfate and 4,5-diphenyl-2-methyhnercapto-oxazole in 98% yield on treatment with silver oxide-methyl iodide. 

Triazanaphthalenes (446) substituted with a single leaving group have been little studied. 4-Aminopyrido[3,2-d]pyrimidine and its 6-methyl derivative have been hydrolyzed with 5N acid (100°, 30 min) and lOA alkali (95°, 3 hr, 10% yield).Attempted replacement of the 4-oxo group (via acyloxy intermediates) with phosphorus oxychloride or pentasulfide failed,in contrast to the successful replacement in the more activated 4-oxo-l,3,8-triaza analog discussed below. Similarly, the 2,4-dioxo derivative could not be thionated with the pentasulfide, and its reaction with the oxychloride was less facile than that of the 2,4-dioxo-l,3,8-triaza compound. 

Triazanaphthalene (449) is the most unstable of the pyrido-pyrimidines to ring-degradation at pH 2 or pH 7.7 The 4-oxo derivative was converted into the 4-thioxo compound via nucleophilic displacement of the acyloxy intermediate formed with phosphorus pentasulfide. The 4-carboxymethylthio-pyridopyrimidine underwent some substitution by hydroxide ion but primarily gave the ring-opening reaction, which is facilitated by resonance activation of the 2-position by the 6-aza moiety. 

It is of note that although the drug can be prepared by the above route, reaction of barbital (96) with phosphorus pentasulfide constitutes an alternate route to thiobarbital (147)... 

Fusion of an additional heterocyclic ring onto that already present in the benzodiazepines has led to some medicinal agents with considerable activity. Treatment of an intermediate like 15 with phosphorus pentasulfide affords the corresponding thio-amide (37). Condensation of this intermediate with acetyl hydra-zide affords triazolam )37). The same agent can be prepared by reaction of the amidine, 38, ° with acetylhydrazide. ... 

Fusion of an additional heterocyclic ring onto a benzodiazepine is well known to considerably increase potency. This increase in potency is apparently maintained when the benzene ring is replaced by thiophene. Thiophene aminoketone 161 is converted to the benzodiazepine analogue 164 via chloroacetamide 162 and then glycine derivative 163 by the same sequence as that used in the benzene series. Treatment of the product 164 with phosphorus pentasulfide gives the thio-amide 165 reaction of that intermediate with hydrazine leads to the amino amidine 166. Conden-... 

A) Preparation of 1-(2,3,5-Tri-0-Acetyl- -D-Arat>inofuranosy/)-4-Thiouracil A mixture of 1.85 g (5.0 mmol) of 1-(2,3,5-tri-0-acetyl-(3-arabinofuranosyl)uracil, 1.23 g (5.55 mmol) of phosphorus pentasulfide, and 30 ml of pyridine was heated under gentle reflux for 2.5 hours with exclusion of moisture. The reaction mixture was cooled, and the supernatant solution was transferred by means of a pipette into a mixture of crushed ice and water. 

Benzazepin-2-amines can be obtained by nucleophilic displacement reactions on a variety of substrates. For example, the benzazepin-2-amine 22 is formed by treating the thiolactam 21, obtained from the benzazepinone 20 with phosphorus pentasulfide in pyridine or triethylamine solution, with ammonia.61... 

The reaction of isoindole 192 with phosphorus pentasulfide in pyridine afforded intermediate 193, which gave with hydrazine hydrate 194 (82S853) (Scheme 40). 

Thienotriazines 209 were prepared by cyclization of 5-oxo[l,2,4]tria-zines of type 208 or 210 by reaction [78C1(L)585 83JHC1709 88MI1 90MI3] with phosphorus pentasulfide in pyridine. Analogously, 2-methyl-... 

The reaction of 6-amino[l,2,4]triazin-5(2//)-ones or its thione derivatives 680 with acetic anhydride gave the 6-acetamido derivatives 681 and 682, respectively. Treatment with phosphorus pentasulfide in pyridine gave thiazolo[5,4-e][l,2,4]triazines 683 (84LA283 87AJC491) (Scheme 142). 

Carius (8) replaced the oxygen in phosphoryl chloride by sulfur. This may be somewhat analogous to the replacement of oxygen in a carbonyl group by sulfur using phosphorus pentasulfide. Prinz (8) used thionyl chloride in his reaction with phosphorus sulfide and De Fazi (2) used carbon tetrachloride in a very interesting preparation of this important intermediate. 

They can be prepared by the thermolysis of 1,2,3-thiadiazoles or by reaction of ketenes with phosphorus pentasulfide.111-113... 

Phosphorus pentasulfide is used to replace oxygen atoms with sulfur atoms the reaction is commonly carried out in a solvent heated under reflux. Solvents employed include carbon disulfide, aromatic hydrocarbons, and pyridine. If an oxygen atom is part of a heterocycle, then the reagent may replace it with sulfur, as in the formation of 2,1-benzisothiazoles from 2,1-benzisoxazoles.119 Such replacements are, however, not general some prior ring opening appears to be necessary before the reagent can act. For example, under normal conditions furan is not attacked. 

Examples of reactions involving replacement and cyclization are the long-known preparation of thiophenes (89) from 1,4-diketones, and the formation of l,2-dithiole-3-thione (90) from the salicylate ester analog (91).120 In the latter instance, oxidative cyclization with formation of an S—S bond has occurred this is a common feature of these reactions, particularly if such a link is needed to complete a five-membered ring. Another example of this aspect is afforded by the reaction of the propane-1,3-dione derivatives (92) which yield 3,5-diaryl-1,2-dithiolylium salts (93) when heated with phosphorus pentasulfide in carbon disulfide, followed by perchloric acid.121... 

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