Phosphorus Pentasulfide In Pyridine Research Articles

An efficient and metal-free synthetic protocol for mono-, bis-, and spiro[1,2,4]triazolo[1,5-a]pyridines utilizing 1,2-diaminopyridine derivative via C–N bond formation

An effective and direct synthetic strategy for a new series of functionalized mono-, bis-, and spiro[1,2,4]triazolo[1,5-a]pyridines from 1,2-diaminopyridine precursor has been described. Reaction of 1,2-diaminopyridine with ethyl orthoformate, acetic anhydride, maleic anhydride, carbon disulfide, or chloral hydrate under metal-free conditions afforded the desired triazolo[1,5-a]pyridine in good yield (62–76%). Furthermore, 1,2-diaminopyridine was converted to mono- and bis-[1,2,4]triazolo[1,5-a]pyridines via metal-free construction with decanoyl chloride, chloroacetyl chloride, terphthaloyl chloride, or diethyl succinate. Finally, spiro[[1,2,4]triazolo[1,5-a]pyridine and [1,2,4,3]triazaphospholo[1,5-a]pyridine derivatives were obtained via reaction of 1,2-diaminopyridine with cyclohexanone/pentanone in acetic acid or phosphorus pentasulfide in pyridine. This protocol aims to present some fundamental advances in the area of organic synthesis such as smart reaction conditions, improved yield, metal-free catalysts, no column purification, and no by-products, in addition to the broad functional scope.

Synthesis and Antimicrobial Activity of 4-Arylthio- and 4 Alkylthiofunctionalized Pyrazolo[1,5-a]pyrazines

The reaction of pyrazolo[1,5-a]pyrazine-4(5H)ones with phosphorus tribromoxide in boiling benzene yielded 4-bromopyrazolo[1,5-a]pyrazines, and the thionation with phosphorus pentasulfide in pyridine at 90 °C led to pyrazolo[1,5-a]pyrazine-4(5H)thiones. The synthesized bromine derivatives are electrophilic, and thiones are nucleophilic substrates. Their subsequent structural modification in the first case was carried out by interaction with thiophenols, and in the second case was conducted with functional halogenoalkanes. It was shown that bromides react with substituted thiophenols in dimethylformamide in the presence of potassium carbonate at 90 °C to form 4-arylthiopyrazolo[1,5-a]pyrazines with yields of 65–83 %. 4-S-methyl-functionalized derivatives of pyrazole[1,5-a]pyrazines with yields of 60–78 % were easily obtained by the alkylation of pyrazole[1,5-a]pyrazin-4(5H)thiones with a-bromoketones, bromoacetic acid, ethyl bromoacetate and bromoacetonitrile in the K2CO3—DMF system at room temperature. The composition of all synthesized compounds is in agreement with the results of elemental analysis and mass spectra. Their structure is confirmed by NMR 1H and 13C spectra. In particular, in the NMR 1H spectra of 4-arylthiopyrazolo[1,5-a]pyrazines, in addition to the characteristic signals of the pyrazole and pyrazine nuclei, signals of protons of thioaryl substituents are present in the range of 7.04 –8.05 ppm, and in NMR spectra of the 1H 4-S-methylfunctionalized derivatives of pyrazole[1,5-a]pyrazines signals of exocyclic methylene protons are present at 4.11– 5.02 ppm. Promising derivatives with antibacterial activity against the test cultures S. aureus (MIC = 7.8 g/mL), M. luteum (MIC = 3.9 g/mL), and antifungal activity against the test culture of fungus A. niger (MIC = 7.8 g/mL) were determined among 4-S-substituted pyrazole[1,5-a]pyrazines as a result of studies of the antimicrobial activity.

Carbonyl and thiocarbonyl stabilized 1,4-dihydropyrazines: synthesis and characterization

Three analogues of the 1,4-dihydropyrazine, 3,4,7,8-tetrahydro-4,4,8,8-tetramethyl-2,6-dioxa-4a,8a-diazaanthracene-1,5-dione (DDTTA), have been synthesized. 2,4,4,6,8,8-Hexamethyl-3,4,7,8-tetrahydro-2,4a,6,8a-tetraazaanthracene-1(2H),5(6H)-dione (HTTA) is synthesized by chlorination of the previously reported 5,6-dihydro-1,3,5,5-tetramethylpyrazin-2(1H)-one with tert-butyl hypochlorite and self condensation of the resulting α-chloromethylimine in the presence of diisopropylethylamine in dimethylformamide (DMF). Thioxo derivatives 3,4,7,8-tetrahydro-4,4,8,8-tetramethyl-5-thioxo-2,6-dioxa-4a,8a-diazaanthracen-1-one (DDTTA–S) and 3,4,7,8-tetrahydro-4,4,8,8-tetramethyl-2,6-dioxa-4a,8a-diazaanthracene-1,5-dithione (DDTTA–S2) have been synthesized by direct thionation of DDTTA with phosphorus pentasulfide in pyridine. All three molecules have been characterized spectroscopically. In addition the crystal structure of HTTA has been determined. Radical cations obtained by one electron oxidation of the dihydropyrazines have been characterized by electron spin resonance spectroscopy.

ONE-FLASK SYNTHESES OF SOME NEW SPIROTHIAZOLOPYRANOPYRAZOLE, SPIROTHIAZOLODIHYDROPYRIDI-NOPYRAZOLE AND SPIROTHIAZOLOTHIOPY-RANOPYRAZOLE DERIVATIVES AS ANTIMICROBIAL AGENTS

1-Thia-4-benzyl-4-azspiro[4,4]nonan-3-one (2a) and/or 1-thia-4-benzyl-4-azaspiro[4,5]decan-3-one (2b) reacted with 4-arylidene-3-methylpyrazolin-5-ones (1a-f) in a mixture of ethanol/pyridine at reflux temperature to give spirothiazolopyranopyrazoles (3a-l) in one flask. The fusion of compounds 1a-f with 2a and/or 2b in the presence of ammonium acetate afforded spirothiazolodihydropyridinopyrazole derivatives (4a-l) in good yields. Also the reaction of compounds 1a-f with 2a and/or 2b with phosphorus pentasulfide in pyridine at reflux temperature yielded the spirothiazolothiopyranopyrazoles (5a-l). All the synthesized spirohetenxyclic derivatives were identified by conventional methods (IR, 1H-NMR) and elemental analyses. All the prepared compounds were tested for their antimicrobial activities in comparison with tetracycline as a reference compound.

Synthesis of 1-acyl- and 1-(thioacyl)-4-benzylpiperazines as potential antidepressants

2-Nitro, 3-nitro- and 4-nitrobenzoyl chloride were reacted with 1-benzylpiperazine in benzene in the presence of triethylamine and gave the amides IV-VI, the first of which is considered a bioisostere of the antidepressant agent piberaline (I). 2-Dimethylamino-, 3-dimethylamino- and 4-dimethylaminobenzoic acid were treated with thionyl chloride in benzene in the presence of triethylamine or pyridine, and the acid chlorides formed were reacted in situ with 1-benzylpiperazine affording the amides VII-IX. The amides I and IV-VI were transformed by treatment with phosphorus pentasulfide in pyridine to the thioamides X-XIII. 4-(Dimethylaminomethyl)benzoic acid was reacted with 1-benzylpiperazine in dimethylformamide in the presence of N,N'-carbonyldiimidazole and afforded the amide XIV. Heating of ethyl 5-methylimidazole-4-carboxylate with 1-benzylpiperazine to 200-210 °C gave the amide XV together with the unexpected 1-benzyl-4-ethylpiperazine (XVI). The oily or crystalline bases of the amino amides or thioamides were mostly transformed to crystalline salts and characterized by spectra. Out of the compounds prepared only X (V⁄FB-17 070) and XIV (V⁄FB-17 114) showed indications of efficacy in tests which are considered indicative of antidepressant activity. Compounds VII, VIII, and X appeared to be mildly antidopaminergic - similarly like piberaline (I), and compounds IV, V, XI, XIV, and XV on the contrary showed signs of dopaminominetic activity.

ChemInform Abstract: A Novel Formation of 1,2,3‐Butatriene Episulfides by Thionation of Methylenecyclopropanones.

AbstractThe alkylidenecyclopropanones (Ia) and (Ic) react with phosphorus pentasulfide in pyridine, yielding the episulfides (II) and the cumulenes (III) and (IV).

A novel formation of 1,2,3-butatriene episulfides by thionation of methylenecyclopropanones

Sterically hindered methylenecyclopropanones were thionated with phosphorus pentasulfide in pyridine to afford novel 1,2,3-butatriene episulfides and thiiranoradialene derivative via methylenecyclopropanethione intermediate.

Heterocyclic Variants of the Purine System. II. Derivatives of Thiazolo[4,5-E]-1,2,4-Triazines, a New Heterocyclic Ring System

.Some representative derivatives of the new thiazolo [4,5- e]-1,2,4-triazine ring system were prepared from 5-acylamino-1,2,4-triazin-6(1 H)-ones by heating with phosphorus pentasulfide in pyridine. Further derivatives of the biheterocyclo system were also made from 6-methylthio-1,2,4-triazin-5-amines by heating with carbon disulfide or phenyl isothiocyanate.

Reaction of 4‐Amino‐1,2,4‐triazines with phosphorus pentasulfide. Deamination during aromatization

AbstractSynthesis of several derivatives of thieno[2,3‐e]‐1,2,4‐triazines has been achieved via the action of phosphorus pentasulfide on 6‐vinyl‐ or 6‐acylmethyl‐5‐oxo‐1,2,4‐triazine derivatives. During these investigations interesting synthetically useful functions for phosphorus pentasulfide in pyridine were observed, among which the deamination of certain N‐amino heterocycles is unprecedented.

3-(4-Methylpiperazino)dibenzo[b,f]-1,2,4-triazolo[4,3-d]-1,4-thiazepine and its 6-chloro and 12-chloro derivatives; Synthesis and pharmacology

Dibenzo[b,f]-1,4-thiazepin-11(10H)-ones IIa-IIc reacted with phosphorus pentasulfide in pyridine under the formation of the thiones IIIa-IIIc which were transformed by treatment with hydrazine hydrate in 1-butanol to the hydrazine derivatives IVa-IVc. Reactions with triethyl orthoformate in ethanol in the presence of sulfuric acid effected cyclization to dibenzo[b,f]-1,2,4-triazolo[4,3-d]-1,4-thiazepine (Va) and its chloro derivatives Vb, Vc which were treated with bromine in a boiling mixture of chlorofom and pyridine and gave the 3-bromo derivatives VIa-VIc. The title compounds Ia-Ic were obtained by substitution reactions with an excess of boiling 1-methylpiperazine. An attempt at preparing an analogous 14H-dibenzo[b,g]-1,2,4-triazolo[4,3-d]-1,4-thiazocine derivative was discontinued in the stage of reaction of the thione X with hydrazine hydrate which resulted in the azine XI. Compounds Ia-Ic on intravenous administration are highly toxic and inactive in tests for CNS effects; compound Ic showed a clear anticholinergic activity.

4-Thia-5-cholesten-3-one and some further steroidal δ-thioenol lactones

δ-Oxo acids VI-IX and XIV were converted to δ-thioenol lactones X-XIII and XV on reaction with phosphorus pentasulfide in pyridine. Under these conditions the ε-oxo acid XVI affords B-norsteroids XVII and XVIII. The proposed structures are confirmed by a number of physico-chemical data. The reduction of these thienol lactones with hydrides is also described.

Synthesis of two 1-substituted 8-bromo-6-(2-chlorophenyl)-4H-s-triazolo[4,3-a]-1,4-benzodiazepines

2-Amino-5-bromo-2'-chlorobenzophenone (VII) afforded by a reaction with phthalimidoacetyl chloride the phthalimido derivative VIII which was transformed by hydrazinolysis to 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one (II). A reaction with phosphorus pentasulfide in pyridine gave the thiolactam IX which reacted with hydrazides of acetic and methylthioacetic acid in boiling 1-butanol and gave the title compounds V and VI. Compound V is very potent in pharmacological tests for anticonvulsant, central depressant and discoordinating activity in mice; compound VI is somewhat weaker.

Synthesis of thieno[2,3‐e]‐1,2,4‐triazines

Abstract3‐Methylmercapto‐5‐oxo‐6‐vinyl‐ and 2‐methyl‐3‐mercapto‐5‐oxo‐6‐vinyl‐2,5‐dihydro‐1,2,4‐triazines were readily converted into the corresponding thieno[2,3‐e]‐1,2,4‐triazine in one step by the action of phosphorus pentasulfide in pyridine. 4‐Methyl‐3‐mercapto‐5‐oxo‐4,5‐dihydro‐1,2,4‐triazine is only converted into the 5‐thioxo analog and no thiophene ring product was obtained under the same conditions. Thieno[2,3‐e]‐1,2,4‐triazines were also more efficiently obtained by the action of phosphorus petnasulfide in pyridine on the appropriate 6‐acylmethyl‐3‐mercapto‐5‐oxo‐2,5‐dihydro‐1,2,4‐triazine.

Synthesis of β-Substituted Tetramethyltetraazacyclotetradecatetraene and Its Metal(II) Complexes

Abstract N,N′-Bis(1-methyl-3-thioxo-1-butenyl)ethylenediamine (3) was prepared by the reaction of N,N′-bis(1-methyl-3-oxo-1-butenyl)ethylenediamine with phosphorus pentasulfide in pyridine. The reaction of 3 with ethylenediamine gave 5,7,12,14-tetramethyl-1,4,8,11-tetraazacyclotetradeca-4,6,11,13-tetraene (4) in a 46% yield. The reactivity of the β positions of 4 and its metal(II) complexes (M=Cu, Ni, Pd) toward various electrophilic reagents was explored, and some β,β′-bissubstituted tetraaza macrocyclic compounds (substituent=Cl, SC6H4NO2(o), N2Ph) and their metal complexes were prepared, respectively. The former also reacted with metal(II) acetates to afford the same metal complexes.

A convenient synthesis of p-nitrophenyl 2-deoxy-2-(thio-acetamido)-β- d-glucopyranoside, -galactopyranoside, and their 1-thio analogs as inhibitors of 2-acetamido-2-deoxy-β- d-glucosidase

The acetamido group of p-nitrophenyl 2-acetamido-2-deoxy-β- d-glucopyranoside, -β- d-galactopyranoside, and their 1-thio analogs was modified by replacement of the amide-carbonyl oxygen atom with sulfur by treatment of their fully acetylated derivatives with phosphorus pentasulfide in pyridine. The resulting p-nitrophenyl 2-deoxy-2-thioacetamido-β- d-hexopyranoside triacetates were O-deacetylated with catalytic amounts of sodium methoxide in methanol to obtain p-nitrophenyl 2-deoxy-2-thioacetamido-β- d-glucopyranoside, -β- d-galactopyranoside, and their 1-thio analogs. These derivatives inhibited 2-acetamido-2-deoxy-β- d-glucosidase from Turbatrix aceti to various extents. Also obtained in significant yields in the aforementioned reaction with phosphorus pentasulfide in pyridine were the two hitherto unreported thiazolines, namely, 2-methyl(2-acetamido-3,4,6-tri- O-acetyl-α- d-glucopyrano)[2′,1′:4,5]-2-thiazoline and 2-methyl(2-acetamido-3,4,6-tri- O-acetyl-α- d-galactopyrano)[2′,1′:4,5]-2-thiazoline.

ChemInform Abstract: SYNTHESIS OF (1,2,3)THIADIAZOLO(5,4‐D)PYRIMIDINES

AbstractDie Umsetzung von (I) mit Phosphorpentasulfid in siedendem Pyridin liefert über die Zwischenstufe (II) das Thiadiazolopyrimidin (III), das mit Thionylchlorid beim Erhitzen zum Dion (IV) reagiert.

A new, facile synthesis of oxazolo[5,4-d]pyrimidines and their conversion into thiazolo[5,4-d]pyrimidines.

The condensation of 5-amino-1, 3-dimethylbarbituric acid (I) with aromatic aldehydes gave 5-benzylideneamino-1, 3-dimethylbarbituric acids (II). Treatment of (II) with thionyl chloride afforded 2-aryl-5, 7-dimethyloxazolo [5, 4-d] pyrimidine-4, 6 (5H, 7H)-diones (IV) in good yields. The reaction of (IV) with phosphorus pentasulfide in pyridine provided 2-aryl-5, 7-dimethylthiazolo [5, 4-d] pyrimidine-4 (5H)-one-6 (7H)-thiones (VI), which were then converted to 2-aryl-5, 7-dimethylthiazolo [5, 4-d] pyrimidine-4, 6 (5H, 7H)-diones (VII) by the action of 30% hydrogen peroxide in acetic acid or thionyl chloride.

Synthesis of [1,2,3]thiadiazolo[5,4-d]pyrimidines.

Treatment of 4, 6-dimethyl-v-triazolo [4, 5-d] pyrimidine-5, 7 (4H, 6H)-dione (I) with phosphorus pentasulfide in pyridine afforded 5, 7-dimethyl [1, 2, 3] thiadiazolo [5, 4-d] pyrimidine-4 (5H)-one-6 (7H)-thione (II) through the v-triazole-thiadiazole rearrangement. The reaction of (II) with thionyl chloride gave 5, 7-dimethyl [1, 2, 3] thiadiazolo [5, 4-d]-pyrimidine-4, 6 (5H, 7H)-dione (III).

Synthesis of a cytosine nucleoside of 2-amino-2-deoxy-β- D-xylofuranose

1-(2-Amino-2-deoxy-β- D-xylofuranosyl)cytosine ( 13) was synthesized by three routes: ( a) coupling of 2-deoxy-3,5-di- O-p-nitrobenzoyl-2-(trifluoroacetamido)- D- xylofuranosyl chloride ( 5) with 2,4-dimethoxypyrimidine and subsequent treatment with methanolic ammonia ( b) coupling of 5 with 4- N-acetyl-2- O,4- N-bis(trimethylsilyl)cytosine followed by treatment with methanolic ammonia, and ( c) thiation of 1-[3,5-di- O-acetyl-2-deoxy-2-(triflouroacetamido)-β- D-xylofuranosyl]uracil ( 6) by treatment with phosphorus pentasulfide in pyridine followed by amination of the resulting 4-thionucleoside 12 with methanolic ammonia. The best yield was obtained via route ( a).

Studies of Nucleosides and Nucleotides. LII. Purine Cyclonucleosides.(17). Synthesis and Properties of Cyclonucleosides derived from Inosine and Thioinosine

8, 2'-Anhydro-8-mercapto- 9-β-D-arabinofuranosyladenine (I), 8, 3'-anhydro-8-mercapto-9-β-D-xylofuranosyladenine (II) and 8, 5'-anhydro-8-mercapto-9-β-D-ribofuranosyladenine (III) were deaminated with barium nitrite in acetic acid to give the corresponding S-cycloinosines (IV-VI). These cyclonucleosides had characteristic properties in ultraviolet (UV), nuclear magnetic resonance (NMR), circular dichroism (CD) and mass spectra, which were as expected from those of adenosine cyclonucleosides. Compounds IV-VI were benzoylated on sugar OH groups and subjected to thiolation reaction using phosphorus pentasulfide in pyridine containing water. Deprotection either with sodium methoxide or ammonia in methanol gave 8, 2'-anhydro-6, 8-dimercapto-9-β-D-arabinofuranosylpurine (XVI), 8, 3'-anhydro-6, 8-dimercapto-9-β-D-xylofuranosylpurine (XVII) and 8, 5'-anhydro-6, 8-dimercapto-9-β-D-ribofuranosylpurine (XVIII), respectively. The structure of these cyclonucleosides was confirmed by their characteristic UV, CD, NMR and mass spectra. 6-Mercaptopurine cyclonucleosides were easily oxidized to form disulfides by air oxidation or iodine treatment.