Synthesis of Some 1,3-Thiazole, 1,3,4-Thiadiazole, Pyrazolo[5,1-c]-1,2,4-triazine, and 1,2,4-Triazolo[5,1-c]-1,2,4-triazine Derivatives Based on the Thiazolo[3,2-a]benzimidazole Moiety

3-(3-Methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile was synthesized by refluxing ethyl 3-methylthiazolo[3,2-a]benzimidazole-2-carboxylate, acetonitrile, and sodium hydride. Treatment of 3-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile with phenyl isothiocyanate, in the presence of KOH, furnished the corresponding potassium salt which was converted into thioacetanilide derivative upon neutralization. The thioacetanilide derivative reacts with α-chloroacetylacetone and ethyl α-chloroacetoacetate to give the 1,3-thiazole derivatives, while the reaction of the'thioacetanilide derivative with hydrazonyl chlorides gave 1,3,4-thiadiazole derivatives. On the other hand, 3-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile reacted with the diazonium salt of both 3-phenyl-5-amino-(1H)-pyrazole and 5-amino-l,2,4-(1H)-triazole to afford the corresponding hydrazones. The latter hydrazones underwent an intramolecular cyclization upon boiling in pyridine to give pyrazolo[5,1-c]-1,2,4-triazine and 1,2,4-triazolo[5,1-c]-1,2,4-triazine derivatives. Moreover, the behavior of thiazolo[3,2-a]benzimidazol-3(2H)-one towards phenyl isothiocyanate followed by the reaction with α-chloroketones or hydrazonyl chlorides was investigated. Some of the latter compounds exhibited moderate effects against some bacterial and fungal species.     

Synthesis of Some 1,3-Thiazole, 1,3,4-Thiadiazole, Pyrazolo[5,1-c]-1,2,4-triazine, and 1,2,4-Triazolo[5,1-c]-1,2,4-triazine Derivatives Based on the Thiazolo[3,2-a]benzimidazole Moiety

Summary. 3-(3-Methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile was synthesized by refluxing ethyl 3-methylthiazolo[3,2-a]benzimidazole-2-carboxylate, acetonitrile, and sodium hydride. Treatment of 3-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile with phenyl isothiocyanate, in the presence of KOH, furnished the corresponding potassium salt which was converted into thioacetanilide derivative upon neutralization. The thioacetanilide derivative reacts with α-chloroacetylacetone and ethyl α-chloroacetoacetate to give the 1,3-thiazole derivatives, while the reaction of the'thioacetanilide derivative with hydrazonyl chlorides gave 1,3,4-thiadiazole derivatives. On the other hand, 3-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile reacted with the diazonium salt of both 3-phenyl-5-amino-(1H)-pyrazole and 5-amino-l,2,4-(1H)-triazole to afford the corresponding hydrazones. The latter hydrazones underwent an intramolecular cyclization upon boiling in pyridine to give pyrazolo[5,1-c]-1,2,4-triazine and 1,2,4-triazolo[5,1-c]-1,2,4-triazine derivatives. Moreover, the behavior of thiazolo[3,2-a]benzimidazol-3(2H)-one towards phenyl isothiocyanate followed by the reaction with α-chloroketones or hydrazonyl chlorides was investigated. Some of the latter compounds exhibited moderate effects against some bacterial and fungal species.     

Condensed Thienopyrimidines. 14. Synthesis of 10H-Thiopyrano[4',3':4',5']thieno[2',3':4,5]pyrimido[2,3-c]-1,2,4-triazines

Reaction of a substituted 2-aminothienothiopyran with methyl(phenyl) isothiocyanate, intramolecular cyclization of the obtained N'-methyl(phenyl) thioureido derivatives, and work up of the cyclization products with hydrazine hydrate gave 2-hydrazinodihydrothiopyranothienopyrimidines. Treatment of the latter with pyruvic acid gave the novel 10H-thiopyrano[4',3':4',5']thieno[2',3':4,5]pyrimido[2,3-c]-1,2,4-triazines.     

Synthesis,reactions, and antimicrobial evaluations of new benzo[e][1,3]thiazine derivatives

4H-Spiro[benzo[d][1,3]oxathiine-2,1′-cyclohexan]-4-one undergoes aminolysis with certain aromatic amines to give the respective 4-benzenesulfonamide, Ethyl benzoate, and 4-acetylphenyl of 4-oxospirobenzo[e][1,3]thiazine derivatives. The Schiff bases prepared by reacting Ethyl benzoate derivative 2a with aldehydes, undergoes cyclocondensation with thioglycolic acid yielding p-methoxyphenyl and 2-(thiophen-2-yl) thiazolidinone derivatives. Treatment of the benzoate derivative with hydrazine hydrate afforded the corresponding benzohydrazide derivative which upon reaction with phenyl isocyanate and phenyl isothiocyanate afforded the urea and thiourea derivatives. New pyrimidine, pyridone, and imino pyridine derivatives of 4-oxospirobenzo[e][1,3]thiazine were also successfully prepared by reacting 2b or 2c with the appropriate organic reagents. Structural elucidations for the new products were based upon compatible microanalytical and spectroscopic measurements. Besides, their biological screening indicated that they possess potent antimicrobial activity in comparison with reference drugs.     

Microwave assisted reactions of 2-[3-(Trifluoromethyl)phenyl]-4-R<Superscript>1</Superscript>-furo[3,2-<Emphasis Type="Italic">b</Emphasis>] pyrrole-5-carboxhydrazides

The effect of microwave irradiation on the reactions of 2-[3-(trifluoromethyl)phenyl]-4-R¹-furo[3,2-b]pyrrole-5-carboxhydrazides 1 with 5-arylfuran-2-carboxaldehydes 2, thiophene-2-carboxaldehyde (3) and methyl 2-formylfuro[3,2-b]pyrrole-5-carboxylates 4 has been studied. Reactions of 1 with formic and acetic acid, respectively, led to acylhydrazides 9a–c. Reaction of 1a with 4-substituted 1,3-oxazol-5(4H)-one 10 led to imidazole derivative 13. 1,2,4-Triazole-3-thiones 15a,b were synthesized by two-step reaction of 1a with potassium isothiocyanate and phenyl isothiocyanate, respectively, and subsequent base-catalyzed cyclization of thiosemicarbazides 14a,b. Pyrazole 16 was prepared by reaction of 1a with pentane-2,4-dione.      

The synthesis of some benzo[4,5]cyclohept[1,2,3-ij]isoquinolines

A facile synthesis and spectroscopic properties of various oxidation states of the novel benzo[4,5]cyclohept[1,2,3-ij]isoquinoline system are described. The synthesis involves the condensation of 5H-dibenzo[a,d]cyclohepten-5-one, or of its 10,11-dihydro derivative, with amino-acetaldehyde diethylacetal, followed by treatment of the resultant imines with polyphosphoric acid to afford the novel tetracyclic system in high yields.     

Synthesis of mesoionic triazolo[4,3-a]quinoxalines

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 1 or 6-chloro-2-(1-methylhydrazino)-quinoxaline 5 with phenyl isothiocyanate under reflux in N,N-dimethylformamide gave 7-chloro-3-methyl-1,2,4-triazolo[4,3-a]quinoxalin-3-ium-1-thioate 4 , which was also obtained by refluxing of 6-chloro-2-[1-methyl-2-(N-phenylthiocarbamoyl)hydrazino]quinoxaline 4-oxide 2b or 6-chloro-2-[1-methyl-2-(N-phenylthiocarbamoyl)hydrazino]quinoxaline 6 in N,N-dimethylformamide.     

四硫脲基杯[4]芳烃衍生物的合成

对叔丁基杯[4]-1,3-二乙酸乙酯与过量的二乙基三胺反应,生成含有游离氨基的杯芳烃酰胺衍物(2),2再与异硫氰酸苯酯反应合成了含4个硫脲基的杯[4]芳烃衍生物,其结构经1H NMR,IR,MS和元素分析表征。     

Two Approaches to the Transformation of (Benzimidazol-2-ylmethyl)triphenylphosphonium Chloride into the Derivatives of Pyrimido[1,6-a]benzimidazole

The reaction of readily accessible (benzimidazol-2-ylmethyl)triphenylphosphonium chloride with acyl isothiocyanates in the presence of triethylamine, as well as consecutive treatment of the above phosphonium salt first with N,N-dimethylformamide dimethyl acetal and then with phenyl or allyl isothiocyanate gives two types of phosphorus-containing derivatives of pyrimido[1,6-a]benzimidazole with the thione group in position 3 or 1 of the condensed system. The structure of one of compounds of the first type, 3-thioxo-1-p-tolyl-3,4-dihydropyrimido[1,6-a]benzimidazol-4-ylidenetriphenylphosphorane, was determined by single crystal X-ray diffraction.     

A convenient synthesis of 1,2,4-triazolo[4,3,2-o,p]-[1,3]diazocino[4,5-b]quinoxalines via a 1,3-dipolar cycloaddition reaction and a ring transformation

The reaction of 6-chloro-2-hydrazinoquinoxaline 4-oxide 5 with triethyl orthoformate gave 7-chloro-1,2,4-triazolo[4,3-a]quinoxaline 5-oxide 6. The reaction of compound 6 with phenyl isocyanate afforded 7-chloro-4-phenylamino-1,2,4-triazolo[4,3-a]quinoxaline 7 , while the reaction of compound 6 with phenyl isothiocyanate resulted in deoxygenation to provide 7-chloro-1,2,4-triazolo[4,3-a]quinoxaline 8. However, the reaction of compound 6 with allyl isothiocyanate effected the 1,3-dipolar cycloaddition reaction, but not deoxygenation, to furnish 9-chloro-4,5-dihydroisoxazolo[2,3-a][1,2,4]triazolo[3,4-c]quinoxalin-5-ylmethylisothiocyanate 9. Moreover, the reduction of compound 9 with iron/acetic acid resulted in ring transformation to give 11 -chloro-7-hydroxy-4-thioxo-4,5,6,7,8,9-hexahydro-1,2,4-triazolo[4,3,2- o,p][1,3]diazocino[4,5-b]quinoxaline 10 , whose acetylation afforded 5-acetyl-11-chloro-7-hydroxy-4-thioxo-4,5,6,7,8,9-hexahydro-1,2,4-triazolo[4,3,2-o,p][1,3]diazocino[4,5-b]quinoxaline 11.     

On the Chemistry of Cinnoline V [1]. Reactions of 4-Aminocinnolines with Amines

Summary. We describe the effect of the solvent during the intra-cyclization of the arylhydrazonomalononitrile to obtain new and useful substituted cinnolines, namely 4-amino-3-cyanocinnolines and (4-amino-cinnolin-3-yl)arylmethanones. 4-Amino-3-cyano-5,7-dimethyl-cinnoline was treated with n-hexylamine, cyclohexylamine, and isopropylamine to yield the corresponding cinnoline-3-carboxamidine derivatives. Furthermore, 4-amino-3-cyano-5,7-dimethylcinnoline was reacted with diaminoethane to give 4-amino-5,7-dimethyl-3-(4,5-dihydroimidazol-2-yl)cinnoline. Treatment of 4-amino-3-cyano-5,7-dimethylcinnoline with hydrazine hydrate provided 3-amino-7,9-dimethyl-1H-pyrazolo[4,3-c]cinnoline. Moreover, (4-aminocinnolin-3-yl)phenylmethanones were treated with hydrazine hydrate to give 3-phenyl-1H-pyrazolo[4,3-c]cinnolines. Finally, reactions of (4-aminocinnolin-3-yl)phenylmethanone with 3,5-dimethylaniline, phenyl hydrazine, hydroxylamine, and phenyl isothiocyanate are discussed. Chemical and spectroscopic evidence for the structures of the new compounds is presented.     

Synthesis of Pyrazolo[1,5‐a][1,3,5]triazine,Pyrazolo[1,5‐a]pyrimidine,and Imidazo[1,2‐b]pyrazole Derivatives Based on Imidazo[2,1‐b]thiazole Moiety

3(5)‐Aminopyrazole derivative ( 6 ) has been synthesized by the reactions of the versatile unreported 2‐cyano‐N ′‐(1‐(3‐methyl‐6‐phenylimidazo[2,1‐b ]thiazol‐2‐yl)ethylidene)acetohydrazide ( 3 ) with phenyl isothiocyanate in KOH/DMF solution followed by reaction with methyl iodide and hydrazine hydrate. Reaction of compound 6 with some 1,3‐dicarbonyl compounds yielded pyrazolo[1,5‐a ]pyrimidine derivatives ( 14 – 17 ). Alkylation of compound 6 with various halo reagents, followed by intramolecular cyclization, yielded the corresponding imidazo[1,2‐b ]pyrazole derivatives 27 , 29 , 31 , and 33 . All newly synthesized compounds were elucidated by considering the data of both elemental analysis and spectral data.     

Synthesis and spectroscopic characterisation of 4,5-dihydro-[1,2,3]triazolo[5,1-f][1,2,4]triazines. A novel condensed heterocyclic ring system

The reaction of the 5-bromomethyl-1-dibenzoylamino-1,2,3-triazole ( 5 ) with aromatic amines gave the corresponding 5-arylaminomethyl-1-benzoylamino-1,2,3-triazoles 9 , which on treatment with phosphorus pentachloride gave the [1,2,3]triazolo[5,1-f][1,2,4]triazine derivatives 10 . Hydrolysis of the amide bond in 9 gave the 1-aminotriazoles 11 , which with ethyl orthoformate gave the [1,2,3]triazolo[5,1-f][1,2,4]triazines 12 , whereas with phosgene the triazolotriazinones 13 were obtained. The spectroscopic characteristics of all the new compounds are also given.     

Synthesis and Reactions of Novel Pyrimido[4,5-c]pyridazine and s-Triazolo[3',4':2,3]pyrimido[4,5-c]pyridazine Derivatives

The reaction of 3-chloro-5,6-diphenylpyridazine-4-carbonitrile with potassium thiocyanate gave the corresponding isothiocyanate derivative. This was reacted with aromatic amines in ethanol to afford pyrimido[4,5-c]pyridazine derivatives. The reaction of the latter compounds with hydrazine hydrate led to the formation of 6-hydrazino derivatives. One hydrazino compound was reacted with a variety of reagents to produce other new pyrimidopyridazines as well as a number of s-triazolo derivatives.     

Acyl- und Alkylidenphosphane. XXIII [1]. Synthese und Struktur der [Bis(trimethylsilylsulfano)methyliden]phosphane

Acyl- and Alkylidenephosphines. XXIII. Synthesis and Structure of [Bis(trimethylsilylsulfano)methylidene]phosphines Analogous to the phenyl derivative 1a [2] tert-butyl- 1b , mesityl- 1c and methylbis-(trimethylsilyl)phosphine 1 d react with carbon disulfide to give the corresponding [bis(trimethylsilylsulfano)methylidene]phosphines 4 . Only in case of the mesitylphosphine 1 c the intermediate compounds 2 and 3 could be detected by n.m.r. spectroscopic methods; thermally unstable [bis(trimethylsilylsulfano)methylidene]methylphosphine 4 d dimerizes rapidly [1]. [Bis(trimethylsilylsulfano)methylidene]phenylphosphine 4 a crystallizes in the monoclinic centrosymmetric space group P2₁/c with following dimensions of the unit cell determined at ?95 ± 3°C: a = 1386.4(8); b = 1036.0(7); c = 1281.7(8) pm; ß = 101.23(4)°; Z = 4. An X-ray structure determination (R = 0.032) proves the constitution of this compound as already derived from its nmr spectra. Characteristic bond lengths and angles are: P?C 170; P? C(phenyl) 183; C? S 176; S? Si 219 pm; C? P?C 107; P?C? S 124 and 120; S? C? S 116 and C? S? Si 111°.     

Oxymercuration. Substituted 9-oxabicyclo[4.2.1]- and 9- oxabicyclo[3.3.1]nonanes

Oxymercuration of cis, cis-1, 5-cyclooctadiene ( 1 ), followed by treatment with potassium iodide and subsequent reaction with iodine, leads to six isomeric diiodides which represent the three possible stereoisomers 2 , 3 , and 4 of 2, 5-diiodo-9-oxabicyclo[4.2.1]nonane as well as 5 , 6 , and 7 of 2, 6-diiodo-9-oxabicyclo[3.3.1]nonane. The isolation, structure determination and some reactions of these diiodo compounds 2 – 7 are described.     

Pyrazolo[1,5‐a]Pyrimidine Derivative as Precursor for Some Novel Pyrazolo[1,5‐a]Pyrimidines and Tetraheterocyclic Compounds

The 2‐(cyanomethyl)‐5,7‐dimethylpyrazolo[1,5‐a ]pyrimidine‐3‐carbonitrile 3 reacted with phenyl isothiocyanate to afford the respective thioanilide derivative 4 that is a novel compound that has been unreported hitherto. The latter was used as a precursor to synthesize several novel polyheterocyclic compounds 9 , 12 , 15 , and 19 . Treatment of the enamine derivative of compound 3 with each of hydrazine hydrate and hydroxylamine hydrochloride yielded the tetraheterocyclic compounds 22 and 23 , respectively. The structures of all the newly synthesized compounds were confirmed on basis of their elemental, spectral data, and plausible mechanism has been postulated to account for their formation. X‐ray crystallography was carried out as a further evidence for the structure of the isolated product 19 .     

Chemical transformations of tetracyclo[3.3.1.1<Superscript>3,7</Superscript>.0<Superscript>1,3</Superscript>]decane (1,3-dehydroadamantane): III. Reactions of 1,3-dehydroadamantane with isothiocyanates

1,3-Dehydroadamantane reacted with phenyl isothiocyanate at 120–130°C under solvent-free conditions to give 4-(adamantan-1-yl)phenyl isothiocyanate. The selectivity of its reactions with benzyl and phenethyl isothiocyanates in which the isothiocyanato group is separated from the benzene ring by methylene or ethylene bridge was lower, and adamantylation of the para position of the benzene ring was accompanied by adamantylation of the methylene groups.     

Formylation of 4,7‐Dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidines Using Vilsmeier–Haack Conditions

Formylation of 5‐methyl‐7‐phenyl‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidine 1a using Vilsmeier–Haack conditions yields 5‐methyl‐7‐phenyl‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidin‐6‐ylcarbaldehyde 3a . 5,7‐Diaryl‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidines 1b , 1c in this reaction apart from formylation undergo recyclization into 5‐aryl‐1,2,4‐triazolo[1,5‐a]pyrimidin‐6‐ylmethane derivatives 4b , 4c , 5b , 5c , and 6 . The structure of the synthesized compounds was determined on the basis of NMR, IR, and MS spectroscopic data and confirmed by the X‐ray analysis of the 6‐(ethoxy‐phenyl‐methyl)‐5‐phenyl‐[1,2,4]triazolo[1,5‐a]pyrimidine 6 , 5‐phenyl‐6‐(1‐phenyl‐vinyl)‐[1,2,4]triazolo[1,5‐a]pyrimidine 11 , and 7‐phenyl‐6‐(1‐phenyl‐vinyl)‐[1,2,4]triazolo[4,3‐a]pyrimidine 12 .     

A series of novel acyclic nucleosides. II. Synthesis of acyclic nucleosides bearing an imidazo[4,5-d] [1,3]oxazine ring

Novel acyclic nucleosides 3a,b,c where N-1 of acyclovir is replaced by oxygen atom were prepared. Thus, 1-[(2-acetoxyethoxy)methyl]-5-amino-4-ethoxycarbonylimidazole ( 9 ) was treated with ethoxycarbonyl isothiocyanate or benzoyl isothiocyanate to give 11e,f . Methylation of the latter with methyl iodide afforded S-methylisothiourea derivative 12f which was treated with alkali and subsequently the mixture was neutralized to give 5-amino-3-[(2-hydroxyethoxy)methyl]-3H-imidazo[4,5-d][1,3]oxazin-7-one ( 3a ). Compounds 3b,c were obtained by treatment of acetic anhydride or propionic anhydride with sodium 5-amino-1-[(2-hydroxyethoxy)methyl]imidazole-4-carboxylate ( 7 ) which was prepared via 5-amino-[(2-acetoxyethoxy)methyl]-imidazole-4-carboxamide ( 5 ). Evaluation of acyclic oxanosine analogs for cytotoxicity and activity against herpes simplex virus type 1 (HSV-1) revealed that all the derivatives tested were inactive, but cytotoxicity were similar or less as compared to that of acyclovir.