Pyridine‐2(1H)‐thiones: Versatile Precursors for Novel Pyrazolo[3,4‐b]pyridine,Thieno[2,3‐b]pyridines,and Their Fused Azines

Pyridine‐2(1H)‐thiones were prepared and reacted with several active halogenated reagents to afford novel thieno[2,3‐b]pyridines in excellent yields. Thieno[2,3‐b]pyridine‐2‐carbohydrazide derivative was prepared by the reaction of either ethyl 2‐((3‐cyanopyridin‐2‐yl)thio)acetate derivative or thieno[2,3‐b]pyridine‐2‐carboxylate derivative with hydrazine hydrate. On the other hand, the reaction of either pyridine‐2(1H)‐thione or ethyl 2‐((pyridin‐2‐yl)thio)acetate derivative with hydrazine hydrate afforded the corresponding 1H‐pyrazolo[3,4‐b]pyridine derivative. Thieno[2,3‐b]pyridine derivatives reacted with several reagents to afford the corresponding pyrimidine‐4(3H)‐ones and [1,2,3]triazin‐4‐(3H)‐one. Moreover, 2‐carbohydrazide derivative reacted with β‐dicarbonyl reagents to give 2‐((3‐methyl‐1H‐pyrazol‐1‐yl)carbonyl)thienopyridines. The structure of the target molecules is elucidated using elemental analyses and spectral data.     

The Reaction Studies of α‐Chloroformylarylhydrazines with Thiols,Thioureas and α‐Cyclodiketones

The reactions of α‐chloroformylarylhydrazines 1 with various types of mercaptan, thiourea and α‐cyclodiketone have been studied intensively. 1‐Arylhydrazinecarbothioates 2 were obtained via thioesterization when α‐chloroformylarylhydrazines reacted with thiols. On the other hand, compounds 3 were obtained when α‐chloroformylarylhydrazines reacted with thio‐containing heterocyclic compounds, which suggested a totally different mechanism in these types of reactions. Further studies on the reaction of α‐chloroformylarylhydrazines 1 with thiourea compounds confirmed a novel cyclization and de‐cyclization mechanism, which led to give 2‐arylhydrazinecarboximidamides 5 and 1,3,4‐thiadiazolin‐5‐ones 6 . In addition, various 1,3,4‐oxadiazines 9 were obtained by reacting α‐chloroformylarylhydrazines with α‐cyclodiketones, showing ring cyclization was involved in this type of reaction.     

α,ω-Dihydroxyalkan-α,α-diphosphonsäuren durch Desaminierung von ω-Aminoalkandiphosphonsäuren

α,ω-Dihydroxyalkane-α,α-diphosphonic Acids by Desamination of ω-Aminoalkanediphosphonic Acids The title compounds represent a new group of complexing diphosphonic acids which are synthesized by desamination of ω-amino-α-hydroxyalkane-α,α-diphosphonic acids. In case of α,ω-dihydroxypropane-α,α-diphosphonic acid ( 1 ) a phosphonylated phostone is formed by dehydration. In contrast, the ω-phenyl drivative of ( 1 ) yields in a smooth reaction under the same conditions 2-hydroxy-5-phenyl-3-phosphono-1.2-oxaphosphol-3-en-2-oxide ( 6 ).     

Study of the reactivity of α‐acylenaminoketones. Synthesis of pyrazoles

The reactions of 4‐(methylamino)‐3‐penten‐2‐one with diazoketones yielded the α‐acylenaminoketones 1–3 in good yields. Preparation of the α‐acylenaminoketone 4 was carried out by treatment of 4‐(t‐butyl‐amino)‐3‐penten‐2‐one with benzoyl chloride being followed by reaction of transamination with methyl‐amine. The reactions were carried out in five different solvents and were submitted to gas chromatogra‐phy/mass spectrometry analysis, with the goal of obtaining substituted pyrazoles and determining which of the carbonyls would preferentially be attacked by the nucleophile. The reactions of compounds 1–4 with hydrazine reagents led to the formation of the pyrazoles 5–7a‐q . Small amounts of 4‐methylamino‐2‐pentenones 10a‐q , amides 11a‐q and pyrazoles 12a‐q were also obtained in these reactions. The unexpected formation of pyrazoles 15d,h,q was detected when methanol and N,N‐dimethylformamide were used as solvents in the reactions of α‐acylenaminoketone 4 with hydrazine reagents.     

Reactivity of p-phenyl substituted β-enamino compounds using K-10/ultrasound. I. Synthesis of pyrazoles and pyrazolinones

The reactivity of the β-enamino ketones, 3-amino-1-(p-phenyl-substituted)-2-buten-1-ones 1a-d and β-enamino esters, ethyl 3-amino-3-(p-phenyl-substituted)-2-propenoates 5a-d was systematically studied when allowed to react with hydrazine and methylhydrazine under solid support K -10/ultrasound conditions and in homogeneous media (reflux in ethanol or dichloromethane). The products were pyrazoles 2a-d , N-methylpyrazoles 3a-d, 4a-d and N-methylpyrazolinones 6a-c and 7a-c . The regiochemistry of the cyclization reactions showed dependence upon the reaction conditions employed as well as upon the sub-stituent in the aromatic ring.     

Synthesis of Tetrahydrothiopyrano[2,3‐b]indole [60]Fullerene Derivatives via Hetero‐Diels–Alder Reaction of C60 and α,β‐Unsaturated Indole‐2‐thiones

Hetero‐Diels–Alder reactions of [60]fullerene with α,β‐unsaturated thio‐oxindoles ( 3a , 3b , 3c ), prepared from thio‐oxindole 1 and heteroaromatic aldehydes ( 2a , 2b , 2c ), to generate tetrahydrothiopyrano[2,3‐b ]indole [60]fullerene cycloadducts ( 5a , 5b , 5c ) under thermal or microwave irradiation were described. The yields were improved, and the reaction time was decreased by conducting the reaction under microwave irradiation.     

Reaktionen mit γ-Chloracetessigesterderivaten

Reactions with derivatives of γ-chloroacetoacetic acid Ethyl γ-chloroacetoacetate reacts with ammonia to give ethyl β-amino-γ-chloro-crotonate; with aniline, however, β-anilino-crotonic acid γ-lactone is formed. The reaction of ethyl α-cyano-γ-chloro-acetoacetate with arylamines yields 1-aryl-2-amino-3-ethoxycarbonyl-pyrrolin-4-ones.     

Reactivity of p-phenyl substituted β-enamino compounds using k-10/ultrasound. I. synthesis of pyrazoles and pyrazolinones

The reactivity of the β-enamino ketones, 3-amino-1-(p-phenyl-substituted)-2-buten-1-ones 1a-d and β-enamino esters. Ethyl-3-amino-3-(p-phenyl-substituted)-2-propenoates 5a-d were evaluated by systematic studies of the reactions with hydrazine and methylhydrazine by reactions with solid support K-10/ultrasound and homogeneous media (reflux in ethanol or dichloromethane) yielding pyrazole rings 2a-d , N-methylpyrazoles 3a-d, 4a-d and N-methylpyrazolinones 6a-c and 7a-c . The regiochemistry of the cyclization showed dependence of the reaction conditions employed as well as the substituent in the aromatic ring.     

Synthesis of α‐Benzylthiobenzimidazoleacetonitriles and Their Chemoselective Reduction of the Double Bond with NaBH4

Condensation of 2‐((1H‐benzimidazol‐2‐yl)thio)acetonitre 1 with aromatic aldehydes in methanol containing piperidine gave the corresponding 2‐((1H‐benzimidazol‐2‐yl)thio)‐3‐arylacrylonitrile 2 , which on treatment with NaBH₄ in ethanol unexpectedly and chemoselectively gave 2‐((1H‐benzimidazol‐2‐yl)thio)‐3‐arylpropanenitrile 3 by the reduction of the double bond of 2 . 3 on methylation with dimethyl sulfate containing K₂CO₃ as a base and tetrabutylammonium bromide as PTC gave 2‐((1‐methylbenzimidazol‐2‐yl)thio)‐3‐arylpropanenitrile 6 . The latter could also be prepared in an alternative way by reaction of 1 with dimethyl sulfate giving the intermediary 2‐((1‐methylbenzimidazol‐2‐yl)thio)acetonitrile 4 , followed by condensation with aromatic aldehydes yielding 5 and subsequent reduction of 5 with NaBH₄ in methanol. 6 could be directly synthesized by treatment of 4 with benzyl chloride in DMF and triethylamine as a base at 60°C for 5 h.     

Mass spectra of some 3-substituted benzo[b]quinuclidines III

The mass spectra of 3-methoxycarbonyl-, 3-ethoxycarbonyl-, 3-(2-dimethylaminoethoxy)carbonyl-, 3-amino-, 3-hydroxymethyl-, 3-chloro-3-methoxycarbonyl-, 3-chloro-3-ethoxycarbonyl-, and 3-chloro-3-cyano-substituted benzo[b]quinuclidines were investigated. The fragmentation of these compounds under electron impact through the open form of the molecular ion is discussed.See [1] for communication II.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 825–832, June, 1972.     

Reactions of acetylenic ketones with methyl α-naphthylacetate. A synthesis of l-amino-2-pyridone derivatives

Reactions of acetylenic ketones (Ia-f) with methyl α-naphthylacetate in the presence of sodium methoxide gave the corresponding 6-aryl-3-α-naphthyl-4-phenyl-2-pyrones (IIa-f) which upon refluxing with hydrazine hydrate in ethanol gave the corresponding 1-amino-2-pyridone derivatives (VIa-f). The structure of the products was established by chemical and spectroscopic evidence.     

Elude de la réaction du β-aminocrotonitrile et du α-formyl phénylacétonitrile avec l'hydrazine: Synthèse d'amino-7 pyrazolo[1,5-a]pyrimidines

The three compounds C₈ H₁₀N₄ which arise from reaction of hydrazine and β-aminocrotonitrile have been identified: the formation of anazine, a 3(5)-amino 5(3)-methyl pyrazole derivative and a 7-amino pyrazolo [1,5-a] pyrimidine has been demonstrated. The relationships among these compounds and with the methyl-aminopyrazole have been studied.     

Substituted γ-lactones. XXX. Reactions of α-Keto-β-Subtituted-γ-butyrolactones with diamines

The condensation reaction between α-keto-β-aroyl (or acyl) -γ-butyrolactones, 4a-4e and o-phenylenediamine or 2, 3-diaminonaphthalene leads under retrograde aldol condensation involving loss of formaldehyde to formation of 3-substituted-3, 4-dihydro-2 (1H) quinoxalinones or benzo [g] quinoxalinones, 7a-7g , respectively as a new convenient synthesis of this type of heterocyclic systems. The reaction of type 4 compound with 4, 5-diaminopyromidine, 8 , was found to proceed differently. 2-[(4-Amino-5-pyrimidinyl)amine]-4-oxo-3-(hydroxymethyl)-4-phenyl-2-butenoic acid 9 was the only product formed when the reaction between 4a and 8 was run in ethanol. The same reaction in glacial acetic acid proceeds with loss of formaldehyde, to afford 7-phenacylidene-7,8-dihydro-6 (1H)-pteridione 10 . The reaction between type 4 compounds and ethylenediamine or 1, 4-phenylenediamine leads to the formation of the bis-condensation products 13–15 , respectively.     

An Efficient Synthesis of Some Novel 3‐Cyano‐4‐imino‐2‐(methylthio)4H‐pyrido[1,2‐a]pyrimidine and Their Derivatives

Pyrazolo pyrimido pyrimidine ( 4a–k ) was prepared by the reaction of compound 3‐cyano‐4‐imino‐2‐(methylthio)4H‐pyrido[1,2‐a]pyrimidine ( 3 ) with hydrazine hydrate, phenyl hydrazine, 2‐hydrazino benzothiazole, and 6‐substituted hydrazine benzothiazole in N,N‐dimethylformamide and anhydrous potassium carbonate. These synthesized compounds were characterized by elemental analysis IR, ¹H NMR, and mass spectral data.     

N-取代-N'-(2', 3', 4', 6'-四-O-乙酰基-β-D-吡喃葡萄糖基) (酰)氨基硫脲 的合成

利用2,3,4,6-四-O-乙酰基-β-D-吡喃葡萄糖异硫氰酸酯(Ⅰ)分别和芳酰肼(Ⅱ),2-氨基-5-烷基/芳基-1,3,4-噻二唑(Ⅲ),3-烷基/芳基-4-氨基-5-巯基-1,2,4-三唑(Ⅳ),O,O-二烷基(硫代)磷酰肼(Ⅴ,Ⅵ)反应,制得了目标物1a～1c,2d～2e,3f～3i,4j～4k和5l等12种新化合物,IR,^1HNMR和MS分析结果证明产物为β构型。     

Selenium-containing pancreatic imaging agents. Synthesis of β-2- and β-3-selenienylalanine

Selenophene-alanines, labelled with γ-emitting selenium-75, are potential diagnostic agents for disorders of the pancreas. Two of the positional isomers of selenienyl-alanine were synthesized, namely 2-selenienylalanine [2-amino-3-(2-selenienyl)propanoic acid] (88% yield) and 3-selenienylalanine [2-amino-3-(3-selenienyl)propanoic acid] (65% yield). Both amino acids were prepared from the known chloromethyl selenophenes (2- and 3-) by reaction with diethyl acetamidomalonate and subsequent hydrolysis. The method employed was found to be more productive than others which were tried.     

Synthesis of heterocyclic compounds. XXIV. Synthesis of pyridines from β-substituted α-phenylacrylonitriles

The reaction of malononitrile with α-phenylcinnamonitriles in ethanolic sodium ethanethiolate is studied as a convenient route to 2-amino-4-aryl-5-cyano-6-ethylthio-3-phenyl-3,4-dihydropyridines ( 5 ) and the corresponding pyridines 6 . From the study of the structure of 5a (Ar = Ph) we can conclude that this cyclization reaction proceeds via a site-selective addition of the ethanethiolate to the cyano group i of the 1,3-tricarbonitrile ( 2 ).     

Ring closures with α-chloroazines

Two series of unsymmetrical 3,6-disubstituted 1,2,3,4-tetrahydro-1,2,4,5-tetrazines and 3,5-disubstituted 4-amino-2,3-dihydro-1,2,4-triazoles were synthesized from unsymmetrical 1,4-disubstituted 1-chloroazines with hydrazine, 1-methylhydrazine, and 1,2-dimethylhydrazine. These partially reduced heterocycles belong to little known and less accessible classes of heterocycles.     

Reactions with the Arylhydrazones of α-Cyanoketones: The Structure of 2-Arylhydrazono-3-ketimino-nitriles

Analysis of the IR., UV., and polarographic data of a variety of 2-arylhydrazono-3-ketimino-nitriles indicated that these derivatives exist mainly in the intramolecularly chelated hydrazone structure 1 . Compounds 1 reacted with hydrazine hydrate to yield the corresponding 5-amino-4-arylazopyrazoles ( 3 ). Compounds 3a reacted with acetylacetone, ethyl acetoacetate, and diethyl malonate to yield the pyrazolo[1, 5-a]pyrimidine derivatives 4, 5 , and 7 respectively. Compound 3a also reacted with benzoylisothiocyanate to yield the pyrazolyl thiourea derivative 8 .     

υ-Triazolines. Part XIII. Reactions of α-ketoenamines with toluene-P-sulphonylazide

Some enamines derived from α-diketones have been reacted with tosylazide yielding unstable 5-amino-υ-triazolines, which were found to undergo cyeloreversion to diazo compounds and arnidines. In the case of the enamines derived from 4-aryl-2,3-butanediones, a competitive rearrangement to (Z)-4-aryl-4-arnino-3-tosylamino-3-butene-2-ones was observed.