Synthesis of imidazo-1,4-oxazinone derivatives and investigation of reaction mechanism

In this study, nine different C-2 aroyl imidazole derivatives were synthesized in a one pot reaction with two steps, and the reduction reactions of these derivatives with NaBH₄ were carried out under mild conditions. Substitution reaction of obtained imidazo methanol derivatives with chloroacetylchloride reagent and ring reaction of substitution products were investigated. It was determined that 1,4-imidazoxazinone derivative was obtained as a result of the cyclization reaction. The intermediate products obtained during the cyclization reaction were isolated, and the path of the reaction under different conditions was discussed.     

Synthesis of new thieno[2,3‐d]pyrimidines,thieno[3,2‐e]pyridines,and thieno[2,3‐d][1,3]oxazines

o‐Aminothiophene dicarbonitrile 1 on neat reaction with cyclic ketones in anhydrous ZnCl₂ yielded mixture of fused aminopyridine 3 and iminospirooxazine 4 derivatives. Similarly, pyrimidine derivatives 5 and 8 were obtained by the reaction of this intermediate 1 with formic acid and DMF‐DMA followed by hydrazine hydrate, respectively. The reaction of o‐amino‐thiophene dicarboxamide 2 at ambient temperature with cyclic ketones yielded spiropyrimidine 10 as a sole product in quantitative yield. The regioselective anellated pyrimidine 9 , 11 , and dihydropyrimidine 12 derivatives were also obtained by the reaction with aromatic aldehydes in presence of piperidine and iodine respectively. J. Heterocyclic Chem., (2012).     

Synthesis of imidazolino [1,2-f]xanthin-2-ones and their methylene-group-substituted derivatives

8-Amino-7-theophyllylacetic acids and their esters were obtained by reaction of 8-amino(alkylamino, arylamino)theophyllines with haloacetic acids and their esters. The structures of the products were established, and the conditions for cyclization to imidazolino[1,2-f]xanthin-2-one derivatives were studied. The corresponding methylene-group-substituted derivatives were synthesized by reaction of the imidazolino[1,2-f]xanthin-2-one derivatives with aldehydes, isatin, aromatic nitroso compounds, and arenediazonium salts. The ylidene derivatives of this threering system were also obtained by reaction of 8-amino-7-theophyllylacetic acids or their esters with carbonyl compounds.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1132–1135, August, 1976.     

A novel synthesis of fused imidazo[5,1-c]-1,2,4-triazoles

The new fused imidazo[5,1-c]-1,2,4-triazoles 4 were obtained by cyclization of the corresponding 2-imidazolidinone 4-phenylhydrazones 2 which were obtained by the action of phenylhydrazine on the arylmethylene derivatives of 4-thioxo-2-imidazolidinone 1 . The benzylimino derivatives 6 were obtained by the reaction of benzylamine with 1 . Alkylation of 1 with phenacyl bromide and/or ethyl bromoacetate afforded the S-alkyl derivatives 7.     

The synthesis of compounds with antithyroid activity

N-Acyl derivatives of imidazole-2-thione and its derivatives were obtained by the reaction of imidazole2-thione and its derivatives with aliphatic anhydrides and with benzoyl chloride in pyridine. The hydrochlorides of 1-methyl and 4 (5)-methyl-S benzoylimidazole-2-thione were obtained by the reaction of 1-methyl- and 4 (5)-methylimidazole-2-thione with benzoyl chloride in dry ethanol. The acylation of imidazole-2-thione and of some of its derivatives was investigated with the aid of their IR spectra, and the importance of the medium in the formation of N- and S -acyl derivatives was shown, as well as the possibility of the migration of substituants from the S — to the N atom under its influence.For part VI see [1].     

2-Bromomethyl derivatives of benzofuran and indole and their reactions with some nucleophilic reagents

The corresponding 2-bromomethyl derivatives of benzofuran and indole were obtained by bromination of 2-methyl-3-carbethoxy-5-methoxybenzofuran and 1,2-dimethyl-3-earbethoxy-5-methoxyindole with N-bromosuccinimide. A number of alkyl(aryl)thiomethyl and dialkylaminomethyl derivatives were obtained by reaction of the 2-bromomethyl derivatives with nucleophilic reagents.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 308–311, March, 1973.     

Stille reaction over cis-halocyclohexadienediol derivatives

Stille reaction was performed with several halo cis-diol derivatives by reaction with allyltributyltin in the presence of a palladium catalyst forming allyl cis-dihydrodiol derivatives. These couplings were conducted with conventional heating as well as with microwave irradiation. Allylbenzene cis-dihydrodiol was obtained with excellent yield using mild conventional heating. However, if the diol moiety is protected with the isopropylidene group, the expected product is obtained only under microwave irradiation. The unusual reactivity observed for the polyoxygenated derivatives suggests assistance of the free hydroxyls in the catalytic cycle.     

One‐pot three‐component synthesis of novel 2‐(3‐nitro‐phenyl)‐quinazoline‐4‐carboxylic acid derivatives

A simple and easy synthesis of 2‐(3‐nitro‐phenyl)‐quinazoline‐4‐carboxylic acid ( 3 ) has been successfully developed through a one‐pot three‐component condensation reaction of (2‐amino‐phenyl)‐oxo‐acetic acid sodium salt ( 1 ) obtained from the hydrolysis of isatin with ammonium acetate and 3‐nitrobenzaldehyde. Some novel quinazoline‐ester derivatives 4‐7 were then obtained by the reaction between the new compound 3 and various alcohols. Then, quinazoline‐amide derivatives 10‐14 were synthesized from the reaction of various amines and 2‐(3‐nitro‐phenyl)‐quinazoline‐4‐carbonyl chloride ( 8 ), obtained by the reaction of compound 3 with SOCl₂. Finally, some novel quinazoline‐azo derivatives 17‐19 were synthesized by the coupling reaction between β‐dicarbonyl compounds and the novel amino‐quinazoline derivative compound 15 , obtained by reduction of nitro‐quinazoline derivative compound 11 . Thus, a new series of quinazoline‐4‐carboxylic acid, ester, amide, and azo derivatives was synthesized and fully characterized by ¹H NMR, ¹³C NMR, IR, and mass spectrometry analysis.     

Use of phosphite amides in the synthesis of polyamides

The preparation of polyamides by the phosphite amide procedure was investigated. The yield of amidation was determined in the reaction of diethyl- or o-phenylenephosphite derivatives of piperidine, piperazine, or trans-2,5-dimethylpiperazine with either mono- or dicarboxylic acids. Higher yields were obtained by using diethyl phosphite derivatives; however, for both types of derivatives the yields were never greater than 90%. Only low molecular weight polymers could be obtained under optimum reaction conditions. In the polycondensation of (+)-trans-1,3-cyclohexanedicarboxylic acid or (+)-trans-1,2-cyclohexanedicarboxylic acid with phosphite derivatives of either piperazine or trans-2,5-dimethylpiperazine, the optical rotation of the polymers was lower than the rotation of the corresponding polyamides prepared by the interfacial condensation procedure with dicarboxylic acid chlorides. It was shown that an intermediate mixed anhydride was formed during the amidation reaction. This may account for the observed racemization.     

One-pot Synthesis of α,β-Dehydroamino Derivatives from β,β-Dicyanostyrene with 1,3-Dibromo-5,5-dimethylhydantoin Promoted by Mild Base

The reaction of β,β-dicyanostyrene derivatives(1) with 1,3-dibromo-5,5-dimethylhydantoin(DBDMH) was systematicly studied. The reaction could generate different products when promoted by different mild bases. When the reaction was promoted by NaOAc(100%, molar ratio to compound 1), β,β-dicyanostyrene derivatives could be directly converted into corresponding α,β-dehydroamino derivatives in good to excellent yields in one-pot. When the reaction was promoted by K₃PO₄(80%, molar ratio to compound 1), the corresponding α,β-dehydroamino and double-α,β-dehydroamino compounds were simultaneously obtained and the total conversion of β,β-dicyanostyrene derivatives was up to 90% or higher.     

PTC‐Promoted Japp–Klingmann Reaction for the Synthesis of Indole Derivatives

Abstract

Indole derivatives have been efficiently synthesized from ethyl 2‐phenylhydrazono‐5‐phthalimido‐pentanoate and its derivatives, which were obtained by Japp–Klingmann reaction under phase‐transfer catalytic (PTC) conditions. Several different phase‐transfer catalysts were investigated and dimethyldioctadecyl ammonium chloride (DMDOA) was found to promote this reaction efficiently. Using DMDOA as the PTC, aryl hydrazones were obtained in yields of 90%. The pure aryl hydrazones were then efficiently cyclized to indole derivatives in yields of more than 80%.     

Synthesis and photophysical properties of azuleno[1′,2′:4,5]pyrrolo[2,1-b]quinazoline-6,14-diones: Azulene analogs of tryptanthrin

Azulene analog of tryptanthrin, azuleno[1′,2′:4,5]pyrrolo[2,1-b]quinazoline-6,14-dione, was successfully prepared by the condensation reaction of azuleno[2,1-b]pyrrole-2,3-dione with isatoic anhydride in the presence of sodium hydride or diisopropylethylamine (DIPEA). Its 2-halo derivatives were also obtained in high yields by the condensation reaction with 5-haloisatoic anhydrides in the presence of DIPEA. Reactivity toward electrophilic reagents was revealed by halogenation with N-bromosuccinimide (NBS) or N-iodosuccinimide (NIS) to afford 12-halo derivatives in high yields. Among the halo derivatives, 2-iodo and 12-iodo derivatives were reactive enough to afford phenylethynyl derivatives under Pd-catalyzed Sonogashira cross-coupling conditions. Within the phenylethynyl derivatives, only 12-phenylethynyl derivative was transformed into its 1,1,4,4-tetracyanobutadiene (TCBD) derivative by the reaction with TCNE. Amphoteric redox properties of the novel azulene analogs of tryptanthrin were characterized by spectroscopic and voltammetric analyses.     

A tactical approach for the synthesis of novel β-lactam-substituted,polycyclic-fused isoxazolidine derivatives via an intramolecular [3+2] cycloaddition reaction

The synthesis of functionalized β-lactam-substituted, tricyclic chromenoisoxazolidine and tetracyclic naphthopyranoisoxazolidine derivatives by intramolecular nitrone cycloaddition reaction is described. The O-allyl hydroxyaldehyde derivatives, obtained from Baylis–Hillman adducts (BHA) derived from β-lactam aldehyde underwent intramolecular cycloaddition reaction to give β-lactam-substituted, polycyclic isoxazolidine derivatives in good yield. All the products were confirmed by spectral analysis. The products with a β-lactam substituent may find good applications in biological chemistry.     

4-Dimethylaminopyridine-catalyzed multi-component one-pot reactions for the convenient synthesis of spiro[indoline-3,4′-pyrano[2,3-c]pyrazole] derivatives

An efficient and clean reaction process was developed for the convenient and cheap synthesis of spirooxindole derivatives. One-pot reactions of isatins, malononitrile (or ethyl cyanoacetate), hydrazine hydrate (or phenylhydrazine), and 1,3-dicarbonyl compounds were compared with one-pot reactions of isatins, malononitrile (or ethyl cyanoacetate), and 5-pyrazolone derivatives. Both sets of reaction were conducted in EtOH in the presence of 4-DMAP catalyst. A series of spiro[indoline-3,4′-pyrano[2,3-c]pyrazole] derivatives were quickly obtained in excellent yields by using the four-component one-pot reaction method.     

SPIONs as a nanomagnetic catalyst for the synthesis and anti-microbial activity of 2-aminothiazoles derivatives

A series of aminothiazole derivatives have been synthesized by using ultrasmall superparamagnetic iron oxide nanoparticles (SPIONs) nanomagnetic catalysis, which were prepared by reducing the Fe(II) and Fe(III) precursors using aqueous ammonia then characterized by the XRD, FTIR, SEM, and TEM. The 2-aminothiazole derivatives were obtained by coupling 2-aminothiazole diazonium salt with active methylene compounds then cyclization with hydrazine hydrate to afford pyrazolyl derivatives. The one-pot reaction of 2-aminothiazole with an aromatic aldehydes in the presence of Fe₃O₄ NPs to give Schiff bases derivatives. An efficient protocol is developed proudest yields and reduction reaction time and easy separation. Therefore, all synthesized compounds were evaluated for anti-microbial activity.     

Synthesis of ether-linked [60]fullerene glycoconjugates by nucleophilic cyclopropanation

Ethyl acetoacetate-sugar derivatives were prepared by standard alkylation of primary or secondary hydroxyls of diacetonide-protected sugars with ethyl 4-chloroacetoacetate. The obtained D-fructose, D-galactose, D-glucose and D-allose derivatives were conjugated to C₆₀ using the Bingel reaction to afford hydrolytically stable, ether-linked fullerene-carbohydrates. Conjugation of an ester-protected mannose derivative to the C₆₀ scaffold was carried out by the combination of the acetoacetate chemistry with the azide-alkyne click reaction.     

l-Proline catalyzed expeditious multicomponent protocol for the synthesis of fused N-substituted-2-pyridone derivatives in aqueous medium

N-substituted-2-pyridone derivatives have many pharmaceutical properties. In our research, we have developed an efficient, green, and multicomponent protocol to synthesize such new fused N-substituted-2-pyridone derivatives. Optimum reaction condition was obtained by employing l-proline as an organocatalyst in aqueous SDS solution at 100 °C. Various 1,3-diketones, including indane 1,3-dione with a range of aromatic and aliphatic amines were utilized to synthesize fused 2-pyridone derivatives. The isolation of a reaction intermediate confirmed our proposed mechanism. Water as a reaction medium improved the scope of the reaction methodology to a large extent.     

2-氨基噻唑5位的羟甲基化和胺甲基化

采用微波法、封管加热以及酯基还原三种方法,在2-氨基噻唑衍生物的5位引入羟甲基,得到一系列新的5位羟甲基取代的新衍生物.并将三种方法进行对比,结果表明,封管加热对底物热稳定性要求苛刻,反应时间长,反应液杂,反应收率低.酯基还原的方法需在合成噻唑前引入酯基后还原,路线长,且收率低.采用微波法,反应时间短,转化率高,反应液副产物少,收率明显高于其他两种合成方法.同时报道了用NaH作碱制得氰基酯钠盐,再经关怀关环、还原得到一系列5位为氨甲基的噻唑新衍生物.     

The chemical transformation of β-bromodifluoromethyl β-enaminoketones: Synthesis of difluoromethylene thioether compounds

A series of 2-bromodifluoromethylquinoline derivatives were synthesized by cyclization of β-bromodifluoromethyl β-enaminoketones catalyzed by polyphosphoric acid. Difluoromethylene thioether or ether derivatives of quinoline and but-2-en-1-one were obtained by the subustitute reaction of CF₂Br with thio- and oxygen nucleophiles.     

Synthesis of triaza-2- cyclohexene derivatives

Di- and trialkyl derivatives of 1,3,4-triaza-2-cyclohexene were synthesized by reaction of N,N'-dimethylethyleneaminohydrazine with monocarboxylic acid and their anhydrides, esters, amides, and hydrazides. Alkyl derivatives of ,-bis [2-(1,3,4-triaza-2-cyclohexenyl)]alkanes were obtained as a result of the reaction of N,N'-dimethylethyleneaminohydrazine with dicarboxylic acids and their derivatives. 1-Ammo-1,3,4-triaza-2-cyclohexene derivatives were obtained from ethylenedihydrazine and monocarboxylic acid esters.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 127–129, January, 1977.