Synthesis of Pyrazoles from 1-Acylmethylene-3,3-dimethyl-1,3-dihydroisobenzofurans

Summary.  1-Acylmethylene-3,3-dimethyl-1,3-dihydroisobenzofurans were found to be useful precursors for pyrazole synthesis. In the reaction with hydrazine monohydrate they yielded 3-(2-(α-hydroxyisopropyl)-phenyl) substituted NH-pyrazoles, whereas using alkyl- or arylhydrazine gave access to 5-(2-(α-hydroxyisopropyl)-phenyl) substituted NR-pyrazoles with good regioselectivity. Treatment with orthophosphoric acid led to C,N-fused and C,C-fused pyrazoles, respectively. Received November 4, 1999. Accepted (revised) December 3, 1999     

Synthesis of 1-substituted-3,3-dimethyl-3,4-dihydroisoquinolines

The Ritter reaction between -substituted propionitriles and dimethylbenzylcarbinols gives 3,3-dimethyl-3,4-dihydroisoquinolines containing substituents in the 1-position corresponding to those in the starting nitrile.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 657–659, May, 1991.     

Synthesis of chiral 1,3-dihydroisobenzofurans (phthalans) containing functional substituents in the 1-position

Chiral 3-methyl-1,3-dihydroisobenzofurans (phthalans) having a carbonyl or α-hydroxybenzyl group in position 1 were synthesized by cyclization of the corresponding trimethyl[(S)-1-phenylethyl]ammonium iodides. The configuration of the chiral centers in the products was determined by X-ray analysis.     

Synthesis of the S-cis-oxime of 3,3-dimethyl-3,4-dihydroisoquinolyl-1-carbaldehyde

The reaction of 1-(2-hydroxy-2-trifluoromethyl-3,3,3-trifluoropropyl)-3,3-dimethyl-3,4-dihydroisoquinoline with a nitrosylating mixture gave only the S-cis-oxime of 3,3-dimethyl-3,4-dihydroisoquinolyl-1-carbaldehyde.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2136–2137, September, 1990.     

Synthesis of 1,3-dihydro-3,3-dimethyl-2H-indol-2-one derivatives as possible nonsteroidal cardiotonics

New substituted 1,3-dihydro-3,3-dimethyl-2H-indol-2-one derivatives 19–29 and 34–43 were synthesized and examined for their inotropic activity in isolated dog ventricular tissues. Among them, compound 26 (2-(2,3-dimethoxybenzylamino)-N-(3,3,7-trimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)acetamide) showed very potent activity.     

Synthesis of Some 3-Substituted-2,4-dimethyl-1,3-pentadienes1

Pyrolysis of various l-bromo-2,2,3,3-tetramethylcyclopropanes leads to the corresponding 3-substituted-2,4-dimethylpenta-1,3-dienes in good yield.     

Addition of carboxylic acids and cyclic 1,3-diketones to 2-dimethylamino-3,3-dimethyl-1-azirine

The reaction of 2 - dimethylamino - 3,3 - dimethyl - 1 - azirine 1 with carboxylic acids 2a-e at room temperature in inert solvents generates rearranged 1:1 adducts in 65–92% yields. These adducts are N-acyl derivatives of 2-amino, -N,N dimethyl-isobutyramide 3a-e resulting from 1,2 addition of the acid followed by 1,2 ring cleavage and transfer of an acyl group. Cyclic enolizable 1,3 diketones 4a-c react similarly with 1 to yield the corresponding rearranged 1:1 adducts 5a-c, whereas acyclic diketones or ethyl acetoacetate are inert under comparable experimental conditions.     

Synthesis of 3,3-dinitroazetidine from 1-t-butyl-3,3-dinitroazetidine

Treatment of 1-t-butyl-3,3-dinitroazetidine (1) with benzyl chloroformate resulted in a novel elimination of isobutylene to yield equimolar amounts of 1-(benzyloxycarbonyl)-3,3-dinitroazetidine (3) and 1-t-butyl-3,3-dinitroazetidine hydrochloride. The carbamate 3 was effectively cleaved by trifluoromethanesulfonic acid to yield 3,3-dinitroazetidinium trifluoromethanesulfonate (4) . Free 3,3-dinitroazetidine (5) has also been isolated.     

Synthesis of new spiropyrans from 2,5-dimethyl-1,3-benzodithiolium salts

New spiropyrans that have thermochromic properties were obtained by the condensation of 2,5-diniethyl-1,3-benzodlthiolium perchlorate with o-hydroxy aromatic aldehydes and subsequent treatment of the resulting 2-styryl derivatives with ammonia in ether.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 318–320, March, 1972.     

Soluble Polymer-Supported Synthesis of Pyrazoles via 1,3-Dipolar Cycloaddition Strategy

Rapid parallel liquid-phase synthesis of pyrazoles has first been developed. The 1,3-dipolar cycloaddition between nitrilimines generated in situ and soluble polymer-supported alkynyl or alkenyl dipolarophiles in parallel one-pot fashion gave the corresponding PEG-supported regioisomeric pyrazoles or regiospecific pyrazolines. The latter was assuredly oxidated by DDQ to PEG-supported regiospecific pyrazoles. Cleavage from the support under mild conditions afforded pyrazoles in good yields and high ouritv.     

Stereoselectivity in the 1,3-dipolar cycloaddition of nitrones to 1-substituted 3,3-methylene-5,5-dimethyl-2-pyrrolidinones

Summary The stereoselectivity of the nitrone cycloaddition with 1-substituted 3,3-methylene-5,5-dimethyl-2-pyrrolidinones1 is discussed. C,N-Diarylnitrones give mixtures of diastereomeric spirocycloadducts3 and4, in which3 always dominates. In contrast, N-methylnitrones react under the formation of4 as major products. Cycloaddition of C-benzoyl nitrones7 with1 affords exclusively single isoxazolidines8. Semi-empirical quantum mechanical methods (AM1) were used to rationalize the regio- and stereoselectivity of the reactions.

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Stereoselektivität der 1,3-dipolaren Cycloaddition von Nitronen an 1-substituierte 3,3-Methylen-5,5-dimethyl-2-pyrrolidinone

Zusammenfassung Die Stereoselektivität der Cycloaddition von Nitronen mit 1-substituierten 3,3-Methylen-5,5-dimethyl-pyrrolidinonen (1) wird diskutiert. C,N-Diarylnitrone ergeben Mischungen der diastereomeren Spirocycloaddukte3 und4, wobei3 immer überwiegt. Im Gegensatz dazu entsteht bei der Reaktion von N-Methylnitronen4 als Hauptprodukt. Die Cycloaddition von C-Benzoylnitronen (7) mit1 liefert ausschließlich Isoxazolidine vom Typ8. Zum besseren Verständnis der Regio- und Stereoselektivität der Reaktionen wurden semiempirische quantenmechanische Berechnungen (AM1) durchgeführt.

     

Synthesis of 4,6-(and 5,7-)dimethoxy-3,3-dimethyl-1-indanones

Grignard reaction of ethyl 3-(3,5-dimethoxyphenyl)-propionate (4) followed by cyclodehydration of the carbinol (5) with conc H₂SO₄ gave 4,6-dimethoxy-3,3-dimethylindane (6). Oxidation of the indane (6) with CrO₃-pyridine complex in methylene chloride gave 4,6-dimethoxy-3,3-dimethylindan-1- one (1) in high yield. Conjugate addition of methyl magnesium iodide to methyl α-cyano-β-methyl-3,5-dimethoxycinnamate (11), prepared from 3,5-dimethoxyacetophenone (10) by Knoevenagel condensation, resulted in methyl 2-cyano-3-(3,5-dimethoxyphenyl)-3,3-dimethylpropionate (12). Refluxing the ester (12) with aq DMSO containing sodium chloride gave the corresponding nitrile (15) which underwent Höesch reaction to yield 5,7-dimethoxy-3,3-dimethylindan-1-one (2).     

1-Methyl-1-phenyl-3,3-dimethyl-3-dimethylamino-1-propanol synthesis

Summary A new tertiary amino alcohol, 1-methyl-1-phenyl-3,3-dimethyl-3-dimethylamino-1-propanol,was prepared; it failed to enter the esterification reaction.The present work was begun during the life of I. N. Nazarov as a small part of a systematic study suggested by him.     

Isomerization of perfluoro-3,3-diethylindan-1-one into perfluoro-1,3-dimethyl-4-ethyl-1 H-isochromen under the action of antimony pentafluoride

The heating of perfluoro-3,3-diethylindan-1-one with SbF₅ at 180°C after treatment of the reaction mixture with anhydrous HF afforded perfluoro-1,3-dimethyl-4-ethylisochromen, and after hydrolysis, perfluoro-1,3-dimethyl-4-ethyl-1H-isochromen-1-ol. The latter under the action of NaHCO₃ converted into 5,6,7,8-tetrafluoro-1,3-bis(trifluoromethyl)-1H-isochromen-1-ol. Both isochromenols reacted with SOCl₂ gave the corresponding polyfluoro-1-chloro-1H-isochromens. On dissolving isochromenols in CF₃SO₃H and isochromens in SbF₅ perfluoro-1,3-dimethyl-4-ethylisochromenyl and 5,6,7,8-tetrafluoro-1,3-bis(trifluoromethyl)isochromenyl cations were generated which by hydrolysis were converted into the corresponding isochromenols.     

1,3-二甲基-4-芳氧乙酰基-5-吡唑啉酮类化合物的合成

以双乙烯酮和甲基肼为原料合成1,3-二甲基-5-吡唑啉酮, 再在氢氧化钙催化下,以异丙醇为溶剂, 与芳氧基乙酰氯缩合制得一纱列标题化合物. 并用红外, 紫外, 质谱研究了它们的结构 . 测定了它们对于家稗的生物活性, 探讨了除草活性与结构的关系.     

Syntheses of 1-substituted 4,4-dimethyl-1,2,3,4-tetrahydrobenzo[b]-1,4-azasilines and 1-substituted 3,3-dimethyl-1,2,3,4-tetrahydrobenzo[e]-1,3-azasilines

1-Substituted 4,4-dimethyl-1,2,3,4-tetrahydrobenzo[b]1,4-azasilines (X) and 1-substituted 3,3-dimethyl-1,2,3,4-tetrahydrobenzo[e]-1,3-azasilines (XIII) were synthesized by the intramolecular benzyne reaction of the corresponding N-substituted 2-(3-chlorophenyl)dimethylsilylethylamines (IX) and N-substituted (3-chlorobenzyl)dimethylsilylmethylamines (XII).     

5,5-二甲基-1-邻氨基苯基-1,3-己二炔的合成与表征

二炔化合物不但是有机合成的重要中间体,而且是许多天然产物以及具有生理活性化合物的基本骨架[1].自1869年以来发展了许多高效合成二炔化合物的方法和技术[2-6],其中用铜做催化剂的Glaser偶联反应是合成1,3-二炔化合物最常用的方法,然而这种方法不能满足合成不对称1,3-二炔化合物的需要.