A simple synthesis of 4-substituted 2,3-benzoxazinones from C-2 arylated 1,3-indanediones

A simple one-pot procedure for the conversion of 2-hydroxy-2-(2′-hydroxy-aryl)-1,3-indanediones to 4-substituted benzoxazinones has been developed. The process constitutes an interesting acid-catalyzed rearrangement followed by condensation with hydroxylamine.     

An efficient method to access 2-substituted benzimidazoles under solvent-free conditions

An expeditious method to access 2-substituted benzimidazoles was developed. Both aromatic (phenols, anilines, and thiophenols) and alkyl nucleophiles (amines and thiols) react with 2-methylsulfonyl benzimidazole under solvent-free conditions to generate a variety of 2-substituted benzimidazoles.     

Epimerization at C-2 of 2-substituted thiazolidine-4-carboxylic acids

2(R,S)-5,5-Trimethylthiazolidine-4-(S)-carboxylic acid ( 1a ), with a 3.3 to 1 predominance of the 2S (cis) isomer, was shown to epimerize at the C-2 position in neutral, protic solvents. This was manifested by mutarotation concomitant to changes in the ratios of the C-4 methine proton resonances in the nmr spectrum. Compound 1a was stable in dilute sodium carbonate solution, but underwent rapid equilibration in 1N hydrochloric acid. Acetylation of 1a gave an acetyl derivative ( 2a ) with exclusively 2S,4S stereochemistry. Chiral integrity at C-2 was proved by conversion of both 2a and its enantiomer 2b via their munchnone derivatives to enantiomeric dimethyl 1,1,3,5-tetramethyl-1H,2H-pyrrolo[1,2-c]thiazole-6,7-dicarboxylates ( 4a and 4b ). Acetylation of 2-(R,S)-phenyl-5,5-dimethylthiazolidine-4(S)-carboxylic acid, afforded both the 2 S ,4S ( 6a ) and 2R,4S ( 6b ) epimers. Epimerization of 6a at C-4 gave the 2S,4R isomer ( 6c ) which was enantiomeric with 6b .     

A convenient synthesis of 2-substituted 4-amino-5-pyrimidinecarbonitriles

Synthesis of the novel 2-halogenated 4-amino-5-pyrimidinecarbonitriles 3a,b starting from ethoxy-methylenemalononitrile 1 and cyanamide is described. Nucleophilic substitution of the reactive halogen atom leads to the derivatives 5a-g, 6 and 7a-h.     

Synthesis of substituted 2-amino-4H-1,3-oxazines

4,4,6-Trimethyl-2-methylarylamino-4H-1,3-oxazines were synthesized by intramolecular cyclization of N-oxoalkyl-S-methylisothioureas.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 764–767, June, 1974.     

Diastereoselective access to trans-2-substituted cyclopentylamines

A highly diastereoselective synthesis of trans-2-substituted cyclopentylamines via a tandem hydrozirconation/Lewis acid-mediated cyclization sequence applied to butenyl oxazolidines is described. The method allows an easy preparation of diversely substituted cyclopentylamines which appear to be useful synthetic intermediates. This was further illustrated by the syntheses of (±)-Rodocaine, (±)-trans-pentacin, and enantiomerically enriched trans-cyclopentane-1,2-diamine.     

Relative thermodynamic stabilities of 2-substituted 4-methylene-1,3-dioxolanes and 4-methyl-1,3-dioxoles

The relative thermodynamic stabilities of 24 pairs of carbon-carbon double-bondexo-endo isomeric 2-substituted 4-methylene-1,3-dioxolanes (a) and 4-methyl-1,3-dioxoles (b) have been determined by base-catalyzed chemical equilibration in DMSO solution. In all cases, theendo isomer (b) is the favored species at thermodynamic equilibrium. A single alkyl substitutent on C-2 gives only a negligible contribution to the relative stability of the isomeric forms, but the presence of two alkyl groups on C-2 increases the relative stability of theendo isomer by 2–3 kL mol^–1. A still higher effect in favor of theendo isomer is produced by introduction of a single alkoxy group on C-2; this effect is further slightly accentuated by 2,2-dialkoxy substitution at C-2. The origin of the favorable effect of 2-alkoxy substitution on the relative stability of theendo isomer is not clear, but it seems to arise from an unexpected stability of theendo isomer rather than from an enhanced destabilization of theexo form.     

Synthesis of 4-substituted 2-aminothiazoles and thiazolium salts derived from 2-chloroacetyl-1,3-cyclohexanediones

The reaction of 2-chloroacetyl-1,3-cyclohexanediones with thiourea and substituted thioureas forms 2-amino-4-(1,3-dioxo-2-cyclohexyl)thiazolium chlorides; in the presence of triethylamine 2-aminothiazole bases are formed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1409–1412, October, 1990.     

Synthesis of 5-substituted 4-methylthio-1,3-thiazoline-2-thiones

Translated from Khimiya Geterotsiklicheskih Soedinenii, No. 2, pp. 276–277, February, 1989.     

5-Acyl-4-amino-2-phenyl-1,3-oxazin-6-ones

Intramolecular cyclization of acyl(ethoxycarbonyl)keteneN-benzoylaminals in boiling Ph₂O gives 5-acyl-4-amino-2-phenyl-1,3-oxazin-6-ones.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1322–1323, July, 1995.This study was financially supported by the Russian Foundation for Basic Research (Grant No. 94-03-08964).     

Versatile routes to C-2- and C-6-functionalized glucose derivatives of iminodiacetic acid

A series of novel d-glucose derivatives, functionalized at the C-2 or the C-6 position with an iminodiacetic acid moiety for transition-metal complexation, has been prepared. The sugar and the metal-chelating parts are separated by either propyl or octyl chains and were introduced by the reaction of bromoalkylamine. Either N-1-Boc-3-bromopropylamine (17) or N-(8-bromooctyl)phthalimide (19) reacted with methyl 3,5,6-tri-O-benzyl-alpha-beta-d-glucofuranoside (4) (C-2 position) and 1,2:3,5-(O-methylene)-alpha-d-glucose (11) (C-6 position), respectively, in the presence of sodium hydride in DMF at room temperature, affording the desired intermediates. For aminopropyl derivatives, yields varied between 57% and 65%, and for aminooctyl derivatives, yields varied between 40% and 71%. After deprotection of the amine functionality, the metal chelate was built up by dialkylation (6a-c and 13a,b) with methyl bromoacetate in the presence of triethylamine under reflux in THF. Yields varied between 56% and 69% for the glucose modified at the C-2 position and between 58% and 62% for the one modified at the C-6 position. All compounds were characterized by 1H or 13C NMR or both, IR, and mass spectroscopy. Final products were isolated as a mixture of alpha and beta anomers.     

Selenium heterocycles. XXX. Synthesis of 4-substituted vinyl 2-thioxo-1,3-dithioles and 5-substituted vinyl 2-thioxo-1,3-thiaselenoles

4-Substituted vinyl and 4-(4-phenyl-1,3-butadienyl)-1,2,3-thiadiazoles were prepared through the reaction of 4-aryl-3-buten-2-one semicarbazone and 6-phenyl-3,5-hexadien-2-one semicarbazone with thionyl chloride, respectively. Decomposition of these 1,2,3-thiadiazoles as well as the corresponding 1,2,3-selenadiazoles with base and subsequent addition of carbon disulfide afforded 4-substituted vinyl 2-thioxo-1,3-dithioles and 5-substituted vinyl 2-thioxo-1,3-thiaselenoles.     

Synthesis of 2-amino-1,3-dihydroxypropylphosphonates from Garner aldehyde

In the presence of triethylamine or ionic fluoride catalysts, the addition of dimethyl or diethylphosphite to Garner aldehyde proceeded with good (1:9) diastereoselectivity leading to a separable mixture of (1S,2S)- and (1R,2S)-hydroxyphosphonates. Almost equal amounts (43:57) of the respective phosphonates were formed when titanium(IV) isopropoxide was applied as a catalyst. The e.e.s of the hydroxyphosphonates reached 93–97% in the reactions catalysed by Ti(OiPr)₄ and dropped to 80–91% when triethylamine was used to catalyse the reaction.     

Synthesis of substituted 2-amino-5,6-dihydro-4h-1,3-oxazines and 2-iminotetrahydro-1,3-oxazines

3,4,4,6-Tetramethyl-2-aryliminotetrahydro-1,3-oxazines were synthesized by intramolecular cyclization of N-aryl-N′-methyl-N′-(2-methyl-4-hydroxy-2-pentyl)-S-methylisothioureas. 4,4,6-Trimethyl-2-(N-methyl-N-arylamino)-5,6-dihydro-4H-1,3-oxazines were obtained by methylation of 4,4,6-trimethyl-2-arylamino-5,6-dihydro-4H-1,3-oxazines.     

Synthesis of substituted 2-amino-5,6-dihydro-4H-1,3-thiazines and 2-iminotetrahydro-1,3-thiazines

N-Aryl-N′-(2-methyl-4-hydroxy-2-pentyl)thioureas are cyclized in acidic media to 4,4,6-trimethyl-2-arylimino-5,6-dihydro-4H-1,3-thiazines, the methylation of which with methyl iodide gives 4,4,6-trimethyl-2-methylarylamino-5,6-dihydro-4H-1,3-thiazines. 3,4,4,6-Tetramethyl-2-aryliminotetrahydro-1,3-thiazines were synthesized by cyclization of Naryl-N′-methyl-N′-(2-methyl-4-hydroxy-2-pentyl)thioureas.     

A versatile synthesis of 2-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-ones

A mild and general strategy for the synthesis of 2-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-ones is described. The seven-membered lactam is prepared by intramolecular amide bond formation from the intermediate amino acid, which is obtained either by reductive alkylation of a variety of amines with N-Boc,N-Me-ortho-formyl-Phe and Phth-ortho-formyl-Phe, or by reductive amination of a variety of aldehydes with N-Boc-ortho-aminomethyl-Phe.     

Acyl-tetrahydroindolyl-capped 1,3-diynes in oxidative [4 + 2]-cycloaddition with benzylamine: a one-pot access to 2-acyl-6-phenyl-5-tetrahydroindolylpyridines

1-Acyl-4-tetrahydroindolyldiynes (available from cross-coupling of 4,5,6,7-tetrahydroindole with 1-acyl-4-bromo-1,3-diynes) undergo oxidative [4+2]-cycloaddition with benzylamine in KOH/DMSO or K3PO4/DMSO systems (80°C, 4 h) to afford 2-acyl-6-phenyl-5-tetrahydroindolyl-pyridines in ～40% yields. Non-catalyzed reaction of the same reactants in boiling MeOH (4 h) or in DABCO/MeCN system (reflux, 1 h) gives 3-benzylaminoalk-2-en-4-ynones in ～40% yields.     

Structure and tautomerism of substituted 2-amino-4H-1,3-thiazines

It is shown by means of the IR, UV, and PMR spectra of substituted 2-amino-4H-1,3-thiazines that they exist primarily in the amino form in the crystalline state and in solution.