Resolution of 3-methyl-3-phospholene 1-oxides by molecular complex formation with TADDOL derivatives

The antipodes of 1-phenyl-3-methyl-3-phospholene 1-oxide 1a were separated in good yield and in high enantiomeric excess (∼99% ee) by resolution via formation of diastereomeric complexes with (4R,5R)-(−)- and (4S,5S)-(+)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane 2 (TADDOL) or (−)-(2R,3R)-α,α,α′,α′-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol 3. The method was also suitable for the resolution of the 1-ethoxy-3-phospholene derivative 1b, suggesting that our novel procedure may be of general value, both for the resolution of chiral phosphine oxides and phosphinates.     

Dynamic kinetic resolution of 1-substituted-3-methyl-3-phospholene oxides via the formation of diastereomeric alkoxyphospholenium salts

A dynamic kinetic resolution method based on the formation of covalent diastereomeric intermediates was elaborated for the preparation of enantiomerically enriched 1-substituted-3-methyl-3-phospholene oxides. The 3-phospholene oxides were first converted to the corresponding chloro-3-phospholenium chlorides. The dynamic interconversion between the enantiomers of the chlorophospholenium salts was verified experimentally, as it is the key step for a dynamic resolution. The cyclic chlorophospholenium salts were reacted with a chiral auxiliary bearing a hydroxy function to form the corresponding diastereomeric alkoxyphospholenium salts in unequal amounts. The diastereomeric species then rearranged into the corresponding optically active 3-phospholene oxides upon heating. After a screening of chiral auxiliaries and the optimization of the reaction conditions, several scalemic 1-aryl- or 1-alkyl-3-methyl-3-phospholene oxides were prepared in excellent yields and with ee-s up to 35%. The key steps of this resolution were investigated by quantum chemical calculations to get some insights into the factors responsible for the stereoselection.     

Reactions of 2-phospholene 1-oxides with bromine in some media: Facile preparation of bromohydrin derivatives of 2-phospholenes

Reactions of 1-phenyl- and 1-methoxy-2-phospholene 1-oxides with bromine in aqueous organic solvents or in a protic medium, such as methanol, easily afforded the corresponding 2-bromo-3-hydroxy- or 2-bromo-3-methoxyphospholane 1-oxide derivatives. The reaction mechanism was postulated based on the stereochemistry of the products.     

Dehydrogenation reactions of 1-substituted-3-aryltetrahydroisoquinoline derivatives

The 1-substituted-3-aryltetrahydroisoquinolines I have been converted into the corresponding 3,4-dihydroor isoquinoline derivatives by treatment with several oxidizing agents: iodine in ethanol, palladium on carbon, DDQ and Fremy's salt. The oxidation reactions with iodine always resulted in the formation of the 3,4-dihydroisoquinolines II, whereas the use of palladium on carbon and the DDQ led to the aromatic isoquinolines. Both the 3,4-dihydro- and the isoquinoline derivatives were obtained by means of Fremy's salt.     

1-Phosphacephalosporin. II. Synthesis of optically active 7-substituted-1-phosphadethia-3-cephem 1-oxides

The synthesis of optically active 7-substituted-l-phosphadethia-3-cephems is described. The stereochemistry in the displacement reaction at C-4 of chiral 3-acylamino-4-acetoxy-2-azetidinones toward trivalent phosphorus nucleophiles is also discussed briefly.     

Cyclization of 1-substituted-3-thiosemicarbazides to triazole derivatives under alkaline conditions

Under both weakly and strongly alkaline conditions, 1-alkyl-2,5-dithiobiureas (1-alkyl-thiocarbamoyl-3-thiosemicarbazides) form 4-alkyl-5-amino-1,2,4-triazoline-3-thiones and 4-alkyl-1,2,4-triazolidine-3,5-dithiones in varying proportions. 1-Alkoxythiocarbonyl-3-thiosemicarbazides expel hydrogen sulfide under weakly basic conditions to form the corresponding 5-alkoxy-1,2,4-triazoline-3-thiones. In a strongly alkaline environment, however, these alkoxy-thiocarbonyl thiosemicarbazides eliminate alcohol to form the appropriate 1,2,4-triazolidine-3,5-dithiones. 1-Alkoxycarbonyl-3-thiosemicarbazides eliminate alcohol in both weakly and strongly basic media to give 5-thiono-1,2,4-triazolidine-3-ones. Cyclization mechanisms of these thiosemicarbazides are postulated.     

Selective reduction of 1,4-diarylimidazoline-3-oxides to imidazolidin-1-ols and hydroxylamine derivatives

Abstract  

C-2-unsubstituted imidazoline-3-oxides were reduced with NaBH₄ in THF to give the corresponding trans-3,5-diarylimidazolidin-1-ols, while under the same conditions C-2-substituted derivatives gave the corresponding ring–chain–ring tautomers. Treatment of the crude reaction mixture from the reduction of C-2-unsubstituted imidazoline-3-oxides with a MeOH–H₂O mixture provided reductive C–N bond cleavage to give hydroxylamines, while under the same conditions ring–chain–ring tautomers remained unchanged.     

Synthesis of 3-dialkylaminomethyl-5-methyl-4-substituted-1H-pyrazoles. Selective functionalization of one methyl group via n-nitration of 3,5-dimethyl-4-substituted-1H-pyrazoles

Treatment of 4-substituted 3,5-dimethyl-1-nitro-1H-pyrazoles 1 and 10a-c with secondary amines in acetonitrile, in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), affords the novel dialkyl-aminomethyl-1H-pyrazoles 5, 6, 7, 8, 11a-c, 12a-c and 13a-c in good to excellent yields. In this way one of the, in general, inert methyl groups of 3,5-dimethyl-4-substituted-1H-pyrazoles is functionalized creating a new synthetic route to azoles containing a coordinating substituent.     

1-Methyl-3-piperidone and 1-methyl-3-pyrrolidone derivatives from a dieckmann reaction

Attempts to prepare 1-methyl-5-carbethoxy-3-piperidone by a Dieckmann cyclization led to formation of its diethyl ketal on workup. The five-membered ring system, 1-methyl-4-(ethoxy-carbonylmethyl)-3-pyrrolidone was also formed in the cyclization.     

5-取代-1H-1,2,4-三氮唑-3-羧酸的合成

三氮唑类化合物具有很强的生物活性[1,2],尤其是利用5 氨基 1H 1,2,4 三氨唑 3 羧酸为原料制得的Schiff碱具有较强的生根性能和较好的细胞分裂活性[3,4]本文以5 氨基 1H 1,2,4 三氨唑 3 羧酸为原料,经Sandmeyer反应将 NH2转变 Cl、 Br、 I和 CN。其合成路线如下:1　实验部分1 1　仪器与试剂Impact 420型傅里叶红外光谱仪;HP8452A二极管阵列紫外/可见光光度计;PE 2400型元素自动分析仪:XL 200MHz超导核磁共振仪;M 80AGC/MS质谱仪。5 氨基 1H 1,2,4 三氮唑 3 羧酸(工业纯,武汉中储鹤翔新技术有限公司,纯度95%以上),其余试剂均…