Diazomethane reaction with 2-pyrazolin-5-ones

A 50% aqueous solution of potassium hydroxide (160 ml) is added at —5° over a period of 30 min to a mixture consisting of 80 g (0.78 moles) N-nitrosomethylurea, 104 g (0.32 moles) 3 -acetoxy-5a-pregna-9(ll),16-dien-20-one and 1 liter of methylene dichloride. The mixture is allowed to come to room temperature and the reaction is continued for 2 hr. The mixture is stirred for 15 min and 1.5 liters of water is added slowly in order to discharge any excess of diazomethane. The layers are separated and the aqueous phase is extracted with 300 ml of methylene dichloride. The organic phase is washed with water dried and concentrated. The residue is triturated with 750 ml of petroleum (bp 100-120°) and the resulting solid is dried in vacuo at 100° to give 106.5 g (92%) of the pyrazoline mp 158° (dec.) [ah 72° (CHCI3) 2 3, 229 mfi (e 1,167). 

To a solution of 4.76 g of 1-(4 -methyl-6 -methoxy-2 -pyrimidinyl)-3-methyl-3-pyrazoline-5-one in 200 ml of ether was added an ether solution containing 6 molar equivalents of diazomethane and the reaction mixture was allowed to stand at room temperature for 20 hours. After distilling off the solvent, the residue was dissolved in 160 ml of water, made alkaline (pH 10) with sodium hydroxide solution and extracted three times with 140 ml of benzene. The extract was washed with a small amount of water, dried over sodium sulfate and evaporated to give a crystalline mass. Recrystallization from isopropylether gave 1-(4 -methyl-6 -methoxy-2 -pyrimidinyl)-3-methyl-5-methoxypyrazole (3.96 g, 84%) as colorless prisms, MP 90° to 92°C. 

Introduction of a 16p-methyl group into the corticosteroid molecule was effected by a reaction (83) whereby a 16-dehydropregnenolone (62) was treated with diazomethane to form the pyrazoline (75) which was decomposed with perchloric acid in acetone to give the 16-methylpregn-16-en-20-one derivative (76). Catalytic hydrogenation yielded the 16p-methyl intermediate (77), which was converted into... 

Addition reactions of diazoalkanes, especially diazomethane, diazopropane, diphenyl-diazomethane and ethyl diazoacetate, onto olefins, substituted with one or two electron-withdrawing groups take place very smoothly affording pyrazolines which upon heating or photolysis can give rise to the corresponding substituted cyclopropanes by elimination of nitrogen. 

General Methods.— The cyclopropanation of alkenes with diazocarbonyl compounds is one of the most widely used procedures for the synthesis of functionalized cyclopropanes. This year has seen the introduction of molybdenum hexacarbonyl/ palladium(ii) carboxylate, and iodorhodium(lll) mesotetraphenylporphrin as useful catalysts for this method of cyclopropanation. Reactions between diazomethane and alkenes often lead to pyrazolines [e.g, (1)] by 1,3-dipolar cycloaddition. Whereas thermolyses of these pyrazolines lead mostly to olefinic products [e.g, (3)], Martelli and Gree have now shown that Ce ions in acetone at 0 °C catalyses their decomposition to give largely cyclopropanes [e.g. (2)]. ... 

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