A-Methylpyrrolidin-2-one

The decarbonylation reaction is not confined to aldehydes, but also embraces those compounds that have aldehyde tautomers. Thus, both carbohydrates and allylic alcohols can be decarbonylated. When glucose is allowed to react with frani -[RhCl(CO)(PPh3)2] in A -methylpyrrolidin-2-one, decarbonylation occurs and arabinitol is formed with retention of configuration. The decarbonylation of fructose to arabinitol is complicated by the simultaneous dehydration to furfinyl alcohol, which is the major product. Analogous reactions occur with lower carbohydrates in the limit, glycolaldehyde is decarbonylated to methanol. Aldose derivatives can also be converted to their C i analogues, but the yields are only about half of those obtained with the parent aldoses. Disaccharides usually give better yields. 

Non-metal catalyzed aziridinations have also been reported. These methods are often more broadly applicable than the metal-catalyzed methods. The use of A -methylpyrrolidine-2-one hydrotribromide (MPHT) and chloramine-T is an effective route for the synthesis of N-tosyl aziridines <06MI16>. The aziridination of olefins using f-BuOI and sulfonamides appears to be a general method for aziridination <06CC3337>. The t-BuOI is prepared in situ from t-BuOCl and Nal. This is a broadly applicable method in that a wide variety of sulfonamides (tosyl, nosyl, SES) can be used with roughly equivalent yields. 

Relative and quantitative acidities in many other solvents have been measured. These solvents have included diethyl ether [396], benzene [397] isopropyl alcohol [521,522], n-hexane, heptane [523,524], ENREF [536] /V,A-dimethylformamide (DMF) [525], methanol [522,526,527], ethanol [522,526], terf-butanol [522], cyclohexylamine [528], glacial acetic acid [529], and A-methylpyrrolidin-2-one [530]. 

The nature of the phenol oxidation catalysts formed from CuCl in pyridine and A -methylpyrrolidin-2-one have been investigated. ... 

Little is known on the metabolic fate of l-methylpyrrolidin-2-one (5.60), an industrial solvent also useful as a solubilizing agent and a penetration enhancer in topical formulations. A preliminary investigation of the disposition and metabolism of labeled l-methylpyrrolidin-2-one in the rat showed that the compound is excreted mainly in urine [171]. Three urinary metabolites were detected, the major of which (ca. 15% of the dose) was 4-(methylami-no)but-2-enoic acid (5.61). This unsaturated product may likely have been formed by H20 elimination from a hydroxylated metabolite. 

In contrast, dipolar aprotic solvents possess large relative permittivities (sr > 15), sizeable dipole moments p > 8.3 10 ° Cm = 2.5 D), and average C.f values of 0.3 to 0.5. These solvents do not act as hydrogen-bond donors since their C—H bonds are not sufficiently polarized. However, they are usually good EPD solvents and hence cation sol-vators due to the presence of lone electron pairs. Among the most important dipolar aprotic solvents are acetone, acetonitrile [75], benzonitrile, A,A-dimethylacetamide [76, 77], A,A-dimethylformamide [76-78], dimethylsulfone [79], dimethyl sulfoxide [80-84], hex-amethylphosphoric triamide [85], 1-methylpyrrolidin-2-one [86], nitrobenzene, nitro-methane [87], cyclic carbonates such as propylene carbonate (4-methyl-l,3-dioxol-2-one) [88], sulfolane (tetrahydrothiophene-1,1-dioxide) [89, 90, 90a], 1,1,3,3-tetramethylurea [91, 91a] and tetrasubstituted cyclic ureas such as 3,4,5,6-tetrahydro-l,3-dimethyl-pyr-imidin-2-(l//)-one (dimethyl propylene urea, DMPU) [133]. The latter is a suitable substitute for the carcinogenic hexamethylphosphoric triamide cf. Table A-14) [134]. 

Other examples of this type of reaction are Sn2 reactions between azide ion and 1-bromobutane [67], bromide ion and methyl tosylate [68], and bromide ion and iodoethane [497]. In changing the medium from non-HBD solvents (HMPT, 1-methylpyrrolidin-2-one) to methanol, the second-order rate constants decrease by a factor of 2 10 [67], 9 10 [68], and 1 10 [497], respectively. The large decrease in these rate constants in going from the less to the more polar solvent is not only governed by the difference in solvent polarity, as measured by dipole moment or relative permittivity, but also by the fact that the less polar solvents are dipolar aprotic and the more polar solvents are protic cf. Section 5.5.2). 

The preparation of disaccharides, from benzyl-protected DISAL donors (e. g. 367,0 Scheme 61), was best carried out in l-methylpyrrolidin-2-one (NMP), a high polar, aprotic solvent. 

A useful synthetic modification has been developed for the synthesis of anhydrous oxazolines. Conventional methods of cyclization of halo-substituted amides (359) generally lead to products with a high percentage of water, which is difficult to remove. The use of sodium hydride in JV-methylpyrrolidin-2-one allows the distillation of the anhydrous product direct from the reaction mixture. 

Only one example in this category has been described in recent years (as of 2003). Treatment of o-phenylenediamine (396) with 3,4,5,6-tetrachloropyridazine (397) in A-methylpyrrolidine at 115°C for 17 h gave a separable mixture of products, one of which was 2,3-bis(benzimidazol-2-yl)quinoxaline (398) (unstated yield). The structure (398) was confirmed by X-ray analysis,and a mechanism for its formation was suggested. ... 

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