Ethanol, 2-nitro syntheses with

Pvrrolor3.2- 1pvridines The synthesis of the aromatic pyrrolo[3,2- ]pyridine ring system was achieved by a variation of the Leimgruber-Bathcho indole synthesis (9.101 The 5-nitro-6-methylpyridine required by this scheme was prepared by treatment of a solution of nitroacetone and 9 in ethanol at -IQPC with sodium acetate, followed by the addition of ammonium acetate and heating at reflux. This reaction proved to be reproducible, reliably affording 26 in modest yield (44%). 

A variety of aromatic diamines have been used for the synthesis of polyimides. It would be too time consuming to report all the pathways described in literature, so here only the most common ones are considered. The biggest part of these different methods leads to nitro compounds generally reduced using H2 or hydrazine monohydrate with catalytic amounts of Pd-C in refluxed ethanol or dioxane. The numbers in parentheses refer to Fig. 5.28 ... 

The synthesis of cyclopropenone imines 3 has been accomplished by several methods. Thus aromatic amines, e.g. p-nitraniline, can be reacted either with diphenyl cyclopropenone in HCl/ethanol or with the ethoxy cation 75 forming the immonium cation 150, which is deprotonated by tertiary bases to the N-(p-nitro-phenyl)-imine /5/llsl ... 

Hydroxy-3-methoxy-B-nitrostyrene. A mixture of methylamine hydrochloride (7 g, see precursor section for synthesis) and 10 g of sodium carbonate in 100 ml of methanol is stirred well, filtered, and added to a solution of 219 g of vanillin and 85 ml of nitromethane in 600 ml of ethanol. Keep this solution in the dark at room temp for 71 hours to make the nitrostyrene crystallize out. Filter and wash with cold methanol. Yield 225 grams, nip 166-168°. This and the other two nitriles are reduced by the method listed in the reduction section, JACS, 72, 2781. This reduction can be used to reduce many of the nitro type compounds. 

Nitro-l,2,4-triazol-5-one (NTO) [Structure (2.49)] or oxynitrotriazole (ONTA)has been reported as another IHE coupled with better performance [152-157]. Almost all aspects of NTO-synthesis, structural aspects, chemical and explosive properties including thermal behavior have been investigated [158-161]. NTO exists in two polymorphic forms, that is, -form and P-form. It has been established that a-NTO is the stable and dominating form whereas P-NTO is only found in the product on recrystallization of NTO from a methanol or ethanol/methylene chloride mixture [162]. French researchers have recently reported its evaluation as an explosive for warhead filling without a binder and also as a PBX [155]. Further, synthesis of NTO is easy consisting of only two steps (Scheme 2.9) and uses inexpensive starting materials. 

SYNTHESIS To 500 mL concentrated nitric acid, stirred and cooled with an external ice-bath there was added, a bit at a time, 50 g of finely powdered piperonal. The temperature must not be allowed to rise above 0 °C during the addition. After two hours of additional stirring, the reaction was poured over chipped ice, the product removed by filtration and washed with H20 to remove all traces of acid. After recrystallization from a 50 / 50 mixture of ethyl acetate and ethanol, the product, 2-nitro-4,5-methylenedioxybenzaldehyde, was obtained as lemon-yellow colored crystals that weighed 47 g... 

Formation of a symmetrical sulphide (a) (e.g. dipropyl sulphide, Expt 5.204), is conveniently effected by boiling an alkyl halide (the source of carbocations) with sodium sulphide in ethanolic solution. Mixed sulphides (b) are prepared by alkylation of a thiolate salt (a mercaptide) with an alkyl halide (cf. Williamson s ether synthesis, Section 5.6.2, p. 583). In the case of an alkyl aryl sulphide (R-S Ar) where the aromatic ring contains activating nitro groups (see Section 6.5.3, p. 900), the aryl halide is used with the alkyl thiolate salt. The alternative alkylation of a substituted thiophenol is described in Section 8.3.4, p. 1160. The former procedure is illustrated by the preparation of isobutyl 2,4-dinitrophenyl sulphide (Expt 5.205) from l-chloro-2,4-dinitrobenzene and 2-methylpropane-1-thiol. 

The synthesis of pazopanib (1) involves sequential animation of 2,4-dichloropyrimidine 25 with 6-amino-2,3-dimethylindazole 24 and 5-amino-2-methyl-benzenesulfonamide 28. The 6-amino-2,3-dimethylindazole 24, on the other hand, was prepared from 2-ethylphenylamine 20 via 5-nitration with fuming nitric acid and concentrated sulfuric acid, followed by treatment with isoamyl nitrite and acetic acid to produce 6-nitro-3-methylindazole 22. The 6-nitro group was reduced with stannous chloride and concentrated HC1 in glyme and subsequently methylated at the C2 position of the indazole ring with trimethyloxonium tetrafluoroborate in acetone to produce 6-amino-2,3-dimethylindazole 24. The resultant indazole 24 was condensed with 2,4-dichloropyrimidine 25 in the presence of sodium bicarbonate in ethanol/THF and subsequent iV-methylation with iodomethane and cesium carbonate to produce 27. The 2-chloro group of pyrimidine was then allowed to react with 5-amino-2-methyl-benzenesulfonamide 28 in catalytic HCl/isopropanol and heated to reflux to deliver pazopanib hydrochloride (1) in good yield. 

Reaction of indole with l,3-dioxolan-2-one leads to 2-(l//-indol-l-yl)-l-ethanol 134 (Equation 24) <2001PLM3023>. Indole 134 was used in the synthesis of a photoconducting nonlinear optical chromophore, 2-[3-(6-nitro-l,3-benzoxazol-2-yl)-lf/-indol-l-yl]-l-ethanol. 

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