Nitro, acids Reduction

Nitro-pJienols and Nitro-acids dissolve in ctiustic alkahs as a rule with a deep yellow or orange colour. On reduction with st. innous chloride or zinc dust, as described above, they yield the amino-derivatives. In the case of the amino-phenol, the solution is made alkaline with caustic soda, satuiated with CO.j, salt added and extracted w ith ether. In the case of the amino-acid, the method used is that desciibed under Prep. 91 (p. 201). 

Bromo-7-methyl-6-methylaminoquinoline was nitrated with ACONO2 to give the 6-N(N02)Me derivative, which rearranged in diluted sulfuric acid to the 5-nitro derivative. Reduction of the latter compound, followed by condensation with BrCN and final hydrogenolysis using H2, led to a product of >99% radiochemical purity (85MI1). 

Palladium proved especially useful in the hydrogenation of 2-hydroxy-3-nitropropanoic acid. Reduction over palladium-on-carbon gave pure, powdery isoserine, whereas platinum failed to reduce the nitro function under neutral or acidic conditions reduction over Raney nickel gave a bright green powder (96). 

The requisite hydroxylamine function for such cyclizations can also be generated from a precursor having a nitro group. This novel route has provided access to hitherto unknown l-hydroxy-6-allyl-, and -6,6-bisallyl-piperazine-2,5-diones (91UP1). The starting material is an W-nitroacetyl amino acid ester that can be either mono-or bis-allylated at the methylene adjacent to the nitro group. Reduction of the N02 to NHOH using zinc/ ammonium chloride, followed by cyclization, leads to the desired products (Scheme 76). Compound (215) is unique in that it possesses a chiral center at C-3 and a quaternary carbon at C-6 on a l-hydroxypiperazine-2,5-dione system. 

Cyclization to the hexahydro-l,4-benzodiazocinone (204) was carried out in 60% yield by hydrogenation of the nitro acid (203) and carbodiimide dehydration. The diamine (205) was obtained by hydride reduction (71CJC2023). 

Waste lead styphnate was destroyed by adding an excess of sodium carbonate most of the lead was then precipitated as a carbonate and a solution of sodium styphnate was formed. This solution was then treated with iron filings and acidified with sulphuric acid, reduction of the nitro groups took place, and the substance ceased to be dangerous. 

The resin-bound phenylene diamine intermediates 3 are then generated by nitro group reduction with tin(II) chloride in NMP and cyclization/ aromatization with a wide variety of aldehydes gave the resin-bound benzimidazole intermediates 4. The treatment of this intermediate with 50% TFA/DCM liberates the substituted 3-(benzoimidazol-l-yl)-propionic acid derivative 4a. Analysis of this intermediate by HPLC and LC-MS gave a measure of the purity of the resin-bound product and enabled the optimization of conditions for the incorporation of the Rl-nitroarenes and R2-aldehydes by an iterative process. 

The resin-bound perfluoroalkylsulfonyl linker is compatible with many common solid-phase reactions, such as tin dichloride-mediated aromatic nitro group reduction, trifluoroacetic acid-mediated tBoc deprotection, reductive amination reactions, acylation, and sulfonation. It is possible to perform several sequential synthetic reactions on the nonflate resin so that multistep syntheses can be carried out. The solid-phase approach provides an operationally simple, inexpensive, and general protocol for the cleavage... 

The following are examples of the reduction of nitro-compounds by ferrous sulphate nitro-phenyl propiolic acid1 and nitro-dichlor-benzaldeliyde2 the method has been used to reduce several nitro-acids to the corresponding amino-acids.3... 

As has already been noted in the section on ethanol deaminations, upon diazotizing some nitroamines in hydrochloric acid, a diazonium salt is obtained in which the nitro group has been replaced by chlorine (pp. 272-273). Consequently, hypophosphorous acid reduction gives a deaminated product Containing chlorine in place of the nitro group. For example, when 5-amino-8-nitroisoquinoline (XVIII) is diazotized with hydrochloric acid and then treated with hypophosphorous acid, 8-chloro-isoquinohne (XIX) is obtained in 60-70% yield instead of 8-nitro-isoquinoline.86... 

Stannous chloride-mediated reductive cyclisation-rearrangement of the nitro-ketone 269 (obtained from the nitro-acid, 268) gave the dibenzothiazepine derivative 270 in good overall yield mechanistically it was proposed that a hydroxylamine intermediate leads to the rearrangement after intramolecular nucleophilic addition to the ketone [02JOC8662]. 

Both aromatic and aliphatic nitro groups are easily reduced to amino groups. The most common methods are catalytic hydrogenation and acidic reduction by an active metal. Stronger reducing agents, such as LiAlH4, may also be used. 

Analogous Sulfonations. Exactly the same method can be used for sulfonating p-nitrochlorobenzene, p-nitrotoluene, o-m trochlorobenzene, chlorobenzene, and many other compounds. On the other hand, it is usually not possible to sulfonate dinitaro compounds in this way. Dinitrochlorobenzene and dinitrotoluene are decomposed explosively by treatment with fuming sulfuric acid. If dinitrochloro-benzenesulfoitic acid is to be prepared, for example, one starts with p-nitrochloro-benzene/ This is sulfonated, as described previously, and the sulfonic acid is converted to dinitrochlorobenzenesulfonic acid by treatment with mixed acid (50 50 sulfuric and nitric acids) at low temperatures. This product yields, on replacement of the chlorine by —OH and partial reduction, 4-nitro-2-aminophenol-6-sulfonic acid (nitro acid III), which is used in preparing chrome dyes. 

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