Amino reduction

The TNT and RDX have been the focus of most biotransformation research on XACs. Virtually all of this work has been related to soil or groundwater ex situ treatment, not in situ biotransformation. Natural in situ biotransformation of nitroaromatics appears to be dominated by a series of nitro-to-amino reduction reactions. The subsequent reactions are less well understood. 

Two general biotransformation pathways have been observed for nitroaromatics, including TNT (1) sequential nitro-to-amino reduction, and (2) elimination of the nitro group to form nitrite. By far, the most commonly reported reactions involve the nitro-to-amino reduction in which the nitro groups are utilized as electron acceptors or cometabolites. 

Reduction of the nitro group that resides para to the methyl group (at the 4 position) is thermodynamically preferable to reduction of those at the 2 and 6 positions, as predicted by the work of McCormick et al. [19]. It is known that the 4-amino reduction product is the predominant reduced form of TNT in aerobic environments, and 2,4-diamino-6-nitrotoluene predominates under mildly acidic (pH 6) anaerobic conditions [33], It also has been reported that 2,4-diamino-6-nitrotoluene (2,4-DANT) can be generated under aerobic conditions by reaction with certain minerals associated with clays, and is stable in the surface soil environment [34],... 

Reduction of the nitro groups of TNT has pronounced toxicological impact because the amino reduction products of TNT differ in toxicity and bioavailability from the parent compound (see examples in Chapter 3). It is important to note that apart from electrochemical reduction, TNT is largely nonreactive. However, conversion of the nitro groups of TNT to less oxidized species in the body or in the environment yields much more reactive compounds. This reactivity is important from the standpoint of bioaccumulation. These reduction products do not differ greatly from the parent compounds in Kow and are therefore insufficiently hydrophobic to bioaccumulate in lipids. However, they differ from their parent compounds in their ability to generate covalent bonds with biological macromolecules and this activity provides alternate routes for bioaccumulation. 

It is important to note that the reduced metabolites of TNT bind to the humic fraction of soil in a manner similar to that seen in plants. After 60 d in a growth chamber, up to half of the applied dose of TNT was converted to aminodinitrotoluenes and was bound to soil [64], It is generally recognized that the amino reduction products can be retained by soil in two ways by covalent bonding to reactive centers and by... 

A chemical reduction, also based on a hydride transfer, was also developed the amino-reduction reaction. One example of such a reaction applied to a bioactive molecule is presented below (Figure 9.9). 

This methodology allowed us, for example, to sjmthesize the product of the amino-reduction of aniline with 2-indanone to obtain the precursor of a series of new molecules helping to treat pain in patients. It was also possible to demonstrate all the utility of a biosourced catalyst, including in the field of the pharmaceutical industry. This methodology has been recently protected by a patent [GRI 14],... 

Azo-compounds can be obtained by reduction of nitro-compounds, or by oxidation of hydrazo-compounds. They are usually prepared, however, by reacting a phenol or amine with a diazonium salt. The coupling usually takes place in the position para to the hydroxyl or amino group, but if this position is occupied it goes to the ortho position, e.g. 

CfiHsNjOs. Red needles m.p. 168-169°C. Soluble in dilute acids and alkalis. Prepared by reduction of picric acid with sodium hydrogen sulphide, ft is used for the preparation of azodyes, which can be after-chromed by treatment with metallic salts owing to the presence of a hydroxyl group ortho to the amino-group. 

The most noteworthy reaction of azo-compounds is their behaviour on reduction. Prolonged reduction first saturates the azo group, giving the hydrazo derivative (C NH-NH C), and then breaks the NH NH linkage, with the formation of two primary amine molecules. If method (1) has been employed to prepare the azo-compound, these two primary amines will therefore be respectively (a) the original amine from which the diazonium salt was prepared, and (6) the amino derivative of the amine or phenol with which the diazonium salt was coupled. For example, amino-azobenzene on complete reduction gives one equivalent of aniline, and one of p-phenylene diamine, NHaCeH NH benzene-azo-2-naphthoI similarly gives one equivalent of aniline and one of... 

It should be noted that only representative substances are indicated in the above list. Substituted derivatives of the compounds in most classes may be encountered, e.g., nitrobenzoic acid in the aromatic carboxylic acids (p. 347). This acid will contain CH(0)N, but the salient properties are still those of a carboxylic acid, CH(0), Section 14, although the properties of an aromatic nitro-compound (e.g.y reduction to an amino-compound) will also be evident. 

Compounds containing two primary amino groups attached to a benzene ring can be prepared by the reduction of dinitro compounds and of nitroanilines, usually with tin or stannous chloride and hydrochloric acid or with iron and very dilute hydrochloric acid. / ara-diamines may also be obtained by the reduction of aromatic amino-azo compounds (e.g., p-aminodimethylanihne from methyl orange, see Section IV,78). p-Phenylenediamine may also be prepared from p-nitroacetanilide reduction with iron and acid yields p-amino-acetaniUde,.which may be hydrolysed to the diamine. 

Hydrolysis of the azlactone leads to the acylaminooinnamic acid the latter may be be reduced catal3rtlcally (Adams PtOj catalyst 40 lb. p.s.i.) and then hydrolysed by hydrochloric acid to the amino acid. Alternatively, the azlactone (say, of a-benzylaminocinnamic acid) may undergo reduction and cleavage with phosphorus, hydriodic acid and acetic anhydride directly to the a-amino acid (d/ p phenylalanine). 

The p-substituted amino ketones can be reduced readily to the more stable P-dialkylamino alcohols, many of which are useful local anaesthetics. Thus the local anaesthetic Tutocaine is made from the Mannich base derived from formaldehyde, methyl ethyl ketone and dimethylamine, followed by reduction and conversion into the p-aminobenzoate ... 

Also the arene-arene interactions, as encountered in Chapter 3, are partly due to hydrophobic effects, which can be ranked among enforced hydrophobic interactions. Simultaneous coordination of an aromatic oc amino acid ligand and the dienophile to the central copper(II) ion offers the possibility of a reduction of the number of water molecules involved in hydrophobic hydration, leading to a strengthening of the arene-arene interaction. Hence, hydrophobic effects can have a beneficial influence on the enantioselectivity of organic reactions. This effect is anticipated to extend well beyond the Diels-Alder reaction. 

With the dicyclohexylcarbodiimide (DCQ reagent racemization is more pronounced in polar solvents such as DMF than in CHjCl2, for example. An efficient method for reduction of racemization in coupling with DCC is to use additives such as N-hydroxysuccinimide or l-hydroxybenzotriazole. A possible explanation for this effect of nucleophilic additives is that they compete with the amino component for the acyl group to form active esters, which in turn reaa without racemization. There are some other condensation agents (e.g. 2-ethyl-7-hydroxybenz[d]isoxazolium and l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline) that have been found not to lead to significant racemization. They have, however, not been widely tested in peptide synthesis. 

The final step can involve introduction of the amino group or of the carbonyl group. o-Nitrobenzyl aldehydes and ketones are useful intermediates which undergo cyclization and aromatization upon reduction. The carbonyl group can also be introduced by oxidation of alcohols or alkenes or by ozonolysis. There are also examples of preparing indoles from o-aminophcnyl-acetonitriles by partial reduction of the cyano group. 

Amino-4-phenylthiazole when heated with Raney Ni is reported to yield acetophenone (469). In the course of a general study on reductive cleavage in heterocyclic systems Hoff et al. studied the reaction of 2-amino-4-methylthiazole with Na in liquid ammonia. Two equivalents of Na are necessary to obtain a mixture of 4-methyl-3-thiazoline (240) and... 

The conditions required for the sodium borohydride reduction of 2-amino-5-acylthiazoles are stronger than those used for the reduction of 2-acylamino-5-acylthiazole (476). 

The preparation of 5-azothiazoles uses the nucleophilic character of C-5 carbon in reaction with the appropriate diazonium salt (402, 586). These 5-azothia2oles form 1 1 complexes with Ag (587). 2-Amino-4-methyl-5-arylazothiazoles give reduction waves involving two-electron transfer the Ej/ values correlate to the angle between the thiazole and phenyl rings (588). 

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