Aniline derivatives reduction

The o-nitrobenzyl and p-nitrobenzyl ethers can b prepared and cleaved by many of the methods described for benzyl ethers. The p-nitrobenzyl ether is also prepared from an alcohol and p-nitrobenzyl alcohol (trifluoroacetic anhydride, 2,6-lutidine, CH2CI2, 67% yield). In addition, the o-nitrobenzyl ether can be cleaved by irradiation (320 nm, 10 min, quant, yield of carbohydrate " 280 nm, 95% yield of nucleotide ). The p-nitrobenzyl ether has been cleaved by electrolytic reduction (—1.1 V, DMF, R4N X, 60% yield) and by reduction with Na2S204 (pH 8-9, 80-95% yield). These ethers can also be cleaved oxidatively (DDQ or electrolysis) after reduction to the aniline derivative. ... 

The Hegedus indole synthesis involves one of the earlier (formal) examples of olefin hydroamination. An ortho-vinyl or ortho-nllyl aniline derivative 1 is treated with palladium(II) to deliver an intermediate resulting from alkene aminopalladation. Subsequent reduction and/or isomerization steps then provide the indoline or indole unit 2, respectively. 

A compound closely related to classical adrenergic agonists in which the para hydroxy function is however replaced by an amino group has been investigated for its activity as a growth promoter in domestic animals. Acylation of the aniline derivative 26 with chloracetyl chloride will afford acetophenone 27 the amino-ketone 28 is obtained on reaction with isopropylamine. Removal of the protecting group (29) followed by reduction of the ketone affords cimaterol (30) 5J. 

One of the most important derivatives of benzene is nitrobenzene. The nitro group is —NOi. Nitrobenzene is important chiefly because it is readily converted into an aromatic amine, aniline, by reduction. One preparative procedure uses zinc as the reducing agent ... 

Meerwein reactions can conveniently be used for syntheses of intermediates which can be cyclized to heterocyclic compounds, if an appropriate heteroatom substituent is present in the 2-position of the aniline derivative used for diazotization. For instance, Raucher and Koolpe (1983) described an elegant method for the synthesis of a variety of substituted indoles via the Meerwein arylation of vinyl acetate, vinyl bromide, or 2-acetoxy-l-alkenes with arenediazonium salts derived from 2-nitroani-line (Scheme 10-46). In the Meerwein reaction one obtains a mixture of the usual arylation/HCl-addition product (10.9) and the carbonyl compound 10.10, i. e., the product of hydrolysis of 10.9. For the subsequent reductive cyclization to the indole (10.11) the mixture of 10.9 and 10.10 can be treated with any of a variety of reducing agents, preferably Fe/HOAc. 

Sodium triacetoxyborohydride is an alternative to NaBH3CN for reductive amination. This reagent can be used with a wide variety of aldehydes or ketones with primary and secondary amines, including aniline derivatives.93 This reagent has been used successfully to alkylate amino acid esters.94... 

Eqs. 9 and 10 make clear predictions about the dependence of quenching rate constants on the free energy change in the quenching step. One way of testing the theory is to observe the quenching of the excited state by a series of related quenchers where the parameters kq(0), K, and k j) should remain sensibly constant and yet where the potentials of the quenchers as oxidants or re-ductants can be varied systematically. Such experiments have been carried out, most notably with the MLCT excited state, Ru(bpy)3 + (1). The experiments have utilized both a series of oxidative nitroaromatic and alkyl pyridinium quenchers, and a series of reductive quenchers based on aniline derivatives. From the data and known redox potentials for the quenchers, plots of RTlnk q vs. 

The syntheses of these three compounds share a common route as described by Brickner et al. [53] and Barbachyn et al. [54]. Namely, the coupling reaction of 3,4-difluoronitrobenzene (82) with piperazine, morpholine, or thiomorpholine to yield the corresponding 4-substituted 3-fluoro-nitrobenzene (83), which upon reduction gives rise to the aniline derivative (84). Carbobenzoxy protection of the active nitrogen of 84 using benzyloxy-carbonyl chloride (CbzCl) results in the formation of carbamates 85a and 85b. Treatment of 85a,b with n-BuLi and (i -glycidyl butyrate yields a 5-(R)-... 

Arylazo tosylates of type 248, which are readily obtained from aniline derivatives 249 in a two-step procedure (equation 162), can be alternatively used as starting materials. This electrophilic nitrogen equivalent 248 reacts with a broad range of functionalized Grignard reagents under mild conditions. Subsequent allylation of the addition products with allyl iodide, followed by reductive cleavage of the resulting hydrazine derivatives... 

Group IV substituents, especially the trimethylsilyl group, apparently enhance the electron affinity of aromatic systems. The effect is particularly noticeable in aniline derivatives. The strong electron-releasing effect of the amino group decreases the electron affinity of the aniline derivatives and hinders reduction to the radical anions. Nitroanilines may be reduced to radical anions (65). The only other aniline radical anions that have been reported bear silyl substituents either at nitrogen (62) or on the ring (83, 85, 86). 

The reduction of aromatic nitro groups by use of electro-generated titanium(III) has also been investigated very intensively, especially in India. Thus, aniline derivatives are generated in high yield Evidently this method has some... 

The alkylation at N-1 of the 1,4-benzodiazepine 51 with imidazole-5-carboxaldehyde is readily accomplished in excellent yield via a reductive amination process that involves simply stirring with triethylsilane in a 1 1 mixture of CH2CI2 and CF3C02H at 25 °C for 4h (Scheme 20) <2001TL1245>. This reaction is notable because of the low reactivity associated with electron-deficient aniline derivatives. 

Many synthetic methods have been developed for the preparation of quinolines and 1,2,3,4-tetrahydroquinolines due to the interesting biological properties of quinoline-type alkaloids. Most of the synthetic methods are based on the elaboration of aniline derivatives and, as for the synthesis of tetrahydroquinolines, reduction of the corresponding quinolines is the main approach. Only a few methods have been reported for the construction of the quinoline skeleton by N-C(8a) bond formation as the key step, such as oxidative cyclization of 2-(3-aminopropyl)benzene-1,4-diol 89 with K2[Fe(CN)e] (Scheme 42)... 

Since alcohols and carbohydrates readily form equilibrium concentrations of alkyl nitrites which are themselves inactive as direct nitrosating agents (see below), it is to be expected that the addition of alcohols and carbohydrates will inhibit N-nitrosation of amines. This has been shown to be the case for aniline derivatives, and the reduction in the measured first order rate constants can be accounted for quantitatively by such equilibria (Aldred and Williams, 1982). But since alkyl nitrite formation is a rapid equilibrium process, it is not possible, at least for the aniline derivatives studied, to suppress N-nitrosation completely this way. This is in contrast to the effect of thiols discussed in Section 9. In another study (Kurechi et al., 1980), the same effect was observed at pH 3 for the nitrosation of dialkylamines, whereas at pH 5 there was claimed to be a rate enhancement on addition of alcohols, an effect which was not explained. 

Although also a special case of a MPV reduction (Section 1.3.3.3) some unusual reactions of practical import will be considered here because of the heterocyclic characteristics. Donation in an intramolecular reaction of a hydride from a tertiary aniline derivative to generate an iminium ion initiates the reaction. An example is given in Scheme 7. Tertiary aniline derivative (99) rearranges thermally apparently via intermediate (100) to pyrrolo[ 1,2-a]quinoline (101). ° The highly electron-deficient double bond is clearly the hydride acceptor in this case exclusively the most substituted iminium salt is formed. Subsequent ring closure provides the end product (101). Formation of the more substituted iminium ion is not always the case. ° ° ... 

A(A -Dimethylaniline was one of the earliest substrates for reduction examined by Birch. This and subsequent studies have shown that a variety of aniline derivatives are reduced initially to the 2,5-dihydro... 

The nitro group of aromatic nitro compounds has been removed with sodium bor-ohydride. This reaction involves an addition-elimination mechanism. Reduction of the C—N bond on aromatic amines with Li metal in THF generates the aryl compounds.Sodium nitrite, sodium bisulfite in EtOH/water/acetic acid does a similar reduction.Conversion of the aniline derivative to the methanesulfona-mide and subsequent treatment with NaH and NH2CI gives the same result. The BuaSnH reagent also reduces isocyanides, RNC (prepared from RNH2 by for-mylation followed by 17-31), to a reaction that can also be accomplished... 

PtCl2(PPhj)2] in the presence of SnCU and EtsN, both in catalytic amounts, catalyzes the reduction of nitroarenes to aniline derivatives by CO and water (equation 74). SnCU was less effective. The reaction requires raised temperature and CO pressure. If alcohols were used in the same reaction in place of water, alkyl aryl carbamates were produced (equation 144). The catalyst precursor was again [PtCU(PPh3)2] with SnCU and EtjN. 

Aromatic amines are found in biologically active natural products, common pharmaceuticals, dyestuffs, materials with conductive and emissive properties, and ligands for transition-metal-catalyzed reactions. For these reasons much effort has been spent for more than a century on methods to prepare aromatic amines. The synthetic methods to obtain these materials range from classical methods, such as nitration and reduction of arenes, direct displacement of the halogens in haloarenes at high temperatures, or copper-mediated chemistry, as well as modem transition-metal-catalyzed processes and improved copper-catalyzed processes. The following sections describe each of these synthetic routes to aromatic amines, including information on the scope and mechanism of most of these routes to anilines and aniline derivatives. 

Derivation Reduction of diazotized aniline, followed by reaction with sodium hydroxide. 

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