Reduction aromatic heterocycles

The preparation of enamines by reduction of aromatic heterocyclic bases and their quaternary salts or of lactams is not the most useful approach (97). The lithium aluminum hydride reduction of N-acyl enamines has been used with both fruitful and unsuccessful results. A series of 3-N-acetyl -d -cholestenes (104) has been prepared by desulfurization of the appropriate thiazolidine (105) (98,99). Lithium aluminum hydride reduction of the... 

Reduction of quinones, quinonimines, nitroaromatics, azoaromatics, and oxidized aromatic heterocycles Oxidation of phenols and amines... 

Aromatic heterocycles containing two nitrogen atoms are best reduced by catalytic hydrogenation. Other reduction methods may cleave some of the rings. Even catalytic hydrogenation causes occasional hydrogenolysis. 

The reduction methods of producing enamines from aromatic heterocyclic bases or their derivatives have thus far found only limited application [30]. 

There are many examples of the preparation of tertiary aliphatic amines by the reductive alkylation of dialkylamines or secondary non-aromatic heterocyclic amines with ketones using platinum5-13, palladium12"17, mixtures of platinum and palladium18,and nickel12. 13. 9-22 catalysts. 

Phenazine (Phen). In aprotic solvents (DMF) this tricyclic aromatic heterocycle ex ts two one-electron reductions that are... 

N-Acylation, reduction of nitro to amino, and condensation produce dihydrotriazine 5.31. This system is readily dehydrogenated with manganese dioxide to afford the fully aromatic heterocycle 5.32. Note how relatively simple chemistry can be used to form a quite complex heterocycle. 

In a study of the lithium aluminum hydride reduction of a series of nitrogen aromatic heterocyclics, Bohlmann97 found that this metal hydride effected a conversion of acridine to 9,1O-dihydroacridine (91) in high yield and purity. The ultraviolet spectrum of the isolated dihydroacridine (Amax 288 mp, loge = 4.18) was confirmed by Braude et al.92 as a part of a study of the hydride donor properties of a series of aromatic nitrogen-heterocycles. These workers found that the dihydroacridine underwent a slow oxidation to acridine in air and a rapid hydrogen transfer in the presence of chloranil to form the quinol and acridine. The dihydroacridine was, however, quite stable under dry nitrogen. 

Reduction of aromatic heterocyclic bases and their quaternary salts is of particular interest. Reduction of pyridine with lithium aluminum hydride gives the unstable 1,2-dihydro derivative,403 whereas sodium in 95% ethanol yields 1,4-dihydropyridine. The latter is readily hydrolyzed with the formation of glutaric dialdehyde.404 Reduction of pyridine and its homologs with sodium in butanol affords a mixture of saturated and unsaturated bases d3-piperideines are formed405 only from those pyridine homologs which possess alkyl groups in positions 3 and 4. Electrolytic reduction always gives a mixture of both bases.406 A3-Piperideines have been obtained by reduction with a mixture of lithium aluminum hydride and aluminum chloride.407... 

Reduction of quaternary salts of aromatic heterocyclic bases occurs much more readily. Quaternary salts of pyridine are reduced preponderantly to 1,2-dihydro derivatives 408 with sodium amalgam and to 1,4-dihydro derivatives409 with sodium hydrosulfite. Potassium... 

Padwa and Kuethe have also used vinylogous Pummerer reactions of amido sulfoxides in the preparation of nitrogen-containing heterocycles. Vinyl amido sulfoxide (224) underwent an additive Pummerer reaction, on treatment with trifluoroacetic anhydride, to yield product 226 (Scheme 57).123 The a-thiocarbo-cation 225 generated from the Pummerer reaction of N-methyl-N-phenyl-2-[2-(toluene-4-sulfinyl)phenyl]acetamide (224) underwent a Friedel-Crafts reaction at the y-carbon with the tethered aromatic ring. Reductive removal of the... 

For the purpose of this review the term heteroaromatic is applied to 7r-radical species when they may be regarded as arising from aromatic heterocyclic molecules or ions by addition or removal of an odd number (usually one) of electrons. Thus, entities such as the anion- and cation-radicals of pyridine (1 and 2) are clearly heteroaromatic. The dilemma whether or not to regard thianthrene (3) as aromatic (its central ring possessing eight electrons) does not arise for the thianthrene cation radical (4) it is heteroaromatic on the grounds that it may formally arise by one-electron reduction of the aromatic thianthrenium dication (5). 

Chlorine in 2-chlorolepidine (21) is very reactive, since the compound can be considered an imide chloride. It is readily replaced by hydrogen to form lepidine (22 equation 48). Similarly (23) is converted to (24) on catalytic hydrogenation (equation 49). The above reductions may be applied to many six-membered aromatic heterocycles containing chlorine on the carbon next to nitrogen thus pyridones,... 

When the dithiole ring is annelated by phenalene, the laws of valence require the resultant aromatic heterocycle to be cationic reduction thus gives the neutral phenaleno[l,9-c(/][l,2]dithiolyl radical (138). This persistent radical has been examined in solution and its hyperfine splittings assigned on the basis of MO calculations. The radical is remarkably stable against dimerization it may be isolated as a paramagnetic solid whose mass... 

Mononitro derivatives of aromatic heterocyclic compounds and condensed aromatic systems behave as described for benzene derivatives. As in the benzene series, any prediction of the most likely reaction route for a given compound must be based upon considerations of the reactivity of the compound and its reduction products in the different types of reactions possible under a given set of parameters. 

The concept of chemical catalysis is applied when an electrochemical regeneration process is involved and proceeds through the formation of an adduct that decomposes before or after an additional electron transfer. The electron may be transferred either directly from the electrode or by indirect means in solution from a reducing (or oxidizing) species to regenerate one member of the catalyst couple P/Q. The indirect reduction of acidic protons in the presence of nitrogen aromatic heterocycles may provide a good example. 

Mostly, electron carriers used in reduction processes are ardical anions of commercially available acceptors like nitroaromatic compounds, polyaromatic rings, aromatic heterocycles, and ketones (dinitrobenzene, benzophenones, acridine, fluorenone, diphenyl anthracene, anthracene, phenanthrene, naphthalene, and so on). Table 1 exhibits some possible mediators within a large cathodic potential range. 

The catalysts that effect the hydrogenation of thiophenes in aqueous-biphase systems (see Section 3.2.13.3.2) are also active for the selective reduction of aromatic heterocycles to cyclic amines using aqueous-biphase catalysts (Structures 6-10). 

Donohoe, T. J., Guyo, P. M., Raoof, A. Birch reduction of aromatic heterocycles. Targets in Heterocyclic Systems 1999, 3,117-145. 

The effectiveness of an oxidant is dependent upon the oxidation-reduction potential of the intermediate a-adduct and the oxidant (Scheme 10) (76RCR454). For the sake of simplicity, pyridine is used to represent a TT-deficient nitrogen aromatic heterocycle. When the a-adduct is formed readily (k, k i) and hydride elimination is facile (kj is large), the product is formed easily. In cases where the adduct formation is facile (k, k.J but hydride elimination is very slow (kj is small), the reaction proceeds to the stage of a-adduct formation and stops there. When [Pg.10]

Birch reduction of aromatic heterocycles is equally rewarding if more challenging mechanistically. The pyridine diester 138 is reduced to an intermediate that could be drawn as 139. Both anions are extended enolates but one has the charge delocalised onto the nitrogen atom and so is less reactive than the other. Alkylation occurs at the a-position38 to give 140. 

As an illustration of a modem and efficient route, 2,3-unsubstituted indoles are obtained from an ortho-nitrotoluene by heating with dimethylformamide dimethylacetal (DMFDMA), generating an enamine that, after reduction of the nitro group, closes with loss of dimethylamine, generating the aromatic heterocycle. 

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