Reduction of the aromatic ring

The hydrogenation of benzenoids to cyclohexane derivatives is a very useful synthetic reaction and various methodologies have been reported. 

Recently, aromatics have been reduced in aqueous medium at 50 atm of H2 and at room temperature with ruthenium trichloride stabilized by trioct-ylamine(RuCl3/TOA)[73]  

The aqueous medium increases the reaction rate by a factor of 12 with respect to the organic solvent. The cis isomer is always the major product, as is usually observed in heterogeneous catalytic hydrogenation. 

Lanthanoid metal-HCl systems are used to reduce aromatic nuclei of heterocyclic compounds [74]. Pyridines, quinolines and isoquinolines are reduced with Sm-20% HCl system with excellent yields (Table 6.9). Surprisingly the amino group is eliminated from aminopyridine, and piperidine is the major reaction product. 

The aromatic ring is also reduced with the Sml2-H20 system (see section 6.8.5). 

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A further simplification of the requirements for activity came from the preparation of two spasmolytic agents that completely lack the aromatic ring. Thus, double alkylation of phenylace-tonitrile (54) with 1,5-dibromopentane leads to the corresponding cyclohexane (55). This intermediate is then saponified and the resulting acid (56) esterified with w,w-diethylethanolamine. Catalytic reduction of the aromatic ring affords dicyclonine (51). ... 

Adsorbability is influenced strongly hysteric hindrance, and because of this almost any function can be reduced in the presence of almost any other function in suitably constructed molecules. A case in point is the reduction of the aromatic ring in I in preference to reduction of the nitro function, producing 2. However, when R = CH3 (3) the nitro group was reduced instead, a fact attributed to a less sterically crowded environment 109). 

Dorner E, M Boll (2002) Properties of 2-oxoglutarate ferredoxin oxidoreductase from Thauera aromatica and its role in enzymatic reduction of the aromatic ring. J Bacterial 184 3975-3983. 

Benzoyl-CoA reductase carries out the two-electron reduction of the aromatic ring dnring the anaerobic degradation of benzoate by Thauera aromatica. This involves two-electron transfer from ferredoxin, and a combination of EPR and Mossbaner spectroscopy showed the presence of three different clusters, while inactivation by oxygen was associated with partial conversion of [4Fe-4S] clnsters to [3Fe-4S] clnsters (Boll et al. 2000). 

A wide range of mechanisms are involved in the degradation and transformation of aromatic compounds with nitro substituents. These include reduction of the nitro group, and dioxygenation, monooxygenation, and reduction of the aromatic ring. A review devoted to 2,4,6-trinitrotolune is available (Esteve-Nunez et al. 2001). 

For some halides, it is advantageous to use finely powdered lithium and a catalytic amount of an aromatic hydrocarbon, usually naphthalene or 4,4 -di- -bu(ylbiphcnyl (DTBB).28 These reaction conditions involve either radical anions or dianions generated by reduction of the aromatic ring (see Section 5.6.1.2), which then convert the halide to a radical anion. Several useful functionalized lithium reagents have been prepared by this method. In the third example below, the reagent is trapped in situ by reaction with benzaldehyde. 

Iridium nanopartides also catalyze the hydrogenation of benzyhnethylketone, with high selectivity in reduction of the aromatic ring (92% selectivity in saturated ketone, 8% in saturated alcohol at 97% benzylmethylketone conversion). This preferential coordination of the aromatic ring can be attributed to steric effects that make carbonyl coordination difficult. Therefore, metallic iridium nanoparticles prepared in ILs may serve as active catalysts for the hydrogenation of carbonyl compounds in both solventless and biphasic conditions. 

Reduction of aromatic nitro group takes preference to the reduction of the aromatic ring. Under certain conditions, however, even the benzene ring was reduced. Hydrogenation of nitrobenzene over platinum oxide or rhodium-platinum oxide in ethanol yielded aniline while in acetic acid cyclohexylamine was produced [55]. Heating of nitrobenzene with formic acid in the presence of copper at 200° gave a 100% yield of aniline, whereas similar treatment in the presence of nickel afforded 67% of cyclohexylamine [71]. 

Partial reduction of the aromatic ring is especially easy in anthracene-9-carboxylic acid which was reduced to 9,10-dihydroanthracene-9-carboxylic acid with 2.5% sodium amalgam in aqueous sodium carbonate at 10° in 80% yield [987]. Aromatic carboxylic acids with hydroxyl groups in the ortho positions suffer ring cleavage during reductions with sodium in alcohols and are converted to dicarboxylic acids after fission of the intermediate j8-keto acids. 

A wide variety of simple transformations on chiral pool materials can lead to unnatural amino acid derivatives. This is illustrated by the Pictet-Spengler reaction of L-phenylalanine, followed by amide formation and reduction of the aromatic ring (Scheme 2.18).52 The resultant amide (11) is an intermediate in a number of commercial human immunodeficiency virus (HIV) protease inhibitors. 

Q Predict the products of oxidation and reduction of the aromatic ring, including hydrogenation, chlorination, and Birch reduction. Predict the products of the oxidation of phenols. 

A partial reduction of the aromatic ring of trinitrobenzene was recently described by Ohno. Yamamoto and Oka [160]. By acting with 1,4-dihydronico-tinic acid derivatives, 13,5-trinitrobenzene was reduced to dihydrotrinitro-benzene at room temperature in dry acetonitryl in the atmosphere of argon and away from light. 

Thep-chlorophenyl ether was used in this synthesis to minimize ring sulfonation during cyclization of a diketo ester with concentrated H2SO4/ACOH. Cleavage occurs by reduction of the aromatic ring to form an enol ether which is hydrolyzed with acid. 

The first step of a Birch reduction is a one-electron reduction of the aromatic ring to a radical anion. Sodium is oxidized to the sodium ion Na. This intermediate is able to dimerize to the dianion. In the presence of an alcohol the second intermediate is a free radical which takes up another electron to form the carbanion. This carbanion abstracts another proton from the alcohol to form the cyclohexadiene. 

Reviews of the biodegradation and biotransformation of nitroaroamatic compounds have been given (Spain 1995a,b Crawford 1995) to which reference should be made for details, so that only a very brief summary is justified here. Three principal reactions are found among aerobic bacteria (1) oxidative elimination of nitrite, (2) partial or complete reduction of the nitro group, and (3) reduction of the aromatic ring (Chapter 6, Section 6.8.2). 

Reduction of the aromatic ring — The degradation of phenols containing several nitro groups has revealed an unusual reaction. Although this occurs with the elimination of nitrite — not apparently by any of the pathways illustrated above — terminal metabolites are formed by reduction of the aromatic ring. 4,6-Dinitrohexanoate is produced from 2,4-dinitrophenol (Lenke et al. 1992) and 2,4,6-trinitrocyclohexanone from 2,4,6-trinitrophenol (Lenke and Knackmuss 1992). 

Partial reduction of the aromatic ring of the CoA ester of benzoate before ring fission. 

Transformations of the conjugated pyrimido[5,4-r/]pyrimidine skeleton have not been extensively studied. One notable example is the reduction of the aromatic ring, whereby hydrogen iodide and diphosphorus tetraiodide can remove the chlorine atom from the ring, accompanied by simultaneous formation of the unsubstituted 3,4-dihydropyrimido[5,4-c/]pyrimidine and the unsubstituted 3,4,7,8-tetrahydropyrimido[5,4- /]pyrimidine.213... 

By reduction of the aromatic rings, the enantiomers of 1,2-dicyclohexyl-l, 2-ethanediol 14 are obtained, which have also found application for the alkylation of carbanions via a-haloboronic acids (Section D.1.1.2.1.). 

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