Birch reduction of anisole

Scheme 158 Mercury-catalyzed Birch reduction of anisole.

In the actual synthesis, Birch reduction of anisole (10, R = CH3) affords the... 

As a further illustration of the regiochemistry associated with the Birch reduction of anisole derivatives, 11 p-acetoxy-O-methylestrone [274] offers an interesting case. 

The Birch reduction of anisole, followed by reaction with acid, provides a... 

Formation of Cyclohexenones. Hydrolysis of the initial enol ether (vinyl ether) formed from Birch reduction of anisole or substituted anisoles under mild acidic conditions leads to P,y-unsaturated cyclohexenones. Under more drastic acidic conditions, these isomerize to the conjugated a, 3-cyclohexenones. Birch reduction of anisoles followed by hydrolytic workup is one of the best methods available for preparing substituted cyclohexenones. ... 

Zimmerman s explanation for the regioselectivity of the Birch reduction of anisole. The Birch reduction on a aromatic system with an electron-withdrawing group should have a similar reaction process but a different position for the solvated electron to attack. 

Birch reduction of anisole (Chapter 21, Section 21.6.1) leads to 1-methoxycyclohexa-l,4-diene. Heating this with aqueous acid leads to cyclohex-2-en-l-one. Draw all of these products and provide a mechanism for the formation of cyclohexanone. Why should this product form ... 

For the Birch reduction of mono-substituted aromatic substrates the substituents generally influence the course of the reduction process. Electron-donating substituents (e.g. alkyl or alkoxyl groups) lead to products with the substituent located at a double bond carbon center. The reduction of methoxybenzene (anisole) 7 yields 1-methoxycyclohexa-1,4-diene 8 ... 

The Birch-type electrochemical reduction (460) (461) has been shown to proceed through the action of tetra-butylammonium amalgam in the steps (460)— (462)— (463), in contrast to a direct electron transfer from the electrode to the aromatics (Scheme 158) [548]. The preparative-scale reduction of anisole, of l,2,3,4-tetrahydro-6-methoxynaphthalene, and several aromatic steroids is performed in an H20-Bu4N0H-(Hg) system. The unique aspect of the reduction is the proposed formation of a tetrabutylammo-nium amalgam complex, BU4N (Hg) (465)... 

Propose mechanisms for the Birch reductions of benzoic acid and anisole just shown. Show why the observed orientation of reduction is favored in each case. 

The Birch reduction of aromatic hydrocarbons and ethers to the 2,5-dihydro derivatives proceeds most satisfactorily when the substitution pattern allows the addition of hydrogen to two unsubstituted positions in a para relationship. If this requirement is satisfied, better yields are obtained from more highly substituted aromatic rings than from (say) anisole itself, which affords a substantial amount (20%) of 1-methoxycyclohexene (c/. Scheme 1). Extra substitution presumably hinders protonation at the terminus of the dienyl anion (which would lead to a conjugated diene and overreduction). The utilization of anisole moieties as precursors to cyclohexenones has been of very limited value with many 1,2,3-substitution patterns and more densely substituted derivatives. Compounds (23) to (26), for example, have only been reduced by employing massive excesses (200-600 equiv.) of lithium metal,2 while the aromatic ring in (28) is completely resistant to reduction. ... 

It should be noted that Birch reduction of 4-substituted anisoles followed by acidic workup (aq HCl, THF) produces mixtures of isomeric cyclohexenones containing an appreciable amount of the P,y-unsaturated product. ... 

Silver fluoroborate, AgBF4 [I, 1007, before Silver iododibenzoate]. Mol. wt. 194.70. Preparation.1 Silver oxide (1.0 g.) is dissolved in 45% fluoroboric acid (7.2 g.). Synthesis of a tropone.1 The natural tropone nezukone (4) has been synthesized by addition of dichlorocarbene (CHClj,-potassium r-butoxide) to l-isopropyl-4-methoxycyclohexadiene-1,4 (2), obtained by Birch reduction of the anisole (1). The resulting adduct (3) was treated with silver fluoroborate to give the tropone (4) in... 

Substituent groups on the benzene ring influence the course of the reaction. Birch reduction of methoxybenzene (anisole) leads to the formation of 1-methoxy-1,4-cyclohexadiene, a compound that can be hydrolyzed by dilute acid to 2-cyclohexenone. This method provides a useful synthesis of 2-cyclohexenones ... 

For aromatic compounds containing electron-donating alkoxy or alkyl groups, the substituent is found in a non-reduced position in the product. Thus, reduction of anisole results in the formation of 1-methoxycyclohexa-1,4-diene and not 3-methoxycyclohexa-l,4-diene. The following protocol for the synthesis of l-methoxy-4-methylcyclohexa-l,4-diene 28 by Birch reduction of 4-methylanisole 27 is representative. 

It was realized that the mechanism of Birch reduction involves protonation of the anion-radical formed by the addition of one electron to the reacting aromatic compound. This is followed by rapid addition of a second electron and protonation of the forming carbanion to yield nonconjugated alicyclic products. Protonation of the anion-radical by added alcohol is the rate-limiting stage. Recent calculations show that the ortho and meta positions in anisole are most enhanced in density by electron introduction. The para position is not appreciably affected (Zimmerman and Alabugin 2001 Scheme 7.9). 

There is no standard, universal, procedure for the Birch reduction. Experiment 7.19 illustrates some of the variants which have been reported in the literature. The original Birch procedure is to add small pieces of sodium metal to a solution of the aromatic compound in a mixture of liquid ammonia and the proton source (ethanol).18 After completion of the reaction, which is usually indicated by the disappearance of the blue colour, it is quenched by the addition of ammonium chloride and the ammonia allowed to evaporate before the cautious addition of water, and isolation of the product by ether extraction. In a modified procedure a co-solvent (ether, tetrahydrofuran, etc.) is initially added to the solution of aromatic compound/liquid ammonia prior to the addition of metal lithium metal is often used in place of sodium.19a,b In general these latter procedures are used for substrates which are more difficult to reduce. Redistilled liquid ammonia is found to be beneficial since the common contaminant iron, in collodial form or in the form of its salts, has a deleterious effect on the reaction.20 A representative selection of procedures is given in Expt 7.19 for the reduction of o-xylene, anisole, benzoic acid, and 3,4,5-trimethoxybenzoic acid. 

PAHs and soils contaminated with PAHs are readily remediated by solvated electrons in NH3. Oligomeric reduced products are obtained. These reactions are slower than dehalogenation, as was demonstrated by the rapid formation of benzene, toluene, and naphthalene in Na/NH3 from their corresponding monochloro derivatives [24,28], Table 12 summarizes data on the destruction of pure PAHs. Soils contaminated with PAHs have been remediated to below detection levels. Mononuclear aromatics (benzene, toluene, anisole, and nitrobenzene) undergo ring reduction according to the well-known Birch reduction [11-18]. 

The use of anisoles (22) as synthetic equivalents to cyclohex-2-enones (Scheme 3) has been widespread since the original observations of Birch, and the literature is replete with examples over the past five decades, e.g. in the syntheses of steroids, terpenoids and alkaloids. The most thorough studies have been carried out within the context of the conversion of estrone derivatives to 19-norandrostane and pregnane derivatives and are instructive for the selection of reagents and reaction parameters for reductions of this general type. ... 

If you want the conjugated dienes as products, it is quite a simple matter to isomerize them using an acid catalyst. In fact, a small amount (about 20%) of the conjugated product is produced anyway in the reaction of anisole above. With anilines, it is impossible to stop the isomerization taking place during the reaction, and Birch reduction always gives conjugated dienamines. 

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