Ammonium 4-methoxybenzoate

It has been demonstrated that the oxygen anion of initially formed product (36) effectively catalysed the [2,3]-Wittig rearrangement as a Lewis base. Other Lewis-base catalysts such as lithio or sodio 2-pyrrolidone promote the same [2,3]-Wittig rearrangement of silyl enolates generated from a-allyloxy ketones, whereas rearrangements of enolates from a-allyloxy esters were efficiently catalysed by ammonium 4-methoxybenzoate.24... 

Benzo[6]furan is cleaved on reduction with excess sodium in liquid ammonia, followed by quenching with ammonium chloride or methanol, to produce 2-ethylphenol (69%). 2-Methyl- and 2-phenyl-benzo[6]furan similarly yield 2-propylphenol (54%) and 2-(2-phenylethyl)phenol (45%) (59JA2795). Similarly, 5-methoxybenzo[6]furan, on reduction with 2 mol of lithium and a limited amount of t- butanol, gives the cleavage product, but by operating with 2 mol each of lithium and f-butanol, 5 -methoxy-2-methylbenzo[6 jfuran supplies the 2,3-dihydro compound. With excess of the alcohol, however, 5-methoxy-2,3,4,7-tetrahydrobenzo[6]furan is secured so that the reduction is stepwise (67JOC2794). 

Aminobenzo[6]thiophene is prepared from 7-hydroxybenzo[6]-thiophene by means of the Bucherer reaction it may be converted into 7-nitrobenzo[6]thiophene via the diazonium salt.84 5,7-Diamino-3-phenylbenzo[6]thiophene and its 2-carboxylic acid are prepared by reduction of the corresponding dinitro compound.334 Partial reduction of o,7-dinitro-3-phenylbenzo[6]thiophene-2-carboxylic acid with ethanolic ammonium sulfide affords 7-amino-5-nitro-3-phenylbenzo-[6]thiophene-2-carboxylic acid, the amino group of which may be replaced by hydrogen or iodine via the diazonium salt.334 7-Amino-4-methoxybenzo[6]thiophene is mentioned in the patent literature.560... 

In a closed system equipped with an oil bubbler, 30 ml of tetrahydrofuran were added to a mixture of 4-amino-5-chloro-2-methoxybenzoic acid, 2.02 g (0.010 mole) and l,l -carbonyldiimidazole, 1.62 g (0.010 mole) with stirring. When evolution of carbon dioxide ceased, nitrogen was bubbled through the reaction mixture for 1 hr. A solution of 3-aminoquinuclidine, 1.26 g (0.010 mole) in 10 ml tetrahydrofuran was added dropwise to the stirred reaction mixture and stirring at room temperature continued for 3 hrs. TLC analysis (3% cone, ammonium hydroxide solution in methanol) showed some product formation. The mixture was heated at reflux temperature for 18 hours and then concentraded to an oil. TLC analysis showed the presence of the product, imidazole and 3-aminoquinuclidine. The oil was dissolved in methylene chloride (75 ml) and washed twice with 50 ml portions of aqueous sodium bicarbonate solution. The methylene chloride layer was dried over anhydrous magnesium sulfate and concentrated to yield 2.0 g (67%) of a glassy amorphous solid, the free base of the title compound. 

Cerium(IV) ammonium nitrate in aqueous acetonitrile is an alternative oxidant for the cleavage of p-methoxybenzyl ethers.335 Compared with DDQ, it is seldom used336 337 but there are circumstances where it will work when DDQ fails. A case in point is shown in Scheme 4.182.338 The ditosylate 182.1 underwent oxidative hydrolysis in the usual way with DDQ to give the alcohol 18U in 80% yield but attempts to deprotect the monotosylate 182.3 failed under the same conditions. However, with CAN, the monotosylate gave the desired diol 182.4 in 30% yield together with the p-methoxybenzoate 1825 in 24% yield. 

The method of choice for the preparation of the 1,4-dihydro compound (99) therefore entails reduction of (95) with lithium in ammonia in the absence of alcohol, followed by quenching with ammonium chloride. Acid (99) is also susceptible to rearrangement under acidic conditions, however, and the isomer (100) is formed at pH 4-5 (conditions which might readily prevail during the isolation procedure). 3-Methoxybenzoic acid (95) undergoes reductive alkylation at C-1 without difficulty, and has been used extensively in synthesis. 

The variable loss of the methoxy substitutent is in fact a feature common to most 2-methoxybenzoic acid derivatives and appears to stem from the ammonium ions which are generated on mixing of the acid with ammonia. Pretreatment with one equivalent of base prevents hydrogenolysis completely in most cases, although the reduced solubility of the carboxylate salt can lead to incomplete reduction. Potassium salts are reasonably soluble, but reduction of the benzoate esters may afford the best solution (see Section 3.4.3.T). 

Preparation from 2-iodophenyl 2-methoxybenzoate by treatment with n-butylUthium in a mixture of ethyl ether, hexane and tetrahydrofuran at -70° for 2 h, followed by treatment with saturated aqueous ammonium chloride (93%) [58]. 

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