2- methoxybenzoate

C9H15NO2 112843-64-8) see Tropenziline bromide ej o-2-(6-methoxy-3,4-xylyl)bornane (CiijHjsO 31467-21-7) see Xibomol methyl 4-acetamido-5-bromo-2-methoxybenzoate (C, H (,BrN04 89481-86-7) see Bromopride methyl 4-acetamido-5-chloro-2-methoxybenzoate (C,iHijClNO 4093-31-6) see Clebopride Metoclopramide... 

The synthesis of longifolene in Scheme 13.30 commenced with a Birch reduction and tandem alkylation of methyl 2-methoxybenzoate (see Section 5.6.1.2). Step C is an intramolecular cycloaddition of a diazoalkane that is generated from an aziridinoimine intermediate. 

Instead of sodium nitrite, isoamyl nitrite is sometimes used as a nitrosating agent in synthesis of the benzotriazole ring. With this reagent, the reaction conditions are very mild allowing survival of acid sensitive groups. In an example of such a reaction, methyl 3,4-diamino-2-methoxybenzoate 1286 is treated with isoamyl nitrite at room temperature. The reaction is fast and provides methyl 4-methoxybenzotriazole-5-carboxylate 1287 in 62% yield, isolated by simple filtration off the precipitate (Equation 31) <2006JME4762>. 

To get a complex set of substituents by direct derivatization of benzotriazole is not feasible. In such situations, it is better to have all the substituents in place first and later construct the heterocyclic ring. High reactivity of anilines and their well-developed chemistry makes them good stating materials. In an example shown in Scheme 215, acetanilide 1288 is nitrated to afford nitro derivative 1289 in 73% yield. Catalytic reduction of the nitro group provides methyl 4-acetylamino-3-amino-5-chloro-2-methoxybenzoate 1290 in 96% yield. Nitrosation of compound 1290 in diluted sulfuric acid leads to intermediate 1291, which without separation is heated to be converted to 7-chloro-4-methoxy-l//-benzotriazole-5-carboxylic acid 1292, isolated in 64% yield <2002CPB941>. 

Methoxybenzoic acid, purchased from Lancaster Synthesis Ltd., was used as received. 

A. N,N-Diethyl-2-methoxybenzamide (2). An oven-dried, two-necked, 500-mL flask equipped with a septum cap, nitrogen bubbler, and magnetic stirrer is charged with 2-methoxybenzoic acid (20 g, 0.13 mol) (Note 1) under nitrogen. Thionyl chloride... 

Methoxybenzoic acid o-Anisic acid (8) Benzoic add, 2-methoxy- (9) (579-75-9) Thionyl chloride (8.9) (7719-09-7)... 

Dicamba (3,6-dichloro-2-methoxybenzoic acid) is primarily used as a postemergence broadleaf herbicide, which interferes with normal plant auxin function, subsequently causing uncontrolled growth and the inhibition of the phototropic and geotropic function. Cumulative response results in plant death. The success of auxinic analogues such as Dicamba and 2,4-dichloropheno-xyacetic acid in weed control has led to widespread manufacturing and use. Estimated U.S. production for Dicamba was 5 million kg in 1990 [391]. 

Other examples of secondary benzamides include the therapeutic class of orthopramides, which are, again, markedly resistant to hydrolysis. Thus, hydrolysis of the amide bond is a minor metabolic pathway in humans for the antiemetic drug metoclopramide (4.76) [49]. Clebopride (4.77), an anti-dopaminergic agent, was found to be hydrolyzed to a limited extent in rabbit liver homogenates and in dogs to 4-amino-5-chloro-2-methoxybenzoic acid (4.78) and to the amine 4.79 [48] [50], Attempts to detect in vivo formation of this metabolite in rats, rabbits, or humans were not successful [50],... 

The Birch reduction of derivatives of 2-methoxybenzoic acid followed by alkylation of the intermediate enolate is of even greater strategic value. The resulting chiral cyclohexa-... 

Lithiation of benzo[6]thiophene occurs exclusively at position 2, leading to good yields of 2-substituted products. 2-Methoxybenzo[6]thiophene is reported to be lithiated at position 3 this is the only known direct lithiation at the /3-position (70AHC(11)177). Competitive metallation of benzo[6]thiophene and N-methylindole affords only 2-benzo[6]thienyl-lithium. 

Hydroxybenzo[6]thiophenes exist as oxo tautomers and are referred to as thiooxindoles. O- Alkylation of thiooxindole is favoured in polar aprotic solvents thus NaH/HMPT/Me2S04 gives a 90% yield of 2-methoxybenzo[6]thiophene. Treatment of thiooxindole with two equivalents of NaOH and dimethyl sulfate, or... 

Chromones are readily oxidized by permanganate or dichromate with opening of the pyran ring and the formation of a salicylic acid (402). Flavones and isoflavones are also degradatively oxidized for example oxidation of munetone (403) with alkaline hydrogen peroxide yields 2-methoxybenzoic acid and 4-hydroxy-2-isopropylbenzofuran-5-carboxylic (isotubaic) acid. 

Salicylic acid derivatives serve a similar purpose to 2-hydroxyacetophenones in a number of chromone syntheses, acting as a precursor of the 1,3-diketone fragment. For instance, a Claisen reaction between methyl 2-methoxybenzoate and acetone takes place in the presence of sodium to give the diketone. Demethylation occurs on reaction with hydriodic acid with concomitant ring closure to the chromone (00CB1998). The corresponding naphthol derivatives are a source of benzochromones (52JOC1419). 

A variant of this method produces xanthones from 2-halogeno-2 -methoxybenzo-phenones, cyclization being brought about by pyridine hydrochloride (72BSF2948). 

Tetrahydrobenzo[6]thiophene103 and several benzo[6]thio-phenes containing electron-donating substituents, e.g., 5,6-dimeth-oxy,180 5,6-methylenedioxy,180 6-ethoxy,424 3-methoxy,183 and 3-methyl,487 are smoothly brominated in the 2-position by iV-bromo-succinimide in carbon tetrachloride or chloroform in the absence of peroxides. Similar treatment of 2-methoxybenzo[6]thiophene gives the 3-bromo derivative.183... 

Bromo-,54,81,294,302,337,483,512,513 and less frequently, chloro-benzo[6]thiophenes81 are readily converted into the corresponding nitriles by heating them with cuprous cyanide in a suitable solvent. 2-Bromobenzo[6]thiophene may be smoothly converted into 2-methoxybenzo[6]thiophene183 or 2-piperidinobenzo[6]thiophene406 by heating it with sodium methoxide in the presence of cupric oxide... 

Methoxybenzo[ >]thiophene may be prepared by treating 2-bromobenzo[6]thiophene with sodium methoxide it is metallated by n-butyllithium, and undergoes electrophilic substitution in the 3-position.183... 

Thiooxindole-3-carboxaldehyde reacts with diazomethane to give a mixture of 3-acetyl-2-methoxybenzo[6]thiophene and a compound for which two possible structures (215 or 216) have been proposed.573 The aldehyde is hydrolyzed by acids to thiooxindole.575... 

Acylation of 2- or 3-methoxybenzo[6]thiophene in the presence of boron trifluoride takes place in the free thiophene position183 concomitant demethylation may occur in the presence of aluminum chloride.272,666 Attempted acetylation of 3-bromo-2-methoxybenzo-... 

Carbonation of the lithium derivative of 2-methoxybenzo[6]thio-phene affords the corresponding 3-carboxylic acid.183 2-Methylbenzo-[6]thiophene-3-carboxylic acid has been obtained (45%) by carbonation of 2-benzo[6]thienylmethylmagnesium chloride (Section VI,D, 4).528 re-Butyllithium reacts selectively with the bromine atom in 3-bromo-2-fluorobenzo[b]thiophene to give a product, which on carbonation affords 2-fluorobenzo[6]thiophene-3-carboxylic acid.482 Benzo[6]thiophene-7-carboxylic acid is obtained by reduction of the corresponding thioindoxyl with amalgamated zinc and acetic acid.315 Benzo[6]thiophene-3-carboxylic acid and its 2-ethyl derivative have been prepared in high yield by treatment of the pyridinium salt of the 3-chloroacetyl derivative with alkali.132... 

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