SYNTHESIS 2-methoxybenzoic acids

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

Liu and Larock reported a new total synthesis of mukonine (11) starting from commercially available 4-amino-3-methoxybenzoic acid (1570) (897). This method... 

N-arylation has been used as the first step in several syntheses of complex molecules. The Ullmann-type reaction of 2-iodo-3-methoxybenzoic acid with l-methylpiperazine-2,5-dione forms the basis of Kishi s total synthesis of dehydrogliotoxin (81T2045) (Scheme 12). 

Dicamba or 3,6-dichloro-2-methoxybenzoic acid Chlorobenzoic acids Affect cell membrane and RNA synthesis, absorbed through leaves and soil for broad leaves, brushes Cereals, pastures, range land 11-4... 

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. 

Hamilton, R. J., Mander, L. N., Sethi, S. P. Improved methods for the reductive alkylation of methoxybenzoic acids and esters. Applications to the synthesis of bicyclic ketones. Tetrahedron 1986, 42, 2881-2892. 

There are a number of organic acids that interfere with plant metabolism. Dicamba (3,6-dichloro-2-methoxybenzoic acid) and tricamba are herbicides which interfere with protein synthesis, while picloram (4-amino-3,5,6-trichloro-2-pyriidinecarboxylic acid) interacts with nucleic acid synthesis in susceptible plants. Dicamba is primarily eliminated in the urine due to its hydrophilic properties. Some benzonitrile derivatives are also employed as herbicides, including dichlobenil (2,6-dichlorobenzonitrile), bromoxynil (3,5-dibromo-4-hydroxybenzonitrile), and ioxynil. Linuron (N -(3,4-dichlorophenyl)-N-methoxy-N-methylurea) is a phenyl urea while trifluralin (a,a,a-trifhiro-2,6-dinitro-N,N-dipropyl-p-toluidine) is a dinitroaniline. The major concern with the substituted ureas is induction of hepatic microsomal enzymes which could modulate the disposition of simultaneously exposed chemicals metabolized by the same enzymes. Finally, one of the most common herbicides presently in use is glyphosphate, or Roundup , a phospho-... 

A conventional synthesis of tecleanthine (50) has been executed. Ullmann reaction of 2-amino-3-methoxybenzoic acid with 3-methoxy-4,5-methylene-dioxyiodobenzene gave the diphenylamine (49). Compound (49) was converted by cyclization (POCI3), hydrolysis (HCl), and methylation into tecleanthine (50). The Ullmann condensation was also used to prepare the natural acridones (48 R = R = R = R = OMe) and xanthoxoline (48 R = OH, R = R = R = H, iV-demethyl). The corresponding 9-thioketones were also synthesized. 

This procedure has been applied to the synthesis of mukonine (201) (Scheme 53) [212]. The o-iodoaniline 222 was prepared in two steps from commercially available 4-amino-3-methoxybenzoic acid. Reaction of compound 222 with the silylaryl triflate 220a in the presence of cesium fluoride leads to an intermediate diarylamine, which is cyclized in situ by addition of catalytic amounts of palladium(II) acetate and tricyclohexylphosphane to afford mukonine (201) (three steps and 76% overall yield). 

The synthesis is outlined as follows gallic acid3,4,5-tri-methoxybenzoic acid — methyl ester of the 3,4,6-trimethoxybenzoic acid — 3,4,5-trimethoxybenzyl alcohol 3,4,5-trimethoxybenzyl chloride - 3,4,5-trimethoxyphenylacetonitrile — mescaline. The reduction of the methyl ester and of the nitrile has been achieved using lithium aluminum hydride. 

The Elbs persulfate oxidation procedure was used by Bach and cowoikers at an early stage of their synthesis of model compounds related to ftedericamycin A. Thus the phenol (59) gave 2,S-dihydroxy-4-methoxybenzoic acid (60) in modest yield (30%). This was then transformed in several steps to the isobenzofutanone (61). Gmeration of the isobenzofuran (62) in situ and Diels-Alder reaction of this with the enedione (63) gave, after loss of die trimethylsilyl group, the desired compound (64 Schone 23) in 62% yield from the isobenzofiiranone (61). 

NMR spectra. See also nuclear magnetic resonance spectroscopy chemical shifts, 573-574 interpretation, 571-573 spin-spin coupling, 574-576 IMS, 582 halide ion, 637 haloform reaction, 403-408 benzoic acid synthesis, 405-406 p-methoxybenzoic acid, 406-407 semimicroscale preparation, 407 08 halogenation... 

Propose a synthesis for 3,5-dichloro-2-methoxybenzoic acid starting from phenol. 

Pellepiphyllin (600), 2-hydroxy-3,4 -dimethoxybibenzyl, has been isolated from Pellia epiphylla (Metzgeriales) 84). Later, Benesova et al. 85) reported that (600) was absent in P. epiphylla and present in P. neesiana. The positions of the substituents were determined by isolation of p-methoxybenzoic acid after oxidation of the monoethoxy derivative of (600) and of 2-acetoxy-3-methoxybenzoic acid from the monoacetoxy derivative of (600). Structure (600) was confirmed by synthesis as outlined in Scheme 72 155). 

The synthesis of one- and two-dimensional polymers has been achieved by Wang et al. via the self-assembly of dicarboxylic acids with trimethyltin chloride. Scheme 55 shows the synthesis of a two-dimensional sheet polymer (223) consisting of dimeric dicarboxylato-telra-organodistannoxane secondary building blocks via reaction of diphenic acid (220) with trimethyltin chloride (221) under hydrothermal conditions. The synthesis of a rhombohedral grid polymer with te/ni-organodistan-noxane units has also been synthesized by reaction of 4-hydroxy-3-methoxybenzoic acid with trimethyltin chloride. ... 

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>. 

A concerted elimination-cyclization mechansim, involving a sulfenyl halide in a 1,3-butadiene-1-thio system, is the most probable mechanism for the formation of benzo[6 Jthiophenes from cinnamic acids or 4-aryl-2-butanones by treatment with thionyl chloride. The reactions shown in Scheme 5 have been carefully worked out, and the intermediates isolated (75JOC3037). The unique aspect of this synthesis is the reduction of the sulfinyl chloride (a) by thionyl chloride to form the sulfenyl chloride (b). The intermediate (b) was isolated and converted in pyridine to the 3-chlorobenzo[6]thiophene-2-carbonyl chloride in 36% yield (73TL125). The reaction is probably initiated by a sulfenyl ion attack on the aromatic ring, since it is promoted by electron-releasing groups para to the site of ring closure. For example, when X in (36) was N02, a 23% yield of (37), a mixture of 5-and 7-nitro derivatives, was obtained, but when X in (36) was OMe, a 54% yield of (37) was obtained, contaminated with some 3,4-dichloro-5-methoxybenzo[6]thiophene-2-carboxylic acid. 

In many cases, the trimethoxybenzoyl group has been introduced into synthetic methyl reserpate as the last or second-to-last step. An optimal yield of 72% of reserpine is reported if a 50% excess of the acid chloride is used (190, 193), the yield diminishing as the amount of acylating agent is increased. In the French synthesis, acylation is carried out with tri-methoxybenzoic anhydride in triethylamine and pyridine (185). 

Vicenzi, J.T. Zhang, T.Y. Robey, R. L. Alt, C. A., Application of Heterogeneous Acid Catalysts to the Large-Scale Synthesis of 2- and 3-(p-Methoxyphenyl)-6-methoxybenzo[6]thiophenes. ... 

The first synthesis modelled on biomimetic lines was directed to obtaining anacardic acids by way of polyketides [237] and later to a (17 l)-orsellinic acid [43]. A less complicated approach based on the Michael addition of ethyl acetoacetate and ethyl octadec-2-enoate, has led to a C15 orsellinic acid, Fig (4)-56, 2,4-dihydroxy-6n-pentadecylbenzoic, considered to be the biogenetic precursor of the cashew phenols [238], notably cardol, by decarboxylation. The use of bromine at the aromatisation stage in this synthesis precluded the extension of the method to components with unsaturated side-chains, although bromination with copper(ii)bromide and thermal debromination offers an alternative procedure. In a more recent approach, by the use of an oxazole intermediate and its addition to ethyl acetoacetate, (15 0) and (15 1) anacardic acid have been obtained [239] as shown in Scheme 5a, b. The 8(Z),1 l(Z)-diene and 8(Z),1 l(Z),14-triene have also been synthesised [240] by way of ethyl 6-(7-formylheptyl)-2-methoxybenzoate (C), prepared from acyclic sources, rather than, as in previous work, by semisynthesis from the ozonisation of urushiol. 

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