3-Hydroxy-5- benzoic acid, synthesis

The constitution of carvestrene has been determined, subject to the limitation above referred to as to the constitution of isocarvestrene, by the masterly synthesis achieved by W. H Perkin, Jr., and his colleagues. The starting-point of this synthesis was t-hydroxy-benzoic acid, which was reduced by sodium and alcohol to cyclohexanol-3-carboxylic acid, of the formula—... 

Scheme 7 Synthesis of HPOA and its polycondensation with para hydroxy benzoic acid.

Suggest syntheses for TMs (9) and (10) needed as intermediates TM (9) in the synthesis of brominated hydroxy benzoic acids and TM (10) in the synthesis of model compounds for studying biological mechanisms of ester hydrolysis,... 

It is an interesting fact that if potassium phenolate is used in the Kolbe synthesis para-hydroxy benzoic acid is obtained, especially at high temperatures. Potassium phenyl carbonate is first formed, and heated up to 150° yields salicylic acid, but if the temperature be further raised, the para-acidis produced in increasing quantities until at 220° potassium para-hydroxy-benzoic acid is the sole product. 

Synthesis from meta- or para-Hydroxy Benzoic Acid.—The constitution is proven by its synthesis by sidphonation and then alkali fusion of either meta-hydroxy benzoic acid or para-hydroxy benzoic acid. As this synthesis introduces into each of these acids first a sulphonic acid group and then in place of this a second hydroxyl group the two hydroxyls in the final product, protocatechuic acid, must be in the 3-4 positions as only such positions could be occupied in a product obtained from either the meta or para hydroxy benzoic acid. 

H. R. Kricheldorf and A. Conradi, New polymers synthesis 16. LC-copolyesters of 3(4-hydroxyphenyl) Propionic Acid and 4-hydroxy benzoic acids, Journal of Polymer Science Part A Polymer Chemistry, 25, 489 (1987). 

Full details have been given concerning the synthesis of die amino-anal< e 59 of Dalqi, an intermediate in the variant of the shikimate pathway leading to 3-amino-S-hydroxy-benzoic acid (see Vol. 26, p.l70).56... 

Yerlikaya Zekeriya, Aksoy Serpil, Bayramli Erdal. (2002). Synthesis and Melt Spinning of Fully Aromatic Thermotropic Liquid Crystalline Copolyesters Containing m-hydroxy-benzoic Acid Units. J. Appl. Polym. Sci, 85(12), 2580-2587. 

A consideration of the biosynthesis of p-aminobenzoic acid (PABA) involves primarily the mechanism of formation of the ring structure of aromatic compounds. Studies with mutants of E. colt indicated that shikimic acid (Fig. 3) was the precursor of the aromatic ring as occurring in PABA and also in tyrosine, tryptophan, phenylalanine, and p-hydroxy-benzoic acid (12). Much is now known about the manner in which kimic acid is formed from intermediates of carbohydrate metabolism (IS, ISa). Certain E. colt mutants also accumulate shikimic acid-5 -phosphate (ISb). Recent work of Weiss and Srinivasan (13c) demonstrated that PABA could be formed from shikimic acid-5 -phosphate and L-glutamine in an enzyme system derived from baker s yeast. Free shikimic acid was utilized very poorly for PABA synthesis but was more active when incubated in the presence of ATP. Glutamine was a specific amino donor and could not be replaced by glutamic acid or asparagine. When uniformly C -labeled shikimic acid was used as substrate for PABA synthesis in the enzyme system, the PABA formed had the same molar specific activity as the initial shikimic acid 5 -phosphate. PABA synthesis was also dependent on small amounts of yeast or liver concentrates but the nature of the cofactor and the mechanism of the over-all reaction are not known. 

Despite the great industrial value of the formation of a C-C bond using CO2, the only industrial application is represented by the synthesis of 2(or 4)-hydroxy-benzoic acid, known for more than a century (Kolbe Schmitt reaction [lb]). This reaction has been reconsidered [57] using other substrates such as 1- and 2-naphthol or hydroxypyridines. 

Benzoic and hydroxybiphenyl carboxylic acids are widely used in the synthesis of drugs, biologically active compounds, and heat-resistant polymers. The known methods for preparation of aromatic hydroxy carboxylic acids include many stages, require not easily accessible starting compounds, and provide poor summary yields of the target products. 

Sulfasalazine. Salicylazosulfapyridine or Azulfadine [599-79-1] (2-hydroxy-5-[[4[(2-pyridylamino)sulfonyl]-phenyl]azo] benzoic acid) (15) is a light brownish yellow-to-bright yellow fine powder that is practically tasteless and odorless. It melts at ca 255°C with decomposition, is very slightly soluble in ethanol, is practically insoluble in water, diethyl ether, chloroform, and benzene, and is soluble in aqueous solutions of alkali hydroxides. Sulfasalazine may be made by the synthesis described in Reference 13. It is not used as an antidiarrheal as such, but is indicated for the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn s disease. Its action is purported to result from the breakdown in the colon to 5-aminosalicylic acid [89-57-6] (5-AS A) and sulfapyridine [144-83-2]. It may cause infertility in males, as well as producing idiosyncratic reactions in some patients these reactions have been attributed to the sulfa component of the compound. The mechanism of 5-ASA is attributed to inhibition of the arachidonic acid cascade preventing leukotriene B4 production and the ability to scavenge oxygen free radicals. The active component appears to be 5-aminosalicylic acid. 

Only para coupling was observed during the alkaline ferricyanide oxidation of 4-hydroxy-3-(3-hydroxybenzoyl)benzoic acid. 7-Hydroxy-9-oxoxanthene-2-carboxylic acid (515) was obtained in 21% overall yield from methyl 4-hydroxybenzoate (78JCS(P1)876). The synthesis utilizes a photochemical Fries rearrangement of methyl 4-(3-methoxybenzoyloxy)benzoate to prepare the benzophenone (514 Scheme 189). A similar route was used to prepare 2-hydroxy-2 -methoxybenzophenones, which undergo intramolecular cyclization with loss of methanol on treatment with base. 

Non-tryptamines.—Glycozoline (1) has been very simply synthesized by the thermal cyclization (350 °C) of 4 -methoxy-4-methyldiphenylamine in the presence of iodine.2 Details of the syntheses of girinimbine and mahanimbine have now been published,3 and the method used in the synthesis of the latter has been extended to the synthesis of ( )-isomahanimbine (2) thus, condensation of 2-hydroxy-6-methylcarbazole with citral in pyridine containing a trace of benzoic acid gave... 

A diastereoselective epoxidation of a tetrasubstituted double bond was accomplished with mCPBA in the total synthesis of (-)-21-isopentenylpaxilline by A.B. Smith et al." The tetracyclic lactone substrate containing the tetrasubstituted double bond was exposed to mCPBA in toluene at room temperature. The reaction mixture also contained sodium bicarbonate to neutralize the by-product m-chloro benzoic acid. The epoxidation exclusively took place from the less hindered a-face of the molecule. At a later stage, this epoxide was converted to the y-hydroxy enone moiety present in the natural product. 

Addition to C=0. Hydrates of a-ketoaldehydes react selectively at the aldehyde group with allylsilanes under the influence of YbfOTfjj at room temperature. The allylation of aldehydes with allylstannanes is accelerated by benzoic acid." Another method for the synthesis of homoallylic alcohols is by the ene reaction, thus y,6-unsaturated a-hydroxy esters are obtained from glyoxylic esters at room temperature in a catalyzed process. ... 

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