Benzoic acid derivatives, synthesis

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

In another application, the group of Berteina-Raboin demonstrated the solid-supported synthesis of the indole core of melatonin analogues under microwave irradiation (Scheme 7.6) [26]. A benzoic acid derivative was coupled to Rink amide resin by... 

Synthetic applications of the asymmetric Birch reduction and reduction-alkylation are reported. Synthetically useful chiral Intermediates have been obtained from chiral 2-alkoxy-, 2-alkyl-, 2-aryl- and 2-trialkylsllyl-benzamides I and the pyrrolobenzodlazeplne-5,ll-diones II. The availability of a wide range of substituents on the precursor benzoic acid derivative, the uniformly high degree of dlastereoselection in the chiral enolate alkylation step, and the opportunity for further development of stereogenic centers by way of olefin addition reactions make this method unusually versatile for the asymmetric synthesis of natural products and related materials. 

The first asymmetric total synthesis of (+)-lycorine is outlined in Scheme 15. While our earlier applications of the Birch reduction-alkylation of chiral benzamide 5 were focused on target structures with a quaternary stereocenter derived from C(l) of the starting benzoic acid derivative, the synthesis of 64 demonstrates that the method also is applicable to the construction of chiral six-membered rings containing only tertiary and trigonal carbon atoms. s... 

Let us consider the synthesis of flavone 9.19, which is the parent of a large series of natural products. Disconnection of the carbon-oxygen bond in the usual way results in enol 9.20 which exists as 1,3-diketone 9.21. This 1,3-dicarbonyl relationship can be exploited in the classical manner yielding orf/m-hydroxyacetophenone 9.22. The synthetic problem centres on methodology for the C-benzoylation of the enolate derived from 9.22 with some activated benzoic acid derivative 9.23. 

The synthesis of 2-aryl-l,3,4-oxadiazoles can be accomplished using (N-isocyanoimino)triphenylphosphorane 172 with benzoic acid derivatives in a clean reaction under mild conditions <07TL1549>. 

This is an example of the Pinner imino ether synthesis (1). In the presence of an aqueous medium, the intermediate is hydrolyzed to the benzoic acid derivative. 

Several C-alkylpurines have been prepared by the Traube protocol. However, metalation and cross-coupling reactions are now also used for the synthesis of C-alkylpurines. 8-Alkyl- and 8-arylpurines are, generally, prepared by the same methods used for unsubstituted derivatives. Acetic or benzoic acid derivatives, such as triethyl orthoacetate, are used as condensation reagents and cyclization normally requires prolonged heating of the reaction mixture. Fusion of the components is also employed. 

Synthesis of 2-monosubstitutedamino-azido-benzoic acid derivatives... 

From a commercial point of view, organic halides are in principle a less attractive feedstock for the synthesis of alkanoic or benzoic acid derivatives compared with alkenes or toluenes, which can lead to the corresponding acids via hydroformyla-tion and oxidation, hydrocarboxylation, or direct air oxidation, respectively. Thus, apart from methanol, an economically viable carbonylation of C-X compounds is restricted to the synthesis of higher-value fine chemicals in cases where alternative starting materials are not easily accessible, e. g., phenylacetic acid derivatives (cf. Section 2.1.2.1). 

Enantiopure l,2-cis-dihydroxycyclohexa-3,5-diene carboxylic acids have considerable synthetic potential as building blocks in chiral synthesis. Such cis-diols can be produced from benzoic acid derivatives by the action of toluate- 1,2-dioxygenase of Pseudomonas putida mt-2125 or homologous enzymes of a different origin (Fig. 16.6-... 

Chand P, Babu YS, Bantia S, Chu NM, Cole LB, Kotian PL, Laver WG, Montgomery JA, Pathak VP, Petty SL, Shrout DP, Walsh DA, Walsh GW. Design and synthesis of benzoic acid derivatives as influenza neuraminidase inhibitors using structure-based drug design. J Med Chem 1997 40 4030-4052. 

It is fortunate that the ortho acid chloride is the major product in the chlorosulfonation because it is needed in the synthesis of saccharin, the first of the non-fattening sweeteners. The formation of the sulfonamide is like that of an ordinary amide, but the oxidation of the methyl group with potassium permanganate is probably new to you. It s a rather vigorous reaction, but one which very usefully turns toluene derivatives into benzoic acid derivatives. 

Mechanosynthetic protocol optimized for sulfonylureas was also applied to preparation of antidiabetic drug glibenclamide 216 (Scheme 3.55). Synthesis was carried out in two reaction steps first, coupling of benzoic acid derivative 212 and p-(2-aminoethyl)... 

The simplest aromatic carboxylic acid is benzoic acid. Derivatives are named by using numbers and prefixes to show the presence and location of substituents relative to the carboxyl group. Certain aromatic carboxylic acids have common names by which they are more usually known. For example, 2-hydroxybenzoic acid is more often called salicylic acid, a name derived from the fact that this aromatic carboxylic acid was finst obtained from the bark of the willow, a tree of the genus SaEx. Aromatic dicarboxylic acids are named by adding the words dicarboxylic acid to benzene. Examples are 1,2-benzenedicarboxyhc acid and 1,4-benzenedicar-boxylic acid. Each is more usually known by its common name phthahc acid and terephthalic acid, respectively. Terephthahc acid is one of the two organic components required for the synthesis of the textile fiber known as Dacron polyester (Section 16.4B). 

It is also worth pointing out that water is a necessary evil since it also converts the aryl iodide into its benzoic acid derivatives, necessitating 4 equiv of Arl to achieve reasonable yields of 1. Nonetheless, this is a highly efficient method for the synthesis of a wide variety of butenolides in one step starting from readily available materials. 

Reaction Procedure (Scheme 2.158) Synthesis of isocoumarin. 2-Iodo-benzoic acid derivative (2.0 mmol) and CS2CO3 (4.0 mmol) were added to a vial containing anhydrous DMSO (8 mL), followed by addition of the appropriate acetylene derivative (2.2 mmol) and Cul (0.2 mmol). The suspension was stirred for 12 h at 100 °C. After cooling, the mixture was poured into the EtOAc (50 mL) and washed with water (2x25 mL) and brine (2x25 mL), then dried over Na2S04. Evaporation of the solvent under reduced pressure provided the crude product, which was purified by column chromatography (hexane-EtOAc, 20 1) or re-crystallized from hexane to afford the final product. 

A similar approach was applied for the synthesis of benzoic acids derived from the closo-dodecaborate [45], cZoio-decaborate [43], and cobalt bis(dicarbollide) [46,47] anions. 

Mahiwal, K.. Kumar, R, 8c Narasimhan, B. (2010). Synthesis, antimicrobial evaluation, ot-QSAR and mt-QSAR studies of 2-amino benzoic acid derivatives. Medicinal Chemistry Research, 1 https //springerlink3.metapress.com/content/ v8rr537t3g832716/resource-secured/ target=full text.pdf8csid=hgvns0moaos2mq3vea5ali2b8csh= www.springerlink.com... 

SCHEME 3.76 Synthesis of 0-methyl hydroxamates from benzoic acid derivatives [81]. 

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