3- Iodobenzoic acid 3- iodobenzoate

The 2-iodobenzoate is introduced by acylation of the alcohol with the acid (DCC, DMAP, CH2CI2, 25°, 96% yield) it is removed by oxidation with CI2 (MeOH, H2O, Na2C03, pH > 7.5). ... 

Iodobenzoic acid [88-67-5] M 248.4, m 162 , pK 2.93. Crystd repeatedly from water and EtOH. Sublimed under vacuum at 100°. 

Iodosalicylic acid (2-hydroxy-5-iodobenzoic acid) [119-30-2] M 264.0, m 197 pKj 2.65, pK 13.05. Crystd from water. 

The cyclization of o-halogenobenzoic acids with copper acetylides mainly leads to the formation of five-membered lactones (66JOC4071 69JA6464) (Scheme 115). Only in the case of the reaction of o-iodobenzoic with CuC=C—n-C3H7 does the formation of a mixture of y- and 5-lactones occur (Scheme 116). 

Cyclocondensation of 2-chloronicotinic acid with 2-amino-5-iodobenzoic acid and methyl 2-amino-4-bromobenzoate in boiling EtOH in the presence of cone. HCl for 18 h gave the 2-iodo and 3-bromo derivatives of 11-0X0-1 l/f-pyrido[2,l-6]quinazoline-6-carboxylic acid (98MIP1, 98MIP2, 99USP5908840, 99USP5914327). 

Ullman condensation of m-trifluoromethylaniline (13) with o-iodobenzoic acid in the presence of copper-bronze affords flu-fenamic acid (14). An analogous reaction of o-chlorobenzolc acid with 2,3-dimethylaniline (15) gives mefenamic acid (16) meclofenamic acid (18) is obtained by Ullman condensation employing 2,6-dlchloro-3-methylaniline (17). 

Ullmann condensation of the sodium salt of p-chlorothiophe-nol (31) with 2-iodobenzoic (32) acid gives 33. Cyclization by means of sulfuric acid affords the thioxanthone, 34. Reaction with the Grignard reagent from 3-dimethylaminopropyl chloride affords the tertiary carbinol (35). Dehydration by means of acetic anhydride affords chlorprothixene as a mixture of geometric isomers, 36. (Subsequent work showed the Z isomer-chlorine and amine on the same side—to be the more potent compound.) Chlorprothixene is said to cause less sedation than the phenothiazines. ... 

The ketone 15 was eventually prepared by Grignard addition to Weinreb amide 21, as shown in Scheme 5.5. The Weinreb amide 21 was prepared from p-iodobenzoic acid (20). The phenol of readily available 3-hydroxybenzaldehyde (22) was first protected with a benzyl group, then the aldehyde was converted to chloride 24 via alcohol 23 under standard conditions. Preparation of the Grignard reagent 25 from chloride 24 was initially problematic. A large proportion of the homo-coupling side product 26 was observed in THF. The use of a 3 1 mixture of toluene THF as the reaction solvent suppressed this side reaction [7]. The iodoketone 15 was isolated as a crystalline solid and this sequence was scaled up to pilot plant scale to make around 50 kg of 15. 

The nucleophilic displacement of the iodine moiety in 2-iodoben-zoates mediated by triphenyltin hydride and di-n-butyltin dichloride in aqueous solution has been demonstrated (Eq. 6.16).33 For example, 2-iodobenzoic acid reacts with a toluene solution of Ph3SnH/l,3-(N02)2 C6H4/aq. NaHC03 to give 89% yield of salicylic acid. 

Recently, iodobenzoates anchored onto an ionic liquid support (6.4) were coupled to various aryl boronic acids (6.5) in aqueous media using Pd(OAc)2 as the catalyst at 80°C to give the coupled product 6.6 (Scheme 6.3). Compounds 6.6 were purified simply by washing the reaction mixture with ether, which removed the unreacted starting materials and the side product 6.7 without the need of chromatography. Compounds 6.6 were then cleaved from the ionic liquid support... 

Reaction of the sodium salt of 2 with 2-iodobenzoic acid results in formation of the corresponding bis-arylsulfide via nucleophilic aromatic substitution. 

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