Benzoic acids, synthesis

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... 

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]. 

We have noted above (Sect. 8.3) that certain substituted benzoic acids have been used in the synthesis of endolipophilic cryptands but it is the glycerol and penta-erythritol units which have been used most commonly in this application. These are discussed separately, below. 

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.

The synthesis of 1 -benzothiepin 1 -oxide (23) can be achieved via complex formation with tricarbonyl iron, and quantitative oxidation of the coordination compound 22 with 3-chloroperoxy-benzoic acid. Subsequent irradiation at — 50 C provides 23, which crystallized as yellow needles after low-temperature (-40 C) chromatography, and was characterized by 1H NMR spectroscopy at — 30 C23 before loosing sulfur within one hour at 13°C to give naphthalene. 

A low stereoselection is also reported for an Ugi reaction which is the central step in the total synthesis of the antibiotic ( + )-furanomycin80. The carbohydrate-derived intermediate, formed from the following acetal and (+ )-a-methyIbenzylamine, reacts with benzoic acid and tert-butyl isocyanide to deliver the precursor 2 of the antibiotic and its diastcreomer 3 in equal amounts80. 

Hydroxyphenylpyruvic acid plays an important role in the biogenesis of compounds with a phenylpropane skeleton, and it has been used as substrate in several enzyme studies. Published procedures for its preparation are unsatisfactory in many ways. The alkaline hydrolysis of the azlactone of a-bcnzoylamino- -acetoxycinnamic acid 7 makes necessary a tedious separation of the resulting benzoic acid, and the yield is only 34% based on -hydroxybenzaldehyde. The hydrolysis of 5- ( -hydroxybenzal)-3-phenylhydantoin 9 requires a separation of phenylurea. Finally, the two-step cleavage of the azlactone of a-acetamino- -acetoxycinnamic acid 8 does not proceed easily, and impure products are obtained. In applying this procedure to the synthesis of a carboxyl-labeled -hydroxyphenylpyruvic acid, the overall yield was only 9%.u It must be kept in mind that any prolonged isolation procedure will cause some decomposition of this sensitive compound. 

SYNTHESIS OF ORTHO SUBSTITUTED ARYLBORONIC ESTERS BY IN SITU TRAPPING OF UNSTABLE LITHIO INTERMEDIATES 2-(5,5-DIMETHYL-l,3,2-DIOXABORINAN-2-YL)BENZOIC ACID ETHYL ESTER... 

Fig. 24 Solid-phase synthesis of 5-carboxamido-iV-acetyltriptamine. Reagents and conditions a piperidine 20%, DMA, rt, 60 min b 4-amino-3-iodo-benzoic acid, TBTU, HOBT, NEt3, DMAP, dioxane, MW 45 W, 3 min, 100%, open vessel c N-(4-Trimethylsilanyl-but-3-ynyl)-acetamide, Pd(OAc)2, PPhs, LiCl, NaOAc, DMA, MW 60 W, 2x13 min, 100%, open vessel d NIS, CH2CI2, MW 60 W, 14 min, 100%, open vessel e cleavage, TFA, 20%, CH2CI2, rt...

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,... 

In this way, the operational range of the Kolbe-Schmitt synthesis using resorcinol with water as solvent to give 2,4-dihydroxy benzoic acid was extended by about 120°C to 220°C, as compared to a standard batch protocol under reflux conditions (100°C) [18], The yields were at best close to 40% (160°C 40 bar 500 ml h 56 s) at full conversion, which approaches good practice in a laboratory-scale flask. Compared to the latter, the 120°C-higher microreactor operation results in a 130-fold decrease in reaction time and a 440-fold increase in space-time yield. The use of still higher temperatures, however, is limited by the increasing decarboxylation of the product, which was monitored at various residence times (t). 

The recent synthesis of (—)-tetracycline by Myers and co-workers incorporates a biocatalytic step in the first stage which oxidizes benzoic acid aerobically to an a,f)-dihydroxy derivative in the presence of a whole-cell mutant strain of Alcaligenes eutrophus. Figure 4.61 shows a reduced tree diagram for the synthesis and Table 4.28 summarizes the metrics parameters. 

Another examination involves a synthesis of thienobenzazepines based on the formation of key intermediate 6 prepared according to the method of McDowell and Wisowaty (Scheme 6.2). ° Selective reduction of this intermediate using zinc dust in 28-30% ammonia solution afforded the benzoic acid 7, which upon subsequent Curtius rearrangement and aluminum trichloride-mediated cyclization furnished the oxo-azepine 8. While this synthetic approach gave the tricycle in a few synthetic transformations, many of the same concerns as above exist when considering large scale preparation of 8 the use of large amounts of zinc, sodium azide, and aluminum trichloride. 

Phthalic anhydride condenses with the aniline derivative in the presence of zinc or aluminum chlorides to yield the intermediate benzoyl-benzoic acid, which subsequently reacts with l,3-bis-V,V-dimethylaniline in acetic anhydride to yield the phthalide. The above compound gives a violet-gray image when applied to a clay developer. Clearly this synthesis is also very flexible and variations in shades of color formers have been obtained by varying the aniline components and also by using phthalic anhydrides substituted, for example, by nitro groups or chlorine atoms. Such products have excellent properties as color formers and have been used commercially. Furthermore, this synthetic route is of great importance for the preparation of heterocyclic substituted phthalides, as will be seen later. 

The synthesis and characterization of tris-chelate Ir111 complexes of 2-(acetylamino)benzoic acid, 2-(benzoylamino)benzoic acid, 2-[(2-aminophenylamino)carbonyl]benzoic acid, maleanilic acid, malea-l-naphthalanilic acid, and 2-[(phenylamino)carbonyl]benzoic acid have been described.245... 

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... 

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