Benzophenone-2-carboxylic acid

Our principal target in P-450 mimics was the selective oxidation of saturated carbons directed by geometric control, not by intrinsic reactivity. In our first study, we examined selective geometrically controlled attack on aliphatic C-H bonds by photo-excited benzophenones [145]. In a process we labeled remote oxidation", photolysis of a long-chain ester 69 of benzophenone-4-carboxylic acid afforded insertion into CH2 groups far into the chain. 

Preliminary work dealing with UV irradiation of long-chain n-alkyl esters of benzophenone-4-carboxylic acid [9,10] allowed cyclic products to be obtained, thus suggesting the formation of intermediate di-radicals by intramolecular hydrogen abstraction (Scheme 3). 

The first example in which a temporarily tethered reagent was directed to attack unactivated C-H bonds remote from the tether point was a study of the products from photolysis of esters of benzophenone-4-carboxylic acid 1 carrying long-chain alkyl groups (Scheme 6-1) [31]. The n-tetradecyl ester was attacked over carbons 8-13, with half the... 

During a synthesis of the protein kinase C inhibitor Balanol. Lampe and co-workers77 found that deprotection of the tert-butyl ester 30.1 [Scheme 6.30] with trifluoroacetic or formic acid was accompanied by substantial quantities of a debenzylated by-product. The same side reaction accompanied thermolytic cleavage of the terf butyl ester in neutral solvents presumably due to add catalysis by the carboxylic acid product 30.2. Thermolysis in quinoline at 205 °C led cleanly to the desired benzophenone carboxylic acid 30.2 in 68% yield. 

Some benzophenone carboxylic acids such as (53) have been quaternlzed with amino alcohols and their aggregation behaviour has been studied. Amphiphilic derivatives of benzophenone carboxylic acid and myristlc acid have been converted to tertiary alcohols by their irradiation in micelles. 

Benzophenone Carboxylic acids Cetyl alcohol Dibutyl phthalate Ethanol Formaldehyde... 

Figure 5.6. Diagram illustrating typical autosampler precision vs. injection volumes. CCA, 4 -chloro-3 -sulfamoyl-2-benzophenone carboxylic acid, is a hydrolysis product tor chlorthalidone. Note that peak area precision increases (lower RSD) with larger injection volumes. This was caused by the finite sampling volume precision of the autosampler sampling syringe and stepper motor, which was about 0.01 pL for this particular autosampler. Reprinted with permission from reference 12. See the same reference for additional experimental details.

The reduction is general for a variety of substituted benzophenones Such substituents as CH3 OH, OCH3, F, Br. N(CH3)2, NO2. COOH, COOCH3, NHCOC Hreaction conditions and do not alter the course of the reduction Diarylmethanols are reduced to diarylmethanes under the same conditions and probably are the intermediates in the reduction of ketones [26] Triethylsilane also can be used as a reducing agent in trifluoroacetic acid medium [27J This reagent is used for the reduction of benzoic acid and some other carboxylic acids under mild condiUons (equation 14) Some acids (phthalic, sue cinic, and 4-nitrobenzoic) are not reduced under these conditions [27]... 

Dihydrobenzothiopyran-3-carboxylic acid derivatives are formed when 2-mercapto-benzophenone reacts with a,p-unsaturated carboxylates and nitriles in the presence of... 

Electron withdrawing substituents stabilize the benzo[c]furan system. l-Cyano-3-phenyl-benzo[c]furan (247) can be obtained from the benzophenone (246) (70TL707) as a crystalline solid. The carboxylic acid (248) could be isolated on base catalyzed hydrolysis of (247), while catalytic hydrogenation led to the l,3-dihydrobenzo[c]furans (249). 

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. 

Figure 7.30 (a) Microdensitometer records of a photographic plate showing the absorption of the triplet state of anthracene-9-carboxylic acid. Horizontal axis, wavelength in nm vertical axis, absorbance, (b) Oscilloscope trace of the absorption of the ketyl radical of benzophenone in ethanol, (c) Second-order plot of the decay kinetics against time t... 

The reaction can be accelerated by the use of sodium hydroxide or sulfonic or carboxylic acids [62] instead of pyridine. Other high-boiling solvents such as nitrobenzene, benzophenone, or naphthalene can be used instead of trichlorobenzene [36,37,63-66],... 

Fig. 8 Examples of benzophenone-containing A/BPs for labeling of kinases. D- pip (R)-piperidine-2-carboxylic acid, GABA y-aminobutyric acid...

This proposal was based on speculation that the work of Homer, L., andFemekess, H. Chem.Ber., 1961, 94, 712 (in which they showed that moderate yields of esters and ethers could be obtained by adding peracetic acid to benzophenone hydrazone in the presence of excesses of carboxylic acids and phenols) may provide a basis for a commercial process to DPM esters. 

Oxidative decarboxylation.1 Sodium hypochlorite is known to effect oxidative decarboxylation of a-hydroxy carboxylic acids to form ketones and C02, but a hydroxyl group is not essential since trisubstituted acetic acids are also subject to this oxidation. Thus triphenylacetic acid is oxidized by NaOCl to triphenylmethanol and benzophenone. In the presence of a phase-transfer catalyst, the rate is enhanced... 

Work on other halides is much more limited. Gera-dibromocyclopropanes give modest yields of alkoxycarbonylation with alkoxide bases419. Aryl iodides may be carbonylated by catalytic mixtures of Fe(CO)5-Co2(CO)8 predominantly to the carboxylic acids or predominantly to the benzophenones, depending upon conditions420. 

It has also been found that certain aldehydes, ketones and carboxylic acids esters form well defined products with nitric acid (Reddelien [5]). For example, bemzaldehyde with 60% nitric acid gives a colourless, unstable oil, and cinnamic aldehyde forms fairly stable white crystals, melting at 60-61°C, with 65% nitric acid. Acetophenone, benzophenone, fluorenone, phenanthrenoquinone and camphor give similar addition products. 

Depending on the substituents in (61) and on the concentration of the catalyst, however, other products may also subsequently be formed. In some cases, SbCl5-complexed primary intermediates of type (65) could even be isolated and characterized by NMR spectroscopy as well as by well-defined chemical reactions (81JA1789). Treatment of tetraphenyl-1,2,4-trioxolane (67) with antimony pentachloride or liquid sulfur dioxide, a mild Lewis acid, gave benzophenone and phenyl benzoate in a molar ratio of 1 1 (80JA288). The formation of the ester corresponds to that of the carboxylic acid from (61) via path A or path B. 

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