Carboxylic acids deuterated, preparation

The DPE reduction is used as a test reaction to characterize the materials and optimize the preparation conditions of the catalyst. Since hydroaluminations can also be used for the synthesis of carboxylic acids, deuterated products, or vinyl halides via quenching with CO2, D2O or Br2 [44], the method is also a valuable organic synthesis tool. However, as compared with molecular catalysts like Cp2TiCl2 that are known to catalyze hydroaluminations [44], the titanium nitride materials described here are solid catalysts and can be separated by centrifugation. Moreover, they can be reused several times, which is an advantage as compared to molecular catalysts. 

It is noteworthy that labeling is often carried out by reactions that normally have only academic interest or that are preparatively unimportant because of their demands on money and labor. For example, one is hardly likely to prepare ethanol by reaction of diazoethane with carboxylic acid and subsequent hydrolysis of the resulting ester, yet this reaction has proved definitely useful5 for the synthesis of deuterated ethanol, in the sense ... 

In the a-position deuterated ( )-2-hydroxy carboxylates have been prepared in H20. Examples are (R)(2- H)-3-dimeAyl-2-hydroxypropanoic acid, (R)(2- H)-(2)-hydroxy-butanoic acid, (R)(2- H)-3-phenyl-2-hydroxypropanoic acid. 

Retinoic acid and other retinoid carboxylic acids, however, can be readily converted to derivatives that are suitable for gas chromatography. Many of these applications have used mass spectrometry for detection (see below). Diazomethane is used, at room temperature, to prepare the methyl esters without apparent isomerization. Pentafluorobenzyl esters of retinoic acid and its analogs have also been prepared for GC-MS (280) or HPLC-MS (281). Deuterated analogs of retinoic acid or other retinoid carboxylic acids have been used as internal standards, with mass spectrometric detection (88,282) (reviewed by Napoli [283] and by De Leenheer and Lambert [89]). The pentafluorobenzyl ester of a synthetic retinoid, Ro 13-7410, was analyzed by column switching the peak of interest from a SE54 colunm was cut to an OV 240 column, with subsequent detection by negative ion chemical ionization mass spectrometry (280). 

Cyclization occurs directly through catalysis by the acid liberated when a pyridine-2(lH)-thione is heated with an a-halo acid ester. The most convenient method for preparing the thiazole, however, seems to be the cyclization of (2-pyridinethio)acetic acids in acetic anhydride in the presence of pyridine. Without base catalysis the reaction is slow, which suggests a mixed anhydride intermediate. Mixed anhydride formation with ethyl chlorofor-mate in pyridine, or carboxyl activation by DCC in pyridine, gives the mesoionic product. The cyclization reaction and the chemical stability of the thiazole are adversely affected by a pyridine 6-substituent. The initially formed acylpyridinium salt (407) undergoes rapid tautomerization to the aromatic thiazole form equilibrium between the forms (407) and (408) is verified by rapid deuteration at C-2 (R1 = H) in AcOH-d (81H(15)1349). 

Sprinson and coworkers [30] conducted the methylmalonyl-CoA mutase reaction in deuterium oxide using a crude mitochondrial preparation. The presence of methylmalonyl-CoA epimerase insured that (1) all substrate molecules incorporated one atom of deuterium into position 2, and (2) in the course of the reaction the (2R)-epimer of methylmalonyl-CoA was continuously supplied by epimerization of the (25)-epimer, which was in turn generated by the enzymic carboxylation of propionyl-CoA. Alkaline hydrolysis of the product and subsequent purification furnished succinic acid which was mainly monodeuterated (70% 2H,-, 15% 2H2-labelled and 13% unlabelled species). A positive ORD curve revealed its (5) configuration indicating stereochemical retention for the AdoCbl-dependent rearrangement (Fig. 22). No plausible explanation could be offered for the formation of doubly deuterated and unlabelled species. Essentially the same results were later obtained with a highly purified mutase preparation from Propionibacterium sher-manii (J. Retey, unpublished). 

The labile bond is always the one perpendicular to the pyridine ring and combined ionic, polar, and hydrophobic interactions on the enzyme determine which conformer predominates. This is easily seen for example in the Newman projection of enzymatic decarboxylation. The conformation required for decarboxylation places the carboxyl group substantially out of the plane of the conjugated system. Consequently, the specificity of the reaction is manifested principally at this stage. For instance, enzymatic decarboxylation of amino acids occurs with retention of configuration and thus allows the preparation of optically pure a-deuterated amines if the reaction is carried out in heavy water (304). 

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