R-2-phenylpropionic acid

Acridine 94 and (R)-( — )-2-phenylpropionic acid (R)-95 formed the chiral 3 2 cocrystal 94 (/ )-95. Irradiation of these cocrystals gave enantiomeric products 96 and 98 as well as the diastereomeric product 97 through photodecarboxylative condensation, with all positive [a]j> values (Scheme 22) [94]. Similarly, the opposite handed cocrystal afforded 96-98 with negative [a] d values. In contrast, photolysis of a 1 1 solution of 94 and (/ )-95 in acetonitrile resulted injhe formation of racemic 96 and biacridane 99. 

The photoisomerisation kinetics and other properties of the 1 1 inclusion complexes formed between aromatic derivatives of norbomadiene and P-cyclo-dextrin have been measured." (S)- or (R)-2-Chloropropiophenone affords partially racemised (S)- or (R)-2-phenylpropionic acid respectively by a photo-induced rearrangement via what is probably an ion or radieal intermediate," and (Z)-N-substituted benzoyl-a-dehydrophenylalanines such as (7) are photo-isomerised to 1-azetidine derivatives (8) by a 1,3-acyl migration. Irradiation of 9,9 -bifluorene-9,9 -diol (9) gives a mixture of fluoren-9-one and spiro[9H-fluorene-9,9 (10 -H)-phenanthren]-10 -one (10) whose composition is solvent dependent with the more polar solvents favouring (10). Laser flash photolysis shows the presence of two transients, one of which can be identified with the 9-fluorenyl cation (11), and which originates from photoheterolysis of the diol (9). There is also evidence to support the view that unimolecular rearrange-... 

In contrast to the above cocrystals (Scheme 14), cocrystals 17-f and 17-g gave the corresponding hetero coupling products HNArH-R and NAr-R as major products (Scheme 16) [40]. This difference may be ascribed to their short Cl C2 (and Cl C3 ) distances (4.2-4.S A). For the cocrystal 17-g, the stereocenter in R-(-)-2-phenylpropionic acid (g) was retained to a certain extent in the course of the decarboxylative condensation. 

Figure 7.7. Electropherogramsof(A) aracemicmixtureof 2-phenylpropionicacid, (B) R(-)-2-phenylpropionic acid and (C) S(+)-2-phenylpropionic acid (using in all three experiments the MI capillary prepared using S(+)-2-phenylpropionic acid as template). Reprinted from Btii emann O, Freitag R, Whitcombe MJ et al. Comparison of polymer coatings of capillaries for capillary electrophoresis with respect to their applicability to molecular imprinting and electrochromamgraphy. J Chromatogr 1997 781 43-53. With permission from Elsevier Science.

In case of primary alcohol substrates, biooxidation can also proceed to the carboxylic acid, enabling a facile separation of the chiral products by simple extraction. Whole-cells of Gluconobacter oxydans were utilized to produce S-2-phenylpro-panoic acid and R-2-phenylpropionic alcohol in excellent yields and optical purities (Scheme 9.4) [46]. 

K. K. Wong, N. Kucharczyk, R. D. Sofia, Isolation and Identification of 3-Carbamoy-loxy-2-Phenylpropionic Acid as a Major Human Metabolite of Felbamate , Drug Metab. Dispos. 1993, 21, 710-716 V. E. Adusumalli, K. K. Wong, N. Kucharczyk, R. D. Sofia, Felbamate in vitro Metabolism by Rat Liver Microsomes , Drug Metab. Dispos. 1991, 19, 1135-1138. 

S)-(-)-2-Methyl-1 -butanol (GC purity > 99.5% [a]p -6.6 0.3° (ethanol, c 10) was purchased from Fluka Chemie AG. Esterification with (R)-(+)-3.3,3-trifluoro-2-methoxy-2-phenylpropionic acid (Mosher s acid)2 and subsequent fH and 19F NMR analyses at 300 MHz of the resulting ester showed an enantiomeric purity of (S)-(-)-2-methyl-1-butanol > 99%. 

C9H10O3 (R)-(-)-2-hydroxy-2-phenylpropionic acid 3966-30-1 32,41 1.1490 2 16917 C9H11NO 1-phenyl-1-propanone oxime 2157-50-8 18.00 1.0639 1... 

Several lactic acid derivatives were used by Gessner et al. for the determination of the enantiomeric purity of flavor substances such as chiral alcohols from natural sources. Diastereomeric 0-acetyl-, propionyl-, and hexanoyllactic acid esters of the chiral alcohols were separated by GLC (155). A report from the same laboratories described characterization of several chiral aroma substances that are S-lactones. The lactones were hydrolyzed to the corresponding hydroxy acids, and the acid moiety was esterified to the isopropyl ester. The remaining hydroxyl group was esterified with (R)-2-phenylpropionic add chloride or [30], and the diastereomeric derivatives were separated using preparative silica gel LC. The derivatives were also separated on an analytical scale by GLC (156). 

Rabbits that had been rendered uremic, by administration of uranyl nitrate, displayed an enantioselective decrease in the plasma protein binding of 2-phenylpropionic acid, the effect being more pronounced for the highly bound R-enantiomer (123). This behavior was repeated in a small group of uremic patients admmistered racemic flurbiprofen. The enantiomeric ratio of free (R) (S) flurbiprofen increased from 1.1 in healthy individuals to 1.4 in the uremic group (55). 

M. E. Jones, B. C. Sallustio, Y. Purdie, and E J. Meffin, Enantioselective disposition of 2-arylpropionic acid non-steroidal anti-inflammatory drugs. II. 2-Phenylpropionic acid binding, /. Pharmacol. Exp Ther., 238 288 (1986). R. A. O Reilly, W. E Trager, C. H. Motley, and W. Howald, Stereoselective interaction of phenylbutazone with (12C/13C) warfarin pseudoracemates in man, /. Cfm. Invest., 65 746 (1980). 

Figure 16.2-47. Resolution of racemic (R,S)-2-phenylpropionic alcohol with whole cells of Gluconobacter oxydans yielding (S)-2-phenylpropanoic acid and (R)-2-phenylpropionic alcohol.

At intervals (1 hr), small aliquots (0.2-0.3 mL) of the reaction mixture are withdrawn, acidified with a few drops of coned HCI (35%), and extracted with diethyl ether (2 mL). Then they are analyzed by GC (DB5 capillary column) both the amide and the acid derived from the reacting nitrile are present. After 4.5 hr, the product is 99% acid 3 (2-phenylpropionic acid). The checkers followed the hydrolysis by TLC analysis SiC>2 plates 4 1 hexane ethyl acetate short-wave UV detection R (acid) = 0.43, Rf (amide) = 0.61. 

Photolysis of solutions of C6o(OH)ig at low solute concentration leads to [C6o(OH)i8] by electron transfer from Me2C(OH) radicals or from hydrated electrons, and this has enabled the reduction potential of the C6o(OH)ig/ [C6o(OH)ig] couple to be estimated. The kinetics of the photoreduction of hexanal using RhCl(PMe3)2CO as catalyst have been measured and the feasibility of a photocatalytic synthesis of hexanol from pentane, CO, and H2 in the presence of rhodium complexes has been demonstrated. Irradiation of a chiral bimolecular crystal of acridine and R-(-)- or S-(+)-2-phenylpropionic acid induces photodecarboxylation followed by stereoselective condensation to give a mixture of three optically active products, and the 3-0-S-methyl dithiocarbo-nate derivatives of oleanolic and ursolic methyl esters have been used as models for the photodeoxygenation of alcohols. ... 

Figure 8 Electropherograms of (a) racemic 2-phenylpropionic acid, (b) R-(-)-2-phenylpro-pionic acid and (c) 5 -(+)-2-phenylpropionic acid (using in all three experiments the MIP coated capillary prepared with 5 -(+)-2-phenylpropionic acid as template (Fig. 7)). Mobile phase 50nunol NaH2P04 (pH 4.65). CEC capillary 43.5 cm x 100 pm ID, effective length 35 cm. Temperature 25°C. Pressure injection 3 s, 50mbar. Separation 10 kV. Detection 200 nm. (From Ref. 20.)...

Internal standard 2-phenylpropionic acid (16 (S), 18 (R)) Limit of detection 500... 

Arzoumanian reported the first example of the use of a metal catalyst bearing chiral ligands under phase-transfer conditions leading to optically active substances. The Pd-catalyzed carbonylation of a-methylbenzyl bromide 18 (Scheme 14) was carried out using 5 N NaOH and CH2CI2 at room temperature (r.t.) and 1 atm of pressure of carbon monoxide in the presence of Pd(dba>2, and a series of 2-substituted 3,1,2-oxazaphospho-lane 20 resulted in the formation of 2-phenylpropionic acid 19 with significant enantiomeric excess. 

Dynamic resolution reactions couple the in situ racemization of a starting material with a kinetic resolution, thereby providing a route for the conversion of both enantiomers of starting material into one enantiomer of product. However, there is an important caveat the reaction product must be essentially inert to racemization. In control studies, 2-phenylpropionic acid (224 R = H) has been shown to racemize only slowly when treated with DABCO (l,4-diazobicyclo[2.2.2]octane) in water-DMSO (1 19) at 40 °C, whereas its phenyl ester (224 R = Ph) treated similarly was almost completely racemized in 7h. This work led to a procedure employing Candida cylindracea lipase (CCL) in which D,L-2-phenylpropanoic acid underwent a promisingly efficient dynamic kinetic resolution (Scheme 40). ... 

A possible way to induce selectivity in the photodecarboxylation process could be through photosensitized reactions in the soHd state. In fact, when a two-component molecular crystal of phenanthridine and 3-indoleacetic acid is irradiated at low temperature (-70°C), 3-methyHndole is formed in high yield as the sole product by contrast, when the same reaction is carried out in acetonitrile solution, four products are obtained.Furthermore, irradiation of two-component molecular crystals of arylalkyl carboxylic acids with stoichiometric amounts of electron acceptor causes decarboxylative condensation between the two components with important selectivities. " Thus, irradiation of (S)-naproxen in a chiral crystal with 1,2,4,5-tetracyanobenzene produces a decarboxylated condensation product retaining the initial chirality." Photolysis of an enantiomorphous bimolecular crystal of acridine with the R or S enantiomer of 2-phenylpropionic acid causes stereoselective condensation to give three optically active products. An absolute asymmetric synthesis has also been achieved by the enantioselective decarboxylative condensation of a chiral molecular crystal formed from achiral diphenylacetic acid and acridine (Scheme 9). ... 

Jimenez, M. C., Miranda, M. A., and Tormos, R., Photodecarboxylation of 2-phenylpropionic acid in solution and included within P-cyclodextrin, Tetrahedron, 51, 2953, 1995. 

Irradiation of a chiral bimolecular crystals formed from acridine with diphenylacetic acid and R/S-2-phenylpropionic acid (2-PPA) results in enantioselective photodecarboxylation, which is followed by stereoselective condensation between the CHMePh radical and the hydroacridine radical species (Scheme 4, enantioselective photodecarboxylation in a chiral bimolecular crystal). The radical coupling occurs in the crystal lattice to give the optically active products II to IV. On the other hand, photolysis in solution phase results in the formation of the optically inactive II and biacridine IV. 

Koshima, H., Nakagawa, X, and Matsuura, X, Enantioselective photoreaction occurring in a chiral bimolecular crystal formed from acridine and R-(-)- or S-(-i-)-2-phenylpropionic acid. Tetrahedron Lett., 38, 6063, 1997. 

Originally, we attempted to separate two pairs of enantiomers, namely, S,R-( )-ibuprofen and 5,/ -( )-2-phenylpropionic acid [1]. The two samples were dissolved in 70% ethanol and then the respective solutions were spotted with the aid of an automatic sampler on to the adsorbent layer. Thin layer chromatographic conditions that are best suited for separation of the APA enantiomers involve silica gel impregnated with L-arginine, which is kept in the cationic form, due to a properly fixed pH value (<4.8). The mobile phases used were the ternary mixtures of acetonitrile (ACN), methanol (MeOH), and H2O (plus several drops... 

FIGURE 9.8 Three-dimensional presentation of the skewed chromatographic peak shapes of 5-(- -)-2-phenylpropionic acid (right-handed) and /f-(-)-2-phenylpropionic acid (left-handed). (From Sajewicz, M., Pietka, R., Drabik, G, Namysto, E., and Kowalska, T., J. Planar Chromatogr. —Mod. TLC, 19, 273-277, 2006. With permission.)... 

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