Indoline-carboxylic acid

A rich family of diazaphospholes 260-262 having hcxahydro- l//-pyrrolo [l,2-c][l, 3, 2]diazaphosphole backbone was readily prepared by the reaction of phenylphosphorodichloridite or another P(III) precursor with anilides of (iS )-proline, (S)-pyroglutamic acid, and (S)-indoline carboxylic acid in high yields diastereoselectively [95],... 

Swan and Waggott (257), on the basis of their various experimental results, suggested that autooxidative dopa-melanin consists in the main of four types of units 10% of uncyclised units, which are diphenolic (3), 10% of indoline-carboxylic acid type (4), 65% of indole type (5), and 15% of pyrrole type (6). Moreover, of the units of types 4 and 5 taken together, one half are quinonoid and the other half are diphenolic 0.5 H2O was included per average polymer unit. 

Reddy, K. H. V., Satish, G., Ramesh, K., Kamakar, K., and Nageswar, Y. V. D. 2012. An efficient synthesis of N-substituted indoles from indoline/indoline carboxylic acid via aromatization followed by C-N cross-coupling reaction by using nano copper oxide as a recyclable catalyst. Tetrahedron Lett. 53(24) 3061-3065. 

This work, some aspects of which are outlined below, has served to show that melanins are in fact highly irregular polymers in which several different types of monomer unit are linked in a variety of ways. From the results of an extensive series of experiments in which D L-dopa deuteriated separately at the 1, 2, 2, 5 and 6 positions and D L-l-[ C]-dopa were converted into dopa-melanin autoxid-atively or by enzymic oxidation in the presence of mushroom polyphenol oxidase. Swan and his collaborators have conclude that the principal structural fragments in the polymer are probably (0 uncyclised units of dopa (68, 0.1), (ii) indoline carboxylic acid units (69, 0.1), ( /) indole units (70, 0.65) and (iv) pyrrole carboxylic acid units (71, 0.15). The indoline (69) and indole (70) units are presumed to exist in the polymer half in the phenolic and half in the quinonoid forms. It was also suggested that the pyrrole carboxylic unit (71) is probably derived by oxidative fission, during the synthesis of the dopa-melanin, of a benzenoid unit such as (70). 

C iH FjNO, J254S3-3I-0) see Dolasetron mesilate indole-3-carboxylic acid imidazolide (CiiHoNjO 99445-26-S) see Tropisetron (S)-indoline-2-carboxylic acid (QjH.jNOj 79815-20-6) see Perindopril ( )-2-(lH-indol-5-yl)-A -methylethenesulfonamide (CiiHijNjOjS 98623-49-5) see Naratriptan 5-(3-indolylmcthyl)hydantoin (Ci2H N,02 21753-16-2) see L-Tryptophan... 

CHIREX 3022 [N-l-[(l-naphthyl)ethyl]amido]indoline-2-carboxylic acid amide 179... 

Chiral butyrolactones of type 27 and 28 have substantial value in asymmetric synthesis because they contain readily differentiable difunctional group relationships e.g. 1,5-di-carboxylic acid, 1,4-hydroxy carboxylic acid, 1,6-hydroxy-carboxylic acid, 1,6-diol etc.) that would be difficult to assemble by existing asymmetric condensation and pericyclic processes. Applications of these chiral derivatives of glutaric acid to syntheses of indole, indoline and quinolinone alkaloids are illustrated in Schemes 16-18. 

The methyl and benzyl esters of proline were also used as chiral auxiliaries in respective acrylamides, but the isoxazoline cycloadducts were obtained with only poor to modest stereoselectivity (189,190). The related indoline-2-carboxylic acid derivative 33, however, showed excellent ability to direct nitrile oxide attack, favoring one rotamer (Scheme 6.37), and thereby leading to 3-phenylisoxazoline-5-carboxamide... 

Perindopril (A), an orally active pharmaceutical for the treatment of hypertension, is an important commercial target compound that has a cyclic a-amino acid as an intermediate in its synthetic route. The bicyclic a-amino acid building block is synthesized by reduction of the chiral indoline-2-carboxylic acid (B, R=R =H) shown in Figure 1.4. This chiral cyclic amino acid has so far proven very difficult to synthesize in a highly enantioselective manner using chiral hydrogenation. 

Therefore better methods for the chiral reduction of indole-2-carboxylic acid derivatives would provide an elegant synthesis of this intermediate. A study by Kuwano and Kashiwabara of the reduction of indole derivatives into the corresponding indohnes found that a range of the more common ligand systems gave almost no enantioselectivity but the TRAP ligand gave the chiral indolines in up to 95 % ee for reduction of the methyl ester (B, R=Me, R =H). Further developments are awaited. 

The 2H-and 3//-pyrroles and -indoles are considerably more basic than the corresponding H-isomers and they readily undergo alkylation to give the quaternary salts, which are then highly susceptible to nucleophilic attack. Thus, for example, methylation of the trialkyl-3//-indole (507), followed by reaction with aqueous base, yields the indolin-2-ol (508). A similar reaction sequence results from the acylation of (507) under Schotten-Baumann conditions to give (509 X = OH). When the benzoylation is conducted in benzene in the absence of the base, the 2-chloroindoline (509 X = C1) is formed and acylation of (507) with a carboxylic acid anhydride produces the ester (509 X = OCOR) (79HC(25-3)l). 

Abou-Basha and Aboul-Enein [22] presented an isocratic and simple HPLC method for the direct resolution of the clenbuterol enantiomers. The method involved the use of a urea-type CSP made of hS )-indoline-2-carboxylic acid and (R)-1 -(naphthyl) ethylamine known as the Chirex 3022 column. The separation factor (a) obtained was 1.27 and the resolution factor (Rs) was 4.2 when using a mobile phase composed of hexane-1,2-dichloroethane-ethanol (80 10 10, v/v/v). The (+)-enantiomer eluted first with a capacity factor (k) of 2.67 followed by a (—)-enantiomer with a k of 3.38. Biesel et al. [23] resolved 1-benzylcyclohexane-1,2-diamine hydrochloride on a Chirex D-penicillamine column. Gasparrini et al. [24] synthesized a series of the chiral selectors based on /ra s -1,2 - d i a m i n o eye I o hexane. The developed CSPs were used for the chiral resolution of arylacetic acids, alcohols, sulfoxides, selenoxides, phosphinates, tertiary phosphine oxides, and benzodiazepines. In another study, the same authors [25] described the chiral resolution of /i-aminocstcrs enantiomers on synthetic CSPs based on a re-acidic derivatives of trans- 1,2-diaminocyclohexane... 

Whereas N-phenylindoles are reduced to the corresponding dihydroindoles with Na/NHs (equations 46 and 47)8 -89 and indole-2-carboxylic acid is reduced to the indoline with Li/NH3/PhNH2 (equation 48), indole itself is reduced to 4,7-dihydroindole (Li/NHs, MeOH) in 51% yield. These latter conditions also reduce carbazole to 1,4-dihydrocarbazole in 73% yield. ... 

Sodium borohydride in concert with AlCb-pyridine also reduces indoles to indolines (equation 71), but this reagent combination is less effective than those reported above using carboxylic acids. 

Y. Sueishi, M. Ohcho, S. Yamamoto, and N. Nishimura, A Kinetic study of the thermal conversion of r,3, 3 -trimethylspiro[2//-l-benzopyran-2,2 -indoline]-8-carboxylic acid, Bull. 

Indolines are useful intermediates for the synthesis of indoles with substituents in the carbocyclic ring. In electrophilic substitutions, they behave like anilines the example shows iV-acetylindoline undergoing regioselective 7-thallation. Nitration of indoline 2-carboxylic acid gives the 6-nitro-derivative separation... 

A-Acylated indolines and 1,2,3,4-tetrahydroquinolines free of osubstituent to the heteroatom are arylated by reaction with ArB(OH)2. Besides Pd(OAc)2, the catalyst system also contains equivalents of Cu(OTf )2 and Ag20 Similarly, a protocol for the Pd-catalyzed o-arylation of acetanilides employs Cu(OTf)2 and AgF, with ArSi(OR)3 as aryl group donors. Further variants of couphng conditions involving oxygen in a carboxylic acid solvent enable the use of ArH as reaction partners. Cyclization of A-aroylindoles proceeds via double C—H activation. ... 

Anthranil is a minor product from the electrolytic reduction of the erythro or threo forms of the o-nitrobenzyl alcohol 114 (R2 = Me, R2 = N02).145 The fluorosulfonic acid-induced cyclization of (o-nitrophenyl)succinic anhydride affords a mixture of 4-hydroxy-2-quinolone and anthranil-3-acetic acid (115 R = CH2C02H), and not, as previously reported, a mixture of 1-hydroxyindole- and 2-hydroxy-A2-indoline-3-carboxylic acids.146... 

Amino acids with side chains containing the benzyl and indoline groups usually show good performance in the esterification. In general, the higher yield is obtained for ethyl esters compared with isopropyl esters. One exception is indoline-2-carboxylic acid, where the yield of isopropyl ester is much higher that the ethyl ester. It is also believed that the N-acetyl ethyl esters are more stable than the N-unprotected ethyl esters and butyl esters (16), which implies that the N-acetyl ethyl esters studied are very valuable for further applications. 

S)-indoline-2-carboxylic acid and -l-(a-naphthyl) ethylamine urea linkage... 

Indoline-2-carboxylic acid (2,3-dihydro-lH-indole-2-carboxylic acid) [78348-24-0] M 163.2, m 168°(dec), pKEst(i) 2.1, pKesi(2) 3.8. Dissolve the acid in hot EtOH, add excess of dry Et20 and cool to... 

Indoline-2-carboxylic acid (2,3-dihydro-lEf-indole-2-carboxylic acid) [78348-24-0] M 163.2, m 168°(dec), pKEst(i) 2.1, pKesi(2) 3.8. Dissolve the acid in hot EtOH, add excess of dry Et20 and cool to yield colourless plates that decompose in the range of 120-150°. The amide (m 208-209°) crystallises as colourless plates which sublime at 150°/1.0mm and has vmax at 1625cm i (paraffin mull) [Hudson Robertson AustJ Chem 20 1935 1967], [Beilstein 22/2 V 421.] See Chapter 6, Catalysts-Part 1 for optical isomers... 

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