Oxindole, 1-phenyl

Methyloxindole has been prepared by the reduction of a-(2-nitro-phenyl)propionic acid,2 by heating j8-propionylphenylhydrazine with lime3 or with sodium alkoxides,4 and by reduction of the benzoyl derivative of oxindole-3-aldehyde.6... 

Spirocyclic oxindole 60 was synthesized by [3,3]-sigmatropic rearrangement of the Af-phenyl-O-acylhydroxamic acid 58 (equation 19). The potassium enolate formed by treatment of 58 with potassium hexamethyldisilazide at low temperature rearranged to 59, which easily cyclized to the spirocyclic oxindole 60. Spirooxindoles were previously synthesized by Wolff and Taddei. The spirooxindole 60 was formed in 51% yield from cyclohexanecarboxylic acid after heating the preformed lithium salts of phenyl hydrazide 61 to 205-210 °C. 

If the substituent at position 3 in the oxindoles 174 or benzoxindole 175 is a CHCOPh group, 2-phenyl-substituted 4-quinolinecarboxylic acids 176 [149] or 4-benzoquinolinecarboxylic acids 177 [150] respectively are formed when they are heated with concentrated hydrochloric acid in alcohol. Compound 174 (R = H) is not transformed into the corresponding acid 176 under the conditions of the Pfitzinger reaction [149],... 

When heated in acidic medium the oxindole derivatives 178 (R = H) undergo recyclization to 2-aryl-1,4-dihydro-4-quinolinecarboxylic acids 179 or to 2-phenyl-4-quinolinecarboxylic acid (cinchophen) [151],... 

Oxindole.—When ortho-nitro phenyl acetic acid is reduced to the ortho-amino phenyl acetic acid, the latter, being a gawwa-amino acid, loses water yielding a lactam which is known as oxindole. 

Di-oxindole.— Similarly a di-hydroxy compound known as di-oxin-dole is obtained as a lactam anhydride from ortho-amino mandellic acid, ortho-amino phenyl hydroxy acetic acid. 

Indoxyl.—One more derivative of indole must be mentioned connected with the synthetic production of indigo. Isomeric with oxindole is another mono-hydroxy indole known as indoxyl. It is prepared from phenyl glycine or//fo-carboxylic acid, anthranil acetic acid. 

When phenyl glycine ortho-caxhoxyMc acid is fused with potassium hydroxide it first loses water yielding an acid, indoi llic acid, and this loses carbon dioxide yielding indoxyl. In indoxyl the hydroxyl group is in the 3-position while in the isomeric oxindole it is in the 2-position. All of these comp>ounds are thus condensed hetero-cyclic compounds of a benzene ring and a pyrrole ring. Indole is the mother substance and the others are hydroxy or ketone derivatives. 

Enantiomerically pure spiro oxindoles (Scheme 35) were prepared by using solid-supported N-cinnamoyl Evans oxazolidinone (164) [265]. Thus, chiral oxazolidi-none prepared from L-tyrosine was attached to a Merrifield resin and then N-acylated with the required unsaturated acyl chloride such as cinnamoyl chloride (not shown). The resin (165) was then suspended in aqueous dioxane and treated with proline and N-phenyl isatin at 80-90 °C overnight to give a highly substituted spiro compound (167). 

Cyclic compounds can be formed by intramolecular alkylation when warmed with aluminum chloride, A-(chloroacetyl)diphenylamine gives 1-phenyl-oxindole in 90% yield 546... 

Moody and coworkers have observed an intriguing enhancement of diastereos-electivity for the C2 to C3 oxidative rearrangement of indole-2-carboxamides in cases where a bulky substituent was present at indole C7 [17]. Accordingly, oxidative migration of the chiral pyrrolidinamide substituent of 10 (X = H) afforded a 1.3 1 mixture of diastereomeric oxindoles 11 and 12 while similar conversions of the 7-bromo or 7-phenyl analogs of 10 afforded the corresponding oxindoles 11 and 12 in diastereomeric ratios of 8 1 and 11 1, respectively (Scheme 3). 

An intermolecular cyclization approach to C3 asymmetric oxindoles has been devised by Smith and coworkers who paired chiral A-phenylnitrone nucleophiles with ketene electrophiles, e.g., intermolecular fusion of 54 and 55 [37]. As illustrated in Scheme 16, the oxindole skeleton 57 materialized in 87% ee following a proposed sequence of nitrone addition to the ketene, a hetero-Claisen rearrangement, imine hydrolysis and, finally, cyclization to generate the lactam linkage. As an extension of this methodology, (5)-3-allyl-3-phenyloxindole 57 was transformed into enantiopure 3-phenyl-hexahydropyrroloindole scaffold 58. 

Startg. m. dissolved in boiling aq. NaOH, and heating continued 3-phenyl-oxindole. Y 88%. Limitation s. D. R. Long and C. G. Richards, Tetrah. Let. 1975,1603. 

Carbenium ions generated from benzhydrols with electron-donating substituents react with the nucleophile (l-phenyl-3-alkyloxazolones), giving the product at the 3-position, in yields ranging from 55 to 84%. Quaternary centres have also been formed at the 3-position of pyrazolones, benzofuranones, and oxindoles in poor to good yields (38-69%), using this technique. 

Another interesting chemoselectivity event is the Stolle reaction the chloroacetyl derivative of 2-aminobiphenyl 15. In the annulation step of the reaction, cyclization occurred exclusively on the nonsubstitued phenyl moiety to give azepinone 17 as opposed to the expected oxindole product 16. Again, substiutent effects are the reason for the unexpected chemoselectivity the amide functionality deactivates the A -phenyl ring relative to the 2-phenyl substituent. ... 

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