No Ring-Chain Tautomerism and Some Reactions of 2-Hydroxyindoline Derivatives

Transcription

1 No Chem. Pharm. Bull. 35( 4 ) (1987) Ring-Chain Tautomerism and Some Reactions of 2-Hydroxyindoline Derivatives TOMOMI KAWASAKI, HIROAKI OHTSUKA, CHUN-SHENG MITSUGU OMATA, and MASANORI SAKAMOTO * Meiji College of Pharmacy, , Nozawa, Setagaya-ku, Tokyo 154, Japan (Received June 30, 1986) CHIEN, The spectral (proton and carbon-13 nuclear magnetic resonance) and chemical properties of the 1-acetyl-2-hydroxyindolines 1-5, which can exist in the ring (A) and chain (B) tautomers, have been investigated. The methylation and acetylation of the 2-hydroxy-3-indolinones 1-3 gave the ring tautomeric methyl ether and acetyl esters of 1-3, while the reaction with Ē-phenylenediamine (9) gave the quinoxalines 10 and 11 as the chain tautomeric products. The reactions of 1-3 with the phosphonium ylide 12 gave the 2- methoxycarbonylmethyl- 3- indolinones 14 (R = Ph) and 16 (R = Me) and/or the 2-hydroxy-3-methoxycarbonylmethyleneindolines 15 (R =Ph) and 18 (R = H), respectively, depending on the nature of the substituent (R) at the 2-position in 1-3. The acetylation and reaction of the 2,3-dihydroxyindoline 4 with 12 are also described. Keywords \ 2-hydroxyindoline; tautomerism; Wittig reaction; acetylation; methylation; 13C -NMR; quinoxaline; furo [3,2-b] indole. It is known that 1-acetyl-2-hydroxyindolines can exist in equilibrium with their openchain tautomers.1) Previously, we have reported the preparation of the 1-acety1-2-hydroxy-3- indolinones 1-3 and the 1-acetyl-2,3-dihydroxyindolines 4 and 5 by the oxidation of 1- acetylindoles with an oxodiperoxomolybdenum comound.2) Since the 2-hydroxyindolines 1-5 may possess two or more reactive sites which are interrelated by their ring-chain tautomerism, they are expected to be attractive synthetic intermediates to heterocyclic compounds.3) We have now examined some reactions of the 2-hydroxyindolines 1-4, and also reinvestigated the spectral properties of 1-5 in order to understand their ring-chain tautomerism. Spectral Properties Since Harrison1 g) had established the ring-chain tautomerism of 2-hydroxyindolines by examination of their 13C-nuclear magnetic resonance (13C-NMR) spectra, we first reexamined 1: R=Ph 2: R=Me 3: R =H A B 4: R=Me 5: R=H Chart 1

2 1340 Vol. 35 (1987)

3 No the 1H and 13C-NMR spectra of the 2-hydroxyindolines 1-5 in detail. The results are presented in Table I. In CDCl3, 1-acetyl-2-hydroxy-2-phenyl-3-indolinone (1) exists as a mixture of ring (1A) and chain (1B) tautomers. Thus, the 13C-NMR spectrum showed signals due to C-2 ( ), C-3 (196.23) and amido carbonyl carbons (171.32) of 1A, and the two keto (192.97, ) and amido carbonyl carbons (169.87) of 1B, and the 1H-NMR spectrum showed signals due to the two acetamido protons at and 2.02, in the ratio of ca. 1 : 2. When the spectra were recorded in dimethylsulfoxide (DMS0)-d6, there was a striking change in the ratio of 1A and 1B; only the signals due to 1A were observed, while no signal due to 1B was seen.4) It was found that the ratio of 1A and 1B depends on the nature of the solvent; 1 tends to exist as the ring form 1A in a polar solvent. Similarly, the 2-methyl- 2 and 2-unsubstituted 2-hydroxy-3-indolinones 3 were found to exist in DMSO-d6 as the ring tautomers 2A and 3A, respectively.4) It is known1b -f) that the ring-chain tautomerism of 2-hydroxyindolines is dependent on the substituent at the 2- position; in DMSO-d6, 2-unsubstituted derivatives exist preferentially as the ring forms, while 2-substituted ones exist as the chain forms. In the case of 1-3, however, the ring tautomers A are predominant in DMSO-d6. This predominance can be explained on the basis of the participation of the carbonyl group at the 3-position in the stabilization of the ring tautomer A, while is analogous to the finding that carbonyl compounds with electron-withdrawing groups tend to form their hydrates, e.g., 1,2,3-indantrione, glyoxal, and so on.5) The "C-NMR spectrum of 1-acetyl-2,3-dihydroxy-2,3-dimethylindoline (4) in CDCl3 was identical to that reported by Harrison,1g) corresponding to a mixture of ring (4A) and chain (4B) tautomers. Although the ring of 4A can exist in two stereoisomers, the and spectra of 4 in CDCl, show no evidence for their existence. When the spectra were recorded in DMSO-d6, the signals due to the cis- and trans-isomers of 4A appeared; the 13C- NMR spectrum showed the 2 Ž ( , 97.51) and 3 Ž(79.52, 79.64) signals of two isomers of 4A. In this case, solvent dependence of the ratio of the equilibrium constituents was observed; in CDCl3 the ratio of 4A and 4B was ca. 1 : 1.8, while in DMSO-d6 it was ca. 3 : 1, and the ratio of the two stereoisomers of 4A was ca. 1 : 1.4. In the case of 1-acetyl-2,3-dihydroxy-3-methylindoline (5), the NMR spectra in DMSOd6 show that 5 is a mixture of cis-and trans-isomers of the ring tautomer 5A, and no peak due to the chain tautomer 5B was detected.4) Chemical Properties Next, we examined some reactions of 1-4; methylation, acetylation, and reaction with ƒíphenylenediamine (9) and with a phosphonium ylide 12. Treatment of the 2-hydroxy-3-indolinone 1 with methyl iodide and potassium tertbutoxide gave the 2-methoxy-3-indolinone 6 in 71 % yield; the structure was assigned on the basis of the analytical and spectral data. The isomeric structure 6' was readily ruled out by the appearance of the signal due to 2 Ž ( ) of 6 in the 13C-NMR spectrum. The methylation of 2 was carried out similarly to give only a complex mixture.6) Acetylation of 1 and 3 gave the O-acetates 7 and 8, respectively, whose structures were confirmed by spectral evidence; the "C-NMR spectrum of 7 showed a signal at due to 2-C of 7, and the 1H-NMR spectrum of 8 showed a singlet peak at due to 2-H of 8. The reaction of 1 and 2 with 9 afforded the quinoxalines 10 and 11 in 98% and 97% yields, respectively. The reaction may proceed via the condensation of their open-chain tautomers B as ƒ -diketones with 9; this is similar to the well-known reaction used for the synthesis of quinoxalines.8) Next, we examined the reactions of 1 3 with the phosphonium ylide 12, and found clear differences. Thus, the reaction of 1 with 12 gave the 2-methoxycarbonylmethyl-3-indolinone

4 1342 Vol. 35 (1987) Chart A 15B A 18B A B Chart 3 14 and the 2-hydroxy-3-methoxycarbonylmethyleneindoline 15 in 29% and 52% yields, respectively. The structures of 14 and 15 were determined on the basis of their analytical and spectral data; the parent ions in the mass spectra (MS) each appeared at m/z 323, indicating that 14 and 15 are isomeric. The infrared (IR) spectrum of 14 showed three carbonyl bands at 1742, 1736, and 1680 cm-1, and in the 1H-NMR spectrum two doublets (J=16 Hz) due to methylene protons were observed at and On the other hand, the 1H-NMR spectrum of 15 in CDCl3 showed two singlets at and 6.36 (one proton in total) due to the olefinic protons and two singlets at and 2.12 (three protons) due to the amidomethyl protons. The spectrum indicated that, at least in CDCl3, the product 15 exists in two forms, the ring and chain tautomers, 15A and 15B, as well as 1. Thus, in the "C-NMR spectrum (CDCl3), there were four singlets due to ester and amido carbonyl carbons at , , , and , and two doublets due to olefinic carbons of 15A and 15B at and , and further a singlet due to the keto carbonyl carbon of 15B at and a singlet due to 2-C of 15A at However, we could not clarify the E and Z stereochemistries of

5 No A and 15B. The formation of 14 may be understood in terms of attack of the ylide 12 on the benzoyl carbonyl of 1B, leading to 13, followed by cyclization (path a), while the formation of 15 may occur by attack of 12 either on the other benzoyl carbonyl of 1B (path b) or on the carbonyl of 1A (path c) as shown in Chart 3. When 2 was allowed to react with 12, the 2-methoxycarbonylmethyl-3-indolinone 16 was obtained in 76% yield, together with 17 in 9% yield. The structures were confirmed by the analytical and spectral data (see Experimental). The preferential formation of 16 may be explained as follows; since the chain form 2B may exist in a small amout under the reaction conditions, the ylide 12 may attack the acetyl carbonyl group of 2B (path a), which is more reactive than the benzoyl of 2B and the 3-keto carbonyl of 2A. In contrast, the reaction of 3 with 12 preferentially gave the 2-hydroxy-3-methoxycarbonylmethyleneindoline 18 in 81 % yield; the structure of 18 was assigned on the basis of its spectral data (see Experimental). In this case, no evidence was found for the existence of the open-chain form 18B in DMSO-d6.4) The formation of 18 may proceed via attack of 12 on the carbonyl of 3A (path c), since, if 12 reacts with 3B, it would attack not the benzoyl carbonyl of 3B, but the more reactive aldehyde carbonyl of 3B (path a) to form another type of product such as 16. These results show that the reaction course is dependent on the substituent at the 2- position of 1-3, since it affects the ring-chain tautomerism. Finally, we examined the acetylation and reaction of the 2,3-dihydroxyindoline 4 with the ylide 12. Treatment of 4 with acetic anhydride in pyridine gave the 2-acetoxymethyl-3-methyland 3-acetoxymethyl-2-methylindoles, 20 and 21, in 41% and 15% yields, respectively; the structures of these products were confirmed by the spectra data (see Experimental). The formation of 20 and 21 can be explained by the acetylation of the ring form 4A, leading to the diacetate 19, followed by elimination and rearrangement of the acetoxy groups, as shown in Chart Chart 4 22 The reaction of 4 with 12 gave the furo[3, 2-b] indole 22 in 31% yield. A plausible mechanism for the formation of 22 is shown in Chart 4. Experimental All melting points are uncorrected. IR spectra were recorded on a Hitachi spectrophotometer. 1H- and spectra were measured with JEOL JNM-PMX 60 and GX-400 spectrometers using tetramethylsilane as an

6 1344 Vol. 35 (1987) internal standard. MS were obtained with a JEOL D-300 spectrometer operating at 70 ev. Column chromatography was carried out on silica gel ( mesh, Kanto Chemical Co., Inc.). Methylation of 1-Acetyl-2-hydroxy-2-phenyl-3-indolinone (1) A solution of 1 (O.267 g, 1 mmol) and potassium tert-butoxide (0.168 g, 1.5 mmol) in dry tetrahydrofuran (THF) (10 ml) was stirred at room temperature for 2 h, then a solution of methyl iodide (0.71 g, 5 mmol) in dry THF (10 ml) was added at room temperature. The mixture was stirred at the same temperature overnight, and concentrated under reduced pressure to give a residue, which was purified by column chromatography on silica gel with C6H6 as an eluent to give 1-acety1-2-methoxy-2- pheny1-3-indolinone (6) (0.199 g, 71%), mp Ž (from C6H6). Anal. Calcd for C17H15NO3: C, 72.58; H, 5.37; N, Found: C, 72.42; H, 5.28; N, IR v CHCl max 3 cm-1: 1734 (C =O), 1683 (N-C =O). 1H-NMR (CDCl3) ƒâ: 2.00 (3H, s, NCOMe), 3.37 (3H, s, -OMe), (8H, m, Ar-H), 8.77 (1H, d, J= 9 Hz, Ar-H). '3C-NMR (CDCl3) : (q, COMe), (q, -OMe), (s, C-2), , , , , , , , , (each d, Ar-C), , , (each s, Ar-C), (s, N-C =0), (s, C-3). Acetylation of 1 A solution of 1 (0.80 g, 3 mmol) and acetic anhydride (0.765 g, 7.5 mmol) in dry pyridine (14 ml) was allowed to stand at room temperature for 1 d. The reaction mixture was diluted with CHCl3 (100 ml) and washed with 10% HCl (80 ml) and water. The CHCl3 layer was dried over MgSO4 and concentrated in vacuo to give a residue. The residue was purified by column chromatography on silica gel with CHCl3 as an eluent to give 2-acetoxy- 1 -acety1-2-pheny1-3-indolinone (7) (0.38 g, 41%), together with recovered 1 (O.44 g, 56%). 7: mp Ž (from C6H6-pet. ether) [lit.") mp Ž]. Anal. Calcd for C NO4: C, 69.89; H, 4.89; N, Found: C, 69.96; H, 4.75; N, IR 1.,,,F:,13cm -1: 1770, 1744 (-COO-, C =O), 1688 (N-C =O). 1H- NMR (CDCl3) ƒâ: 2.03, 2.26 (each 3H, each s, NCOMe, OCOMe), 7.26 (1H, d, J= 8 Hz, Ar-H), (5H, m, Ar-H), (2H, m, Ar-H), 8.68 (1H, d, J =8 Hz, Ar-H). "C-NMR (CDCl3) ƒâ: 20.51, (each q, Me), (s, C-2), , , , , , (each d, Ar-C), , , (each s, Ar-C), , (each s, O-C =O, N-C =O), (s, C-3). MS m/z: 309 (M t). Acetylation of 1-Acetyl-2-hydroxy-3-indolinone (3)-Using a procedure similar to that described above for the acetylation of 1, 3 (0.35 g, 1 mmol) was treated with acetic anhydride (0.47 g, 4.6 mmol) in dry pyridine (5 ml) for 4 d to give 2-acetoxy- 1 -acetyl-3-indolinone (8) (0.34 g, 81%), mp C (from ether). Anal. Calcd for C12H1 NO,: C, 61.80; H, 4.75; N, Found: C, 61.70; H, 4.62; N, IR v ii,:,13cm-1: 1762, 1740 (-COO-, C =O), 1696 (N-C =O). 1H-NMR (CDCl3) ƒâ: 2.18, 2.30 (each 3H, each s, NCOMe, OCOMe), 6.33 (1H, s, N-CH-O), (3H, m, Ar-H), 8.41 (1H, d, J =8 Hz, Ar-H). MS m/z: 233 (M t). Reaction of 1 with o-phenylenediamine (9) A solution of 1 (0.765 g, 3 mmol) and 9 (0.324 g, 3 mmol) in acetic acid (10 ml) was heated at 100 (DC for 1 h. After removal of the solvent under reduced pressure, the residue was purified by column chromatography on silica gel with CHCl3-ethyl acetate (50 : 1). as an eluent to give 2-(2-acetylaminophenyl)-3-phenylquinoxaline (10) (1.00 g, 98%), mp C (from C61-16-n-hexane). Anal. Calcd for C22H,N3O: C, 77.85; H, 5.05; N, Found: C, 77.69; H, 4.84; N, IR v CHCl max 3 cm-1: 3400 (NH), 1688 (C =O). (DMSO-d6) ƒâ: 1.73 (3H, s, NCOMe), (13H, m, Ar-H), 9.35 (1H, br s, NH, exchangeable with D20). MS m/z: 339 (M t). Reaction of 1-Acetyl-2-hydroxy-2-methyl-3-indolinone (2) with 9 By using a procedure similar to that described above for the reaction of 1 with 9, 2 (0.615 g, 3 mmol) was treated with 9 (0.324 g, 3 mmol) to give 2-(2- acetylaminopheny1)-3-methylquinoxaline (11) (0.81 g, 97%), mp Ž (from C6H6). Anal. Calcd for C17H15N3O: C, 73.63; H, 5.45; N, Found: C, 73.91; H, 5.33; N, IR vchcl max 3cm-1: 3400 (NH), 1691 (C =O). 1H-NMR (DMSO-d6) ƒâ: 1.80 (3H, s, NCOMe), 2.53 (3H, s, Me), (8H, m, Ar-H), 9.45 (1H, br, NH, exchangeable with D2O). Reaction of 1 with Methoxycarbonylmethylenetriphenylphosphorane (12) A solution of 1 (0.563 g, 2.1 mmol) and 12 (1.20 g, 3.6 mmol) in dry toluene (20 ml) was refluxed for 17 h. The reaction mixture was concentrated in vacuo and the crude material was subjected to column chromatography on silica gel with CHCl3 as an eluent to give 1- acety1-2-methoxycarbonylmethy1-2-phenyl-3-indolinone (14) (0.199 g, 29%) and 1-acetyl-2-hydroxy-3-methoxycarbonylmethylene-2-phenylindoline (15) (0.357 g, 52%) successively, in that order. 14: mp Ž (from C6H6). Anal. Calcd for C19H17NO4: C, 70.57; H, 5.30; N, Found: C, 70.33; H, 5.18; N, IR vchcl max 3cm -1: 1742, 1736, 1680 (C =O). (CDCl3) ƒâ: 2.18 (3H, s, NCOMe), 3.47 (3H, s, COOMe), 3.68, 4.02 (each 1H, each d, J= 16 Hz, -CH2COO-), (8H, m, Ar-H), 8.67 (1H, br, Ar-H). MS m/z: 323 (M+). 15: mp C (dec.) (from ether-n-hexane). Anal. Calcd for C19H17NO4: C, 70.57; H, 5.30; N, Found: C, 70.74; H, 5.21; N, IR vchcl max 3cm-1: 3594 (OH), 1715, 1665, 1637 (C =O). '14-NMR (CDCl3) ƒâ: 1.82, 2.12 (together 3H, each s, NCOMe), 3.59, 3.63 (together 3H, each s, COOMe), 5.O8 (ca. 0.8H, br s, OH or NH), 5.82, 6.36 (together 1H, each s, C =CH-), (m, Ar-H), 8.40, 8.74 (each 0.8H, each s, Ar-H). "C-NMR (CDCl3) ƒâ: 24.42, (each q, NCOMe), 51.56, (each q, OMe), (s, C-2 of 15A), , (each d, =CH-), , , , (each s, N-C =O, O-C = (s, Ph-C =O of 15B). MS m/z: 323 (M t). Reaction of 2 with 12 A solution of 2 (0.87 g, 4.24 mmol) and 12 (3.12 g, 9.32 mmol) in CHCl3 (50 ml) was refluxed for 7 h. After removal of the solvent under reduced pressure, the residue was chromatographed on a silica gel column. Elution with CH2Cl2 gave 1-acetyl- 2- methoxycarbonylmethy1-2- methyl -3- indolinone (16) (0.84 g, 76%).

7 No Elution with CH2Cl2-ethyl acetate (50 : 1) gave dimethyl 2 - (2-acetylaminophenyl) -3 -methyl -2, 4- hexadienedioate (17) (0.125 g, 9%). 16: mp Ž (from C6H6). Anal. Calcd for C14H15NO4: C, 64.36; H, 5.79; N, Found: C, 64.44; H, 5.75; N, IR v CHCl max 3 cm-1: 1730, 1668 (C =0). 1H-NMR (CDCl3) ƒâ: 1.55 (3H, s, Me), 2.51 (3H, s, NCOMe), 3.10, 3.90 (each 1H, each d, J=17 Hz, -CH2COO-), 3.45 (3H, s, COOMe), (4H, m, Ar-H). MS m/z: 261 (M +). 17: mp Ž (from C6H6-ether). Anal. Calcd for C17H19NO5: C, 63.34; H, 6.04; N, Found: C, 64.13; H, 5.92; N, IR v CHCl max cm-1: (NH), 1717 (C =0), 1615 (C =C). 'H-NMR (CDCl3) 6: 2.02 (3H, s, Me), 2.38 (3H, s, NCOMe), 3.55, 3.63 (each 3H, each s, COOMe), 5.65, 6.45 (each 1H, each s, C =CH-) (5H, m, Ar-H, NH). MS m/z: 317 (M+). Reaction of 3 with 12 \ A solution of 3 (1.00 g, 5.2 mmol) and 12 (2.10 g, 6.3 mmol) in CHCl3 (58 ml) was stirred at room temperature for 6 h. After removal of the solvent under reduced pressure, the residue was purified by column chromatography on silica gel with CHCl3-ethyl acetate (9 : 1) as an eluent to give 1-acetyl-2-hydroxy-3- methoxycarbonylmethyleneindoline (18) (1.04 g, 81%), mp Ž (from ether). Anal. Calcd for C13H13NO4: C, 63.15; H, 5.30; N, Found: C, 63.22; H, 5.27; N, IR v CHCl max cm 3-1: 3500 (OH), 1690 (O-C =0), 1640 (N-C=O). 1H-NMR (DMSO-d6) ƒâ: 2.36 (3H, s, NCOMe), 3.74 (3H, s, COOMe), 6.57 (1H, d, 1.5 Hz, C = CH-), 6.60 (1H, d, J =8 Hz, O-CH-C=), 6.98 (1H, d, J=8 Hz, OH, exchangeable with D2O), 7.12, 7.43 (each 1H, each t, Ar-H), 7.84, 8.14 (each 1H, each d, J = 8 Hz, Ar-H). 13C-NMR (DMSO-d6) ƒâ: (q, NCOMe), (q, OMe), (d, C-2), (d, =CH-), , , , (each d, Ar-C), , , (each s, Ar-C, C-3), , (each s, N-C=O, O-C =O). MS 247 (M + ). Acetylation of 1-Acetyl-2,3-dihydroxy-2,3-dimethylindoline (4) \ By using a procedure similar to that described above for the acetylation of 1,4 (0.443 g, 2 mmol) was treated with acetic anhydride (1.74g, 17 mmol) in dry pyridine (4 ml) at 50 Ž for 2 d. The reaction mixture was purified by column chromatography on silica gel with CH2Cl2 as an eluent to give 2-acetoxymethy1-1-acety1-3-methylindole (20) (0.202 g, 41%) and 3-acetoxymethy1-1-acety1-2- methylindole (21) (0.075 g, 15%). 20: mp Ž (from ether-n-hexane). Anal. Calcd for C14H15NO3: C, 68.55; H, 6.16; N, Found: C, 68.43; H, 6.09; N, IR v CHCl max cm 3-1: 1738 (O-C =O), 1703 (N-C =O). 1H-NMR (CDCl3) ƒâ: 2.05 (3H, s, OCOMe), 2.32 (3H, s, Me), 2.75 (3H, s, NCOMe), 5.47 (2H, s, -CH2OCO-), (4H, m, Ar-H). MS m/z: 245 (M +). 21: mp Ž (from ether-n-hexane). Anal. Calcd for C14H15NO3: C, 68.55; H, 6.16; N, Found: C, 68.45; H, 6.19; N, IR 1736 (O-C =O), 1708 (N-C =O).1H-NMR (CDC13) ƒâ: 2.03 (3H, s, OCOMe), 2.63 (3H, s, Me), 2.70 (3H, s, NCOMe), 5.25 (2H, s, -CH2OCO-), (4H, m, Ar-H). MS ml z: 245 (M +). The introduction of the acetoxy groups in 20 and 21 was confirmed by comparison of the chemical shifts of the methyl groups at the 2- and 3-positions with those of 1-acetyl-3-methoxymethyl-2-methyl- (ƒâ2.58) and 1-acety1-2- methoxymethy1-3-methylindole (ƒâ 2.26).9) Reaction of 4 with 12 \ By using a procedure similar to that described above for the reaction of 1 with 12, 4 (0.663 g, 3 mmol) was treated with 12 (1.10 g, 3.3 mmol) in dry toluene (30 ml) for 7 h. The reaction mixture was purified by column chromatography on silica gel with CH2Cl2 as an eluent to give 4-acety1-3,3a,4,8b-tetrahydro- 3a,8b-dimethylfuro [3,2-b]indo1-2(H)-one (22) (0.229 g, 31%), mp Ž (from C6H6). Anal. Calcd for C14H15NO3: C, 68.55; H, 6.16; N, Found: C, 68.45; H, 6.15; N, IR v CHCl max 3 cm -1: 1770 (O-C =O), 1662 (N-C =0). 1H-NMR (CDC13) ƒâ: 1.53, 1.73 (each 3H, each s, Me), 2.47 (3H, s, NCOMe), 2.83, 3.83 (each 1H, each d, J=19 Hz, -CH2COO-), (4H, m, Ar-H). MS m/z: 245 (M+). Acknowledgement The authors wish to thank the staff of the Analysis Center of this college for elemental analysis (Miss A. Koike), and measurements of NMR (Miss Y. Takeuchi) and MS (Mr. K. Sato). References and Notes 1) a) C. W. Rees and C. R. Sabet, J. Chem. Soc., 1965, 870; b) O. Buchardt and C. Lohse, Tetrahedron Lett., 1966, 4355; c) O. Buchardt, J. Becher, and C. Lohse, Acta Chem. Scand., 20, 2467 (1966); d) O. Buchardt, B. Jensen, and I. K. Larsen, ibid., 21, 1841 (1967); e) O. Buchardt, P. L. Kumler, and C. Lohse, ibid., 23, 159 (1969); f) Idem, ibid., 23, 1155 (1969); g) D. M. Harrison, Tetrahedron Lett., 1984, 6063; h) For reviews dealing with the ring-chain tautomerism; P. R. Jones, Chem. Rev., 63, 461 (1963); R. Valters, Russ. Chem. Rev., 43, 665 (1974). 2) a) T. Kawasaki, C.-S. Chien; and M. Sakamoto, Chem. Lett., 1983, 855; b) C.-S. Chien, T. Suzuki, T. Kawasaki, and M. Sakamoto, Chem. Pharm. Bull., 32, 3945 (1984); c) C.-S. Chien, T. Takanami, T. Kawasaki, and M. Sakamoto, ibid., 33, 1843 (1985). 3) The know reactions of 1-acetyl-2-hydroxyindolines are dehydration,3a) acetylation,1a) oxidations,3a,b) and rearrangements1a, 3b-e); a) O. Buchardt, J. Becher, C. Lohse, and J. Moller, Acta Chem. Scand., 20, 262 (1966); b) C. M. Atkinson, J. W. Kershaw, and A. Taylor, J. Chem. Soc., 1962, 4426; c) B. Witkop, J. Am. Chem. Soc., 72, 614 (1950); d) J. B. Patrick and B. Witkop, ibid., 72, 633 (1950); e) J. W. Kershaw and A. Taylor, J. Chem. Soc., 1964, 4320.

8 1346 Vol. 35 (1987) 4) The cyclic tautomer B, if present, may exist only at very low concentrations under the conditions employed. 5) S. H. Pine, J. B. Hendrickson, D. J. Cram, and G. S. Hammond, "Organic Chemistry," 4th ed., McGraw-Hill, Inc., Tokyo, 1981, pp ) The methylation of 2 was achieved by the use of diazomethane.7) 7) C.-S. Chien, A. Hasegawa, T. Kawasaki, and M. Sakamoto, Chem. Pharm. Bull., 34, 1493 (1986). 8) A. E. A. Porter, "Comprehensive Heterocyclic Chemistry," Vol. 3, ed. by A. R. Katritzky, Pergamon Press, New York, 1984, pp ) S. F. Vice and G. I. Dmitrienko, Can. J. Chem., 60, 1233 (1982).