Reactions of  melatonin and other 1-hydroxyindole derivatives
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                        Melatonin (2) was used to prepared 1-hydroxy indole derivative as shown in the scheme 1 above. Yield of melatonin was raised by up to 80% by reacting it with BF3-MeOH complex in reflusing MeOH. Then it was reduced to 2,3-dihydroindole (3a) with triethylsilane (Et3SiH) and trifluoroacetic acid (TFA) in 86% yield. Subsequence oxidation of (3a) with sodium tungstate dihydrate (Na2WO4.2H2O) afforded the desired 1-hydroxymelatonin (4a) in 28% yield.While bromination of 2,3-dihydro-N-methoxycarbonyltryptamine (5) with bromine in acetic acid generated monobromo (3b) and dibromo (3c) compounds in 61% and 30% yields respectively. Oxidation of (3b) and (3c) with Na2WO4.2H2O and 30% H2O2 produced the corresponding 1-hydroxytryptamines (4b)  and (4c) in 57% and 51% yields . For the preparation of 1,4-dihydroxy-5-nitroindole (13), 4-hydroxy -5-nitroindole (11) was required as a starting material. It was also possible to form (11) by oxidation of 5-aminoindole (6) with m-chloroperbenzoic acid (mCPBA) in acetone. However, the yield was miserable (4%). In order to incrase the yield, an alternative synthesis method was developed. First, the reaction for obtaining 4-hydroxyindole-3-carboxaldehyde (8) from indole carboxaldehyde (7). The yield is now incrased to 70% with good reproducibility employing thallation with thallium tris(tris-fluoroacetate) and subsequenct treatment of the resultant thallium compound with cupric sulfate pentahydrate (2 mol eq.) in  N,N-dimethylformamide and H2O at 120-130 oC. Nitration of (8) with cupric nitrate and acetic anhydride produced 5-nitro (9a) and 7-nitro (9b) compounds in 45% and 46% yields respectively. Since,direct conversion of (9a) to (11) was unsuccessful, (9a) was transformed to diacetyl compound  (10) in 82% yield by treatment with refluxing acetic anhydride. Oxidation of 3-formyl group of (10 ) to carboxyl group with sodium chloride and subsequent treatment with 1N aqeuous sodium hydroxide caused hydrolysis and simultaneous decarboxylation to afford (11) in 90% yield. The reduction of (11) with Et3SiH and TFA  afforded (12) in 91% yield. Subsequent oxidation of (12) with mCPBA (3 mol eq.) afforded the desired (13) in 66% yield, whereas with  Na2WO4.2H2O and 30% H2O2 only 14% yield of (13) was produced.
                        1-hydroxy-3-methlsulfinylmethylindole (16a) was prepared as followed. 3-Methylthiomethylindole (14) was first prepared in 80% yield by reacting gramine with sodium methyl sulfide. Reduction of (14)  with sodium cyanoborohydride (NaBH3CN) in AcOH successfully generated 2,3-dihydroindole (15) in 55% yield. Subsequent oxidation of (15) with  Na2WO4.2H2O and 30% H2O2 produced (16a) in 27% yield. Formation of unstable 1-hydroxy-3-methylsulfonylmethylindole (16b) is confirmed as a 1-methoxy derivative but its isolation was not successful.
                        5-Acetyl-1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinoline (18) is a readily available from 4-nitroindole-3-acetonitrile (17).  (18) was reduced with NaBH3CN in AcOH and TFA to afford 90% yield of 2,3-dihydroindole (19). Oxidation of (19) with Na2WO4.2H2O and 30% H2O2 produced the desired 5-acetyl-1,3,4,5-tetrahydro-1-hydroxypyrrolo[4,3,2-de]quinoline (20) in 69% yield. 

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