4-Nitrobenzaldehyde → Methyl 6-nitro-1H-indole-2-carboxylate

HRID 1266450Notes

Reaction equation

HRID 1266450 reaction equation
[N+]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]([O:15][CH3:16])=[O:14])=[CH:9]2)([O-])=O.[N+:17](C1C=C2C(=CC=1)NC(C(OC)=O)=C2)([O-:19])=[O:18].[N+](C1C=CC(C=O)=CC=1)([O-])=O.N(CC(OC)=O)=[N+]=[N-]>C1(C)C(C)=CC=CC=1.C(Cl)Cl>[N+:17]([C:5]1[CH:4]=[C:12]2[C:8]([CH:9]=[C:10]([C:13]([O:15][CH3:16])=[O:14])[NH:11]2)=[CH:7][CH:6]=1)([O-:19])=[O:18]

Participants

7

Reactant 4

HCID 5414-NitrobenzaldehydeHCID 4020482Methyl 2-azidoacetateHCID 12032225Methyl 5-nitro-1H-indole-2-carboxylateHCID 18550960Methyl 7-nitro-1h-indole-2-carboxylate

Product 1

HCID 11816863Methyl 6-nitro-1H-indole-2-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 7237O-XyleneSolvent

Procedure

Condensation of 3-nitrobenzaldehyde with methyl 2-azidoacetate (8 equiv, 6 equiv NaOCH3, CH3OH, −23 to 0° C., 6 h, 88%) both reagents commercially available from Aldrich, followed by thermolysis of the resulting methyl 2-azidocinnamate (xylene, reflux, 4.5 h, 81%) provided a readily separable mixture (4:1) of methyl 5- and 7-nitroindole-2-carboxylate. For methyl 7-nitroindole-2-carboxylate (164): mp 122-125° C. (CH2Cl2, light yellow fine needles); 1H NMR (CDCl3, 400 MHz) 10.37 (br s, 1H, NH), 8.31 (d, 1H, J=8.0 Hz, C4-H), 8.06 (d, 1H, J=8.0 Hz, C6-H), 7.36 (d, 1H, J=2.4 Hz, C3-H), 7.28 (t, 1H, J=8.0 Hz, C5-H), 3.99 (s, 3H, CO2CH3); IR (film)max 3372, 1727, 1531, 1445, 1344, 1298, 1249, 1188, 1107, 830, 763 cm−1; FABHRMS (NBA) m/e 221.0560 (M++H, C10H8N2O4 requires 221.0562). For methyl 5-nitroindole-2-carboxylate (168): 1H NMR (DIMETHYLSULFOXIDE-d6, 400 MHz) 12.65 (br s, 1H, NH), 8.73 (d, 1H, J=2.3 Hz, C4-H), 8.14 (dd, 1H, J=2.0, 8.0 Hz, C6-H), 7.60 (d, 1H, J=8.0 Hz, C7-H), 7.45 (d, 1H, J=0.7 Hz, C3-H), 3.90 (s, 3H, CO2CH3); IR (film)max 3316, 1701, 1614, 1531, 1435, 1343, 1261, 1203, 992, 746 cm−1. Similarly, condensation of 4-nitrobenzaldehyde with methyl 2-azidoacetate (8 equiv, 6 equiv NaOCH3, CH3OH, −23 to 0° C., 7 h, 84%) followed by thermolysis (xylene, reflux, 4 h, 83%) provided methyl 6-nitroindole-2-carboxylate (166): 1H NMR (CDCl3, 400 MHz) 9.27 (br s, 1H, NH), 8.39 (d, 1H, J=2.0 Hz, C7-H), 8.04 (dd, 1H, J=2.0, 8.0 Hz, C5-H), 7.78 (d, 1H, J=8.0Hz, C4-H), 7.28 (d, 1H, J=2.3 Hz, C3-H), 4.00 (s, 3H, CO2CH3).

Sources & evidence

ORD record
ord-73b0e4226fc7422790fd59c9cd011752
Source dataset
uspto-grants-2003_04
Patent number
US06548530B1

Reaction notes

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