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Synlett 2008(17): 2597-2600  
DOI: 10.1055/s-0028-1083504
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Magnesium Nitride as a Convenient Source of Ammonia: Preparation of Pyrroles

Gemma E. Veitch, Katy L. Bridgwood, Karen Rands-Trevor, Steven V. Ley*
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK
Fax: +44(1223)336442; e-Mail: svl1000@cam.ac.uk;
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Publication History

Received 12 July 2008
Publication Date:
01 October 2008 (online)

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Abstract

The synthesis of a diverse array of pyrroles is reported from the cyclocondensation of 1,4-dicarbonyl compounds with magnesium nitride in methanol.

Key words

pyrroles - heterocycles - ammonia - magnesium nitride - combinatorial chemistry

10

Representative Procedure for the Microwave-Assisted Synthesis of 1 H -Pyrroles: To a stirred solution of 1-phenyl-pentane-1,4-dione (100 mg, 0.57 mmol) in MeOH (5.5 mL) at 0 ˚C was added magnesium nitride (143 mg, 1.43 mmol). The reaction vessel was sealed and allowed to warm to r.t. over 1 h during which time the brown solution became white, indicating the formation of magnesium alkoxide species and the release of NH3. The reaction was then heated to 120 ˚C for 1 h in the microwave. After cooling to r.t., the reaction was partitioned between CH2Cl2 (20 mL) and H2O (20 mL). The aqueous layer was acidified to pH 7 using 1 N HCl then the organic layer was separated, dried (MgSO4) and concentrated in vacuo. Flash column chromatography on silica (10% EtOAc in hexanes) afforded 2 as an off-white solid (96 mg, 99%). ¹H NMR (400 MHz, CDCl3): δ = 8.09 (br s, 1 H), 7.42 (d, J = 7.6 Hz, 2 H), 7.33 (t, J = 7.4 Hz, 2 H), 7.16 (t, J = 7.4 Hz, 1 H), 6.39 (br s, 1 H), 5.95 (br s, 1 H), 2.32 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 133.0, 130.8, 129.1, 128.9, 125.7, 123.4, 108.0, 106.3, 13.2. IR (film): 3397, 2921, 1603, 1511, 1216, 899, 772, 750, 687 cm-¹. HRMS (ESI): m/z [M + H]+ calcd for C11H12N: 158.0971; found: 158.0964. Data consistent with literature values.¹8

11

Representative Procedure for the Thermally Assisted Synthesis of 1 H -Pyrroles (Table 2): To a stirred solution of 1-phenylpentane-1,4-dione (100 mg, 0.57 mmol) in MeOH (5.5 mL) at 0 ˚C was added magnesium nitride (143 mg, 1.43 mmol). The reaction vessel was sealed and heated to 80 ˚C for 24 h. After cooling to r.t., the reaction was subjected to workup and column chromatography as before.

12

Physical Data for 2-(4-Bromophenyl)-5-methyl-1 H -pyrrole (4): ¹H NMR (400 MHz, CDCl3): δ = 8.06 (br s, 1 H), 7.44 (d, J = 8.5 Hz, 2 H), 7.28 (d, J = 8.5 Hz, 2 H), 6.39 (t, J = 2.4 Hz, 1 H), 5.95 (br s, 1 H), 2.33 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 131.9, 131.8, 129.6, 129.6, 124.7, 118.9, 108.2, 106.8, 13.2. IR (film): 3437, 2921, 2851, 1506, 819, 768 cm-¹. HRMS (ESI): m/z [M + H]+ calcd for C11H11BrN: 236.0077; found: 236.0080.

13

Physical Data for 2-Methyl-5-[4-(trifluoromethyl)phe-nyl]-1 H -pyrrole (5): ¹H NMR (400 MHz, CDCl3): δ = 8.17 (br s, 1 H), 7.57 (d, J = 8.6 Hz, 2 H), 7.49 (d, J = 8.4 Hz, 2 H), 6.51 (t, J = 2.9 Hz, 1 H), 5.99 (br s, 1 H), 2.35 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 136.0, 130.5, 129.2, 127.1 (q, J = 31.5 Hz), 125.8 (q, J = 3 Hz), 124.3 (q, J = 270 Hz), 122.9, 108.6, 108.1, 13.2. IR (film): 3397, 2918, 2852, 1617, 1333, 1112, 844, 778 cm-¹. HRMS (ESI): m/z [M + H]+ calcd for C12H11F3N: 226.0839; found: 226.0849.

14

General Procedure for the Thermally Assisted Synthesis of 1 H -Pyrroles (Table 3): To a stirred solution of the 1,4-dicarbonyl compound (0.13 mmol) in MeOH (1.3 mL) at
0 ˚C was added magnesium nitride (1.3 mmol). The reaction vessel was sealed and allowed to stir for 10 min before heating to 80 ˚C for 24 h. After cooling to r.t., the reaction was subjected to workup and column chromatography as before. For pyrroles 10 and 11, neutral alumina was employed for chromatography to prevent decomposition.

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Physical Data for 3-(Thiophen-2-yl)-2- p -tolyl-5-[4-(trifluoromethyl)phenyl]-1 H -pyrrole (11): ¹H NMR (600 MHz, CDCl3): δ = 8.41 (br s, 1 H), 7.59 (AB q, J = 8.6 Hz, 4 H), 7.44 (d, J = 8.1 Hz, 2 H), 7.23 (d, J = 7.9 Hz, 2 H), 7.21 (dd, J = 5.0, 1.0 Hz, 1 H), 6.99 (dd, J = 5.0, 3.5 Hz, 1 H), 6.96 (dd, J = 3.5, 1.0 Hz, 1 H), 6.66 (d, J = 2.8 Hz, 1 H), 2.38 (s, 3 H). ¹³C NMR (150 MHz, CDCl3): δ = 138.0, 137.0, 136.1, 133.4, 129.7, 128.8, 128.8 (q, J = 33 Hz), 127.6, 127.4, 127.3, 125.6 (q, J = 3 Hz), 124.2 (q, J = 273 Hz), 124.7, 124.1, 124.0, 118.0, 109.0, 21.2. IR (film): 3427, 2919, 2849, 1616, 1324, 1164, 1121, 1068 cm-¹. HRMS (ESI):
m/z [M]+ calcd for C22H16NF3S: 383.0956; found: 383.0960.

16

Physical Data for 2-Phenyl-4,5-dihydro-1 H -benzo[ g ]indole (14): ¹H NMR (600 MHz, CDCl3): δ = 8.46 (br s, 1 H), 7.53 (d, J = 7.6 Hz, 2 H), 7.39 (t, J = 7.6 Hz, 2 H), 7.21-7.26 (m, 4 H), 7.08 (t, J = 7.2 Hz, 1 H), 6.43 (d,
J = 1.8 Hz, 1 H), 2.96 (t, J = 7.2 Hz, 2 H), 2.78 (t, J = 7.2 Hz, 2 H). ¹³C NMR (150 MHz, CDCl3): δ = 135.0, 132.6, 132.5, 129.0, 128.9, 128.4, 126.6, 126.2, 125.2, 123.7, 122.2, 118.2, 106.1, 29.9, 29.7. IR (film): 3442, 2923, 2850, 1609, 1507, 1291, 1263 cm-¹. HRMS (ESI): m/z [M]+ calcd for C18H15N: 245.1205; found: 245.1192.

17

Physical Data for 2-(4-Fluorophenyl)-3-(4-methoxy-phenyl)-5-(naphthalen-2-yl)-1 H -pyrrole (15): ¹H NMR (500 MHz, CDCl3): δ = 8.47 (br s, 1 H), 7.90 (br s, 1 H), 7.81-7.87 (m, 3 H), 7.71 (dd, J = 8.5, 1.4 Hz, 1 H), 7.48 (td, J = 8.0, 1.0 Hz, 1 H), 7.38-7.45 (m, 3 H), 7.31 (d, J = 8.8 Hz, 2 H), 7.04 (d, J = 8.7 Hz, 2 H), 6.86 (dt, J = 9.6, 2.9 Hz, 2 H), 6.77 (d, J = 2.6 Hz, 1 H), 3.82 (s, 3 H). ¹³C NMR (125 MHz, CDCl3): δ = 161.9 (d, J = 245 Hz), 158.1, 133.8, 132.2, 132.1, 129.5, 129.5, 129.2, 129.2, 128.7, 128.6, 128.3, 127.8, 127.7, 126.6, 125.5, 123.7, 123.0, 121.0, 115.7 (d, J = 21.5 Hz), 113.9, 109.1, 55.2. IR (film): 3425, 2922, 1629, 1604, 1519, 1506, 1483 cm-¹. HRMS (ESI): m/z [M + H]+ calcd for C27H21NOF: 394.1607; found: 394.1617.