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DOI: 10.1055/s-0028-1083504
Magnesium Nitride as a Convenient Source of Ammonia: Preparation of Pyrroles
Publication History
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
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References and Notes
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
11Representative 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.
12Physical 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.
13Physical 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.
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.
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.
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.