6718 J . Org. Chem., Vol. 63, No. 19, 1998
Notes
(7.0%) during the preparation of 2e. 1H NMR (CDCl3) δ 4.8 (2H,
d, J ) 8.4), 4.9 (2H, s), 5.0 (1H, s), 5.75 (1H, m), 5.9 (1H, t, J )
2.4), 6.1 (1H, t, J ) 3.6), 6.15 (1H, t, J ) 2.4), 6.55 (1H, t, J )
2.4), 6.6 (1H, t, J ) 2.4), 6.8 (12H, m); 13C NMR (CDCl3) δ 41.5,
49.8, 52.6, 106.9, 109.1, 109.3, 114.8, 115.1, 115.3, 115.4, 115.6,
115.7, 119.8, 121.2, 121.5, 128.0, 128.2, 128.5, 128.6, 129.8, 129.9,
134.0, 134.3, 136.0, 139.5, 159.6, 160.3, 163.3, 164.1; CIMS (NH3)
m/z 457 (M + H)+, 100), 349, 282, 176, 126, 109; HRFAB Calcd
for C29H23N2F3 (M+) 456.1813, found 456.1881.
N-(1-Ca r boxy-2-p h en yleth yl)-1H-p yr r ole (2h ). Prepared
from L-phenylalanine using methods A and B, respectively.
PTLC yielded the compound as an off brown solid via method A
(45%) and via method B (83%), mp 94-97° C. 1H NMR (CDCl3)
δ 3.3 (1H, dd, J ) 8.8, 8.8), 3.5 (1H, dd, J ) 5.0, 5.0), 4.8 (1H,
dd, J ) 5.0, 5.0), 6.15 (2H, t, J ) 2.2), 6.7 (2H, t, J ) 2.2), 7.05
(2H, m), 7.25 (3H, m); 13C NMR (CDCl3) δ 39.2, 63.5, 109.1,
120.0, 136.0, 176.0; MS m/z 215 (M+), 170; HRMS Calcd for
C
13H13NO2 (M+) 215.0946, found 215.0946.
4-Cya n oben zylh exa m in e Hyd r obr om id e. Condensation
of 1-bromomethyl-4-cyanobenzene with hexamethylene tetra-
mine in chloroform according to general procedures21,22 afforded
a colorless solid (97%), mp 230 (C (decom). 1H NMR (DMSO-
d6) δ 4.20 (2 H, s), 4.45 (3 H, d, J ) 14.0), 4.60 (3 H, d, J )
14.0), 5.10 (6 H, s), 7.70 (2 H, d, J ) 6.7), 8.00 (2 H, d, J ) 6.7).
4-Cya n oben zyla m in e Hyd r och lor id e. Hydrolysis of 4-
cyanobenzylhexamine hydrobromide in EtOH/HCl according to
general procedures21,22 afforded a colorless solid (90%), mp 270
°C (dec); 1H NMR (CDCl3) δ 4.10 (2 H, s), 7.67 (2 H, d, J ) 9.0),
7.81 (2 H, d, J ) 9.0); MS m/z 132 ([M - HCl]+), 131 ([M - H2-
Cl]+), 104, 75, 51, 36; HRMS Calcd for C8H8N2 ([M - HCl]+),
132.0687, found 132.0687.
1-((4-Cyan oph en yl)m eth yl)-1H-pyr r ole (2f). Prepared from
4-cyanobenzylamine hydrochloride (12 mmol) after conversion
to the free amine base by dissolving in a mixture of pyridine
(0.19 mol), water (2.0 mL), and DMAP (0.9 mol %) and heating
at (70 °C; 0.5 h). Then AcOH (0.19 mol) and DMT were added
(70 °C; 50 h). PTLC (CHCl3/light petroleum (1:4)) yielded the
compound as a colorless solid (44%), mp 46-49 °C; 1H NMR
(CDCl3) δ 5.05 (2 H, s), 6.38 (2 H, d, J ) 2.1), 6.80 (2 H, d, J )
2.1), 7.22 (2 H, d, J ) 9.0), 7.61 (2 H, d, J ) 9.0); 13C NMR
(CDCl3) δ 52.6, 109.2, 111.4, 118.5, 121.1, 127.2, 132.4, 143.7;
MS m/z 182 (M+), 154, 116, 89; HRMS Calcd for C12H10N2 (M+)
182.0844, found 182.0844. Anal. Calcd for C12H10N2: C, 79.12;
H, 5.49; N, 15.38. Found: C, 78.85; H, 5.38; N, 15.49.
N-(1-Car boxy-2-(4-h ydr oxyph en yl)eth yl)-1H-pyr r ole (2i).
Prepared from L-tyrosine using method A. PTLC yielded the
compound as an off white solid (20%), mp 140-144 °C. 1H NMR
((CD3)2CO) δ 3.3 (1H, dd, J ) 8.8, 8.8), 3.45 (1H, dd, J ) 5.8,
5.8), 5.0 (1H, dd, J ) 5.8, 5.8), 6.1 (2H, t, J ) 2.0), 6.8 (2H, d, J
) 8.2), 6.9 (2H, t, J ) 2.0), 7.0 (2H, d, J ) 8.8); 13C NMR (CDCl3/
DMSO-d6) δ 38.0, 63.3, 107.8, 115.0, 126.6, 129.3, 155.6; MS m/z
231 (M+), 107; HRMS Calcd for C13H13NO3 (M+) 231.0895, found
231.0895.
N-(1,3-Dica r boxyp r op yl)-1H-p yr r ole (2j). Prepared from
L-glutamic acid using methods A and B, respectively, and PTLC
to yield the compound as an oil (12%) via method A and (21%)
by method B, respectively. 1H NMR (CDCl3) δ 2.35-2.55 (4H,
m), 4.8 (1H, dd, J ) 5.8, 5.8), 6.2 (2H, s), 6.75 (2H, s); 13C NMR
(CDCl3/DMSO-d6) δ 27.0, 28.8, 59.6, 107.3, 119.0, 171.0, 173.0;
CIMS (NH3) m/z 198 (M + H)+, 154; HRMS Calcd for C9H14NO4
(M + H)+ 198.0766, found 198.0766.
(D,L)-N-(1,2-Dica r b oxyet h yl)-1H -p yr r ole(2k ). Prepared
from D,L-aspartic acid according to methods A and B respec-
tively and PTLC to yield the compound as an oil via method A
(9%) and by method B (56%), respectively. 1H NMR ((CD3)2CO)
δ 3.05 (1H, dd, J ) 7.1, 7.1), 3.35 (1H, dd, J ) 8.0, 8.0), 5.15
(1H, t, J ) 7.1), 6.2 (2H, s), 6.75 (2H, s); 13C NMR (CDCl3/DMSO-
d6) δ 36.6, 57.7, 107.7, 120.0, 170.4, 170.5; CIMS (NH3) m/z 184
(M + H)+, 140, 94; HRMS Calcd for C8H11NO4 (M + H)+
184.0610, found 184.0610.
1-((4-Nitr oph en yl)m eth yl)-1H-pyr r ole (2g). Prepared from
4-nitrobenzylamine hydrochloride (7.8 mmol) after conversion
of the salt in situ to the free amine base by dissolving in a
mixture of pyridine (0.19 mol), water (6.0 mL), DMAP and (0.16
mol %) and heating at (70 °C; 1.0 h). Then AcOH (0.19 mol)
and DMT were added according to method B (78 °C; 48 h),
excluding water. PTLC yielded the compound as an off white
solid (94%), mp 56-59 °C; 1H NMR (CDCl3) δ 5.30 (2 H, s), 6.40
(2 H t, J ) 2.0), 6.90 (2 H, t, J ) 2.1), 7.30 (2 H, d, J ) 8.9), 8.20
(2 H, d, J ) 8.9); 13C NMR (CDCl3) δ 52.4, 109.3, 121.1, 123.8,
127.2, 145.6, 147.3; MS m/z 202 (M+), 156, 136, 106, 89, 78;
HRMS Calcd for C11H10N2O2 (M+) 202.0742, found 202.0742.
Anal. Calcd for C11H10N2O2: C, 65.53; H, 4.95; N, 13.86.
Found: C, 65.68; H, 5.12; N, 13.92.
2-(Eth ylsu lfon ic a cid )-1H-p yr r ole (2l). Prepared from
taurine using method B. The compound was obtained as an off
white solid (87%), mp 327-328 °C (dec). 1H NMR (D2O) δ 3.4
(2H, t, J ) 7.1), 4.4 (2H, t, J ) 7.1), 6.2 (2H, s), 6.9 (2H, s); 13C
NMR (D2O) δ 49.6, 57.16, 113.2, 126.7; ESIMS m/z 173.5 ([M -
H]-, 45.3).
Ack n ow led gm en t. Financial support from EPSRC
under Grant GR/F 20937 is gratefully acknowledged,
and Dr. Ballintine and B. Stein of the EPSRC MS
service center, Swansea, for EI/CI, FAB, and ESIMS
measurements.
Su p p or tin g In for m a tion Ava ila ble: Copies of NMR
spectra (14 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
(19) Badger, G. M.; Alan J ones, R.; Laslett, R. L. Aust. J . Chem.
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(20) Bruckner, C.; Sternberg, E. D.; Boyle, R. W.; Dolphin, D. J .
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(21) Dele´phine, M. Bull. Soc. Chim. Fr. 1895, 13, 358.
(22) Blazevic, N.; Kolbah, D.; Belin, B.; Sunjic, V.; Kajfez, F.
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