8
K. Sudheendran et al. / Tetrahedron xxx (2014) 1e11
1633, 1591, 1461, 1436, 1381, 1356, 1121, 1072, 875, 857, 729,
procedure I for 24 h to deliver ethyl-4-fluorobenzimidate hydro-
chloride (4j) as a white solid in 92% yield (2.81 g, 13.8 mmol).
670 cmꢂ1; UV (CH3CN) lmax (log ε) 248 nm (4.02); 1H NMR
(300 MHz, CD3OD)
d
1.62 (t, 3J¼6.9 Hz, 3H, 40-H), 2.47 (s, 100-H), 4.67
(q, 3J¼6.9 Hz, 2H, 30-H), 7.53 (t-like, 3J (4-H, 5-H), (5-H, 6-H)¼7.8 Hz,
1H, 5-H), 7.65 (d, 3J (4-H, 5-H)¼7.8 Hz, 1H, 4-H), 7.88 (overlapped,
4.2.9. Ethyl-2-naphthimidate hydrochloride (4m). Compound 3m
(2.30 g, 15 mmol) was reacted under the conditions of general
procedure I for 24 h to deliver ethyl-2-naphthimidate hydrochlo-
ride (4m)ꢀas a white solid in 85% yield (3.54 g, 12.7 mmol): mp
~
2H, 2-H and 6-H); 13C NMR (75 MHz, CD3OD)
d
13.9 (C-40), 21.2 (C-
100), 71.3 (C-30), 127.1 (C-1), 127.2 (C-2), 130.3 (C-6), 130.4 (C-5), 137.6
(C-4), 141.0 (C-3), 174.5 (C-10); MS (ESI) m/z (%) 186 (10)
[MꢂHClþNa]þ, 164 (55) [MꢂHClþ1]þ, 136 (100), 119 (8); HRMS
(ESI) calcd for C10H14NO 164.1075, found 164.1064.
193e195 C; Rf 0.64 (EtOAc/CH3OH¼4:1); IR (ATR)
n
2979, 2807,
1616, 1599, 1482, 1439, 1384, 1342, 1281, 1119, 1068, 1001, 924, 846,
816, 770, 752, 718 cmꢂ1; UV (CH3CN) lmax (log ε) 288 (3.37), 250
(4.06), 241 nm (4.07); 1H NMR (300 MHz, CD3OD)
d
1.66 (t, 3J (30-H,
4.2.2. Ethyl-4-methylbenzimidate hydrochloride (4c).28c,31 Compound
3c (1.76 g, 15 mmol) was reacted under the conditions of general
procedure I for 24 h to deliver ethyl-4-methylbenzimidate hydro-
chloride (4c) as a white solid in 95% yield (2.85 g, 14.0 mmol).
40-H)¼7.2 Hz, 3H, CH3), 4.71 (q, J (30-H, 40-H)¼7.2 Hz, 2H, CH2),
7.64e7.77 (m, 2H, 6-H and 7-H), 7.98 (overlapped, 2H, 3-H and 5-H),
8.10 (overlapped, 2H, 4-H and 8-H), 8.69 (d-like, 4J (1-H, 3-H)¼
3
1.5 Hz, 1H, 1-H); 13C NMR (75 MHz, CD3OD)
d 14.05 (CH3), 71.46
(CH2), 124.19 (C-3), 124.22 (C-2), 129.05 (C-7), 129.14 (C-5), 130.57
(C-4), 130.93 (C-8), 131.35 (C-6), 132.84 (C-1), 133.61 (C-8a), 137.90
(C-4a), 174.38 (C-10); MS (ESI) m/z (%) 222 (10) [MꢂHClþNa]þ, 200
(73) [MꢂHClþ1]þ, 172 (100), 129 (42); HRMS (ESI) calcd for
4.2.3. Ethyl-3-methoxybenzimidate
hydrochloride
(4d).28b,31
Compound 3d (2.00 g,15 mmol) was reacted under the conditions of
general procedure I for 24 h to deliver ethyl-3-methoxybenzimidate
hydrochloride (4d) as a white solid in 82% yield (2.65 g, 12.3 mmol).
C13H14NO 200.1075, found 200.1050.
4.2.4. Ethyl-4-methoxybenzimidate
hydrochloride
(4e).28b,31
4.3. General procedure II for the synthesis of amidine hy-
drochlorides 1d-h,j,m25a
Compound 3e (2.00 g, 15 mmol) was reacted under the conditions of
general procedure I for 24 h to deliver ethyl-4-methoxybenzimidate
hydrochloride (4e) as a white solid in 78% yield (2.52 g, 11.7 mmol).
The ethyl imidate hydrochloride 4 (10 mmol) was dissolved in
ethanol (10 mL) and placed in a round-bottomed flask equipped
with a magnetic stir bar. After sealing the flask with a rubber
septum ammonia in methanol (10 mL) was added to the reaction
mixture using a syringe. The reaction mixture was stirred at room
temperature for 24 h. After evaporation in vacuo, the crude product
was purified by flash column chromatography over silica gel
(EtOAc/methanol¼4:1) to afford the amidine hydrochloride 1.
4.2.5. Ethyl-3,4-dimethoxybenzimidate hydrochloride (4f).28a,31
Compound 3f (2.45 g, 15 mmol) was reacted under the conditions
of general procedure
I
for 48
h
to deliver ethyl-3,4-
dimethoxybenzimidate hydrochloride (4f) as a white solid in 83%
yield (3.06 g, 12.5 mmol).
4.2.6. Ethyl-3,4,5-trimethoxybenzimidate
Compound 3g (2.9 g, 15 mmol) was reacted under the conditions of
general procedure for 48 to deliver ethyl-3,4,5-
hydrochloride
(4g).
4.3.1. 3-Methoxybenzenecarboximidamide hydrochloride (1d).29d,31
Compound 4d (2.16 g, 10 mmol) was reacted under the conditions of
general procedure II to deliver 3-methoxybenzenecarboximidamide
hydrochloride (1d) as a white solid in 74% yield (1.38 g, 7.4 mmol).
I
h
trimethoxybenzimidate hydrochloride (4g) as a white solid in
79% yield (3.27 g, 11.9 mmol): mp 165e167 ꢀC; Rf 0.58 (EtOAc/
~
CH3OH¼4:1); IR (ATR)
n
2839, 1624, 1587, 1469, 1427, 1357, 1315,
1243, 1121, 1071, 998, 856, 735, 704 cmꢂ1; UV (CH3CN) lmax (log ε)
4.3.2. 4-Methoxybenzenecarboximidamide hydrochloride (1e).29a,31
Compound 4e (2.16 g, 10 mmol) was reacted under the conditions of
general procedure II to deliver 4-methoxybenzenecarboximidamide
hydrochloride (1e) as a white solid in 67% yield (1.25 g, 6.7 mmol).
217 (4.43), 295 nm (3.97); 1H NMR (300 MHz, CD3OD)
d
1.63 (t, 3J
(30-H, 40-H)¼6.9 Hz, 3H, 40-H), 3.88 (s, 3H, 200-H), 3.93 (s, 6H, 100-H
and 30-H), 4.66 (q, 3J (30-H, 40-H)¼6.9 Hz, 2H, 30-H), 7.39 (s, 2H, 2-H
and 6-H); 13C NMR (75 MHz, CD3OD) 14.0 (C-40), 57.2 (C-100 and C-
d
300), 61.5 (C-200), 71.3 (C-30),108.0 (C-2 and C-6),121.6 (C-1),146.0 (C-
4), 155.0 (C-3 and C-5), 173.6 (C-10); MS (EI, 70 eV) m/z (%) 239 (20)
[MꢂHCl]þ, 211 (10), 193 (24), 178 (12), 150 (4); HRMS (EI, Mþ) calcd
for C12H17NO4 239.1158, found 239.1161.
4.3.3. 3,4-Dimethoxybenzenecarboximidamide
hydrochloride
(1f).29e,31 Compound 4f (2.46 g, 10 mmol) was reacted under
the conditions of general procedure II to deliver 3,4-
dimethoxybenzenecarboximidamide
hydrochloride
(1f)
as
a white solid in 91% yield (1.97 g, 9.1 mmol).
4.2.7. Ethyl-3-chlorobenzimidate hydrochloride (4h). Compound 3h
(2.06 g, 15 mmol) was reacted under the conditions of general pro-
cedureIfor 24htodeliverethyl-3-chlorobenzimidate hydrochloride
(4h) as awhite solid in 73% yield (2.41 g,11.0 mmol): mp 107e108 ꢀC;
~
4.3.4. 3,4,5-Trimethoxybenzenecarboximidamide
hydrochloride
(1g).29b,31 Compound 4g (2.76 g, 10 mmol) was reacted under
the conditions of general procedure II to deliver 3,4,5-
trimethoxybenzenecarboximidamide hydrochloride (1g) as
a white solid in 78% yield (1.93 g, 7.8 mmol).
Rf 0.63 (EtOAc/CH3OH¼4:1); IR (ATR)
n
1720, 1623, 1569, 1426, 1382,
1365, 1291, 1279, 1254, 1122, 1072, 1012, 747, 674 cmꢂ1; UV (CH3CN)
lmax (log ε) 204 (4.73), 276 nm (2.92); 1H NMR (300 MHz, CD3OD)
d
1.63 (t, 3J (30-H, 40-H)¼7.2 Hz, 3H, CH3), 4.69 (q, 3J¼7.2 Hz, 2H, CH2),
4.3.5. 3-Chlorobenzenecarboximidamide
hydrochloride
(1h).
7.66 (t, 3J (4-H, 5-H), (5-H, 6-H)¼7.8 Hz,1H, 5-H), 7.79e7.88 (m,1H, 4-
H), 8.01 (dd, 3J (5-H, 6-H)¼7.8 Hz,1H, 6-H), 8.08 (ddd, 4J (2-H, 4-H), 4J
Compound 4h (2.20 g, 10 mmol) was reacted under the conditions of
general procedure II to deliver 3-chlorobenzenecarboximidamide
hydrochloride (1h) as a white solid in 69% yield (1.32 g, 6.9 mmol):
~
(2-H, 6-H)¼1.8 Hz,1H, 2-H); 13C NMR (75 MHz, CD3OD)
d 14.0 (CH3),
71.9 (CH2), 128.6 (C-6),129.4 (C-1), 130.0 (C-2), 132.3 (C-5),136.5 (C-
3), 136.6 (C-4), 173.4 (C-10); MS (EI, 70 eV) m/z (%) 182 (2)
[MꢂHClþ1]þ, 155 (9), 139 (25), 111 (8), 75 (4); HRMS (EI, Mþ) calcd
for C9H10ClNO 183.0451, found 183.0464.
mp 121e123 ꢀC; Rf 0.45 (EtOAc/methanol¼5:3); IR (ATR)
n
1656,
1525, 1466, 1088, 799, 713 cmꢂ1; UV (CH3CN) lmax (log ε) 203 (4.55),
231 (3.93), 280 nm (2.79); 1H NMR (300 MHz, DMSO-d6) 7.64 (t, 3J
d
(5-H, 6-H)¼7.8 Hz, 3J (4-H, 5-H)¼8.1 Hz, 1H, 5-H), 7.78e7.85 (m, 2H,
4-H and 6-H), 7.97 (s, 1H, 2-H), 9.52 (br s, 4H); 13C NMR (75 MHz,
4.2.8. Ethyl-4-fluorobenzimidate hydrochloride (4j).28b,31 Compound
3j (1.82 g, 15 mmol) was reacted under the conditions of general
DMSO-d6) d 126.9 (C-6),128.0 (C-2),130.0 (C-1),130.9 (C-5),133.5 (C-
3),133.6 (C-4),164.6 (C-10); MS (EI, 70 eV) m/z (%) 154 (28) [MꢂHCl]þ,