S.S. Khan et al. / Tetrahedron 66 (2010) 5082e5088
5087
3.3. Preparation of 1,2,3-triazolium salts 1, 2, 6 and 10,
general procedure
(CH2eCH2eNeN), 26.4(CH2eCH2eCH2eNeN), 22.7 (CH2eCH2e
Ctriazole), 22.3 (CH2eCtriazole), 21.3 (CH3eCH2), 13.0 (CH3eCH2). HRMS
(ESI): m/z [M]þ calcd for C19H37N4Oþ2 : 353.2917; found: 353.2927.
A solution of the 1, 2, 3-triazole 5aec or 9 (20 mmol) and 5 equiv
of MeI (14,3 g, 100 mmol) in dry MeCN (30 ml) was refluxed for
12 h. All volatile compounds were removed under vacuum with
a rotary evaporator leaving behind the ionic liquid as oil or sticky oil
that was washed with diethyl ether to remove the traces of im-
purities. The resulting iodide was transmitted to salt metathesis
with AgBF4 using a procedure published before.29,30
3.3.5. 5-(((3R,5R)-1,5-Bis(benzyloxycarbonyl)pyrrolidin-3-yloxy)
methyl)-3-(carboxymethyl)-1-methyl-3H-1,2,3-triazol-1-ium iodide
22
(6a). Brownish yellow oil, yield 94%. [
a
]
ꢂ6.6 (c 1, CH3OH). 1H
D
NMR (CDCl3, 300 MHz):
d
(ppm)¼7.28e7.36 (m, 11H, CHar-
*
omaticþCHtriazole), 5.05e5.13 (m, 4H, 2
CH2ePh), 4.91e5.01 (m, 4H,
O]CeCH2eNeNþCH2eOeCH), 4.67 (m, 1H, CH2eOeCH), 4.09 (m,
1H, CHeC]O), 3.81 (s, 3H, CH3eN), 3.61e3.66 (m, 2H, CH2eNeC]
3.3.1. 3-(Carboxymethyl)-5-(((3R,5R)-5-carboxypyrrolidin-3-yloxy)
O), 1.18e1.23 (m, 2H, CH2eCHeC]O). 13C NMR (CDCl3, 75 MHz):
d
methyl)-1-methyl-3H-1,2,3-triazol-1-ium tetrafluoroborate (1a).
(ppm)¼165.6 (O]CeOH), 154.6 (O]CeOeCH2), 140.9 (Ctriazole),
136.0 (Caromatic), 128.5 (CHaromatic), 128.2 (CHaromatic), 128.1 (CHar-
omatic), 127.9 (CHaromatic), 127.8 (CHaromatic), 127.5 (CHaromatic), 127.0
(CHtriazole), 69.0 (CH2eOeCH), 67.4 (CH2ePh), 67.3(CH2ePh), 64.9
(CHeC]O), 59.0 (CH2eOeCH), 58.2 (O]CeCH2eNeN), 53.9
(CH2eNeC]O), 39.5 (CH3eN), 36.5 (CH2eCHeC]O). HRMS (ESI):
m/z [M]þ calcd for C26H29N4Oþ7: 509.2036; found: 509.203.
22
Light yellow sticky oil, yield 85%. [
(CD3OD, 300 MHz):
a
]
ꢂ2.5 (c 1, CH3OH). 1H NMR
D
d
(ppm)¼8.71 (s, 1H, CHtriazole), 5.61 (s, 2H,
CH2eNeN), 4.59 (m, 1H, CHeC]O), 4.54 (m, 1H, CH2eOeCH), 4.36
(s, 2H, CH2eOeCH), 3.85 (s, 3H, CH3eN), 3.32 (m, 1H, CH2eNH),
2.72e2.77 (m, 1H, CH2eNH), 2.58e2.61 (m, 1H, CH2eCHeC]O),
2.24e2.32 (m, 1H, CH2eCHeC]O). 13C NMR (CD3OD, 75 MHz):
d
(ppm)¼168.0 (O]CeOH), 165.0 (CH2eC]O), 140.5 (Ctriazole), 130.9
(CHtriazole), 78.1 (CH2eOeCH), 71.2 (CHeC]O), 58.2 (CH2eOeCH),
53.1 (CH2eNeC]O), 51.0 (CH2eNH), 37.7 (CH3eN), 34.1
(CH2eCHeC]O). HRMS (ESI): m/z [M]þ calcd for C11H17N4O5þ:
285.1198; found: 285.1199.
3.3.6. 5-(((3R,5R)-1,5-Bis(benzyloxycarbonyl)pyrrolidin-3-yloxy)
methyl)-3-(2-methoxy-2-oxoethyl)-1-methyl-3H-1,2,3-triazol-1-ium
iodide (6b). Light brown oil, yield 81%. [
NMR (CDCl3, 300 MHz):
10H, CHaromatic), 4.97e5.13 (m, 4H, 2
CH2eNeN), 4.27e4.38 (m, 4H,
CHþNeCHeC]O), 4.07e4.18 (m, 2H, CH2eNeC]O), 3.78 (s, 3H,
CH3eN), 3.65 (s, 3H, CH3eO), 1.22e1.26 (m, 2H, CH2eCHeC]O). 13
NMR (CDCl3, 75 MHz):
a
]
ꢂ7.2 (c 1, CH3OH). 1H
22
D
d
(ppm)¼9.04 (s,1H, CHtriazole), 7.27e7.33 (m,
*
CH2ePh), 4.84e4.93 (m, 2H,
CH2eCtriazoleþCH2eOe
3.3.2. 5-(((3R,5R)-5-Carboxypyrrolidin-3-yloxy)methyl)-3-(2-me-
thoxy-2-oxoethyl)-1-methyl-3H-1,2,3-triazol-1-ium tetrafluoroborate
22
(1b). Light yellow oil, yield 92%. [
(CD3OD, 300 MHz):
a
]
D
ꢂ2.3 (c 1, CH3OH). 1H NMR
C
d
(ppm)¼8.69 (s, 1H, CHtriazole), 4.59 (s, 2H,
d
(ppm)¼171.6 (NeCHeC]O), 165.1
CH2eNeN), 4.35 (m, 3H, NeCHeC]OþNeCH2eCHeO), 3.84 (s, 3H,
CH3eN), 3.36 (s, 3H, CH3eO), 3.36 (m, 2H, CH2eOeCH), 2.91 (s, 1H,
CH2eOeCH), 1.31e1.32 (m, 2H, CH2eCHeN). 13C NMR (CD3OD,
(CH3eOeC]O), 154.5 (NeC]O), 136.8 (Ctriazole), 132.0 (Caromatic),
128.4 (CHaromatic), 128.2 (CHaromatic), 128.0 (CHaromatic), 127.9 (CHar-
omatic), 127.8 (CHaromatic), 127.4 (CHaromatic), 127.0 (CHtriazole), 79.1
(CH2eOeCH), 74.9 (CH2ePh), 67.2 (CH2ePh), 65.8 (CH2eOeCH), 64.9
75 MHz):
d
(ppm)¼169.7 (OHeC]O), 166.8 (CH3eOeC]O), 141.8
(Ctriazole), 129.7 (CHtriazole), 79.4 (CH2eOeCH), 59.5 (NeCHeC]O),
59.4 (CH2eOeCH), 54.4 (CH3eO), 54.0 (CH2eNeN), 45.4
(NeCH2eCHeO), 39.0 (CH3eN), 35.4 (CH2eCHeN). HRMS (ESI): m/z
[M]þ calcd for C12H19N4Oþ5 : 299.1355; found: 299.1374.
(NeCHeC]O),
56.4
(CH3eO),
53.7
(CH2eNeN),
45.3
(NeCH2eCHeO), 39.1 (CH3eN), 36.5 (CH2eCHeN). HRMS (ESI): m/z
[M]þ calcd for C27H31N4Oþ7: 523.2193; found: 523.2185.
3.3.7. 3-((R)-5-(Benzyloxycarbonylamino)-5-carboxypentyl)-5-
(((3R,5S)-1,5-bis(benzyloxycarbonyl)-pyrrolidin-3-yloxy)methyl)-1-
methyl-3H-1,2,3-triazol-1-ium iodide (6c). Light yellow oil, yield
3.3.3. 3-((R)-5-Amino-5-carboxypentyl)-5-(((3R,5S)-5-carbox-
ypyrrolidin-3-yloxy)methyl)-1-methyl-3H-1,2,3-triazol-1-ium tetra-
fluoroborate (1c). Colourless solid, yield 67%, mp 104 ꢀC. [
a
]
22 þ5.9
92%. [
a
]
22 ꢂ3.5 (c 1, CH3OH). 1H NMR (CDCl3, 300 MHz):
d
(ppm)¼
D
D
(c 1, CH3OH). 1H NMR (CD3OD, 300 MHz):
d
(ppm)¼8.94 (s, 1H,
9.01 (s, 1H, CHeNH), 7.29e7.34 (m, 16H, CHaromaticþCHtriazole),
*
CHtriazole), 4.77e4.87 (m, 2H, CHeNH2þCHeCH2eCHeC]O), 4.61
(s, 2H, CH2eCtriazole), 4.23 (s, 3H, CH3eN), 3.32e3.34 (m, 1H,
CHeOeCH2), 3.10e3.20 (m, 2H, CH2eNeN), 2.49e2.51 (m, 2H,
CH2eNH), 1.90 (m, 2H, CHeCH2eCH), 1.73 (m, 2H, CH2eCHeNH),
1.16e1.21 (m, 4H, CH2eCH2eNeNþCH2eCH2eCH2eNeN). 13C NMR
4.86e5.10 (m, 6H, 3 CH2ePh), 4.66 (s, 2H, CH2eCtriazole), 4.54 (m,
2H, CHeNHþCHeCH2eCHeC]O), 4.37(m, 2H, CH2eNeN), 4.13 (s,
3H, CH3eN), 3.56e3.60 (m, 2H, CH2eNeC]O), 2.29e2.47 (m, 1H,
CHeOeCH2), 1.79e1.81 (m, 2H, CHeCH2eCHeC]O), 1.41 (m, 2H,
CH2eCHeNH), 1.16e1.21 (m, 2H, CH2eCH2eNeN), 1.07e1.12 (m,
(CD3OD, 75 MHz):
d
(ppm)¼171.5 (O]CeOH), 140.6 (Ctriazole), 129.5
2H, CH2eCH2eCH2eNeN). 13C NMR (CDCl3, 75 MHz):
d
(ppm)¼
(CHtriazole), 79.4 (CHeOeCH2), 58.2 (CH2eCtriazole), 57.7 (CHeNH2),
53.2(CHeCH2eCHeC]O), 52.5 (CH2eNH), 51.0 (CH2eNeN), 38.0
(CH3eN), 35.2 (CHeCH2eCH), 29.4 (CH2eCHeNH2), 27.9
(CH2eCH2eNeN), 21.4 (CH2eCH2eCH2eNeN). HRMS (ESI): m/z
[M]þ calcd for C15H26N5Oþ5 : 356.1933; found: 356.1939.
173.7 (O]CeOH), 156.3 (O]CeOeCH2), 140.9 (Ctriazole), 136.3
(Caromatic), 128.5 (CHaromatic), 128.4 (CHaromatic), 128.1 (CHaromatic),
127.9 (CHaromatic), 127.8 (CHaromatic), 127.5 (CHaromatic), 127.0
(CHtriazole), 77.8 (CHeOeCH2), 66.8 (CH2ePh), 65.8 (CH2ePh), 64.9
(CH2eCtriazole), 57.7 (CHeNH), 53.8 (CH2eNeC]O), 53.5
(CHeCH2eCHeC]O), 52.1 (CH2eNeN), 39.3 (CH3eN), 36.6
(CHeCH2eCHeC]O), 30.7 (CH2eCHeNH), 28.5 (CH2eCH2eNeN),
21.5 (CH2eCH2eCH2eNeN). HRMS (ESI): m/z [M]þ calcd for
C38H44N5Oþ9 : 714.3139; found: 714.3133.
3.3.4. (R)-3-(5-Amino-5-carboxypentyl)-5-decyl-1-methyl-3H-1,2,3-
triazol-1-ium tetrafluoroborate (2). Off white solid, yield 83%, mp
91 ꢀC. [
a]
D
22 þ4.6 (c 1, CH3OH). 1H NMR (CD3OD, 300 MHz):
d
(ppm)¼
8.80 (s, 1H, CHtriazole), 4.59 (t, J¼6.98 Hz, 2H, CH2eNeN), 4.20 (s, 3H,
CH3eN), 3.73 (m, 1H, CHeNH2), 2.82e2.89 (m, 2H, CH2eCtriazole),
2.01e2.10 (m, 2H, CH2eCH2eNeN),1.87e1.97 (m, 2H, CH2eCHeNH2),
3.3.8. (R)-3-(5-(Benzyloxycarbonylamino)-5-carboxypentyl)-5-
decyl-1-methyl-3H-1,2,3-triazol-1-ium iodide (10). Brownish yellow
1.72.1.82 (m, 2H, CH2eCH2eCtriazole), 1.30e1.52 (m, 16H, 7
*
CH2(alkyl
oil, yield 93%. [
a
]
22 ꢂ4.3 (c 1, CH3OH). 1H NMR (CDCl3, 300 MHz):
d
D
chain)þCH2eCH2eCH2eNeN), 0.90 (t, J¼6.52 Hz, 3H, CH3eCH2). 13C
(ppm)]8.80 (s, 1H, O]CeOH), 8.29 (s, 1H, NHeCH), 7.28e7.32 (m,
6H, CHaromaticþCHtriazole), 5.06 (s, 2H, CH2ePh), 4.61 (t, J¼6.66 Hz, 2H,
CH2eNeN), 4.23e4.30 (m, 1H, CHeNH), 4.17 (s, 3H, CH3eN),
2.79e2.86 (m, 2H, CH2eCtriazole),1.79e2.06 (m, 2H, CH2eCH2eNeN),
1.76e1.88 (m, 2H, CH2eCHeNH),1.66.1.76 (m, 2H, CH2eCH2eCtriazole),
NMR (CD3OD, 75 MHz):
d
(ppm)¼144.9 (Ctriazole), 127.6 (CHtriazole),
53.6(CHeNH2), 52.9(CH2eNeN), 36.3(CH3eN), 31.6(CH2eCHeNH2),
29.7(CH2(alkyl chain))29.3(CH2(alkyl chain))29.2(CH2(alkyl chain))29.0(CH2
)
28.9 (CH2(alkyl chain)), 28.7 (CH2(alkyl chain)), 28.2
(alkyl chain)