T. Abe et al. / Journal of Fluorine Chemistry 105 (2000) 149±157
155
F-carboxylic acids (9 and 4). The separation of the methyl
ester (4b) of 4 was conducted repeatedly until a suf®cient
amount of 4b for the studies on the preparation of its
derivatives was obtained.
F-(N-methyl-methylpiperidine) (10) [28] had bp 108.0±
108.58C, d420 1.8327 and n2D0 1.2860. IR (gas): 1353 (vs),
1308 (ms), 1284 (m), 1260±1230 (vs), 1179 (m), 1161 (m),
1149 (m), 1124 (w), 1106 (w), 1023 (w), 1002 (w), 963 (w),
919 (m), 870 (w), 736 (w), 716 (w), 665 (w), 683 (w). Mass:
(s), 933 (s), 944±930 (s), 876 (w), 863 (m), 846 (ms), 834 (m,
sh), 793 (ms), 743 (s), 665 (ms), 685 (m), 638±648 (m).
Mass: 404 [M±F] (0.8), 364 [M±C(O)OMe] (6.1), 314
C5F12N (0.6), 176 C4F6N (1.4), 169 C3F7 (2.6), 145
C3F5N (1.7), 131 C3F5 (7.8), 119 C2F5 (2.7), 114
C2F4N (9.1), 109 CF2C(O)OMe (11.6), 100 C2F4
(4.2), 93 C3F3 (1.0), 81 C2F3 (5.7), 78 FC(O)OMe
(1.9), 76 C2F2N (1.0), 69 CF3 (21.4), 59 C(O)OMe
(100), 50 CF2 (2.6). 19F NMR (CDCl3): d 86.6 (m, 2F, ±
NCF2), d 117.3 (quintet, 4F, a-CF2 J11.3 Hz), d 123.5
(s, 4F, b-CF2), d 128.7 ppm (s, 4F, g-CF2). 1H NMR: d 3.98
(s, CH3).
364 [M±F] (14.4), 314 [M±CF3] (3.1), 276 C6F8N
(13.1), 214 C4F8N (1.7), 188 C5F6N (2.1), 181 C4F7
(9.6), 164 C3F6N (7.8), 150 C3F6 (1.7), 145 C3F5N (1.8),
131 C3F5 (11.1), 119 C2F5 (80.8), 114 C2F4N (18.8),
100 C2F4 (54.9), 95 C2F3N (1.7), 93 C3F3 (5.3), 76
3.7. Preparation of F-(N-iododifluoromethyl-
hexahydroazepine) (4e)
C2F2N (2.0), 69 CF3 (100), 50 CF2 (4.9). 19F NMR: d
70.0 (m, NCF3), d 70.2 (m, NCF3), d 86.6 (t, CF3,
J15.5 Hz), d 86.9 (t, CF3, J15.5 Hz), d 95.3 to 140.7
(m, CF2), d 182.8 (m, CF), d 190.6 (m, CF). The mixing
ratio of two isomers was determined by the integration of
two CF peaks on the piperidine ring to be F-(1-methyl-
3-methylpiperidine):F-(1-methyl-4-methylpiperidine)
1:0.51.
A total of 5.0 g of the cell drained product from the
¯uorination of 3 (containing 1.0 g of F-(methylpiperidino-
acetyl ¯uoride) (9) and 2.3 g of F-(1-hexahydroazepine-
acetyl ¯uoride) (4) by GC) and 0.88 g (6.5 mmol) anhydrous
LiI was placed in a 75 ml stainless steel container equipped
with a Hoke miniature valve, evacuated while cooling at
788C, and heated at 1808C for 16 h. The volatile com-
pounds were removed via a vacuum line after cooling the
cylinder at 788C, the pressure in the cylinder was removed
by ®lling it with Ar and ®nally the product was collected
with a syringe. The pink-colored liquid (3.42 g) was found to
contain 0.37 g of F-(N-iodomethyl-hexahydroazepine) (4e)
and 0.71 g of F-(N-iodomethyl-methylpiperidine) (13) in
addition to the unreacted 9 and 4 by GC analysis. The yields
of F-(N-iodomethyl-hexahydroazepine) (4e) and F-(N-iodo-
methyl-methylpiperidine) (13) were 42 and 36%, respec-
tively, based on the sample consumed.
F-(N-methyl-hexahydroazepine) (11) (nc) had bp 111.5±
112.58C, d420 1.8741 and n2D0 1.2928. IR (gas): 1347 (vs),
1297 (m), 1242 (vs), 1206 (m), 1174 (m), 1163 (m), 1142
(m), 1098 (w), 1047 (w), 1003 (ms), 955 (m), 936 (m), 917
(m), 886 (m), 745 (w), 730 (w). Mass: 364 [M±F] (4.1), 314
[M±CF3] (0.7), 276 C6F8N (6.5), 226 C5F8N (1.5), 181
C4F7 (2.7), 176 C4F6N (1.8), 169 C3F7 (3.2), 164
C3F6N (1.9), 145 C3F5N (1.7), 131 C3F5 (67.3), 119
C2F5 (11.1), 114 C2F4N (12.0), 100 C2F4 (20.3), 93
C3F3 (3.3), 76 C2F2N (1.4), 69 CF3 (100), 50 CF2 (3.4).
19F NMR (CDCl3): d 50.2 (quintet, 3F, CF3, J18.9 Hz), d
88.6 (m, 4F, a-CF2), d 124.7 (m, 4F, b-CF2), d 129.0
(m, 4F, g-CF2).
F-(N-iodomethyl-hexahydroazepine) (4e) (nc) had bp
113±1148C, d420 2.1407 and n2D0 1.3556. IR (gas): 1329
(ms), 1290 (s), 1236 (vs), 1210 (w), 1188 (w), 1162 (m),
1131 (w), 1116 (w), 1098 (m), 1079 (w), 1045 (w), 1011 (s),
965 (m), 933 (ms), 839 (w), 965 (m), 934 (ms), 839 (w), 794
Methyl F-(methylpiperidino-acetate) (nc) had bp 160±
1628C, d420 1.7520 and n2D0 1.3237. IR (capillary ®lm): 2968
n(CH) (m), 1788 n(C=O) (vs), 1444 (m), 1314 (vs, broad),
1250±1139 (vs, broad), 1029 (s), 1017 (s), 958 (s), 931 (w),
893 (s), 876 (ms), 845 (w), 820 (ms), 740 (s), 707 (s), 692
(m), 643 (ms), 630 (m), 583 (m), 555 (w). Mass: 364 [M±
(ms), 768 (m), 752 (w). Mass: 364 [M±I] (4.2), 177 CF2I
(8.5), 145 C3F5N (2.7), 131 C3F5 (13.4), 127 I (100),
119 C2F5 (2.1), 114 C2F4 (20.3), 100 C2F4 (42.3), 95
C(O)OMe] (9.4), 181 C4F7 (1.4), 159 C3F7 (6.0), 145
C2F3N (2.6), 93 C3F3 (4.9), 81 C2F3 (2.0), 76 C2F2N
C3F5N (1.8), 131 C3F5 (14.8), 119 C2F5 (11.7), 100
(3.2), 69 CF3 (53.9), 50 CF2 (27.0). 19F NMR (CDCl3): d
15.8 ppm (quintet, 2F, NCF2I, J25.9 Hz), d 89.0 ppm
(t, 4F, a-CF2, J24.2 Hz), d 124.3 (s, 4F, b-CF2), d 128.7
(s, 4F, g-CF2).
C2F4 (21.2), 97, 2.4, 81 C2F3 (8.4), 69 CF3 (32.5), 59
C(O)OMe (100), 50 CF2 (1.2). 19F NMR (CDCl3): d
70.1 (m, CF3), d 70.4 (m, CF3), d 91.4 (m,
NCF2C(O)O), d 92.2 (m, NCF2C(O)O), d 182.6 (m,
2F, CF), d 190.5 (m, CF). 1H NMR: d 3.98 (s, CH3), d 3.96
(s, CH3). The mixing ratio of two isomers was determined to
be methyl F-(3-methylpiperido-acetate):methyl F-(4-
methylpiperido-acetate)1:0.52 by the integration of two
CF peaks on the piperidine ring.
Methyl F-(1-hexahydroazepine-acetate) (4b) (nc) had bp
163±1658C, d420 1.7749 and n2D0 1.3278. IR (capillary ®lm):
2968 n(CH) (m), 1794 n(C=O) (vs), 1445 (m), 1334±1275
(vs), 1220 (vs), 1186 (s), 1159 (vs), 1119 (s), 1072 (s), 1042
F-(N-iodomethyl-methylpiperidine) (13) (nc): IR (gas):
1343 (m), 1313 (vs), 1284 (m), 1262 (s), 1231 (ms), 1213
(ms), 1184 (ms), 1173 (ms), 1153 (m), 1138 (w), 1102 (m),
1030 (ms), 998 (m), 975 (m), 961 (m), 889 (ms), 877 (w),
763 (ms), 703 (w). Mass: 364 [M±I] (3.1), 195 CF3I (1.3),
177 CF2I (7.0), 131 C3F5 (8.3), 127 I (52.2), 119 C2F5
(2.6), 114 C2F4N (10.3), 100 C2F4 (10.4), 95 C2F3N
(2.1), 93 C3F3 (2.6), 69 CF3 (100). 50 CF2 (16.1). 19F
NMR (CDCl3): d 17.8 to 18.2 ppm (m, ±NCF2I), d 70.9
to 138.0 ppm (m, CF2), d 182.7 (m, CF), d 189.9 (m,