D. J. Aitken et al. / Tetrahedron 58 (2002) 5933±5940
5939
2
6
1
2
2
6
.68±1.77 (m, 4H, 2CH b), 2.35 (t, J7.6 Hz, 2H), 2.44±
4.5.3. N-Pentylpiperidine. To a solution of piperidine
(12.1 mmol) and triethylamine (24.4 mmol) in THF
(5 mL) wasadded dropwi se 1-bromopentane (13.7 mmol).
The reaction mixture was stirred at rt for 5 days, ®ltered, and
evaporated. The residue was treated with distilled water
(10 mL) and extracted with dichloromethane (4£8 mL).
2
1
3
.52 (m, 4H, 2CH a), 3.28 (s, 2H); C NMR d 13.0 (2),
2
1.5 (1), 23.2 (2C; 1), 25.6 (1), 39.1 (1), 53.2 (2C; 1),
4.6 (1), 207.6 (1); MS m/z: 170 [MH] .
1
1
.4.4. N-(2-Oxohexyl)piperidine. Bp 1208C (2 mmHg);
7
4
1
IR n 1715; H NMR d 0.84 (t, J7.3 Hz, 3H, CH ), 1.24
The combined organic phases were dried (MgSO ), ®ltered
3
4
(
(
2
1
sext, J7.5 Hz, 2H, MeCH ), 1.35 (m, 2H, CH g), 1.48
1
CH a and RCH CO), 3.09 (s, 2H, NCH CO); C NMR d
and evaporated, then distilled under reduced pressure to
give the title amine asa yellow liquid (1.53 g; 82 %). Bp
2
2
quint, J7.4 Hz, 2H), 1.54 (m, 4H, 2CH b), 2.35 (m, 6H,
2
3
1
2
2
2
678C (9 mmHg); H NMR d 0.82 (t, J7.3 Hz, 3H, CH ),
3
3.8 (2), 22.4 (1), 23.8 (1), 25.6 (2C; 1), 25.8 (1), 40.0
1.16±1.28 (m, 4H), 1.36±1.46 (m, 4H), 1.49±1.51 (m, 4H,
2CH b), 2.19 (dd, J7.8 and 5.5 Hz, 2H, NCH ), 2.31 (m,
(1), 54.7 (2C; 1), 68.3 (1), 209.2 (1); MS m/z: 184
[MH] .
2
2
1
13
4H, 2CH a); C NMR d 14.0 (2), 22.6 (1), 24.5 (1), 26.0
2
(2C; 1), 26.7 (1), 30.0 (1), 54.6 (2C; 1), 59.7 (1); MS
m/z: 154 [MH] .
1
4
(
.4.5. N-(Cyanomethyl)pyrrolidine dimer. Bp 2008C
1 mmHg); IR n 1650, 2180, 3350, 3480; H NMR d
1
1
4
.83±1.85 (m, 8H), 2.61±2.64 (m, 4H), 2.72±2.75 (m,
H), 3.42 (s, 2H), 5.27 (br s, 2H, NH2); C NMR d 23.6
1
3
Acknowledgements
(
9
2C; 1), 24.2 (2C; 1), 51.6 (2C; 1), 53.8 (2C; 1), 54.7 (1),
1
2.5 (1), 117.5 (1), 153.1 (1); MS m/z: 221 [MH] .
We thank undergraduate students E. Conchon, S. Lagoute
and C. Servagnat for some experiments or calculations,
Professors P. E. Hoggan and J.-C. Gramain for helpful
discussions and the CNRS for AIP funding.
1
.4.6. N-(Cyanomethyl)piperidine dimer. Bp 2208C
0.7 mmHg); IR n 1645, 1635, 2180, 3360, 3490; H
NMR d 1.43±1.44 (m, 4H), 1.53±1.64 (m, 8H), 2.37 (m,
7
4
(
1
4
H), 2.54±2.57 (m, 4H), 3.16 (s, 2H), 5.24 (br s, 2H, NH2);
C NMR d 23.1 (1), 23.9 (1), 25.6 (2C; 1), 26.4 (2C; 1),
2.6 (2C; 1), 54.3 (2C; 1), 57.8 (1), 95.9 (1), 117.6 (1),
1
3
References
5
1
1
52.0 (1); MS m/z: 249 [MH] .
1
. Le Bail, M.; P e rard, J.; Aitken, D. J.; Bonin, M.; Husson, H.-P.
Tetrahedron Lett. 1997, 38, 7177±7180.
2. Le Bail, M.; Pe
Ârard, J.; Aitken, D. J.; Husson, H.-P.
Tetrahedron Lett. 1999, 40, 5309±5313.
4.5. General procedure for preparation of tertiary
amines
3
. (a) Salem, L. J. Am. Chem. Soc. 1968, 90, 543±553. (b) Fukui,
K.; Yonezawa, T.; Shingu, H. J. Chem. Phys. 1952, 20, 722±
725. (c) Fukui, K. Bull. Chem. Soc. Jpn 1966, 39, 498±503.
. Stewart, J. J. P. QCPE # 455, 1990.
2
4
A modi®cation of the method of Alunni and Tijskens was
used for the preparation of the following tertiary amines.
4
2
.5.1. N-Ethylpyrrolidine. To a solution of pyrrolidine
14.4 mmol) and triethylamine (28.0 mmol) in THF
5 mL) wasadded dropw ie s bromoethane (17.0 mmol).
The reaction mixture was stirred at rt for 4 days, then
ltered. The solids were washed through with THF
15 mL) and the combined ®ltrate distilled at atmospheric
pressure to give the title amine as a yellow liquid (1.14 g;
4
4
5. (a) Stewart, J. J. P. J. Comput. Chem. 1989, 10, 209±221.
(b) Stewart, J. J. P. J. Comput. Chem. 1989, 10, 221±231.
(c) Stewart, J. J. P. J. Comput. Chem. 1991, 12, 320±341.
6. Sybyl package, TriposInc., 1699 South Hanley Rd., St. Louis,
MO 63144-2917.
7. Safont, V. S.; Moliner, V.; Oliva, M.; Castillo, R.; Andr eÁ s, J.;
Gonzalez, F.; Carda, M. J. Org. Chem. 1996, 61, 3467±3475.
8. Boutahir, D. Etude Th e orique de la Structure et de la
R e activit e desRe Âactifsde Grignard. Doctoral TheisNo
249, University of Nancy I, 1992.
(
(
®
(
1
8
0%). Bp 1038C (760 mmHg); H NMR d 0.96 (t,
J7.1 Hz, 3H, CH ), 1.78 (br s, 4H, 2CH b), 2.41±2.46
3
2
1
3
(
(
m, 6H, MeCH and 2CH a); C NMR d 14.0 (2), 23.3
2 2
1
2C; 1), 50.1 (1), 53.8 (2C; 1); MS m/z: 100 [MH] .
9. (a) Guggenberger, L. J.; Rundle, R. E. J. Am. Chem. Soc. 1964,
6, 5344. (b) Stucky, G.; Rundle, R. E. J. Am. Chem. Soc.
8
2
.5.2. N-Pentylpyrrolidine. To a solution of pyrrolidine
14.4 mmol) and triethylamine (28.0 mmol) in THF (5 mL)
5
4
1964, 86, 4825±4830. (c) Guggenberger, L. J.; Rundle, R. E.
J. Am. Chem. Soc. 1968, 90, 5375±5378.
(
wasadded dropw ies 1-bromopentane (16.1 mmol). The
reaction mixture was stirred at rt for 5 days, ®ltered, and
the ®ltrate evaporated. The residue was treated with distilled
water (10 mL) and extracted with dichloromethane
10. Explicit evocation appearsin the following: (a) Higa sh iyama,
K.; Inoue, H.; Takahashi, H. Tetrahedron 1994, 50, 1083±
1092. (b) Takahashi, H.; Hsieh, B. C.; Higashiyama, K.
Chem. Pharm. Bull. 1990, 38, 2429±2434. (c) Takahashi,
H.; Niwa, H.; Higashiyama, K. Heterocycles 1988, 27,
2099±2102. (d) Takahashi, H.; Suzuki, Y.; Kametani, T.
Heterocycles 1983, 20, 607±610.
(
(
4£8 mL). The combined organic phases were dried
MgSO ), ®ltered and evaporated, and the residual oil
4
distilled under reduced pressure to give the title amine as
a yellow liquid (1.70 g; 83%). Bp 538C (10 mmHg); H
1
11. For mechanistic discussions relating to similar systems, see:
(a) Ishii, A.; Miyamoto, F.; Higashiyama, K.; Mikami, K.
Tetrahedron Lett. 1998, 39, 1199±1202. (b) Yamazaki, N.;
Kibayashi, C. Tetrahedron Lett. 1997, 38, 4623±4626.
(c) Andr e s, C.; Nieto, J.; Pedrosa, R.; Villama nÄ a n, N.
J. Org. Chem. 1996, 61, 4130±4135. (d) Wu, M.-J.; Pridgen,
L. N. J. Org. Chem. 1991, 56, 1340±1344.
NMR d 0.89 (t, J6.9 Hz, 3H, CH ), 1.28±1.35 (m, 4H),
3
1
2
2
.48±1.55 (quint, J7.5 Hz, 2H), 1.76±1.80 (m, 4H,
CH b), 2.39±2.42 (dd, J7.7 and 7.9 Hz, 2H, NCH ),
2
2
1
.46±2.48 (m, 4H, 2CH a); C NMR d 14.0 (2), 22.6
3
2
(
(
1), 23.3 (2C; 1), 28.8 (1), 29.9 (1), 54.2 (2C; 1), 56.7
1); MS m/z: 142 [MH] .
1