6224 J . Org. Chem., Vol. 62, No. 18, 1997
Katritzky et al.
NMR δ 7.7, 29.1, 50.8, 74.5, 113.1, 117.4, 129.1, 148.8. Anal.
Calcd for C12H19NO: C, 74.57; H, 9.91; N, 7.25. Found: C,
74.84; H, 10.16; N, 7.27.
procedure gives cleaner reactions, higher yields, and a
novel route to dianions. On the other hand, the limited
availability of the starting R-aminoalkyl sulfones, means
that the benzotriazole approach possesses wider synthetic
utility.
2-[(P h en yla m in o)m eth yl]-2-p en ta n ol (3g): colorless oil;
1H NMR δ 0.93 (t, 3H, J ) 7.2 Hz), 1.21 (s, 3H), 1.30-1.56 (m,
4H), 1.94 (br s, 1H), 3.03 and 3.06 (AB, 2H, J AB ) 12.6 Hz),
3.93 (br s, 1H), 6.64 (d, 2H, J ) 7.5 Hz), 6.70 (t, 1H, J ) 7.5
Hz), 7.16 (t, 2H, J ) 7.7 Hz); 13C NMR δ 14.6, 17.1, 24.9, 42.6,
53.5, 72.6, 113.1, 117.5, 129.2, 148.7. Anal. Calcd for
C12H19NO: C, 74.54; H, 9.91; N, 7.25. Found: C, 74.84; H,
10.30; N, 7.28.
Exp er im en ta l Section
Gen er a l Com m en ts. Melting points were measured on a
hot-stage microscope and are uncorrected. 1H and 13C NMR
data were collected on a 300 MHz NMR spectrometer (300 and
75 MHz, respectively), with TMS as internal reference in
CDCl3. All mass spectra were determined on a HP5890 Series
II Capillary GC operating in split mode with helium carrier
gas and fitted with a mass selective detector (MSD). The
column used was a HP5 capillary column 30 m × 0.25 mm,
with 0.25 µm film thickness of 5% phenylmethylsilicone gum.
The temperature program used the initial temperature of 50
°C for 1 min and then ramped at 10 °C min-1 to 250 °C.
Column chromatography was carried out using 230-400 mesh
silica.
Gen er a l P r oced u r e for On e-Step Tosylm eth yla m in es
Rea ction s. A solution of the appropriate tosylmethylamines
(2 mmol) and electrophiles (2 mmol) in THF (10 mL) was added
dropwise to the SmI2 (4.5 mmol) solution in THF-HMPA (20:
1) at 0 °C under argon or nitrogen. The reaction was kept
stirring until the deep purple color disappeared (generally 2-4
h) and then quenched with saturated aqueous NaHCO3
solution (40 mL) at the same temperature. The reaction
mixture was separated, and the aqueous phase was extracted
with diethyl ether (2 × 40 mL). The combined organic extracts
were washed with saturated aqueous NaCl, dried, and evapo-
rated to give the crude product which was purified by flash
column chromatography on silica gel (eluent: hexanes-ethyl
acetate-0.5% triethylamine) to afford the pure product.
1-[(N-P h en yl-N-eth ylam in o)m eth yl]-3-pen tan ol (3a): col-
orless oil; 1H NMR δ 0.92 (t, 6H, J ) 7.5 Hz), 1.11 (t, 3H, J )
7.2 Hz), 1.55 (q, 4H, J ) 7.5 Hz), 1.83 (s, 1H), 3.26 (s, 2H),
3.43 (q, 2H, J ) 7.2 Hz), 6.71 (t, 1H, J ) 7.2 Hz), 6.89 (d, 2H,
J ) 8.1 Hz), 7.21 (t, 2H, J ) 7.5 Hz); 13C NMR δ 7.9, 10.6,
29.2, 46.6, 58.2, 75.9, 113.9, 116.9, 129.0, 149.6. Anal. Calcd
for C12H23NO: C, 75.97; H, 10.47; N, 6.33. Found: C, 75.87;
H, 10.75; N, 6.54.
1-C y c lo h e x y l-2-(N -p h e n y l-N -e t h y la m in o )e t h a n o l
1
(3h ): colorless oil; H NMR δ 1.12 (t, 3H, J ) 7.1 Hz), 1.15-
1.36 (m, 5H), 1.37-1.52 (m, 1H), 1.64-1.84 (m, 4H), 1.85-
1.98 (m, 1H), 2.33 (br s, 1H), 3.12 (dd, 1H, J ) 10.2, 14.7 Hz),
3.25-3.55 (m, 3H), 3.58-3.68 (m, 1H), 6.74 (t, 1H, J ) 7.2
Hz), 6.80 (d, 2H, J ) 7.8 Hz), 7.23 (t, 2H, J ) 7.2 Hz); 13C
NMR δ 11.5, 26.0, 26.2, 26.5, 28.2, 29.0, 41.8, 46.2, 55.3, 72.5,
113.9, 117.2, 129.1, 148.7. Anal. Calcd for C16H25NO: C,
77.68; H, 10.19; N, 5.66. Found: C, 77.91; H, 10.40; N, 5.83.
N-Eth yl-N-(m on od eu ter iom eth yl)a n ilin e (5, 82% D):
colorless oil; 1H NMR δ 1.11 (t, 3H, J ) 7.2 Hz), 2.87 (t, 2H, J
) 1.5 Hz, D-5) [2.89 (s, 3H), H-5], 3.39 (q, 2H, J ) 7.2 Hz),
6.63-6.76 (m, 3H), 7.23 (t, 2H, J ) 8.4 Hz); 13C NMR δ 11.2,
36.9 (t, J CD ) 20.5 Hz, D-5) [38.2, H-5], 46.8, 112.4, 116.0,
129.1, 149.2.
N -Isop r op yl-(N -m e t h yl-N -p h e n yla m in o)a ce t a m id e
(6):1 white solid, mp 91-93 °C (lit.1 92-94 °C); 1H NMR δ
1.12 (d, 6H, J ) 6.6 Hz), 2.99 (s, 3H), 3.81 (s, 2H), 4.08-4.22
(m, 1H), 6.44 (br s, 1H), 6.73 (d, 2H, J ) 8.2 Hz), 6.84 (t, 1H,
J ) 7.4 Hz), 7.28 (t, 2H, J ) 7.7 Hz); 13C NMR δ 22.5, 39.6,
41.0, 58.9, 113.1, 118.5, 129.2, 149.3, 169.3.
Gen er a l P r oced u r e for th e Dia n ion Rea ction s. Gen-
eral procedure for one-step tosylmethylamine reactions were
followed, except that 4 equiv of SmI2 was used instead of 2
equiv.
N-Met h yl-N-(2-h yd r oxy-2-et h ylbu t yl)-4-(2-h yd r oxy-2-
eth ylbu tyl)a n ilin e (8a ): colorless oil; 1H NMR δ 0.91 (t, 6H,
J ) 7.5 Hz), 0.94 (t, 6H, J ) 7.2 Hz), 1.24 (br s, 1H), 1.44 (q,
4H, J ) 7.5 Hz), 1.57 (q, 4H, J ) 7.5 Hz), 1.82 (br s, 1H), 2.63
(s, 2H), 2.97 (s, 3H), 3.27 (s, 2H), 6.84 (d, 2H, J ) 8.7 Hz),
7.06 (d, 2H, J ) 8.4 Hz); 13C NMR δ 7.9, 8.0, 29.2, 30.2, 41.1,
43.6, 61.4, 74.5, 76.0, 112.8, 125.6, 131.1, 150.2. Anal. Calcd
for C19H33NO2: C, 74.22; H, 10.82; N, 4.56. Found: C, 74.02;
H, 11.05; N, 4.65.
1-[(N -P h e n y l-N -m e t h y la m in o )m e t h y l]-3-p e n t a n o l
1
(3b):1 colorless oil; H NMR δ 0.93 (t, 6H, J ) 7.4 Hz), 1.55
N-E t h yl-N-[(1-h yd r oxycyclop en t yl)m et h yl]-4-[(1-h y-
d r oxycyclop en tyl)m eth yl]a n ilin e (8b): colorless oil; 1H
NMR δ 1.13 (t, 3H, J ) 7.2 Hz), 1.43 (br s, 1H), 1.49-1.98 (m,
16H), 2.13 (br s, 1H), 2.77 (s, 2H), 3.37 (s, 2H), 3.43 (q, 2H, J
) 6.9 Hz), 6.83 (d, 2H, J ) 8.7 Hz), 7.08 (d, 2H, J ) 8.4 Hz);
13C NMR δ 11.0, 23.5, 38.6, 39.2, 46.0, 46.2, 59.8, 82.2, 82.9,
114.0, 126.7, 130.7, 148.1. Anal. Calcd for C20H31NO2: C,
75.67; H, 9.84; N, 4.41. Found: C, 75.25; H, 10.30; N, 4.36.
N -Isop r op yl-[N -(4-m e t h ylp h e n yl)-N -m e t h yla m in o]-
a ceta m id e (9): mp 83-85 °C; 1H NMR δ 1.12 (d, 6H, J ) 6.3
Hz), 2.27 (s, 3H), 2.95 (s, 3H), 3.76 (s, 2H), 4.06-4.21 (m, 1H),
6.47 (br s, 1H), 6.65 (d, 2H, J ) 9.0 Hz), 7.08 (d, 2H, J ) 8.1
Hz); 13C NMR δ 20.2, 22.7, 39.9, 41.0, 59.5, 113.5, 128.1, 129.8,
147.5, 169.6. Anal. Calcd for C13H20N2O: C, 70.87; H, 9.15;
N, 12.72. Found: C, 70.69; H, 9.49; N, 12.68.
Tw o-Step Rea ction P r oced u r e. A solution of N-(tosyl-
methyl)-N-ethylaniline (1a ) (0.73 g, 2.5 mmol) in dry THP (10
mL) was added to a stirred SmI2/THP-HMPA solution6b (4.5
mmol) at room temperature under argon for approximately 5
min. Benzaldehyde (0.32 g, 2 mmol) was then added and after
1.5 h, the reaction was quenched with water. After the usual
workup, 1-phenyl-2-[(N-phenyl-N-ethylamino)methyl]ethanol
(3e) was isolated in 45% yield.
(q, 4H, J ) 7.5 Hz), 1.92 (br s, 1H), 2.96 (s, 3H), 3.28 (s, 2H),
6.73 (t, 1H, J ) 7.4 Hz), 6.89 (d, 2H, J ) 8.0 Hz), 7.22 (t, 2H,
J ) 7.5 Hz); 13C NMR δ 11.5, 46.2, 59.3, 71.4, 113.7, 117.3,
125.9, 127.7, 128.4, 129.3, 142.0, 148.2.
1-[(N -P h e n yl-N -m e t h yla m in o)m e t h yl]-1-cyclop e n -
ta n ol (3c): colorless oil; 1H NMR δ 1.53-1.74 (m, 6H), 1.75-
1.95 (m, 2H), 2.11 (br s, 1H), 2.94 (s, 3H), 3.37 (s, 2H), 6.72 (t,
1H, J ) 7.2 Hz), 6.85 (d, 2H, J ) 8.5 Hz), 7.20 (t, 2H, J ) 7.5
Hz); 13C NMR δ 23.4, 38.3, 40.1, 62.2, 83.2, 112.9, 117.0, 128.9,
151.0. Anal. Calcd for C13H19NO: C, 76.06; H, 9.33; N, 6.82.
Found: C, 76.08; H, 9.68; N, 6.77.
1-[(N -P h e n yl-N -m e t h yla m in o)]-3-m e t h yl-2-b u t a n ol
1
(3d ):1 colorless oil; H NMR δ 1.01 (d, 3H, J ) 6.9 Hz), 1.05
(d, 3H, J ) 6.8 Hz), 1.70-1.83 (m, 1H), 2.32 (br s, 1H), 2.95
(s, 3H), 3.17-3.37 (m, 2H), 3.65-3.74 (m, 1H), 6.79 (t, 1H, J
) 7.4 Hz), 6.84 (d, 2H, J ) 8.2 Hz), 7.26 (t, 2H, J ) 7.4 Hz);
13C NMR δ 17.7, 18.7, 31.9, 39.2, 58.4, 73.5, 113.7, 117.6, 129.1,
150.7.
1-P h en yl-2-(N-p h en yl-N-eth yla m in o)eth a n ol (3e): col-
1
orless oil; H NMR δ 1.09 (t, 3H, J ) 7.1 Hz), 2.71 (br s, 1H),
3.46 (q, 2H, J ) 7.1 Hz), 3.36-3.51 (m, 2H), 4.92 (dd, 1H, J )
4.4, 8.5 Hz), 6.76 (t, 1H, J ) 7.4 Hz), 6.84 (d, 2H, J ) 8.2 Hz),
7.20-6.45 (m, 7H); 13C NMR δ 11.5, 46.2, 59.3, 71.4, 113.7,
117.3, 125.9, 127.7, 128.4, 129.3, 142.0, 148.2. Anal. Calcd
for C16H19NO: C, 79.63; H, 7.94; N, 5.80. Found: C, 79.64;
H, 7.70; N, 6.08.
Gen er a l P r oced u r e for P r ep a r in g Tosylm eth yla m in es
(1). Aqueous formaldehyde (37%, 1.70 g, 21 mmol) and a
solution of the substituted aniline (20 mmol) in methanol (20
mL) were added, in turn, to a solution of p-toluenesulfinic acid
(20 mmol) in methanol (20 mL) at 0 °C and stirred for 2 h.
The precipitate was filtered with suction and dried under
vacuum to give the product 1.
3-[(P h en yla m in o)m eth yl]-3-p en ta n ol (3f): colorless oil;
1H NMR δ 0.89 (t, 6H, J ) 7.4 Hz), 1.55 (q, 4H, J ) 7.5 Hz),
1.87 (br s, 1H), 3.05 (s, 2H), 3.89 (br s, 1H), 6.64 (d, 2H, J )
7.8 Hz), 6.70 (t, 1H, J ) 7.3 Hz), 7.16 (t, 2H, J ) 8.3 Hz); 13C