3550 J . Org. Chem., Vol. 65, No. 11, 2000
Notes
O2.11 The one-pot conversions described here using TiCl4
involving aryltitanium intermediates have good synthetic
potential in such applications.
In CH2Cl2 (25 mL), N,N-diethylaniline (1.6 mL, 10 mmol) and
benzophenone (0.92 g, 5 mmol) were added at 0 °C under N2.
TiCl4 (3.3 mL of 1:1 solution of TiCl4/CH2Cl2, 15 mmol) in 10
mL of CH2Cl2 was added dropwise for 5 min. The reaction
mixture was stirred at 0 °C for 0.5 h and stirred further at 0-25
°C for 8 h. A saturated K2CO3 solution (20 mL) was added and
stirred for 0.5 h. The reaction mixture was filtered through a
Buchner funnel. The organic layer was separated, and the
aqueous layer was extracted with CH2Cl2 (2 × 25 mL). The
combined organic extract was washed with brine solution (10
mL) and dried over anhydrous MgSO4. The solvent was removed,
and the residue was chromatographed on a silica gel column.
The unreacted amine was eluted using 1:99 EtOAc/hexane
mixture. The alcohol 6 was isolated using 3:97 EtOAc/hexane
mixture as eluent (1.15 g, 85%).
Exp er im en ta l Section
Gen er a l. 1H NMR (200 MHz) and 13C NMR (50 MHz) spectra
were recorded in CDCl3 unless otherwise stated, and TMS was
used as reference (δ ) 0 ppm). The chemical shifts are reported
in ppm on the δ scale relative to CDCl3 (77.0 ppm). Melting
points are uncorrected. Dichloromethane was distilled over
calcium hydride and dried over molecular sieves. Aromatic
tertiary amines were prepared by the reported procedure12 and
were distilled over CaH2. N-Phenylpiperidine was prepared from
aniline and 1,5-dibromopentane.13 Chromatographic purification
was conducted by column chromatography using 100-200 mesh
silica gel obtained from Acme Synthetic Chemicals, India. All
reactions and manipulations were carried out under a dry
nitrogen atmosphere. All yields reported are isolated yields of
materials, adjudged homogeneous by TLC analysis.
6: mp 71-72 °C (lit.19 mp 73 °C); IR (cm-1): νO-H 3474; 13C
NMR δ 147.61, 147.03, 133.92, 129.26, 127.99, 127.77, 126.90,
111.03, 81.87, 44.35, 12.71; 1H NMR δ 7.3 (m, 10H), 7.1 (d, 2H),
6.6 (d, 2H), 3.3 (q, 4H), 2.8 (s, 1H), 1.2 (t, 6H); mass: M+ (m/e)
331.
7: mp 75 °C; 13C NMR δ 146.08, 132.88, 130.16, 111.90, 54.14,
Rep r esen ta tive P r oced u r e for th e Rea ction of N,N-
Dia lk yla r yla m in es. Oxid a t ive Cou p lin g of N,N-Diet h yl-
a n ilin e. In CH2Cl2 (25 mL), N,N-diethylaniline (1.6 mL, 10
mmol) was added at 0 °C under N2. TiCl4 (3.3 mL of 1:1 solution
of TiCl4/CH2Cl2, 15 mmol) in 10 mL of CH2Cl2 was added
dropwise for 5 min. The reaction mixture was stirred at 0 °C
for 0.5 h and stirred further at 0-25 °C for 8 h. A saturated
K2CO3 solution (20 mL) was added and stirred for 0.5 h. The
reaction mixture was filtered through a Buchner funnel. The
organic layer was separated, and the aqueous layer was ex-
tracted with CH2Cl2 (2 × 25 mL). The combined organic extract
was washed with brine solution (10 mL) and dried over anhy-
drous MgSO4. The solvent was removed and the residue was
chromatographed on a silica gel column. The unreacted amine
was eluted using 1:99 EtOAc/hexane mixture. The benzidine 1a
was isolated using 2:98 EtOAc/hexane mixture as eluent (0.65
g, 92%).
1
44.46, 12.78; H NMR δ 7.0 (d, 6H), 6.7 (d, 6H), 5.3 (s, 1H), 3.3
(q, 12H), 1.2 (t, 18H); (Structure was also confirmed by X-ray
crystal structure analysis).
8: mp 110 °C; 13C NMR δ 148.45, 139.12, 138.90, 136.13,
135.69, 133.54, 133.17, 128.37, 128.22, 128.13, 119.94, 111.73,
111.57, 44.29, 12.66; 1H NMR δ 3.4 (q, 6H), 1.2 (t, 4H); mass:
M+ (m/e) 333.
9: mp 60 °C (lit.17 mp 62 °C); 13C NMR δ 146.45, 146.08,
132.15, 130.46, 129.71, 128.30, 125.99, 112.13, 55.45, 44.66,
1
13.02; H NMR δ 6.9-7.5 (m, 13H), 5.7 (s, 1H), 3.6 (q, 8H), 1.5
(t, 12H); mass: M+ (m/e) 386.
10: IR (cm-1): νO-H 3385; 13C NMR δ 147.48, 144.55, 131.09,
128.28, 128.13, 127.07, 126.48, 111.87, 76.02, 44.44, 12.67; 1H
NMR δ 7.5-7.3 (m, 5H), 7.2 (d, 2H), 6.7 (d, 2H), 5.8 (s, 1H), 3.4
(q, 4H), 1.2 (t, 6H); mass: M+ (m/e) 255.
Rep r esen ta tive P r oced u r e for N-Dem eth yla tion . Rea c-
tion of N,N,2,6-Tetr a m eth yla n ilin e. In CH2Cl2 (25 mL),
N,N,2,6-tetramethylaniline (1.6 mL, 10 mmol) was added at 0
°C under N2. TiCl4 (3.3 mL of 1:1 solution of TiCl4/CH2Cl2, 15
mmol) in 10 mL of CH2Cl2 was added dropwise for 5 min. The
reaction mixture was stirred at 0 °C for 0.5 h and stirred further
at 0-25 °C for 8 h. A saturated K2CO3 solution (20 mL) was
added and stirred for 0.5 h. The reaction mixture was filtered
through a Buchner funnel. The organic layer was separated, and
the aqueous layer was extracted with CH2Cl2 (2 × 25 mL). The
combined organic extract was washed with brine solution (10
mL) and dried over anhydrous MgSO4. The solvent was removed,
and the residue was chromatographed on a silica gel column.
The unreacted amine was eluted using 1:99 EtOAc/hexane
mixture. The compound 11a was isolated using 2:98 EtOAc/
hexane mixture as eluent (0.55 g, 85%).
1a : mp 85 °C (lit.14 mp 85 °C); 13C NMR δ146.40, 129.01,
127.19, 112.43, 44.58, 12.85; 1H NMR δ 7.5 (d, 4H), 6.8 (d, 4H),
3.5 (q, 8H), 1.3 (t, 12H); mass: M+ (m/e) 297.
2a : mp 197-198 °C (lit.14 mp 195 °C); 13C NMR δ 149.40,
130.01, 127.03, 113.25, 40.83; 1H NMR δ 7.6 (d, 4H), 6.9 (d, 4H),
3.1 (s, 12H).
3a : mp 108 °C (lit.15 mp 110 °C); 13C NMR δ 147.82, 129.49,
127.06, 112.94, 47.02, 37.60, 11.39; 1H NMR δ 7.6 (d, 4H), 6.9
(d, 4H), 3.5 (q, 4H), 3.0 (s, 6H), 1.2 (t, 6H).
4a : mp 208 °C; 13C NMR δ 150.78, 132.02, 127.02, 116.75,
50.79, 25.87, 24.36; 1H NMR δ 7.5 (d, 4H), 7.1 (d, 4H), 3.2 (s,
8H), 1.6-1.8 (m, 12H); mass: M+ (m/e) 320.
5a : mp 135 °C (lit.16 mp 130 °C); 13C NMR δ 150.54, 134.48,
133.59, 128.86, 128.04, 127.37, 125.74, 125.03, 124.34, 113.68,
1
45.45; H NMR δ 8.4 (d, 2H), 7.2-7.6 (m, 10H), 3.1(s, 12H).
11a : IR (cm-1): νN-H 3387; 13C NMR δ 147.99, 129.37, 129.17,
Rep r esen ta tive P r oced u r e for th e Electr op h ilic Rea c-
1
122.06, 35.52, 18.50; H NMR δ 7.3 (d, 2H), 7.1 (m, 1H), 3.4 (s,
tion . Rea ction of N,N-Dieth yla n ilin e w ith Ben zop h en on e.
1H), 3.1 (s, 3H), 2.6 (s, 6H).
12a : IR (cm-1): νN-H 3412; 13C NMR δ 147.36, 129.83, 126.49,
1
(11) Imaizumi, H.; Sekiguchi, S.; Matsui, K. Bull. Chem. Soc. J pn.
1977, 50, 948.
(12) (a) Baumgarten, H. E. Organic Syntheses; Wiley: New York,
1973; Coll. Vol. 5, p 1085. (b) Gribble, G. W.; Lord, P. D.; Skotnicki, J .;
Dietz, S. E.; Eaton, J . T.; J ohnson, J . L. J . Am. Chem. Soc. 1974, 96,
7812.
(13) N-Phenylpiperidine was prepared by adding aniline (4.6 mL,
50 mmol), 1,5-dibromopentane (6.8 mL, 50 mmol), and K2CO3 (6.9 g,
50 mmol) to 50 mL of acetonitrile, and the mixture was refluxed for
12 h. The reaction mixture was filtered through a Buchner funnel,
and the CH3CN solvent was removed. The organic residue was
extracted with ether (2 × 30 mL) and washed with water. The aqueous
layer was extracted with ether (2 × 20 mL). The combined organic
extract was washed with brine solution (10 mL) and dried over
anhydrous MgSO4. The solvent was removed, and the amine was
distilled under reduced pressure, bp 96-98 °C/5 mm (lit.18 95-98 °C/5
mm).
(14) Michler, W.; Pattinson, S. Ber. 1881, 14, 2161.
(15) Frohlich, E. Ber. 1911, 44, 1057.
(16) Miras, M. C.; Silber, J . J .; Sereno, L. J . Electroanal. Chem. 1986,
201 (2), 367.
(17) Dobner, O. Ann 1883, 217, 223.
(18) Bunnett, J . F.; Brotherton, T. K. J . Org. Chem. 1957, 22, 832.
(19) Reynaud, R. Bull. Soc. Chim. Fr. 1967, 8, 2686.
112.75, 31.16, 20.52; H NMR δ 7.1 (d, 2H), 6.6 (d, 2H), 3.5 (s,
1H), 2.9 (s, 3H), 2.4 (s, 3H).
13a : IR (cm-1): νN-H 3427; 13C NMR δ 148.12, 129.06, 121.63,
113.57, 30.77; 1H NMR δ 7.1 (d, 2H), 6.5 (d, 2H), 3.6 (s, 1H), 2.8
(s, 3H).
14a : IR (cm-1): νN-H 3435; 13C NMR δ 147.50, 129.98, 127.26,
122.50, 116.97, 109.28, 30.80, 17.32; 1H NMR δ 7.3-7.1 (m, 2H),
6.8-6.6 (m, 2H), 3.0 (s, 3H), 2.2 (s, 3H).
Ack n ow led gm en t. We are grateful to the UGC and
DST (New Delhi, India) for financial support. K.N.J .
thanks CSIR, and P.B. thanks UGC for fellowships. We
are also thankful to the UGC for support under Special
Assistance Program.
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectra for
compounds 1a -5a , 6-10, 11a -14a . This material is available
J O991864+