Bedford and Betham
4i. 2-Chloroaniline (52.5 µL, 0.5 mmol) and 2-bromoanisole
(63.5 µL, 0.51 mmol) gave 4i as an off-white solid: 82 mg (83.0%);
0.02 mmol), and [HPtBu3][BF4] (0.008 g, 0.025 mmol) were
suspended in toluene (3 mL). The appropriate 2-chloroaniline (0.5
mmol) and aryl bromide (0.51 mmol) were then added, and the
microwave vial was sealed. The reaction was then heated in the
microwave reactor at 160 °C for 3 h, allowed to cool, and then
quenched by addition of HCl(aq) (2 M, 3 mL). The organic phase
was extracted with CH2Cl2 (2 × 20 mL), dried (MgSO4), then
filtered, and the solvent was removed under reduced pressure. The
crude product mixture was then filtered through a SiO2 plug and
used in the cyclization step without further purification.
3c. 3-Amino-4-chlorobenzotrifluoride (68.7 µL, 0.50 mmol) and
2-bromoanisole (63.5 µL, 0.51 mmol) gave 3c as a light brown
oil: 116 mg (77.0%); Rf 0.91 (CHCl3); 1H NMR (400 MHz, CDCl3)
δ 3.81 (s, 3H, OMe), 6.45 (br s, 1H, NH), 6.86-6.91 (m, 2H),
6.91-6.99 (m, 2H), 7.23 (br d, J ) 7.8 Hz, 1Hanisole), 7.36 (br d,
J ) 8.3 Hz, 1H, Ar Haniline), 7.42 (br d, J ) 2.0 Hz, 1H, Ar Haniline);
13C NMR (100 MHz, CDCl3) δ 55.7 (s, OMe), 111.4 (s, CH), 111.6
(s, CH), 116.3 (q, JCF ) 4 Hz, CH), 119.0 (s, CH), 121.0 (s, CH),
123.4 (s, CH), 125.0 (s, C), 125.1 (s, C), 129.7 (q, JCF ) 140 Hz,
CH), 130.1 (s, CH), 140.9 (s, C), 150.5 (s, C).
3d. 2-Chloro-5-methoxy-4-methylaniline (85.8 mg, 0.5 mmol)
and 4-bromoanisole (63.8 µL, 0.51 mmol) gave 3d as a light brown
oil: 98 mg (81.5%); Rf 0.62 (CHCl3); 1H NMR (400 MHz, CDCl3)
δ 2.02 (s, 3H, Me), 3.57 (s, 3H, OMe), 3.73 (s, 3H, OMe), 5.73
(br s, 1H, NH), 6.44 (s, 1H, Ar H6aniline), 6.81 (d, J ) 8.8 Hz, 2H,
Ar H2,6anisole), 6.97 (s, 1H, Ar H3aniline), 7.03 (d, J ) 8.8 Hz, 2H, Ar
H3,5anisole); 13C NMR (100 MHz, CDCl3) δ 15.3 (s, Me), 55.6 (s,
OMe), 97.9 (s, CH), 111.3 (s, C), 114.9 (s, CH), 118.2 (s, C), 123.5
(s, CH), 130.8 (s, CH), 135.0 (s, C), 140.4 (s, C), 156.0 (s, C),
157.1 (s, C).
3e. 2-Chloro-5-methoxy-4-methylaniline (85.8 mg, 0.5 mmol)
and 3-bromoanisole (64.1 µL, 0.51 mmol) gave 3e as a clear oil:
121 mg (82.5%); Rf 0.69 (CHCl3); 1H NMR (400 MHz, CDCl3) δ
2.02 (s, 3H, Me), 3.64 (s, 3H, OMe), 3.70 (s, 3H, OMe), 5.86 (br
s, 1H, NH), 6.45 (ddd, J ) 0.8, 2.5 & 8.2 Hz, 1H, Ar H6anisole),
6.59 (dd, J ) 2.4 & 2.5 Hz, 1H, Ar H2anisole), 6.62 (ddd, J ) 0.8,
2.0 & 7.8 Hz, 1H, Ar H4anisole), 6.77 (s, 1H, Ar H4aniline), 7.02 (s,
1H, Ar H3aniline), 7.11 (t, J ) 8.0 Hz, 1H, Ar H5anisole); 13C NMR
(100 MHz, CDCl3) δ 15.5 (s, CH3), 55.3 (s, OMe), 55.5 (s, OMe),
100.6 (s, CH), 107.4 (s, CH), 111.3 (s, CH), 113.2 (s, CH), 113.4
(s, C), 120.2 (s, C), 122.9 (s, C), 123.9 (s, CH), 130.6 (s, CH),
138.0 (s, C), 156.9 (s, C), 160.8 (s, C) (sample contaminated with
∼5% 3-bromoanisole).
1
Rf 0.62 (CHCl3); mp 65-67 °C; H NMR (400 MHz, CDCl3) δ
3.92 (s, 3H, OMe), 6.82 (d, J ) 7.8 Hz, 1H, Ar H2), 7.08 (t, J )
7.8 Hz, 1H, Ar H3), 7.14 (ddd, J ) 1.0, 6.8 & 7.8 Hz, 1H, Ar H7),
7.33 (dd, J ) 1.0, & 7.8 Hz, 1H, Ar H8), 7.36 (ddd, J ) 1.0, 6.8
& 7.8 Hz, 1H, Ar H6), 7.60 (d, J ) 7.8 Hz, 1H, Ar H4), 7.98 (dd,
J ) 1.0 & 7.8 Hz, 1H, Ar H5), 8.17 (br s, 1H, NH); 13C NMR (100
MHz, CDCl3) δ 55.50 (s, OMe), 105.9 (s, CH), 110.9 (s, CH),
112.8 (s, CH), 119.4 (s, CH), 119.7 (s, CH), 120.5 (s, CH), 123.6
(s, C), 124.3 (s, C), 125.7 (s, CH), 129.8 (s, C), 139.2 (s, C), 145.7
(s, Ar C-O); HRMS (EI) calcd for C13H11NO [M+] 197.084 064,
found 197.084 053. Anal. calcd for C13H11NO: C, 79.17; H, 5.62;
N, 7.10. Found: C, 79.26; H, 5.20; N, 6.88.
4j. 2-Chloroaniline (52.5 µL, 0.5 mmol) and 2-bromo-p-xylene
(70.5 µL, 0.51 mmol) gave 4j as an off-white powder: 77 mg
1
(79.0%); Rf 0.53 (CHCl3); mp 90-92 °C; H NMR (400 MHz,
CDCl3) δ 2.46 (s, 3H, 1-Me), 2.78 (s, 3H, 4-Me), 6.86 (d, J ) 7.3
Hz, 1H, Ar H3), 7.06 (d, J ) 7.3 Hz, 1H, Ar H2), 7.17 (dt, J ) 1.0
& 8.1 Hz, 1H, Ar H6), 7.33 (dt, J ) 1.2 & 7.7 Hz, 1H, Ar H7),
7.40 (dd, J ) 1.0 & 8.0 Hz, 1H, Ar H8), 7.90 (br s, 1H, NH), 8.10
(br d, J ) 7.7 Hz, 1H, Ar H5); 13C NMR (100 MHz, CDCl3) δ
16.6 (s, 1-Me), 20.5 (s, 4-Me), 110.4 (s, CH), 116.9 (s, C), 119.4
(s, CH), 120.9 (s, CH), 121.4 (s, C), 122.6 (s, CH), 124.5 (s, C),
125.0 (s, CH), 126.1 (s, CH), 130.8 (s, C), 138.7 (s, C), 139.3 (s,
C); HRMS (EI) calcd for C14H13N [M+] 195.104 800, found
195.105 160. Anal. calcd for C14H13N: C, 86.12; H, 6.71; N, 7.17.
Found: C, 86.27; H, 6.70; N, 7.12.
4k. 2-Chloro-6-methylaniline (60.3 µL, 0.5 mmol) and 2-bro-
motoluene (61.4 µL, 0.51 mmol) gave 4k as a white powder: 89
1
mg (91.5%); Rf 0.90 (CHCl3); mp 171-173 °C; H NMR (400
MHz, CDCl3) δ 2.63 (s, 6H, Me), 7.21 (t, J ) 7.3 Hz, 2H, Ar H3
& H6), 7.27 (d, J ) 7.3 Hz, 2H, Ar H2 & H7), 7.82 (br s, 1H, NH),
7.96 (d, J ) 7.3 Hz, 2H, Ar H4 & H5); 13C NMR (100 MHz, CDCl3)
δ 16.9 (s, Me), 118.0 (s, Ar CH), 119.6 (s, Ar CH), 119.8 (s, Ar
C), 123.3 (s, Ar C), 126.2 (s, Ar CH), 138.7 (s, Ar C); HRMS (EI)
calcd for C14H13N [M+] 195.104 800, found: 195.108 132. Anal.
calcd for C14H13N: C, 86.12; H, 6.71; N, 7.17. Found: C, 85.99;
H, 6.74; N, 7.05.
4l. 2-Chloro-6-methylaniline (60.3 µL, 0.5 mmol) and 2-bro-
moanisole (63.5 µL, 0.51 mmol) gave 4l as a light brown solid:
93 mg (88.0%); Rf 0.67 (CHCl3); mp 104-106 °C; 1H NMR (400
MHz, CDCl3) δ 2.58 (s, 3H, Me), 4.04 (s, 3H, OMe), 6.90 (d, J )
7.8 Hz, 1H, Ar H2), 7.16 (t, J ) 7.3 Hz, 1H, Ar H3), 7.16 (t, J )
7.8 Hz, 1H, Ar H6), 7.23 (d, J ) 7.3 Hz, 1H, Ar H4), 7.67 (d, J )
7.8 Hz, 1H, Ar H7), 7.91 (d, J ) 7.8 Hz, 1H, Ar H5), 8.15 (br s,
1H, NH); 13C NMR (100 MHz, CDCl3) δ 16.9 (s, Me), 55.5 (s,
OMe), 105.7 (s, CH), 113.0 (s, CH), 118.2 (s, CH), 119.5 (s, CH),
119.8 (s, CH), 120.1 (s, C), 123.1 (s, C), 124.8 (s, C), 126.2 (s,
CH), 129.6 (s, C), 138.6 (s, C), 145.7 (s, C); HRMS (EI) calcd for
C14H13NO [M+] 211.099 714, found 211.098 998. Anal. calcd for
C14H13NO‚0.2H2O : C, 78.75; H, 6.37; N, 6.56. Found: C, 78.82;
H, 6.19; N, 6.51.
4m. 2-Chloro-5-methoxyaniline hydrochloride (97.0 mg, 0.5
mmol) and 2-bromoanisole (63.5 µL, 0.51 mmol) gave 4m as an
off-white powder: 57 mg (50.0%); Rf 0.38 (CHCl3); mp 164-166
°C; 1H NMR (400 MHz, CDCl3) δ 3.81 (s, 3H, OMe), 3.92 (s, 3H,
OMe), 6.76 (d, J ) 7.8 Hz, 1H, Ar H2), 6.77 (dd, J ) 2.4 & 8.5
Hz, 1H, Ar H6), 6.84 (d, J ) 2.4 Hz, 1H, Ar H8), 7.04 (t, J ) 7.8
Hz, 1H, Ar H3), 7.49 (d, J ) 7.8 Hz, 1H, Ar H4), 7.82 (d, J ) 8.6
Hz, 1H, Ar H5), 8.07 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3)
δ 55.5 (s, OMe), 55.6 (s, OMe), 94.8 (s, CH), 105.0 (s, CH), 108.3
(s, CH), 112.2 (s, CH), 117.6 (s, C), 119.9 (s, CH), 121.2 (s, CH),
124.5 (s, C), 129.5 (s, C), 140.4 (s, C), 145.4 (s, C), 159.0 (s, C);
HRMS (EI) calcd for C14H13NO2 [M+] 227.094 629, found
227.094 402. Anal. calcd for C14H13NO2‚0.2H2O: C, 73.27; H, 5.92;
N, 6.10. Found: C, 73.21; H, 5.83; N, 5.74.
3f. 2-Chloro-5-methoxy-4-methylaniline (85.8 mg, 0.5 mmol)
and 3-bromo-m-xylene (69.3 µL, 0.51 mmol) gave 3f as a clear
oil: 115 mg (83.0%); Rf 0.9 (CHCl3); 1H NMR (400 MHz, CDCl3)
δ 2.04 (s, 3H, Me), 2.20 (s, 6H, Me), 3.63 (s, 3H, OMe), 5.78 (br
s, 1H, NH), 6.56 (br s, 1H, Ar H2,5xylene), 6.68 (br s, 2H, Ar H4xylene),
6.74 (s, 1H, Ar H6aniline), 7.01 (s, 1H, Ar H3aniline). Rf 0.9 (CHCl3);
1H NMR (400 MHz, CDCl3) δ 2.04 (s, 3H, Me), 2.20 (s, 6H, Me),
3.63 (s, 3H, OMe), 5.78 (br s, 1H, NH), 6.56 (br s, 1H, Ar H2,5xylene),
6.68 (br s, 2H, Ar H4xylene), 6.74 (s, 1H, Ar H6aniline), 7.01 (s, 1H,
Ar H3aniline); 13C NMR (100 MHz, CDCl3) δ 15.7 (s, CH3), 21.4 (s,
CH3), 55.7 (s, OMe), 100.4 (s, CH), 116.9 (s, CH), 119.7 (s, C),
123.8 (s, CH), 130.8 (s, CH), 138.5 (s, C), 138.6 (s, C), 139.2 (s,
C), 142.4 (s, C), 156.9 (s, C) (sample contaminated with ∼5%
3-bromo-m-xylene).
General Method for the Synthesis of Carbazoles, 4n-q. NaOt-
Bu (0.240 g, 2.5 mmol), Pd(OAc)2 (0.005 g, 0.02 mmol), and [HPt-
Bu3][BF4] (0.008 g, 0.025 mmol) were suspended in dioxane (2
mL). The crude 2-chloro-N-arylaniline was then added as a solution
in dioxane (1 mL), and the mixture was then heated at reflux
temperature overnight, allowed to cool, and then quenched by
addition of HCl(aq) (2 M, 3 mL). The organic phase was extracted
with CH2Cl2 (2 × 20 mL), dried (MgSO4), then filtered, and the
solvent was removed under reduced pressure. The crude product
mixture was then subjected to column chromatography (SiO2).
4n. 2-Chloro-5-trifluoromethyl-N-(2-methoxyphenyl)aniline (116
mg, 0.38 mmol) gave 4n as an off-white powder: 76 mg (65.5%);
General Method for the Syntheses of 2-Chloro(N-aryl)-
anilines, 3c-f. NaOtBu (0.240 g, 2.5 mmol), Pd(OAc)2 (0.005 g,
9408 J. Org. Chem., Vol. 71, No. 25, 2006