Tang et al.
37
R
OCH3
OCH3
ZnI2
Cl
Cl SO H
CH OCH Cl
CH Cl
R
3
3
2
2
Scheme 2. Plausible mechanism of chloromethylation of aromatic derivatives catalyzed by ZnI2.
2
4
(
boiling range 60–90°C) were used. NMR spectra were
1-(tert-Butyl)-4-(chloromethyl)benzene (5a): Colorless
1
taken on a Bruker AM-500 spectrometer with TMS as an liquid; R = 0.60 (petroleum ether); H NMR (500 MHz,
f
internal standard and CDCl as solvent. Reaction monitor- CDCl ): δ 7.46 (d, J = 8.4 Hz, 2H), 7.42–7.39 (m, 2H),
3
3
H
1
3
ing was accomplished by thin-layer chromatography (TLC) 4.64 (s, 2H), 1.40 (s, 9H); C NMR (125 MHz, CDCl ): δ
3
C
on silica gel Polygram SILG/UV 254 plates. HRMS were 151.4, 134.5, 128.3, 125.6, 46.0, 34.5, 31.3.
determined on a Waters GCT Premier spectrometer. All
O-Carbethoxy-3,5-dimethyl-4-chloromethylphenol
compounds were identified by H and C NMR, which (6a):25 Colorless liquid; R = 0.39 (10% EtOAc in petro-
1
13
f
1
were in good agreement with literature spectra.
leum ether); H NMR (500 MHz, CDCl ): δ 6.90 (s, 2H),
3
H
4
.65 (s, 2H), 4.32 (q, J = 7.1 Hz, 2H), 2.44 (s, 6H), 1.40 (t,
1
3
J = 7.2 Hz, 3H); C NMR (125 MHz, CDCl ): δ 153.4,
3
C
Chloromethylation of aromatic compounds
catalyzed by zinc iodide; general procedure
1
1
50.6, 139.1, 131.7, 129.0, 120.5, 120.3, 64.6, 40.2, 19.1,
8.5, 14.0.
A flask was charged with 5 mol% of ZnI (1.3 mmol), chlo-
O-Carbethoxy-2,6-dimethyl-3-chloromethylphenol
2
rosulfonic acid (31 mmol) and CH Cl (30 mL), followed (7a):26 Colorless liquid; R = 0.40 (10% EtOAc in petro-
2
2
f
1
by dropwise addition of dimethoxymethane (31 mmol) at leum ether): H NMR (500 MHz, CDCl ): δ 7.16 (d, J =
3
H
−
10°C. After stirring the reaction mixture at −10°C for 30 7.8 Hz, 1H), 7.10–7.06 (m, 1H), 4.61 (s, 2H), 4.35 (q, J =
min, the aromatic compound (26 mmol) was slowly added. 7.1 Hz, 2H), 2.28 (s, 3H), 2.23 (s, 3H), 1.42 (t, J = 7.1 Hz,
1
3
The resulting mixture was then stirred at 5–10°C for the 3H); C NMR (125 MHz, CDCl ): δ 152.9, 148.6, 134.8,
3
C
time recorded in Table 1. The reaction was monitored by 131.2, 129.8, 128.4, 127.6, 65.0, 44.6, 16.2, 14.2, 11.7.
TLC analysis. After completion, the reaction was quenched
O-Carbethoxy-2,3-dimethyl-4-chloromethylphenol
by addition of water (10 mL) in an ice bath. After extraction (8a):26 Colorless liquid; R = 0.39 (10% EtOAc in petro-
f
1
with CH Cl (3 x 20 mL), the organic phase was washed leum ether); H NMR (500 MHz, CDCl ): δ 7.21 (d, J =
2
2
3
H
with 5% sodium carbonate solution (2 x 10 mL), water (2 x 8.3 Hz, 1H), 6.99 (d, J = 8.3 Hz, 1H), 4.62 (s, 2H), 4.34
1
0 mL) and brine (2 x 20 mL), then evaporated to dryness (q, J = 7.1 Hz, 2H), 2.37 (s, 3H), 2.19 (s, 3H), 1.41 (t, J
1
3
under reduced pressure. The residue was purified by flash = 7.1 Hz, 3H); C NMR (125 MHz, CDCl ): δ 153.4,
3
C
column chromatography on a silica gel using petroleum 149.7, 137.9, 133.4, 129.6, 128.1, 119.0, 64.7, 45.0, 15.3,
ether (boiling range: 60–90°C) and ethyl acetate as eluents 14.1, 12.5.
to give the desired product.
O-Carbethoxy-2,4-dimethyl-5-chloromethylphenol
(
9a): Colorless liquid; R = 0.40 (10% EtOAc in petro-
f
1
leum ether); H NMR (500 MHz, CDCl ): δ 7.11 (s, 1H),
7
3
3
H
Spectroscopic data for the products (Table
.08 (s, 1H), 4.56 (s, 2H), 4.33 (q, J = 7.1 Hz, 2H), 2.38 (s,
1
, entries 1–12)
1
3
H), 2.22 (s, 3H), 1.41 (t, J = 7.1 Hz, 3H); C NMR (125
2
4
4
-(Chloromethyl)-1,1’-biphenyl (2a): Light yellow solid; MHz, CDCl ): δ 153.4, 147.5, 134.8, 134.1, 133.3, 130.4,
3
C
2
5
m.p. 71–73°C (lit. 71–73°C); R = 0.42 (petroleum ether); 122.5, 64.8, 44.0, 18.0, 15.5, 14.1; HRMS (EI) calcd for
f
1
35
+
H NMR (500 MHz, CDCl ): δ 7.65–7.62 (m, 2H), 7.57 C H O Cl: [M] : 242.0710; found: 242.0701; calcd for
3
H
12 15
3
3
7
+
(
d, J = 8.3Hz, 2H), 7.50 (dd, J = 7.0, 1.3 Hz, 4H), 7.42 (dd, C H O Cl: [M] : 244.0680; found: 244.0702.
1
2
15
3
1
3
J = 4.9, 3.7 Hz, 1H), 4.56 (s, 2H); C NMR (125 MHz,
O-Carbethoxy-2-methyl-5-chloromethylphenol (10a):
CDCl ): δ 140.8, 140.5, 138.3, 129.2, 128.8, 127.5, 127.4, Colorless liquid; R = 0.30 (10% EtOAc in petroleum
3
C
f
1
1
27.0, 5.6.
ether); H NMR (500 MHz, CDCl ): δ 7.31–7.26 (m, 1H),
3
H
2
4
1
-(Chloromethyl)-4-ethylbenzene (3a): Colorless liq- 7.24 (d, J = 1.8 Hz, 1H), 7.12 (d, J = 8.3 Hz, 1H), 4.56 (s,
1
uid; R = 0.70 (petroleum ether); H NMR (500 MHz, 2H), 4.34 (q, J = 7.1 Hz, 2H), 2.26 (s, 3H), 1.41 (t, J = 7.1
f
1
3
CDCl ): δ 7.41 (d, J = 8.1 Hz, 2H), 7.30 (d, J = 8.1 Hz, Hz, 3H); C NMR (125 MHz, CDCl ): δ 153.3, 149.6,
3
H
3
C
2
(
H), 4.67 (s, 2H), 2.75 (q, J = 7.8 Hz, 2H), 1.42–1.29 135.4, 131.5, 130.6, 127.3, 121.8, 65.0, 45.6, 15.9, 14.2;
1
3
35
+
t, 3H); C NMR (125 MHz, CDCl ): δ 141.8, 131.5, HRMS (EI) calcd for C H O Cl: [M] : 228.0553;
3
C
11 13
3
3
7
+
1
28.8, 127.9, 46.2, 28.4, 15.6.
found: 228.0563; calcd for C H O Cl: [M] : 230.0524;
11 13 3
2
4
1
-(Chloromethyl)-4-isopropylbenzene (4a): Colorless found: 230.0545.
1
liquid; R = 0.73 (petroleum ether); H NMR (500 MHz,
O-Carbethoxy-8-chloromethyl-1-naphthol (11a): White
f
CDCl ): δ 7.41 (d, J = 8.1 Hz, 2H), 7.32 (d, J = 8.1Hz, solid; m.p. 58–59°C. R = 0.30 (10% EtOAc in petroleum
3
H
f
1
2
6
1
H), 4.66 (s, 2H), 3.05–2.93 (m, 1H), 1.35 (d, J = 7.4 Hz, ether); H NMR (500 MHz, CDCl ): δ 8.18 (d, J = 8.3 Hz,
3
H
1
3
H); C NMR (125 MHz, CDCl ): δ 146.3, 138.7, 128.6, 1H), 8.09 (dd, J = 8.3, 0.6 Hz, 1H), 7.66 (ddd, J = 8.4, 6.9,
3
C
26.7, 46.0, 33.9, 23.9.
1.2 Hz, 1H), 7.61 (ddd, J = 8.1, 6.9, 1.2 Hz, 1H), 7.54 (d, J