1592 J. Am. Chem. Soc., Vol. 119, No. 7, 1997
Tomioka et al.
1
26% yield as yellowish solid: mp 187-189 °C; H NMR (CDCl3) δ
2,3,4-trimethylbenzene (4.7 g, 15 mmol) was treated with LiAlH4 (0.65
g, 17 mmol) in anhydrous THF (30 mL) as described above to give
1,3-bis(dideuteriomethyl)-4,5,6-trimethylbenzene in 91% yield as a
white solid: mp 47-49 °C; 1H NMR (CDCl3) δ 2.17 (s, 6 H), 2.21 (s,
3 H), 2.24 (bs, 2 H), 6.83 (s, 1 H). The bis(dideuteriomethyl)benzene
(2.1 g, 14 mmol) was reacted with Br2 (2.2 g, 14 mmol) in CCl4 (20
mL) in the presence of Fe/I2 to afford 1-bromo-2,6-bis(dideuterio-
methyl)-2,3,4-trimethylbenzene in 71% yield as a white solid: mp
2.14 (s, 12 H), 2.19 (s, 12H), 2.25 (s, 6 H). The ketimine (0.45 g, 1.4
mmol) was subjected to nitrosation-LiAlH4 treatment as described
above to give the diazomethane (1c-d0) in 16% yield as an orange
1
solid: mp 156-158 °C dec; H NMR (CDCl3) δ 2.10 (s, 12 H), 2.22
(s, 12 H), 2.26 (s, 6H); IR (KBr) 2032 cm-1
.
2,2′,6,6′-Tetrakis(trideuteriomethyl)-3,3′,4,4′,5,5′-hexamethyl-
diphenyl]diazomethane (1c-d12). A mixtue of 1,3-dibromo-4,5,6-
trimethylbenzene54 (34.7 g, 125 mmol) and CuCN (24.5 g, 274 mmol)
in anhydrous DMF (150 mL) was refluxed overnight. The mixture
was poured into ice-water (400 mL), and the resulting precipitate was
filtered. The solid was transfered to a beaker containing ethylenedi-
amine (40 mL) and H2O (80 mL) and the precipitate formed was
extracted with PhH. The organic layer was washed with a 10% NaCN
solution and water, dried, and evaporated. 1,3-Dicyano-4,5,6-tri-
methylbenzene was obtained as a brownish solid in 60%: mp 156.2-
1
142-144 °C; H NMR (CDCl3) δ 2.20 (s, 3 H), 2.26 (s, 6 H), 2.40
(bs, 2 H). The bromide (1.2 g, 5.2 mmol) was treated with CuCN
(0.56 g, 6.3 mmol), and the reaction was worked up as usual to obtain
2,6-bis(dideuteriomethyl)-3,4,5-trimethylbenzonitrile in 74% yield
as a white solid: mp 150-153 °C; 1H NMR (CDCl3) δ 2.21 (s, 6 H),
2.26 (s, 3 H), 2.44 (bs, 2 H). [2,2′,6,6′-Tetrakis(dideuteriomethyl)-
3,3′,4,4′,5,5′-hexamethyldiphenyl]ketimine was prepared by the reac-
tion of [2,6-bis(dideuteriomethyl)-3,4,5-trimethylphenyl]lithium, ob-
tained by treating the corresponding bromide (1.11 g, 4.8 mmol) with
n-BuLi (1.71 M in n-hexane, 6.0 mL), with 2,6-(CD2H)2-3,4,5-
(CH3)3C6CN (0.67 g, 3.8 mmol) followed by column chromatography,
1
159.8 °C; H NMR (CDCl3) δ 2.30 (s, 3 H), 2.57 (s, 6 H), 7.73 (s, 1
H); IR (KBr) 2224 cm-1. A mixture of the dicyanide (14.5 g, 85 mmol),
concentrated H2SO4 (40 mL), and H2O (80 mL) was refluxed for 2
days. The usual workup afforded 4,5,6-trimethylisophthalic acid as
a brownish solid in 98% yield, mp 296.0-299.1 °C. A solution of the
acid (17.1 g, 82 mmol) and concentrated H2SO4 (2 mL) in absolute
EtOH (200 mL) was refuxed overnight. Workup, followed by column
chromatography on silica gel with CH2Cl2-n-hexane (1:1), gave diethyl
4,5,6-trimethylisophthalate as a yellowish liquid in 40% yield: 1H
NMR (CDCl3) δ 1.39 (t, J ) 7.26 Hz, 6 H), 2.27 (s, 3 H), 2.51 (s, 6
H), 4.36 (q, J ) 7.26 Hz, 4 H), 8.01 (s, 1 H). To a solution of the
diester (6.1 g, 23 mmol) in anhydrous THF (30 mL) was added LiAlD4
(Aldrich, 2.0 g, 47 mmol) at 0 °C with stirring, and the mixture was
refluxed overnight. After the usual workup, 1,3-bis(hydroxydideu-
teriomethyl)-4,5,6-trimethylbenzene was obtained as white crystals
in 90% yield: mp 165.0-167.6 °C; 1H NMR (CDCl3) δ 2.24 (s, 3 H),
2.30 (s, 6 H), 3.49 (bs, 2 H), 7.17 (s, 1 H). A solution of the diol (20
mmol) and PBr3 (7.3 g, 27 mmol) in anhydrous dioxane (20 mL) was
stirred overnight at room temperature. The reaction was worked up
as usual to obtain 1,3-bis(bromodideuteriomethyl)-4,5,6-trimethyl-
benzene in 73% yield as a pale yellow solid: mp 152.8-154.2 °C; 1H
NMR (CDCl3) δ 2.23 (s, 3 H), 2.32 (s, 6 H), 7.15 (s, 1 H). To a
solution of the dibromide (4.7 g, 15 mmol) in anhydrous THF (30 mL)
was added LiAlD4 (0.63 g, 15 mmol) at 0 °C, and the mixture was
refluxed overnight. After the usual workup, 1,3-bis(trideuterio-
methyl)-4,5,6-trimethylbenzene was obtained in 99% yield as a white
solid: mp 48.3-51.0 °C; 1H NMR (CDCl3) δ 2.17 (s, 6 H), 2.21 (s, 3
H), 6.83 (s, 1 H). To a mixture of the hexadeuteriopentamethylbenzene
(2.3 g, 15 mmol) and Fe/I2 (catalytic amount) was added a solution of
Br2 (15 mmol) in CCl4 (3 mL) at 0 °C, and the mixture was stirred for
1 h at room temperature. The reaction was worked up as usual, and
the crude product was Kugelrohr-distilled under reduced pressure at
140-143 °C/2 mmHg to give 1-bromo-2,6-bis(trideuteriomethyl)-
3,4,5-trimethylbenzene in 60% yield as a white solid: mp 125.5-
128.0 °C; 1H NMR (CDCl3) δ 2.20 (s, 3 H), 2.26 (s, 6 H). A mixture
of the 1-bromohexadeuteriopentamethylbenzene (0.46 g, 1.97 mmol)
and CuCN (0.54 g, 6 mmol) in anhydrous DMF (5 mL) was refluxed
overnight, and the reaction was worked up as described above. The
crude product was purified by Kugelrohr distillation at 160-165 °C/3
mmHg to afford 2,6-bis(trideuteriomethyl)-3,4,5-trimethylbenzoni-
1
in 32% yield as an orange solid: mp 190-193 °C; H NMR (CDCl3)
δ 2.10 (s, 4 H), 2.19 (s, 12 H), 2.25 (s, 6 H). The ketimine (0.40 g,
1.2 mmol) was treated with N2O4 followed by LiAlH4 of the resulting
N-nitroso compound to produce the diazomethane (1c-d8) in 11% yield
as an orange solid: mp 151-153 °C dec; 1H NMR (CDCl3) δ 2.06 (s,
4 H), 2.22 (s, 12 H), 2.26 (s, 6 H); IR (KBr) 2034 cm-1
.
(2,4,6-Tri-tert-butyldiphenyl)diazomethane (13): (2,4,6-Tri-tert-
butyldiphenyl)ketimine was prepared by the reaction of (2,4,6-tri-
tert-butylphenyl)lithium, obtained by treating the corresponding bro-
mide55 (1.00 g, 3.07 mmol) with n-butyllithium (1.65 M in n-hexane,
2.8 mL), with benzonitrile (0.50 g, 4.9 mmol), followed by column
chromatography (silica gel, CHCl3-n-hexane) in 45% yield as a brown
solid: 1H NMR (CDCl3) δ 1.20 (s, 18 H), 1.36 (s, 9 H), 6.80-7.40
(m, 7 H). The ketimine (0.45 g, 1.3 mmol) was subjected to
nitrosation-LiAlH4 treatment to produce the diazomethane (13) in 29%
1
yield as red crystals: mp 80-85 °C; H NMR (CDCl3) δ 1.34 (s, 18
H), 1.40 (s, 9 H), 6.88-7.60 (m, 7 H); IR (KBr) 2050 cm-1
.
[2,4,6-Tris(perdeuterio-tert-butyl)diphenyl]diazomethane (13-d27).
Treatment of 2,4,6-tris(perdeuterio-tert-butyl)benzene (0.90 g, 3.3
mmol) with Br2 (1.23 g, 7.7 mmol) in P(O)(OMe)3 (10 mL) in the
presence of Fe gave 1-bromo-2,4,6-tris(perdeuterio-tert-butyl)ben-
zene in 70% yield as white prisms: mp 60-63 °C; 1H NMR (CDCl3)
δ 1.34 (s, 2 H). [2,4,6-Tris(perdeuterio-tert-butyl)diphenyl]ketimine
was prepared by the reaction of [2,4,6-tris(perdeuterio-tert-butyl)phen-
yl]lithium, obtained by the reaction of the corresponding bromide (0.81
g, 2.3 mmol), with n-BuLi (1.64 M in n-hexane, 2.5 mL), and then
with benzonitrile (0.61 g, 5.9 mmol), followed by column chromatog-
raphy in 25% yield as yellow oil: 1H NMR (CDCl3) δ 6.98 (d, J )
6.93 Hz, 1 H), 7.19-7.41 (m, 4 H), 7.48 (s, 2 H), 8.47 (d, J ) 7.92
Hz, 1 H). The ketimine (0.57 mmol) was treated with N2O4 followed
by LiAlH4 to afford the diazomethane (13-d27) in 21% yield as red
1
crystals: mp 82-83 °C; H NMR (CDCl3) δ 6.27 (d, J ) 7.59 Hz, 1
H), 6.90 (d, J ) 7.26 Hz, 1 H), 6.98 (dd, J ) 7.26, 7.59 Hz, 1 H), 7.13
(dd, J ) 7.26, 7.59 Hz, 1 H), 7.36 (dd, J ) 7.26, 7.59 Hz, 1 H), 7.55
(s, 2 H); IR (KBr) 2042 cm-1
.
Irradiation for Product Identification. In a typical run, a solution
of the diazo compound (ca. 10 mg) in solvent was placed in a Pyrex
tube and irradiated with a high-pressure, 300-W mercury lamp at room
temperature until all the diazo compound was destroyed. The irradiation
mixture was then concentrated on a rotary evaporator below 20 °C.
Individual components were isolated by column chromatography or
by preparative TLC and identified by NMR and MS. In the irradiation
of polymethylated diazomethanes (1), the irradiations were conducted
at high (∼50 °C) and low (∼0 °C) temperatures in order to isolate
benzocyclobutenes and carbene dimers, respectively.
1
trile in 81% as a white solid: mp 150-152 °C; H NMR (CDCl3) δ
2.21 (s, 6 H), 2.26 (s, 3 H). [2,2′,6,6′-Tetrakis(trideuteriomethyl)-
3,3′,4,4′,5,5′-hexamethyldiphenyl]ketimine was obtained by the reac-
tion of [2,6-bis(trideuteriomethyl)-3,4,5-trimethylphenyl]lithium, pre-
pared from the corresponding bromide (0.49 g, 2.1 mmol) with n-BuLi
(1.7 M in n-hexane, 1.59 mL), with 2,6-(CD3)2-3,4,5-(CH3)3C6CN
followed by column chromatography, in 52% yield as an orange solid:
1
mp 189-192 °C; H NMR (CDCl3) δ 2.18 (s, 12 H), 2.24 (s, 6 H).
The ketimine (0.27 g, 0.81 mmol) was subjected to nitrosation-LiAlH4
treatment as described above to afford the diazomethane (1c-d12) in
In this way, products 3b, 4b, 5b (from 1b), 3c-d0, 4c-d0, 5c-d0 (from
1c-d0), 3c-d12, 4c-d12, 5c-d12 (from 1c-d12), 3c-d8, 4c-d8, 4c′-d8, 5c-d8
(from 1c-d8), 15 (from 13), 15-d27 (from 13-d27), and 10 (from 8) were
isolated and characterized. Spectral data of those compounds are
described in the supporting information.
1
11% yield as an orange solid: mp 139-142 °C; H NMR (CDCl3) δ
2.22 (12 H), 2.26 (6 H); IR (KBr) 2030 cm-1
.
[2,2′,6,6′-Tetrakis(dideuteriomethyl)-3,3′,4,4′,5,5′-hexamethyl-
diphenyl]diazomethane (1c-d8). 1,5-Bis(bromodideuteriomethyl)-
(54) Suzuki, H.; Mishina, T.; Hanafusa, T. Bull. Chem. Soc. Jpn. 1978,
51, 3099.
(55) Pearson, D. E.; Frazer, M. G.; Frazer, V. S.; Washburn, L.C.
Synthesis 1976, 621.