First General Synthesis of (p-Nitroaryl)diarylmethanes via Vicarious Nucleophilic Substitution of Hydrogen

Article abstract of DOI:10.1021/jo9624197

A general regiospecific method for the synthesis of (p-nitroaryl)diarylmethanes has been developed starting from diarylmethanols and 2- and/or 3-substituted nitrobenzenes. This utilizes the quantitative condensation between benzotriazole and diarylmethanols under acidic catalysis and in the presence of perfluorocarbon fluids, followed by vicarious nucleophilic substitution of the resulting diarylmethylbenzotriazoles upon nitrobenzenes in moderate to high yield, Oxidative nucleophilic substitution of hydrogen is observed as a side process. These vicarious nucleophilic substitutions complement Friedel-Crafts reactions for the synthesis of triarylmethanes.

Full text of DOI:10.1021/jo9624197

J . Org. Chem. 1997, 62, 4137-4141
4137
F ir st Gen er a l Syn th esis of (p-Nitr oa r yl)d ia r ylm eth a n es via
Vica r iou s Nu cleop h ilic Su bstitu tion of Hyd r ogen
Alan R. Katritzky* and Dorin Toader
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received December 30, 1996X
A general regiospecific method for the synthesis of (p-nitroaryl)diarylmethanes has been developed
starting from diarylmethanols and 2- and/or 3-substituted nitrobenzenes. This utilizes the
quantitative condensation between benzotriazole and diarylmethanols under acidic catalysis and
in the presence of perfluorocarbon fluids, followed by vicarious nucleophilic substitution of the
resulting diarylmethylbenzotriazoles upon nitrobenzenes in moderate to high yield. Oxidative
nucleophilic substitution of hydrogen is observed as a side process. These vicarious nucleophilic
substitutions complement Friedel-Crafts reactions for the synthesis of triarylmethanes.
In tr od u ction
Ta ble 1. Dia r ylm eth a n ols for th e Syn th esis of
p-Nitr oa r yl)d ia r ylm eth a n es
(
Substituted triarylmethanes are of considerable inter-
1
2
est as leuco dyes, photochromic agents, and substrates
for theoretical studies.3 While many methods are avail-
able for the preparation of symmetrical triarylmethanes,4-7
syntheses of unsymmetrical triarylmethanes are less
developed. General methods include (i) condensation of
yield
(%)
1
Ar1
Ar2
8
unsymmetrical benzhydrols with phenols under acidic
a
b
c
d
e
f
g
h
i
phenyl
phenyl
phenyl
phenyl
phenyl
phenyl
9
2-methylphenyl
4-chlorophenyl
4-biphenylyl
4-methoxyphenyl
phenyl
or basic conditions or with N,N-dimethylaniline or
alkoxybenzenes under acidic conditions1
0,11
and (ii) dis-
placement of benzotriazole in (benzotriazol-1-yl)diphen-
ylmethanes either by an electron-rich arene catalyzed by
4-methylphenyl
4-(N,N-dimethylamino)phenyl phenyl
4-methylphenyl
4-(N,N-dimethylamino)phenyl 4-n-hexyloxyphenyl
1
1
98
88
56
ZnCl
2
or by [4-(N,N-dimethyamino)phenyl]magnesium
bromide.1 Unsymmetrical diarylmethylindoles, -pyrroles,
2-methoxyphenyl
and -pyridines were synthesized by condensation of the
j
k
4-(N,N-dimethylamino)phenyl 3,4,5-trimethoxyphenyl 73
4-methoxyphenyl 5-methylthien-2-yl 47
1
corresponding heterocycle with diarylmethanols or by
Lewis acid-catalyzed displacement of benzotriazole in
(
benzotriazol-1-yl)diphenylmethanes.11 However, to the
been used for syntheses of (nitroaryl)arylmethanes,12b,c
best of our knowledge, unsymmetrical nitro-substituted
triarylmethanes have not been previously synthesized:
such compounds could be of significant versatility due
to the easy reduction of the nitro group and subsequent
transformations of the resulting amino derivatives.
no such syntheses of (nitroaryl)diarylmethanes have
appeared.
Reactions of tris(benzotriazol-1-yl)methane with ni-
13
troarenes in our laboratory showed that benzotriazole
derivatives readily undergo VNS with benzotriazolate
anion acting as a leaving group. We now demonstrate
that nitroarenes undergo VNS when treated with ben-
zotriazolyldiarylmethanes in THF in the presence of
potassium tert-butoxide, that condensation of benzotria-
zole with diarylmethanols in the presence of catalytic
amounts of p-toluenesulfonic acid14 is a useful umpolung
Vicarious nucleophilic substitution of hydrogen (VNS)
using carbon nucleophiles, developed by Makosza et
al.,1 has become a useful tool for introducing C-linked
substituents into electrophilic arenes. While VNS has
2ab
X
Abstract published in Advance ACS Abstracts, April 15, 1997.
(
1) Muthyala, R.; Katritzky, A. R.; Lan, X. Dyes Pigm. 1994, 25, 303.
in building triarylmethanes, and that oxidative nucleo-
(2) Aldag, R. Photochromism Based on Dissociation Processes. In
15ab
philic substitution of hydrogen in nitroarenes
is a
Photochromism: Molecules and Systems; D u¨ rr, H., Bouas-Laurent, H.,
Eds.; Elsevier: London, 1990.
common side process in benzotriazole-mediated VNS
chemistry.
(
3) Terrier, M.; Boubaker, T.; Xiao, L.; Farrell, P. G. J . Org. Chem.
992, 57, 3924.
4) (a) Casiraghi, G.; Casnati, G.; Cornia, M. Tetrahedron Lett. 1973,
79. (b) Casiraghi, G.; Casnati, G.; Cornia, M.; Sartori, G.; Ungaro, R.
1
(
Resu lts a n d Discu ssion
6
J . Chem. Soc., Perkin Trans. 1 1974, 2077.
(
5) Pindur, U.; Flo, C. J . Heterocycl. Chem. 1989, 26, 1563.
A series of diarymethanols 1 were used as substrates
for this study (Table 1). While compounds 1a -f were
commercially available materials, we carried out the
synthesis of compounds 1g-k . Compound 1g was ob-
tained in 98% yield by reduction of the corresponding
(6) Ungnade, H. E.; Crandall, E. W. J . Am. Chem. Soc. 1949, 71,
2
209.
(
(
(
7) Snyder, H. R.; Konecky, M. S. J . Am. Chem. Soc. 1958, 80, 4388.
8) Burmester, A.; Stegmann, H. B. Synthesis 1981, 125.
9) Lapkin, I. I.; Belonovich, M. I. J . Gen. Chem. USSR (Engl.
Trans.) 1958, 28, 586.
(
(
10) Pratt, E. F.; Green, L. Q. J . Am. Chem. Soc. 1953, 75, 275.
11) Katritzky, A. R.; Gupta, V.; Garot, C.; Stevens, C. V.; Gordeev,
(13) Katritzky, A. R.; Xie, L. Tetrahedron Lett. 1996, 37, 347.
(14) Katritzky, A. R.; Perumal, S.; Fan, W.-Q. J . Chem. Soc., Perkin
Trans. 2 1990, 2059.
(15) (a) Makosza, M.; Stalinski, K.; Klepka, C. Chem. Commun.
(Cambridge) 1996, 837. (b) Makosza, M.; Sypniewski, M. Tetrahedron
1994, 50, 4913.
M. F. Heterocycles 1994, 38, 345.
12) (a) Makosza, M.; Winiarski, J . Acc. Chem. Res. 1987, 20, 282.
b) Makosza, M. Synthesis 1991, 103. (c) Makosza, M.; Winiarski, J .
(
(
J . Org. Chem. 1984, 49, 1494. (d) Makosza, M.; Golinski, J . Angew.
Chem., Int. Ed. Engl. 1982, 21, 451.
S0022-3263(96)02419-X CCC: $14.00 © 1997 American Chemical Society

4
138 J . Org. Chem., Vol. 62, No. 12, 1997
Katritzky and Toader
Ta ble 2. o- a n d /or m -Su bstitu ted
Sch em e 1a
(
p-Dia r ylm eth yl)n itr oben zen es
yield
(%)
6
X
Ar1
Ar2
a
H
2-F
2-Cl
2-Cl
phenyl
phenyl
2-methoxyphenyl
phenyl
phenyl
4-methylphenyl
82
87
86
79
b
c
d
4-(N,N-dimethylamino)- phenyl
phenyl
e
2-Cl
4-(N,N-dimethylamino)- 3,4,5-trimethoxy- 68
phenyl
phenyl
phenyl
phenyl
phenyl
phenyl
phenyl
f
2-Br
2-Br
4-methylphenyl
4-biphenylyl
phenyl
4-chlorophenyl
2-methylphenyl
5-methylthien-2-yl
52
38
68
76
31
a
1
2
For designation of Ar , Ar , and X see Table 2.
g
h
i
j
k
l
2-MeO
2-MeO
2-MeO
2-MeO
2-MeO
benzophenone with sodium borohydride. Compound 1h
was obtained by the reaction of (4-methylphenyl)magne-
sium bromide with o-anisaldehyde in 88% yield. Com-
pounds 1i and 1j were synthesized by the reaction of the
corresponding aldehyde with [4-(N,N-dimethylamino)-
4-methoxyphenyl 28
4-(N,N-dimethylamino)- 4-(n-hexyloxy)-
48
phenyl
4-biphenylyl
4-methoxyphenyl
phenyl
phenyl
phenyl
m
n
o
2-Ph
2-t-Bu
2-CF3
91
33
50
phenyl]magnesium bromide in 56 and 73% yield, respec-
tively by means of our previously reported procedure.1
4-(N,N-dimethylamino)- phenyl
phenyl
2,3-(CH)4 4-chlorophenyl
In an effort to test a heterocyclic substrate, compound
p
q
r
phenyl
phenyl
phenyl
94
56
52
1
6
1
k was synthesized by R-lithiation of 2-methylthiophene
3-F
3-MeO
4-methoxyphenyl
4-chlorophenyl
and subsequent reaction with p-anisaldehyde in 47%
yield. New compounds 1h -k were fully characterized.
Sch em e 2
(Diarylmethyl)benzotriazoles of type 2 (Scheme 1) were
previously prepared in our group from benzotriazole and
diarylmethanols in the presence of a catalytic amount of
p-toluenesulfonic acid (PTSA) in benzene with azeotropic
removal of water.14 We now find that the use of perfluo-
rocarbon fluids for water removal,17 diarylmethanols,
benzotriazole in 1.3 molar excess, and a catalytic amount
of PTSA (or even without catalyst in case of 1e,g-k ) gives
the 1- and 2-(diarylmethyl)benzotriazole mixtures 2a -k
in almost quantitative yields with respect to the diaryl-
methanols 1a -k (Scheme 1). These mixtures were used
as such after removal of excess benzotriazole.
products of oxidative nucleophilic substitution (ONSH),15a
The (diarylmethyl)benzotriazoles 2 were reacted with
a series of o- and m-substituted nitrobenzenes 4. An
equimolar mixture of 2 and 4 was added to a solution of
potassium tert-butoxide in dry THF to give a deep red
reaction mixture. Upon quenching with saturated am-
monium chloride solution, (nitroaryl)diarylmethanes 6
were obtained (Scheme 1 and Table 2). Reaction times
were limited to 4 h since longer reaction times lower the
observed yields of the desired product 6. The tempera-
ture needs to be carefully controlled: studies showed that
carbanions of types 3 generated from the corresponding
and their formation indicates a high concentration of
adduct 5 in the early stages of the reaction.
19
The elimination of the benzotriazole from adducts of
type 5 (Scheme 1) works well for unsubstituted and
o-chloro-, o-fluoro-, and o-phenyl-substituted nitroben-
zenes 4 to give 6a -e,m in good to excellent yields
regardless of the structure of compound 1 (Table 2) but
is slow with o-bromonitrobenzene (4, X ) 2-Br) (affording
6
f and 6g in only 52 and 38% yields, respectively) and
does not work at all for o-iodonitrobenzene (4, X ) 2-I).
The reactions of o-methoxynitrobenzene (4, X ) 2-MeO)
show how the structure of the diarylmethanol 1 influ-
ences the outcome of the reaction: the electron-rich 1i
and 1k and the sterically hindered 1b gave low yields of
the VNS product. A comparison between the reaction of
1
-(diarylmethyl)benzotriazoles 2 with ca. 5 equiv of
potassium tert-butoxide in dry THF are stable at -20 °C.
However higher temperatures cause triazole ring frag-
mentation as evidenced by detection of benzophenones
in the GCMS spectra of the reaction mixture, probably
through a pathway previously described.18
1
a with unsubstituted nitobenzene (4, X ) H) and
o-methoxynitrobenzene (4, X ) 2-MeO) suggests that the
more electron-rich adduct 5h eliminates benzotriazole
more slowly than 5a . o-tert-Butylnitrobenzene (4, X )
The addition step of anions 3 to nitroarenes 4 to form
σ -adducts of type 5 (Scheme 1) is fast, as evidenced by
H
a reaction between 3-nitroanisole and 2c that was
quenched at -20 °C after 10 min with a nondegassed
aqueous acidic solution to give compound 7r as the only
product observed (Scheme 2). Compounds of type 7 are
2
-t-Bu) and o-(trifluoromethyl)nitrobenzene (4, X ) 2-CF
3
)
underwent VNS to give only 33% and 50% yields,
respectively, of the corresponding nitroaryldiarylmethanes.
m-Substituted nitrobenzenes 4 show the same slow
elimination rate to give the VNS products: m-fluoro- and
m-methoxynitrobenzenes 4 gave the VNS products in
(
16) Chadwick, D. J .; Willbe, C. J . Chem. Soc., Perkin Trans. 1 1977,
8
77.
(
(
17) Zhu, D.-W. Synthesis 1993, 953.
18) Katritzky, A. R.; Lan, X.; Lam, J . N. Chem. Ber. 1991, 124, 1431.
(19) Makosza, M. Pol. J . Chem. 1992, 66, 3.

Synthesis of (p-Nitroaryl)diarylmethanes
J . Org. Chem., Vol. 62, No. 12, 1997 4139
moderate yields. In case of the latter, compound 7r was
isolated and fully characterized in 8% yield. Surpris-
ingly, 1-nitronaphthalene reacts cleanly and gives the
amino)phenyl]magnesium bromide 1 M solution in THF was
prepared according to literature procedure.1
P r ep a r a tion of 4-(N,N-Dim eth yla m in o)-r-p h en ylben -
zen em eth a n ol (1g). Sodium borohydride was added (0.83
g, 22 mmol) to a solution of 4-(N,N-dimethylamino)benzophe-
none (4.51 g, 20 mmol) in ethanol (50 mL). The mixture was
stirred at rt for 6 h, solvent was distilled off under reduced
pressure, and water (20 mL) and methylene chloride (30 mL)
were added to the residue. The organic layer was separated,
washed with water (20 mL) and brine (20 mL), and dried
VNS product in 94% yield.
Most likely, the bimolecular12a elimination step 5 f 6,
which needs elevated temperatures and high base con-
centration to achieve a reasonable rate, is rate control-
ling. Process 5 f 6 probably requires a high degree of
order in the transition state, in which case steric effects
should be important. Further study is needed to support
these postulates.
(MgSO
4
). After solvent removal, 4.50 g (98%) of product was
2
1
obtained as a light green solid: mp 68-69 °C (lit. mp 69-70
1
°
C); H NMR 2.42 (br s, 1H), 2.87(s, 6H), 5.68 (br s, 1H), 6.65
The regiochemistry of the reaction is always para with
respect to the nitro group with both 2- and 3-substituted
nitrobenzenes. This preference is probably due to the
bulkiness of the anion. Despite the fact that our base
and solvent are the ones held responsible for the “ortho
effect” in VNS, i.e., t-BuOK/THF,1 no ortho substitution
was observed.
(
d, J ) 8.6 Hz, 2H), 7.15-7.22 (m, 3H), 7.26-7.35 (m, 4H);
13
C NMR 40.5 (2C), 75.8, 112.5 (2C), 126.3 (2C), 127.0, 127.7
(2C), 128.2 (2C), 132.1, 144.3, 150.0.
P r ep a r a t ion of 2-Met h oxy-r-(4-m et h ylp h en yl)b en -
zen em eth a n ol (1h ). To a suspension of Mg (0.48 g, 0.02 mol)
in THF (10 mL) was added 4-bromotoluene (2.07 g, 0.012 mol).
After 3 h reflux, 10 mL of the resulting cold solution was added
to 2-methoxybenzaldehyde in THF (30 mL) at 0 °C and stirred
under reflux for 5 h. The resulting mixture was treated with
saturated ammonium chloride solution (40 mL) and extracted
with methylene chloride (3 × 30 mL). The organic extract was
2a
Oxidative nucleophilic substitution of hydrogen has
H
previously been observed by Bernard with σ -adducts
derived from benzotriazole-stabilized anions and ni-
troarenes.20 No systematic study of the factors that
influence this process has been published so far. At-
tempts to measure the ratio of the VNS and ONSH
products by GCMS were unsuccesful due to decomposi-
4
dried (MgSO ), the solvent was removed to yield an oil that
was dissolved in ethanol (10 mL), sodium borohydride (0.019
g, 0.005 mol) was added, and the mixture was stirred at rt for
5 h. The solvent was removed under reduced pressure, and
water (20 mL) was added and extracted with methylene
chloride (2 × 20 mL). The organic extract was washed with
water (2 × 20 mL) and brine (10 mL) and the solvent removed
to yield an oil that was subjected to column chromatography
1
tion of the ONSH product. However, H NMR allows
quantitative evaluation of the ratio of the two products:
the Csp3-H bond in compound 6 gives a signal at 5.5-5.8
ppm, while Csp2-H in position 7 of the benzotriazolyl ring
with hexanes:ethyl ether (3:1) to give 2.02 g (88%) of a colorless
in compound 7 gives a signal at 6.5 ppm. By this means,
the ratios of the VNS and ONSH products could be
quantified. When the quenching solution was degassed
prior to its addition to the reaction mixture, only traces
of ONSH product were observed. A study of the ONSH
of benzotriazole bearing anionic σ-adducts is under way
in our laboratory.
oil: 1H NMR δ 2.30 (s, 3H), 3.09 (s, 1H), 3.73 (s, 3H), 5.98 (s,
1H), 6.82 (d, J ) 8.0 Hz, 1H), 6.90 (t, J ) 7.4 Hz, 1H), 7.09 (d,
1
3
J ) 8.0 Hz, 2H), 7.19-7.25 (m, 4H); C NMR δ 21.0, 55.2,
7
1
7
1.8, 110.6, 120.6, 126.4 (2C), 127.6, 128.4, 128.7 (2C), 132.1,
36.6, 140.3, 156.6. Anal. Calcd for C15
.06. Found: C, 79.32; H, 7.26.
16 2
H O : C, 78.92; H,
Gen er a l P r oced u r e for th e P r ep a r a tion of Com p ou n d s
1
i a n d 1j. To a solution of the appropriate aldehyde (20 mmol)
In conclusion, a general regiospecific method for syn-
thesis of (p-nitroaryl)diarylmethanes was developed start-
ing from diarylmethanols and 2- and 3-substituted
nitrobenzenes, making use of the quantitative reaction
between benzotriazole and diarylmethanols under acidic
catalysis and in the presence of perfluorocarbon fluids.
In the presence of Br o¨ nsted or Lewis acids, diarylmetha-
nols are highly electrophilic, reacting with electron-rich
arenes in Friedel-Crafts fashion. In contrast, (diaryl-
methyl)benzotriazoles in the presence of strong bases are
highly nucleophilic, allowing reactions with electron poor
arenes. Hence, our present VNS procedure complements
Friedel-Crafts approaches to similar compounds, as
in dry THF (30 mL) was added a solution of [4-(N,N-dimeth-
ylamino)phenyl]magnesium bromide in THF (1 M, 20 mL, 20
mmol) with stirring and cooling at 0 °C. After 10 h reflux,
the solution was treated with saturated ammonium chloride
solution (40 mL) and extracted with methylene chloride (2 ×
5
0 mL), and the combined organic layer was washed with
NaOH 5% (2 × 20 mL) and brine (20 mL) and dried (MgSO
The solvent was removed to give an oil that was dissolved in
ethanol (20 mL), NaBH (0.38 g, 10 mmol) was added, and
4
).
4
the mixture was stirred at rt for 1 h. The solvent was removed,
the remaining oil was treated with water (50 mL), extracted
with methylene chloride (3 × 50 mL), and dried (MgSO ), and
4
the solvent was removed to give an oil that was recrystallized
from the appropriate solvent.
1
9
4-(N,N-Dim et h yla m in o)-r-(4-n -h exyloxyp h en yl)b en -
zen em eth a n ol (1i): 3.55 g (56%) of white needles; mp 62-
pointed out by Makosza.
o
1
6
4 C (hexanes:methylene chloride); H NMR δ 0.87-0.92 (t,
Exp er im en ta l Section
J ) 6.4 Hz, 3H), 1.31-1.45 (m, 6H), 1.69-1.76 (m, 2H), 2.46
(
(
(
d, J ) 2.4 Hz, 1H), 2.87 (s, 6H), 3.89 (t, J ) 6.5 Hz, 2H), 5.63
s, 1H), 6.65 (d, J ) 8.6 Hz, 2H), 6.81 (d, J ) 8.5 Hz, 2H), 7.15
d, J ) 8.8 Hz, 2H), 7.22 (d, J ) 8.5 Hz, 2H); 13C NMR δ 14.0,
Gen er a l Meth od s. Melting points were determined on a
capillary melting point apparatus and are uncorrected. NMR
spectra were recorded in CDCl
3
with tetramethylsilane as the
1
22.5, 25.6, 29.2, 31.5, 40.5 (2C), 67.9, 75.3, 112.4 (2C), 114.1
(2C), 127.5 (2C), 127.5 (2C), 132.4, 136.4, 149.9, 158.1. Anal.
Calcd for C21
internal standard for H (300 MHz) or solvent as the internal
1
3
standard for C (75 MHz). Tetrahydrofuran was distilled
under nitrogen immediately prior to use from sodium ben-
zophenone ketyl. Potassium tert-butoxide was reagent grade
purchased from Acros Organics and was handled in a drybox
under nitrogen. All reactions involving potassium tert-butox-
ide and Grignard reagents were carried out under argon
atmosphere. Column chromatography was conducted with
silica gel 230-400 mesh. Compounds 1a -f were reagent-
grade commercially available materials. Perfluorocarbon fluid
2
H29NO : C, 77.03; H, 8.93; N, 4.28. Found: C,
7.02; H, 9.06; N, 4.18.
4-(N,N-Dim et h yla m in o)-r-(3,4,5-t r im et h oxyp h en yl)-
7
ben zen em eth a n ol (1j): 4.64 g (73%) of a white solid; mp
139-141 °C (methanol); H NMR δ 2.32 (br s, 1H), 2.92 (s,
6H), 3.82 (s, 9H), 5.67 (s, 1H), 6.62 (s, 2H), 6.68 (d, J ) 8.6
Hz, 2H), 7.21 (d, J ) 8.5 Hz, 2H); 13C NMR δ 40.4 (2C), 55.9
(2C), 60.6, 75.7, 103.3 (2C), 112.4 (2C), 127.5 (2C), 131.8, 136.7,
1
(bp 104 °C) was purchased from 3M Co. [4-(N,N-Dimethyl-
(
21) Balfe, M. P.; Downer, E. A. W.; Evans, A. A.; Kenyon, J .; Poplett,
(20) Bernard, M. K. Tetrahedron Lett. 1995, 36, 2169.
R.; Searle, C. E.; Tarnoky, A. L. J . Chem. Soc. 1946, 797.

4
140 J . Org. Chem., Vol. 62, No. 12, 1997
40.0, 150.0, 152.9 (2C). Anal. Calcd for C18
Katritzky and Toader
1
H
23NO
4
: C, 68.12;
Hz, 1H); 13C NMR δ 40.4 (2C), 55.4, 112.5 (2C), 125.5, 126.8,
127.1, 128.4, 128.6 (2C), 129.1 (2C), 129.3, 129.8 (2C), 132.5,
142.4, 145.8, 149.4, 151.6. Anal. Calcd for C21H19ClNO : C,
2
68.76; H, 5.22; N, 7.64. Found: C, 68.91; H, 5.45; N, 7.62.
2-Ch lor o-4-[[4-(N,N-d im et h yla m in o)p h en yl]-3,4,5-t r i-
m eth oxyp h en yl]m eth yl]n itr oben zen e (6e). Hexanes:di-
ethyl ether (3:1) was used as the eluent to give orange
H, 7.30; N, 4.41. Found: C, 68.05; H, 7.50; N, 4.33.
P r ep a r a tion of r-(4-Meth oxyp h en yl)-5-m eth yl-2-th io-
p h en em eth a n ol (1k ). To a solution of 2-methylthiophene
(
1.96 g, 20 mmol) in THF (80 mL) at -40 °C was added, n-BuLi
(2 M, 10.5 mL, 21 mmol). After 30 min of stirring, the
temperature was lowered to -78 °C, and p-anisaldehyde (2.72
g, 20 mmol) in THF (20 mL) was added. The mixture was
allowed to warm to rt, treated with saturated ammonium
chloride solution (90 mL), and extracted with methylene
chloride (2 × 50 mL). The organic layer was washed with
NaOH solution (5%, 2 × 50 mL), brine (2 × 50 mL), and water
1
prisms: mp 58-60 °C; H NMR δ 2.95 (s, 6H), 3.75 (s, 6H),
3.84 (s, 3H), 5.40 (s, 1H), 6.30 (s, 2H), 6.68 (d, J ) 8.6 Hz,
2H), 6.94 (d, J ) 8.5 Hz, 2H), 7.15-7.17 (m, 1H), 7.31 (s, 1H),
7.81 (d, J ) 8.3 Hz, 1H); 13C NMR δ 40.4 (2C), 55.6, 56.1 (2C),
60.8, 106.4 (2C), 112.5 (2C), 125.5, 127.1, 128.3, 129.1, 129.7
(2C), 132.4, 136.8, 138.0, 145.8, 149.5, 151.5, 153.3 (2C). Anal.
(
2 × 50 mL) and dried (MgSO
4
), and solvent was removed to
give an oil that was recrystallized from ether-hexanes to yield
25 2 5
Calcd for C24H N O Cl: C, 63.09; H, 5.51; N, 6.13. Found:
1
2
.21 g (47%) of a white solid: mp 67.5-68 °C; H NMR δ 2.40
s, 3H), 2.68 (s, 1H), 3.76 (s, 3H), 5.83 (s, 1H), 6.54 (d, J ) 3.0
Hz, 1H), 6.61 (d, J ) 3.3 Hz, 1H), 6.84 (d, J ) 8.7 Hz, 2H),
.30 (d, J ) 8.4 Hz, 2H); 13C NMR δ 15.2, 55.1, 71.2, 113.7
2C), 124.5, 124.5, 127.4 (2C), 135.5, 139.8, 146.0, 159.1. Anal.
Calcd for C13 14OS: C, 66.64; H, 6.02. Found: C, 66.73; H,
C, 63.06; H, 5.51; N, 6.00.
(
2-Br om o-4-[(4-m eth ylp h en yl)p h en ylm eth yl]n itr oben -
zen e (6f). Hexanes:diethyl ether (3:1) was used as the eluent
to give an orange oil: H NMR δ 2.31 (s, 3H), 5.51 (s, 1H),
6.95 (d, J ) 8.0 Hz, 2H), 7.05-7.32 (m, 8H), 7.48 (d, J ) 1.5
Hz, 1H), 7.73 (d, J ) 8.3 Hz, 1H); 13C NMR δ 20.9, 55.7, 114.5,
125.5, 127.0, 128.7 (2C), 129.0 (3C), 129.1 (2C), 129.4 (2C),
135.6, 136.7, 138.7, 141.9, 147.8, 150.7. Anal. Calcd for
1
7
(
H
6
.25.
Gen er a l P r oced u r e for P r ep a r a tion of Com p ou n d s
6
a -o a n d 7r . The mixture of corresponding diphenylmetha-
20 2
C H16BrNO : C, 62.84; H, 4.22; N, 3.66. Found: C, 62.45;
H, 4.30; N, 3.80.
nol (2 mmol), benzotriazole (0.31 g, 2.6 mmol), p-toluene-
sulfonic acid monohydrate (0.042 g, 0.2 mmol) (no catalyst was
used for the preparation of compounds 2e,g-k ), and perfluo-
rocarbon fluid (bp 104 °C) (20 mL) was refluxed overnight. The
perfluorocarbon fluid was removed on cooling, the remaining
oil was dissolved in methylene chloride (20 mL), and the
solution was washed with NaOH solution (5%, 2 × 20 mL),
2-Br om o-4-[(4-b ip h e n ylyl)p h e n ylm e t h yl]n it r ob e n -
zen e (6g). Hexanes:diethyl ether (3:1) was used as the eluent
1
to give orange prisms: mp 59-61 °C; H NMR δ 5.57 (s, 1H),
7.09-7.43 (m, 11H), 7.52-7.57 (m, 5H), 7.75 (d, J ) 8.3 Hz,
1H); 13C NMR δ 55.8, 114.7, 125.6, 127.0 (2C), 127.2, 127.4
(3C), 128.8 (4C), 129.1, 129.2 (2C), 129.6 (2C), 135.7, 140.0,
brine (20 mL), and water (20 mL) and dried (MgSO
4
). The
140.3, 140.7, 141.6, 147.9, 150.4. Anal. Calcd for C25
BrNO : N, 3.15. Found: N, 3.21.
18
H -
solvent was removed under reduced pressure to give a solid
that was mixed with the appropriate nitroarene (2 mmol) (air
replaced with argon) and dissolved in THF (10 mL). The
solution was added dropwise via a cannula (over 40 min) to a
solution of potassium tert-butoxide (1.12 g, 10 mmol) in THF
2
4-(Diph en ylm eth yl)-2-m eth oxyn itr oben zen e (6h ). Hex-
anes:diethyl ether (3:1) was used as the eluent to give orange
1
prisms: mp 142-144 °C (methanol); H NMR δ 3.80 (s, 3H),
5.58 (s, 1H), 6.75 (dd, J
1
) 8.4 Hz, J ) 1.0 Hz, 1H), 6.83 (s,
2
(10 mL) at -20 °C with stirring. After an additional 4 h of
1H), 7.09 (d, J ) 6.8 Hz, 4H), 7.22-7.36 (m, 6H), 7.78 (d, J )
8.5 Hz, 1H); 13C NMR δ 56.2, 56.7, 114.6, 121.2, 125.6, 126.8
(2C), 128.5 (4C), 129.2 (4C), 137.7, 142.2 (2C), 151.4, 153.0.
stirring at -20 °C, saturated ammonium chloride solution (30
mL) was added, and when the deep red color disappeared the
reaction mixture was extracted with methylene chloride (3 ×
3
Anal. Calcd for C20H17NO : C, 75.22; H, 5.37; N, 4.39.
Found: C, 75.17; H, 5.30; N, 4.23.
2
0 mL). The organic layer was dried (MgSO
4
) and solvent
removed under reduced pressure. The remaining oil was
dissolved in methylene chloride (40 mL), washed with NaOH
solution (5%, 20 mL), brine (2 × 20 mL), and water (20 mL),
4-[(4-Ch lor oph en yl)ph en ylm eth yl]-2-m eth oxyn itr oben -
zen e (6i). Hexanes:diethyl ether (3:1) was used as the eluent
to give an orange oil: H NMR δ 3.80 (s, 3H), 5.55 (s, 1H),
6.72 (dd, J ) 8.5 Hz, 1.4 Hz, 1H), 6.82 (d, J ) 1.4 Hz, 1H),
7.03 (d, J ) 8.3 Hz, 2H), 7.06-7.09 (m, 2H), 7.25-7.34 (m,
5H), 7.77 (d, J ) 8.3 Hz, 1H); 13C NMR δ 56.1, 56.3, 114.5,
121.1, 125.8, 127.1, 128.7 (4C), 129.1 (2C), 130.6 (2C), 132.7,
1
and dried (MgSO
4
), solvent was removed under reduced
pressure, and the remaining oil was subjected to column
chromatography.
4
-(Dip h en ylm eth yl)n itr oben zen e (6a ). Hexanes:diethyl
ether (3:1) was used as the eluent to give yellow plates: mp
137.9, 140.8, 141.7, 150.8, 153.1. Anal. Calcd for C20
ClNO : C, 67.90; H, 4.56; N, 3.96. Found: C, 67.52; H, 4.60;
N, 4.11.
16
H -
6
1
9
7
5-97 °C (hexanes) (lit. mp 93 °C); H NMR δ 5.63 (s, 1H),
.09 (d, J ) 6.9 Hz, 4H), 7.25-7.34 (m, 8H), 8.14 (d, J ) 8.5
3
1
3
Hz, 2H); C NMR δ 56.6, 123.5, 126.9, 128.6, 129.3, 130.2,
1
2-Met h oxy-4-[(2-m et h ylp h en yl)p h en ylm et h yl]n it r o-
42.3, 145.5, 151.6.
-(Dip h en ylm eth yl)-2-flu or on itr oben zen e (6b). Hex-
ben zen e (6j). Hexanes:diethyl ether (3:1) was used as the
1
4
eluent to give yellow prisms: mp 126-127 °C; H NMR δ 2.21
anes:diethyl ether (3:1) was used as the eluent to give yellow
(s, 3H), 3.76 (s, 3H), 5.70 (s, 1H), 6.69 (dd, J
1
) 8.5 Hz, J )
2
1
plates: mp 59-60 °C (hexanes); H NMR δ 5.58 (s, 1H), 6.99-
1.7 Hz, 1H), 6.76 (d, J ) 1.1 Hz, 1H), 6.79 (s, 1H), 7.03 (d, J
7
.10 (m, 6H), 7.25-7.36 (m, 6H), 7.99 (t, J ) 7.8 Hz, 1H); 13
C
) 6.7 Hz, 2H), 7.13-7.29 (m, 6H), 7.75 (d, J ) 8.4 Hz, 1H);
1
3
NMR δ 56.5, 119.0 (d, J ) 21.2 Hz, 1C), 125.5 (d, J ) 37.6 Hz,
C), 127.2 (2C), 128.8 (4C), 129.2 (4C), 141.6 (2C), 153.7 (d, J
18.4 Hz, 1C), 155.4 (d, J ) 275.0 Hz, 1C). Anal. Calcd for
: C, 74.26; H, 4.59; N, 4.56. Found: C, 74.36; H,
.73; N, 4.66.
-Ch lor o-4-[(2-m et h oxyp h en yl)(4′-m et h yld ip h en yl)-
C NMR δ 19.8, 53.5, 56.2, 114.6, 121.4, 125.6, 125.9, 126.8,
1
126.9, 128.5 (2C), 129.0, 129.3 (2C), 130.6, 136.5, 137.7, 140.7,
141.7, 151.1, 153.0. Anal. Calcd for C21 : C, 75.66; H,
)
19
H19NO
3
C
H
14FNO
2
5.74; N, 4.20. Found: C, 75.63; H, 5.89; N, 4.14.
4
2-Meth oxy-4-[(2-m eth oxyp h en yl)(5-m eth ylth ien -2-yl)-
m eth yl]n itr oben zen e (6k ). Hexanes:diethyl ether (3:1) was
2
1
m eth yl]n itr oben zen e (6c). Hexanes:diethyl ether (3:1) was
used as the eluent to give a yellow oil; H NMR δ 2.44 (s, 3H),
1
used as the eluent to give a yellow oil: H NMR δ 2.33 (s, 3H),
3.81 (s, 3H), 3.87 (s, 3H), 5.59 (s, 1H), 6.49 (d, J ) 3.3 Hz,
1H), 6.61 (d, J ) 2.5 Hz, 1H), 6.88 (d, J ) 8.5 Hz, 3H), 6.96 (s,
3
.72 (s, 3H), 5.86 (s, 1H), 6.80 (d, J ) 6.4 Hz, 1H), 6.86-6.95
1
3
(m, 4H), 7.08-7.12 (m, 3H), 7.22-7.28 (m, 2H), 7.77 (d, J )
1H), 7.13 (d, J ) 8.5 Hz, 2H), 7.80 (d, J ) 8.2 Hz, 1H);
C
1
3
8
1
1
6
.5 Hz, 1H); C NMR δ 21.0, 49.0, 55.4, 110.7, 120.5, 125.4,
NMR δ 15.2, 51.4, 55.2, 56.3, 113.9 (3C), 120.6, 124.7, 125.8,
126.4, 129.6 (2C), 134.4, 137.8, 139.6, 143.8, 151.5, 153.1,
27.0, 128.3, 128.4, 129.3 (4C), 130.0, 130.5, 132.3, 136.5,
38.5, 145.8, 151.3, 156.8. Anal. Calcd for C21
8.57; H, 4.93; N, 3.81. Found: C, 68.38; H, 5.07; N, 3.87.
-Ch lor o-4-[[4-(N,N-Dim et h yla m in o)p h en yl]p h en yl-
H
18NO
3
Cl: C,
158.6. Anal. Calcd for C20
4
H19NO S: C, 65.02; H, 5.18; N, 3.79.
Found: C, 65.37; H, 5.26; N, 3.70.
2
4-[[4-(N ,N -Dim e t h yla m in o)p h e n yl][4′-(n -h e xyloxy)-
p h en yl]m eth yl]-2-m eth oxyn itr oben zen e (6l). Hexanes:
diethyl ether (4:1) was used as the eluent to give an yellow
m eth yl]n itr oben zen e (6d ). Hexanes:diethyl ether (3:1) was
1
used as the eluent to give an orange oil: H NMR δ 2.93 (s,
1
6
2
H), 5.46 (s, 1H), 6.67 (d, J ) 8.5 Hz, 2H), 6.92 (d, J ) 8.5 Hz,
H), 7.07-7.15 (m, 3H), 7.22-7.33 (m, 4H), 7.78 (d, J ) 8.5
oil: H NMR δ 0.85-0.91 (t, J ) 6.6 Hz, 3H), 1.27-1.47 (m,
6H), 1.71-1.78 (m, 2H), 2.90 (s, 6H), 3.79 (s, 3H), 3.91 (t, J )

Synthesis of (p-Nitroaryl)diarylmethanes
J . Org. Chem., Vol. 62, No. 12, 1997 4141
6
.4 Hz, 2H), 5.41 (s, 1H), 6.65 (d, J ) 8.7 Hz, 2H), 6.75 (d, J
8.3 Hz, 1H), 6.81 (d, J ) 8.5 Hz, 2H), 6.85 (s, 1H), 6.93 (d,
7.66 (t, J ) 7.4 Hz, 1H), 8.02-8.09 (m, 2H), 8.52 (d, J ) 8.8
Hz, 1H); 13C NMR δ 52.9, 56.3, 122.9, 123.7, 124.8, 125.4,
126.0, 127.2, 127.7, 128.8 (4C), 129.4 (2C), 130.8 (2C), 132.5,
)
J ) 8.5 Hz, 2H), 6.98 (d, J ) 8.5 Hz, 2H), 7.74 (d, J ) 8.3 Hz,
1
3
1
5
H); C NMR δ 13.9, 22.5, 25.6, 29.2, 31.5, 40.4 (2C), 55.2,
132.9, 141.0, 141.9, 146.2, 146.5. Anal. Calcd for C23
ClNO : C, 73.90; H, 4.31; N, 3.75. Found: C, 73.77; H, 3.96;
N, 3.59.
16
H -
6.2, 67.9, 112.4 (2C), 114.3 (2C), 114.4, 121.2, 125.5, 129.7
2
(
2C), 130.0 (2C), 130.3, 134.9, 137.5, 149.2, 152.8, 153.0, 157.8.
Anal. Calcd for C28 C, 72.70; H, 7.41; N, 6.06.
Found: C, 72.73; H, 7.64; N, 6.23.
-[(4-Bip h e n ylyl)p h e n ylm e t h yl]-2-p h e n yln it r ob e n -
H
34
N
2
O
4
:
3-Flu or o-4-[(4-m eth oxyph en yl)ph en ylm eth yl]n itr oben -
zen e (6q). Hexanes:diethyl ether (3:1) was used as the eluent
to give a yellow oil: 1H NMR δ 3.76 (s, 3H), 5.81 (s, 1H), 6.84
(d, J ) 8.7 Hz, 2H), 6.98 (d, J ) 8.7 Hz, 2H), 7.06-7.15 (m,
4
zen e (6m ). Hexanes:diethyl ether (5:1) was used as the eluent
to give yellow prisms: mp 55-57 °C; H NMR δ 5.65 (s, 1H),
7
1
13
3H), 7.24-7.32 (m, 3H), 7.86-7.93 (m, 2H); C NMR δ 48.8,
.14-7.43 (m, 18H), 7.55 (t, J ) 7.5 Hz, 3H), 7.78 (d, J ) 8.4
55.2, 111.2 (d, J ) 27.6 Hz, 1C), 111.3, 114.0 (2C), 119.0, 127.0,
128.6 (2C), 129.0 (2C), 130.1 (2C), 131.3 (d, J ) 3.5 Hz, 1C),
132.9, 139.4 (d, J ) 14.2 Hz, 1C), 141.3, 147.3 (d, J ) 8.6 Hz,
1
3
Hz, 1H); C NMR δ 56.2, 124.3, 127.0 (2C), 127.3 (2C), 127.9
(2C), 128.1, 128.6 (2C), 128.7 (2C), 128.8 (2C), 129.0, 129.3 (2C),
1
1
5
29.7 (2C), 131.9, 132.2 (2C), 132.9, 136.4, 137.4, 139.7, 140.5,
41.4, 147.5, 149.0. Anal. Calcd for C31 : C, 84.33; H,
.25; N, 3.17. Found: C, 83.95; H, 5.50; N, 3.35.
-ter t-Bu t yl-4-[(4-m e t h oxyp h e n yl)m e t h yl]n it r ob e n -
1C), 158.6, 159.9 (d, J ) 250.4 Hz, 1C). Anal. Calcd for C20
FNO : C, 71.21; H, 4.78; N, 4.15. Found: C, 71.14; H, 4.88;
N, 4.14.
16
H -
H
23NO
2
3
2
4-[(4-Ch lor oph en yl)ph en ylm eth yl]-3-m eth oxyn itr oben -
zen e (6r ). Hexanes:diethyl ether (3:1) was used as the eluent
to give a yellow oil: 1H NMR δ 3.80 (s, 3H), 5.90 (s, 1H), 6.96-
zen e (6n ). Hexanes:diethyl ether (3:1) was used as the eluent
to give a yellow oil: 1H NMR δ 1.32 (s, 9H), 3.79 (s, 3H), 5.51
1
3
(
)
5
s, 1H), 6.84 (d, J ) 8.6 Hz, 2H), 6.98-7.01 (m, 3H), 7.07 (d, J
7.05 (m, 5H), 7.22-7.30 (m, 5H), 7.71-7.75 (m, 2H); C NMR
δ 49.2, 56.0, 105.4, 115.5, 126.8, 128.5 (4C), 129.1 (2C), 130.3,
130.5 (3C), 132.3, 139.7, 140.8, 141.6, 147.6, 157.2. Anal.
1
3
7.4 Hz, 2H), 7.22-7.33 (m, 5H); C NMR δ 30.6 (3C), 35.6,
5.2, 55.8, 113.9 (2C), 123.9, 126.6, 127.6, 128.5 (2C), 129.2
(
2C), 129.7, 130.2 (2C), 134.9, 141.3, 143.2, 147.2, 149.5, 158.3.
Anal. Calcd for C24 C, 76.77; H, 6.71; N, 3.73.
Found: C, 76.78; H, 6.82; N, 3.81.
-[[4-(N,N-Dim et h yla m in o)p h en yl]p h en ylm et h yl]-2-
Calcd for C20
67.99; H, 4.54; N, 3.95.
3
H16ClNO : C, 67.90; H, 4.56; N, 3.96. Found: C,
H
3
25NO :
4-[(Ben zotr ia zol-1-yl)(4-ch lor op h en yl)p h en ylm eth yl]-
3-m eth oxyn itr oben zen e (7r ). Hexanes:diethyl ether (3:1)
was used as the eluent to give yellow microcrystals: mp 124-
4
(
(
8
tr iflu or om eth yl)n itr oben zen e (6o). Hexanes:diethyl ether
1
3:1) was used as the eluent to give orange prisms: mp 86-
126 °C; H NMR δ 3.38 (s, 3H), 6.54 (d, J ) 8.5 Hz, 1H), 7.06-
1
8 °C; H NMR δ 2.90 (s, 6H), 5.55 (s, 1H), 6.67 (d, J ) 8.5
7.19 (m, 6H), 7.25-7.31 (m, 6H), 7.72 (d, J ) 1.7 Hz, 1H), 7.79
1
3
Hz, 2H), 6.93 (d, J ) 8.5 Hz, 2H), 7.07 (d, J ) 7.3 Hz, 2H),
.22-7.32 (m, 3H), 7.39 (d, J ) 8.3 Hz, 1H), 7.62 (s, 1H), 7.74
(dd, J ) 1.9, 8.6 Hz, 1H), 8.05 (d, J ) 8.3 Hz, 1H); C NMR δ
55.8, 76.7, 107.5, 112.7, 115.0, 120.1, 123.7, 127.0, 127.9 (2C),
128.0 (2C), 128.3, 129.4 (2C), 129.8, 131.1 (2C), 133.5, 134.0,
137.6, 138.0, 139.0, 146.5, 149.3, 158.8. Anal. Calcd for
7
(
1
1
1
1
3
d, J ) 8.3 Hz, 1H); C NMR δ 40.3 (2C), 55.5, 112.5 (2C),
22.0 (q, J ) 271.9 Hz, 1C), 123.4 (q, J ) 33.5 Hz, 1C), 125.1,
26.9, 128.6 (3C), 129.1 (2C), 129.8 (2C), 133.5, 142.3, 146.1,
C
26
H
19ClN
4
O
3
: N, 11.90. Found: N, 11.77.
49.5, 150.9. Anal. Calcd for C22
19 3 2 2
H F N O : C, 65.99; H, 4.78;
N, 7.00. Found: C, 66.23; H, 4.84; N, 7.05.
-[(4-Ch lor op h en yl)p h en ylm et h yl]-1-n it r on a p h t h a -
Ack n ow led gm en t. The authors wish to thank Dr.
Linghong Xie and Dr. J ulian Levell for helpful discus-
sions during this work.
4
len e (6p ). Hexanes:diethyl ether (3:1) was used as the eluent
1
to give yellow plates: mp 70-74 °C; H NMR δ 6.27 (s, 1H),
7
.00-7.07 (m, 5H), 7.24-7.34 (m, 5H), 7.53 (t, J ) 8.0 Hz, 1H),
J O9624197