The synthesis of benzylphosphine oxidesvia vicarious nucleophilic substitution and alkenes via VNS-Horner-Wittig reactions

Article abstract of DOI:10.1039/b206144a

A range of substituted nitrobenzenes react with the anion of (chloromethyl)diphenylphosphinoyl oxide to give the substituted nitrobenzyldiphenylphosphine oxide by vicarious nucleophilic substitution. The novel stereoselective synthesis of E-stilbenes via a one-pot vicarious nucleophilic substitution-Horner-Wittig reaction is described.

Full text of DOI:10.1039/b206144a

View Article Online / Journal Homepage / Table of Contents for this issue
The synthesis of benzylphosphine oxides via vicarious nucleophilic
substitution and alkenes via VNS–Horner–Wittig reactions
Nicholas J. Lawrence,*a,b John Liddleb and David Jackson†c
1
a Department of Chemistry, Cardiff University, PO Box 912, Cardiff, CF10 3TB.
E-mail: lawrencenj1@cardiff.ac.uk
b Department of Chemistry, UMIST, PO Box 88, Manchester, UK M60 1QD
c ZENECA Process Technology Department, Huddersfield Works, PO Box A38, Leeds Road,
Huddersfield, UK HD2 1FF
Received (in Cambridge, UK) 27th June 2002, Accepted 14th August 2002
First published as an Advance Article on the web 19th September 2002
A range of substituted nitrobenzenes react with the anion of (chloromethyl)diphenylphosphinoyl oxide to give the
substituted nitrobenzyldiphenylphosphine oxide by vicarious nucleophilic substitution. The novel stereoselective
synthesis of E–stilbenes via a one–pot vicarious nucleophilic substitution–Horner–Wittig reaction is described.
base such as KOH, NaOH, t-BuOH, or NaH in DMSO, liquid
ammonia or DMF. Base is also consumed in the elimination
step (2 3) and therefore at least two molar equivalents of
Introduction
The direct aromatic substitution of hydrogen is an efficient
method to functionalise arenes.1 This is most often accom-
plished by reaction of the arene with an electrophile. An altern-
ative route involves the substitution of hydrogen by the action
of an appropriate nucleophilic species.2 One such reaction of
this type is vicarious nucleophilic substitution (VNS), an area
pioneered by Makosza and co-workers.3
The VNS reaction is characterised by reaction of a nucleo-
phile 1, that also bears a nucleofugal group (X) at the same
nucleophilic centre, with an electron-deficient arene, as illus-
trated in Scheme 1. The general mechanistic pathway of the
base are required with respect to the conjugate acid.
The VNS reaction offers a strategy for the functionalis-
ation of arenes complementary to existing methods such as
electrophilic substitution,1 ortho–lithiation,10 and conventional
nucleophilic aromatic substitution.11
As part of an investigation into the synthesis of alkenes via
Wittig and Horner–Wittig chemistry12 we were interested in the
application of VNS chemistry to the synthesis of nitrobenzyl
substituted phosphonium derivatives and phosphine oxides. As
far as we are aware there are only two examples of the VNS
reaction of the type arene
4 with a phosphorus moiety as the
electron-withdrawing group. These involve the use of chloro-
methyldiphenylphosphine oxide13 (5) and dimethyl α-chloro-
benzylphosphonate (7) as the VNS nucleophiles (Scheme 2). We
now report the full details of our own study into the VNS
synthesis of phosphine oxides.14
Scheme 1 Mechanism of vicarious nucleophilic substitution.
reaction has been established as a fast and reversible addition
of the carbanion to the nitroarene, resulting in the formation of
the σ-adduct 2, from which base induced β-elimination takes
place to generate the anion 3.4 In typical VNS reactions, nucleo-
philes are often carbanions stabilised by an adjacent electron-
withdrawing species such as an alkoxy carbonyl,5 sulfonyl,6
cyano,7 dialkylsulfoxonium,8 trialkylammonium and triphenyl-
phosphonium thioacetal9 group. These are generally prepared
in situ from their corresponding conjugate acid by action of a
Scheme 2 Reagents and conditions: i, KOH, DMSO; ii, H3Oϩ;
iii, NaOH, liq. NH3.
Results and discussion
We initially attempted the VNS reaction between an ylid
derived from a phosphonium salt (Scheme 3). The VNS nucleo-
phile (bromomethyl)triphenylphosphonium bromide (9a) was
† Current address: Syngenta Crop Protection AG, Breitenloh 5,
433 Muenchwilen, Switzerland.
2260
J. Chem. Soc., Perkin Trans. 1, 2002, 2260–2267
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b206144a

View Article Online
the yield of 6b was lower (26%). Sodium hydride was found to
be a superior base. Addition of a mixture of 5 and 4-bromo-
nitrobenzene to NaH in DMSO, immediately gave a deep violet
coloured solution that after stirring at room temperature over-
night and workup gave 6b in 55% yield. These conditions were
found to be reliable and gave consistent results. A variety of
other substituted nitroarenes were reacted with 5 under the
same conditions. The results are shown in Scheme 5.
Addition to 4-chloro, 4-bromo and 4-fluoro nitrobenzenes
takes place, as expected, exclusively ortho to the nitro group.
1
The H NMR signal of the hydrogen positioned ortho to the
nitro group was especially diagnostic, since it is shifted down-
field of the other aryl signals. For example the H5 signal is
found at δ 7.81 (d, J 8.8 Hz) for 6a, δ 7.74 (d, J 8.8 Hz) for 6b
and at δ 7.90 (dd, JHH 9.1 and JHF 5.2 Hz) for 6c. Reaction of
4-chloronitrobenzene with 5 overnight afforded the phosphine
oxide 6a in 61% yield. 4-Fluoronitrobenzene was much less
reactive towards the VNS nucleophile and gave 6c in only 14%
yield. Halogen substitution was not observed in any of the
VNS reactions even though displacement of fluoride has been
found to occasionally occur in VNS reactions.20 Nitrobenzene
did not undergo a VNS reaction with 5. However, 1,3-dinitro-
benzene proved to be sufficiently electrophilic to undergo the
reaction efficiently. The major product of the reaction was the
6-substituted isomer 15. A small amount of the 2-substituted
isomer 14 was also isolated. The isomers were clearly identifi-
Scheme 3 VNS reactions of halomethylphosphonium salts.
prepared from triphenylphosphine and dibromomethane.15 The
expected products 10 and 11 of the VNS reaction between
nitrobenzene and 9a were prepared from their corresponding
benzylbromides16 to aid the interpretation of the NMR spectra
of the VNS reaction products. We never observed the presence
of 10 or 11 in the NMR spectra of the crude reaction mix-
tures. Unfortunately all attempts to facilitate the VNS reaction
between nitrobenzene and the ylid derived from 9a were un-
1
successful. Inspection of the H NMR spectrum of the crude
reaction mixture showed that the nitrobenzene was still present.
The ylid of 9a was prepared by using LDA or potassium
tert-butoxide,17 either before the addition of nitrobenzene or in
its presence.
1
able from their H NMR spectra. The 6-substituted isomer 15
has a coupling pattern expected of a 1,2,4-trisubstituted aryl
group. The signal of the H3 hydrogen atom located between the
two nitro groups in 15 was observed at δ 8.69 ppm (1H, J 2.3
Hz), as expected. A doublet (2H, J 8.2 Hz) at δ 8.02 ppm
We also prepared the phosphonium salt (chloromethyl)-
triphenylphosphonium chloride (9b) by sequential treatment of
triphenylphosphine with HCl–formaldehyde and thionyl chor-
ide.18 The ylid derived from 9b also did not react in the VNS
reaction (again the nitrobenzene did not react). The stability of
the ylid was checked by treatment with 2 equivalents of LDA in
THF at 0 ЊC for 20 minutes followed by an aqueous work-up.
Analysis by NMR revealed complete decomposition of the ylid.
It seems therefore that the ylid is not stable to the excess of base
required to effect the VNS reaction.
1
corresponding to H3 and H5 was observed in the H NMR
spectrum of the minor product 14. Haglund and Nilsson have
shown that the presence of pyridine and Cu() salts in VNS
reactions of 1,3-dinitrobenzene leads to the preferential form-
ation of the 1,2,3-trisubstituted isomer.21 However addition of
pyridine and Cu() chloride under our reaction conditions or
using Haglund and Nilsson’s procedure lead only to small
amounts of the VNS products. Clearly the VNS reaction is
sensitive to changes in substrates and conditions.
We chose the phosphine oxide 12, analogous to the known
phosphonate 8a as our next target. The required VNS nucleo-
phile 13 was easily prepared by heating a mixture of benzalde-
hyde and chlorodiphenylphosphine at 150 ЊC (Scheme 4).19 The
The VNS reaction allows the synthesis of substituted arenes
bearing trifluoromethyl groups. The reaction of 3-trifluoro-
methylnitrobenzene with 5 was complete after 5 h and produced
a 7 : 2 mixture of 6-substituted isomer 16 and the 4-substituted
isomer 17 in 73% (total) yield. We were able to obtain pure 16
by recrystallisation of the mixture twice from propan-2-ol. The
1H NMR spectrum of 16 clearly shows the H3 proton as a
singlet at δ 8.10 ppm. The regioselectivity agrees with that
found by Makosza in the reaction of 3-trifluoromethylnitro-
benzene with the anion of chloromethyl phenyl sulfone.20
The 6-substituted isomer 18 is the exclusive product of the
reaction of 3-trifluoromethyl-4-chloronitrobenzene. It is pro-
duced in 74% yield when the reaction is stirred at room
1
temperature for four hours. The H NMR of 18 supports the
expected substitution pattern. A singlet corresponding to H5 is
observed at δ 8.20 ppm. The same pattern of selectivity is
observed in the reaction of 3-trifluoromethyl-4-chloronitro-
benzene with chloromethyl phenyl sulfone.22
Scheme 4 Reagents and conditions: i, Ph2PCl, 150 ЊC; ii, NaH, DMSO,
13; iii, H3Oϩ.
The VNS reaction of 2-chloro-5-(trifluoromethyl)nitro-
benzene with 5 is much slower. After thirty hours at room tem-
perature the yield of 19 is only 46%. Makosza has emphasised
the need for rapid quenching in VNS chemistry, to avoid
decomposition of the first-formed product 3 and then 4.2c Most
VNS reactions reported in the literature are quenched within
two hours of reaction time. However it is clear that under an
inert atmosphere VNS reactions of phosphinoyl anions can be
left overnight to afford good to moderate yields of product.
Having prepared the series of nitrobenzyldiphenylphosphine
oxides we next investigated their Horner–Wittig chemistry in
the synthesis of a variety of novel stilbenes. Our own studies12
VNS reaction between nitrobenzene and phosphine oxide 13
was attempted using NaH in DMSO. Unfortunately the
1
reaction was unsuccessful in our hands and H NMR showed
no signs of the expected product; the nitrobenzene remained
unreacted and the starting phosphine oxide had decomposed.
We next focussed our attention on the VNS chemistry of
chloromethyldiphenylphosphine oxide. Makosza has reported13
that 5 undergoes the VNS reaction with 4-chloro and 4-bromo-
nitrobenzene in the presence of KOH in DMSO to give 6a and
6b in 41% and 52% yields respectively. However in our hands
J. Chem. Soc., Perkin Trans. 1, 2002, 2260–2267
2261

View Article Online
Scheme 5 Reagents and conditions: i, NaH, DMSO; ii, H3Oϩ.
and those of Warren and co-workers23 have shown that such
lithiated phosphine oxides react with aromatic aldehydes gener-
ating the (E)-stilbene directly, without the isolation of the
intermediate phosphinoyl alcohols. As expected, the lithium
anion of the phosphine oxide 6a, formed from n-butyllithium in
THF at 0 ЊC, reacted with benzaldehyde giving exclusively the
trans stilbene 20a, but in a disappointing 31% yield (Scheme 6).
Scheme 7 General mechanism of the Horner–Wittig reaction.
successful this process would constitute a one-pot VNS–
Horner–Wittig reaction that might improve the yields of the
(E)-stilbenes. Our hopes were immediately met. Quenching the
VNS reaction of 5 and 4-chloronitrobenzene with benzalde-
hyde gave the expected (E)-stilbene 20a in a moderate, but
improved, 47% yield (Scheme 8). The yield obtained via this
Scheme 6 Horner–Wittig reactions of nitrobenzylphosphine oxides.
On addition of the aldehyde to the deep purple coloured solu-
tion of the lithium anion, a white precipitate of lithium
diphenylphosphinate slowly forms.
Increasing the reaction time and temperature did not increase
the yield of the alkene but led to the apparent decomposition of
1
the anion of 6a. A H NMR spectrum of the crude reaction
mixture indicated that 6a had been consumed. The remaining
mass balance proved to be base-line material (visible by TLC).
Similarly, the reaction of 6b with 4-nitrobenzaldehyde gave the
(E)-stilbene 20b only, again in a moderate yield (Scheme 6). The
low yield of this Horner–Wittig reaction is probably due to
the high stability of the nitrobenzylic anion. Warren and co-
workers have shown that the first step of the Horner–Wittig
reaction is reversible (Scheme 7).23 Addition of the phosphine
oxide anion to the benzaldehyde generally produces a mixture
of erythro- and threo-phosphinoyl alkoxides. Elimination of
sodium diphenylphosphinate is fastest from the threo-precursor
to produce the (E)-alkene. It seems that the stability of the
anion of a nitrobenzylic phosphine oxide reduces the form-
ation of the erythro and threo adducts to such an extent
that undesired processes compete with aldehyde addition. The
measure of this stabilisation can be seen by comparing the equi-
librium acidity of p-NO2C6H4CH2POPh2 (pKa 17.7 in DMSO)
with PhCH2POPh2(pKa 27.5 in DMSO).24
Scheme 8 One-pot VNS–Horner–Wittig synthesis of (E)-stilbenes.
one-pot process compares well with that obtained via the separ-
ate VNS and Horner–Wittig reaction (31% overall). The VNS
reaction was carried out according to our standard conditions;
chloromethyldiphenylphosphine oxide and the substituted
nitrobenzene were added to a slurry of sodium hydride in
DMSO under nitrogen. The disappearance of 5 was followed
by proton NMR and when complete, the aldehyde was added to
the reaction mixture. It was necessary to heat the mixture at this
stage to effect formation of the stilbene. When the reaction was
stirred overnight at ambient temperature very little stilbene was
formed. When potassium or lithium hydride was used as the
base no VNS reaction took place.
The anion formed by deprotonation of the phosphine oxide
6a in the Horner–Wittig reaction is actually the same anion of
type 3 (Scheme 1) generated in the VNS reaction. It seemed
possible that the anion from the VNS could be reacted directly
with benzaldehyde to form a corresponding nitrostilbene. If
2262
J. Chem. Soc., Perkin Trans. 1, 2002, 2260–2267

View Article Online
The one-pot VNS–Horner–Wittig reaction works with other
combinations of nitroarenes and aldehydes (Scheme 8). In each
case (20c–20e) the (E)-alkene was formed exclusively, albeit in
moderate yield. On quenching the VNS reaction of 4-chloro-
nitrobenzene and 5 with 4-tolylaldehyde the stilbene 20c was
accompanied by the alcohol by-product 21 that was isolated in
10% yield (Fig. 1). The formation of 21 is most likely associated
13C NMR spectra were recorded using a Bruker AC 300 spectro-
meter. 13C NMR spectra were recorded using Distortionless
1
Enhancement by Polarization Transfer. Both H and 13C spec-
tra were recorded using CHCl3 as internal standard. Chemical
ionization (CI) mass spectra were recorded using a Kratos
MS25 mass spectrometer; fast atom bombardment (FAB) mass
spectra were recorded with a Kratos MS50 with a m-nitro-
benzyl alcohol matrix. Accurate mass determinations were
carried out on a Kratos Concept IS spectrometer. Elemental
analyses were performed using a Carlo-Erba 1106 elemental
analyzer. Infrared spectra were recorded using a Perkin-Elmer
783 spectrometer equipped with a PE 600 data station. Melting
points were determined using an electrothermal melting point
apparatus and were uncorrected. Column chromatography was
conducted using silica gel 60 230–400 mesh (Merck & Co.).
Silica TLC was conducted on precoated aluminum sheets
(60 F254) with a 0.2 mm thickness (Aldrich Chemical Co.).
DMSO was distilled from calcium hydride and stored under
nitrogen prior to use. Anhydrous methanol and DMF were
obtained from Aldrich Chemical Co. and used as supplied.
Fig. 1 Structure of the by-product from the reaction of 4-chloronitro-
benzene, 5, and 4-tolylaldehyde.
with the acidity of the methyl group in the stilbene 20c
and results from the addition of the anion of the first-formed
stilbene to a second molecule of 4-tolylaldehyde.
Bromomethyltriphenylphosphonium bromide (9a)
It is worthy of note that our method joins another VNS route
to nitroalkenes. Makosza and Tyrala have reported the syn-
thesis of nitroalkenes via a two step process involving the initial
VNS reaction of chloromethyl phenyl sulfone and a nitroarene
Triphenylphosphine (15 g, 57.25 mmol) and dibromomethane
(19.92 g, 114.48 mmol) were dissolved in toluene (125 cm3) and
the solution refluxed for 7 days. The mixture was cooled to 0 ЊC,
the crystals filtered and washed with toluene to yield the phos-
phonium salt 9a (16.5 g, 66%) as a white solid, mp 238–240 ЊC
(lit.15 mp 232–235 ЊC) after recrystallisation from isopropanol.
νmax (KBr disc)/cmϪ1 3020 (md), 2840 (md), 2210 (w), 1590
(md), 1440 (st), 1130 (md), 1110 (st), 995 (md), 840 (md), 750
(st), 680 (st), 620 (md), 505 (st), 480 (md), 380 (w); δH (300
MHz; CDCl3) 5.84 (2H, d, JPH 5.8 Hz, CH2), 7.65–7.82 (9H, m,
aryl), 7.90–7.97 (6H, m, aryl); δC (75 MHz; CDCl3) 18.32 (d, JPC
54.6 Hz, CH2), 116.73 (d, JPC 89.2 Hz, C, ipso-PPh3), 130.23 (d,
JPC 12.8 Hz, CH, m-PPh3), 134.28 (d, JPC 10.5 Hz, CH, o-PPh3),
135.42 (d, JPC 2.9 Hz, CH, p-PPh3); m/z (FAB) 357 [(M(79Br) Ϫ
BrϪ), 98], 355 [(M(79Br) Ϫ BrϪ), 100], 307 (3), 275 (22), 183 (8).
(e.g. 4-chloronitrobenzene
22, Scheme 9).25 Alkylation of this
Chloromethyltriphenylphosphonium chloride (9b)
Paraformaldehyde (3.3 g, 0.11 mol) was added to an anhydrous
solution of hydrochloric acid in ether (1 M solution, 100 cm3,
0.10 mol). Triphenylphosphine (26.2 g, 0.10 mol) was dissolved
in anhydrous ether (50 cm3), added to the paraformaldehyde
slurry and the mixture stirred for 2 h. The reaction mixture
was filtered, the resulting hydroxymethyltriphenylphosphonium
chloride was washed with ether and dried in air. The salt was
dissolved in dichloromethane (40 cm3) and filtered to remove
the insoluble paraformaldehyde. Thionyl chloride (15 cm3,
24.47 g, 0.21 mol) was added to the liquors and the mixture
refluxed for 1 h. The excess thionyl chloride and dichloro-
methane were removed under reduced pressure and the remain-
ing solid washed well with ether. The phosphonium salt 9b
(18.0 g, 52%) was obtained as a white solid, mp 262–264 ЊC
(lit.27 mp 260–263 ЊC) after recrystallisation from isopropanol.
νmax(KBr disc)/cmϪ1 3060 (md), 2980 (md), 2850 (st), 2760 (md),
2500 (md), 1435 (st), 1160 (w), 1110 (st), 1000 (md), 840 (md),
750 (st), 730 (st), 685 (st), 520 (st), 450 (st); δH (300 MHz;
CDCl3) 6.13 (2H, d, JPH 5.8 Hz, CH2), 7.67–7.74 (6H, m, aryl),
7.79–7.84 (3H, m, aryl), 7.89–7.96 (6H, m, aryl); δC (75 MHz;
CDCl3) 33.75 (d, JPC 55.8 Hz, CH2), 116.42 (d, JPC 88.4 Hz,
ipso-PPh3), 130.57 (d, JPC 12.8 Hz, CH, m-PPh3), 134.31 (d, JPC
9.8 Hz, CH, o-PPh3), 135.59 (d, JPC 2. 9 Hz, CH, p-PPh3); m/z
(FAB) 313[(M(37Cl) Ϫ ClϪ), 35], 311[(M(35Cl) Ϫ ClϪ), 100], 275
(5), 183 (15), 165 (3), 108 (4), 77 (3).
Scheme 9 A route to alkenes via a consecutive VNS alkylation–
elimination process.
isolated VNS product 22 with an alkylating agent bearing an
electron-withdrawing group generates the intermediate sulfone
23 which undergoes an elimination reaction to provide the
alkene 24.
In conclusion, we have developed a convenient method for
the synthesis of a range of nitrobenzyldiphenylphosphine
oxides that compares favourably with current procedures. In
addition, a simple route to trans-nitrostilbenes has been
reported which effectively represents the substitution of aro-
matic hydrogen with a vinyl group. This stereoselective prepar-
ation of nitrostilbenes represents the first example of a VNS-
derived anion 3 being quenched with anything other than a
proton. This finding has subsequently led us to explore the use
of other electrophiles and has led to the development of a
VNS–alkylation process.26
Experimental
General information
4-Nitrobenzyltriphenylphosphonium bromide (10)
1
The 200 MHz H NMR spectra were recorded using a Bruker
Triphenylphosphine (1.0 g, 3.82 mmol) and 4-nitrobenzyl
bromide (0.82 g, 3.82 mmol) were dissolved in tetrahydrofuran
AC 200 NMR spectrometer while all 300 MHz 1H and 75 MHz
J. Chem. Soc., Perkin Trans. 1, 2002, 2260–2267
2263

View Article Online
(6 cm3) and the solution refluxed for 2 h. The solution was
allowed to cool to ambient temperature, the crystals filtered and
washed with tetrahydrofuran to give the phosphonium bromide
10 (1.10 g, 60%) as a white solid, mp 280–282 ЊC (lit.28 275.0–
275.5 ЊC) after recrystallisation from methanol–ethyl acetate;
νmax (KBr disc)/cmϪ1 3060 (w), 2860 (md), 1590 (md), 1480
(md), 1440 (st), 1350 (st), 1110 (st), 1000 (md), 870 (st), 750 (st),
690 (st), 630 (md), 550 (md), 505 (st), 495 (st); δH (300 MHz;
CDCl3) 5.97 (2H, d, JPH 15.7 Hz, CH2), 7.46 (2H, dd, JHH
8.9 Hz, JPH 2.5 Hz, H2 and H6), 7.57–7.64 (6H, m, aryl), 7.73–
7.86 (11H, m, aryl); δC (75 MHz; CDCl3) 29.80 (d, JPC 47.2 Hz,
CH2), 117.08 (d, JPC 86.2 Hz, C, ipso-PPh3), 123.25 (d, JPC
3.3 Hz, CH, C3 and C5), 130.23 (d, JPC 12.7 Hz, CH, m-PPh3),
132.79 (d, JPC 5.3 Hz, CH, C2 and C6), 134.31 (d, JPC 10.2 Hz,
CH, o-PPh3), 135.10 (d, JPC 3.0 Hz, CH, p-PPh3), 135.56 (d, JPC
8.5 Hz, C, C1), 147.37 (d, JPC 4.2 Hz, C, C4); m/z (FAB) 877
[(2M Ϫ BrϪ), 4%], 398 [(M Ϫ BrϪ), 100], 382 (7), 352 (9), 262
[(Ph3P), 15], 183 (17), 165 (5), 108 (7), 89 (5).
7.43–7.58 (6H, m, aromatic), 7.72–7.79 (4H, m, aromatic);
δC (75 MHz; CDCl3) 61.30 (d, JPC 82 Hz, CH2), 128.65
(d, JPC 12.0 Hz, CH, m-Ph2PO), 130.49 (d, JPC 96.7 Hz, C,
ipso-Ph2PO), 131.33 (d, JPC 10.5 Hz, CH, o-Ph2PO), 132.12
(d, JPC 2.2 Hz, CH, p-Ph2PO); m/z (FAB) 465 [(2M ϩ H)ϩ, 7%],
233 [(M ϩ H)ϩ, 100], 183 (7), 140 (23), 91 (7).
Chloromethyldiphenylphosphine oxide (5)
Hydroxymethyldiphenylphosphine oxide (4.0 g, 17.24 mmol)
was dissolved in dichloromethane (25 cm3). Thionyl chloride
was added (2.5 cm3, 34.26 mmol) and the solution stirred for 3 h
at ambient temperature. The reaction was carefully quenched
with water (50 cm3), neutralised with aqueous sodium bicarbon-
ate and extracted with dichloromethane (3 × 20 cm3). The
organic layers were combined, dried (magnesium sulfate), fil-
tered and the solvent removed under reduced pressure to give
the phosphine oxide 5 (2.84 g, 66%) as a white solid, mp 133–
135 ЊC (lit.31 mp 137–138 ЊC) after recrystallisation from ethyl
acetate. Found: C, 62.1; H, 4.5; Cl, 13.8; P, 12.2. C13H12ClOP
requires C, 62.3; H, 4.8; Cl, 14.1; P, 12.4%; Rf 0.38 (silica, ethyl
acetate); νmax (KBr Disc)/cmϪ1 3070 (w), 2920 (w), 1490 (w),
1445 (st), 1435 (st), 1195 (st), 1130 (st), 1000 (w), 815 (st),
745 (md), 700 (st), 490 (st), 415 (md), 300 (md); δH (300 MHz;
CDCl3) 4.05 (2H, d, JPH 6.6 Hz, CH2), 7.50–7.63 (6H, m,
aryl), 7.78–7.85 (4H, m, aryl); δC (75 MHz; CDCl3) 37.79
(d, JPC 72.0 Hz, CH2), 128.92 (d, JPC 12.0 Hz, CH, m-Ph2PO),
131.11 (d, JPC 90.0 Hz, C, ipso-Ph2PO), 131.72 (d, JPC 9.0 Hz,
CH, o-Ph2PO), 132.82 (d, JPC 2.2 Hz, CH, p-Ph2PO); m/z
(FAB) 501 [(2M(35Cl) ϩ H)ϩ, 4%], 251 [(M(37Cl ϩ H)ϩ, 30], 251
[(M(35Cl) ϩ H)ϩ, 100], 215 (5), 183 (5), 91 (7).
2-Nitrobenzyltriphenylphosphonium bromide (11)
2-Nitrobenzyltriphenylphosphonium bromide was prepared
from triphenylphosphine (2.0 g, 7.63 mmol) and 2-nitrobenzyl
bromide (1.65 g, 7.64 mmol) in a similar way to the phosphon-
ium bromide 10. The phosphonium salt 11 (2.32 g, 64%) was
obtained as a white solid, mp 172–174 ЊC (lit.16 mp 161–162 ЊC)
after recrystallisation from isopropanol; νmax(KBr disc)/cmϪ1
3460 (st), 3020 (md), 2880 (md), 1585 (md), 1520 (st), 1440 (st),
1340 (md), 1110 (st), 870 (md), 790 (md), 760 (st), 685 (st), 520
(md), 495 (md); δH (300 MHz; CDCl3) 6.11 (2H, d, JPH 14.9 Hz,
CH2), 7.45–7.51 (1H, m, aryl), 7.59–7.81 (19H, m, aryl), 7.93
(1H, d, JHH 8.2 Hz, CH H2), 8.09–8.13 (1H, m, CH H6); m/z
(FAB) 877 [(2M Ϫ BrϪ), 48%], 398 [(M Ϫ BrϪ), 100], 351 (20),
262 [(Ph3P), 7], 183 (6), 108 (2).
(3-Chloro-6-nitrobenzyl)diphenylphosphine oxide (6a)
Sodium hydride (60% dispersion in oil, 800 mg, 20 mmol) was
added to anhydrous dimethyl sulfoxide (9 cm3) and the
mixture flushed with nitrogen. Chloromethyldiphenylphosphine
oxide (5) (2.0 g, 7.98 mmol) and 4-chloronitrobenzene (1.40 g,
8.89 mmol) were dissolved in anhydrous dimethyl sulfoxide
(11 cm3) and added dropwise to the sodium hydride slurry. The
mixture was stirred at ambient temperature overnight. The
reaction was quenched with distilled water, acidified with
hydrochloric acid (1 M solution) and extracted with dichloro-
methane (3 × 20 cm3). The combined extracts were washed with
distilled water (3 × 20 cm3), dried (magnesium sulfate), filtered
and the solvent removed under reduced pressure to yield the
phosphine oxide 6a (1.8 g, 61%) as a cream coloured solid, mp
186–188 ЊC (lit.13 mp 188–189.5 ЊC) after recrystallisation from
ethanol. Found: C, 61.5; H, 4.1; N, 4.0; Cl, 9.7; P, 8.3.
C19H15ClNO3P requires C, 61.4; H, 4.1; N, 3.8; Cl, 9.5; P, 8.3%;
Rf (silica, ethyl acetate); νmax (KBr Disc)/cmϪ1 3110 (w), 1605
(md), 1525 (st), 1440 (md), 1415 (md), 1350 (st), 1155 (md),
1130 (md), 1110 (md), 905 (st), 750 (md), 700 (st), 610 (md), 520
(st); δH (300 MHz; CDCl3) 4.21 (2H, d, JPH 13.8 Hz, CH2), 7.30
(1H, dt J 8.8 and 2.0 Hz, H4), 7.42–7.57 (7H, m, aryl), 7.65–
7.72 (4H, m, aryl), 7.81 (1H, d, J 8.8 Hz, H5); δC (75 MHz;
CDCl3) 34.61 (d, JPC 62.2 Hz, CH2), 126.47 (d, JPC 1.9 Hz, CH,
C5), 127.96 (d, JPC 2.2 Hz, CH, C4), 128.62 (d, JPC 11.8, CH,
m-Ph2PO), 129.19 (d, JPC 8.4 Hz, C, C1), 130.99 (d, JPC 101.0
Hz, C, ipso-Ph2PO), 130.88 (d, JPC 9.5 Hz, CH, o-Ph2PO),
132.18 (d, JPC 2.9 Hz, CH, p-Ph2PO), 133.02 (d, JPC 4.3 Hz, CH,
C2), 139.12 (d, JPC 3.1 Hz, C, C3), 147.17 (d, JPC 5.4 Hz, C, C6);
m/z (FAB) 374 [(M(37Cl) ϩ H)ϩ, 40%], 372 [(M(35Cl) ϩ H)ϩ,
100], 325 (11), 77 (11).
(ꢀ-Chlorobenzyl)diphenylphosphine oxide (13)
Chlorodiphenylphosphine (6.24 g, 28 mmol) was added to
benzaldehyde (3 g, 28 mmol) and the mixture heated at 150 ЊC
overnight. The resulting solid was washed with hexane and
dried in air to give the phosphine oxide 13 (6.3 g, 68%) as
a white solid, mp 197–199 ЊC (lit.29 mp 197–199 ЊC) after
recrystallisation from ethyl acetate. Found: C, 70.0; H, 4.9; Cl,
10.9; P, 9.6. C19H16ClOP requires C, 69.9; H, 5.0; Cl, 10.9; P,
9.5%; Rf 0.75 (silica, ethyl acetate); νmax (KBr disc)/cmϪ1 3050
(md), 2940 (md), 1590 (w), 1455 (md), 1435 (st), 1315 (w), 1200
(st), 1180 (st), 1160 (md), 1070 (md), 1000 (w), 840 (w), 745 (st),
545 (st); δH (300 MHz, CDCl3) 5.42 (1H, d, JPH 4.3 Hz, CHCl),
7.19–7.63 (13H, m, aryl), 7.87–7.93 (2H, m, aryl); m/z (FAB)
329 [(M(37Cl) ϩ H)ϩ, 32%), 327 [(M(35Cl) ϩ H)ϩ, 100], 292
[(M Ϫ Cl)ϩ, 30], 201 [(Ph2PO), 15], 185 (17), 167 (47), 152 (5),
125 (33).
Hydroxymethyldiphenylphosphine oxide
Chlorodiphenylphosphine (6.1 g, 5.0 cm3, 28.0 mmol) was
added to 37% aqueous formaldehyde solution (50 cm3, 617.0
mmol) and concentrated hydrochloric acid (50 cm3) and the
mixture heated at 100 ЊC overnight. Evaporation of the reaction
mixture at reduced pressure left an oil, which was neutralised
with aqueous sodium bicarbonate solution and extracted with
chloroform (3 × 20 cm3). The organic layers were combined,
dried (magnesium sulfate), filtered and the solvent removed
under reduced pressure to give the phosphine oxide (4.60 g,
71%) as a white solid, mp 141–143 ЊC (lit.30 mp 137–139 ЊC)
after recrystallisation from ethyl acetate. Found: C, 67.1; H, 5.5;
P, 13.0. C13H13O2P requires C, 67.2; H, 5.7; P, 13.4%; Rf 0.45
(silica, 9 : 1, ethyl acetate : methanol, v/v); νmax (KBr Disc)/cmϪ1
3220 (st), 2900 (w), 1485 (md), 1445 (st), 1215 (st), 1150 (st),
1125 (st), 1070 (md), 850 (md), 720 (st), 545 (st), 490 (st), 435
(md); δH (300 MHz; CDCl3) 4.40 (2H, d, JPH 0.9 Hz, CH2),
(3-Bromo-6-nitrobenzyl)diphenylphosphine oxide (6b)
The phosphine oxide 6b was prepared from chloromethyl-
diphenylphosphine oxide 5 (2.50 g, 9.98 mmol) and 4-bromo-
nitrobenzene (2.20 g, 10.89 mmol) in a similar way to the
diphenylphosphine oxide 6a. The phosphine oxide 6b (2.3 g,
2264
J. Chem. Soc., Perkin Trans. 1, 2002, 2260–2267

View Article Online
55%) was obtained as a cream coloured solid, mp 193–195 ЊC
(lit.13 mp 195–197.5 ЊC) after chromatography (silica, 2 : 1,
chloroform : ethyl acetate, v/v). Found: C, 55.1; H, 3.3; N, 3.6;
Br, 18.9; P, 7.4. C19H15BrNO3P requires C, 54.8; H, 3.6; N, 3.4;
Br, 19.2; P, 7.4%; Rf 0.49 (silica, ethyl acetate); νmax (KBr Disc)/
cmϪ1 3000 (w), 1600 (md), 1530 (st), 1480 (w), 1435 (st), 1350
(st), 1230 (w), 1190 (st), 1120 (md), 880 (st), 820 (md), 760 (md),
740 (st), 690 (st), 520 (st); δH (300 MHz; CDCl3) 4.20 (2H, d, JPH
13.8 Hz, CH2), 7.42–7.57 (7H, m, aryl), 7.64–7.72 (5H, m, aryl),
7.74 (1H, d, J 8.8 Hz, H5); m/z (FAB) 418 [(M(81Br) ϩ H)ϩ,
100%], 416 [(M(79Br) ϩ H)ϩ, 100], 371 (8), 369 (8), 307 (5), 210
[(Ph2PO), 43], 165 (8), 107 (12), 89 (20).
[2-Nitro-4-(trifluoromethyl)benzyl]diphenylphosphine oxide (16)
The phosphine oxide 16 was prepared from chloromethyl-
diphenylphosphine oxide (5) (2.5 g, 9.98 mmol) and 3-trifluoro-
methylnitrobenzene (2.10 g, 10.98 mmol) in a similar way to
diphenylphosphine oxide 6a. The phosphine oxide 16 (1.5 g,
37%) was obtained as white needles, mp 188–189 ЊC after two
recrystallisations from isopropanol. Found: C, 59.2; H, 3.4; N,
3.6; F, 13.8; P, 7.8. C20H15F3NO3P requires C, 59.3; H, 3.7; N,
3.5; F, 14.1; P, 7.6%; Rf 0.36 (silica, 4 : 1, chloroform : ethyl
acetate, v/v); νmax (KBr Disc)/cmϪ1 3080 (w), 2930 (md), 1630
(md), 1540 (st), 1440 (st), 1360 (md), 1330 (st), 1220 (md), 1130
(st), 1000 (md), 860 (md), 750 (md), 720 (st), 630 (st); δH (300
MHz; CDCl3) 4.29 (2H, d, JPH 13.9 Hz), 7.45–7.51 (4H, m,
aryl), 7.55–7.60 (2H, m, aryl), 7.68–7.72 (4H, m, aryl), 7.76
(1H, d, JHH 9.0 Hz, H5), 7.79 (1H, dd, JHH 9.0 Hz and JPH
1.5 Hz, H6), 8.10 (1H, s, H3); m/z (FAB) 811 [(2M ϩ H)ϩ,
17%], 406 [(M ϩ H)ϩ, 100], 359 (20), 201 [(Ph2PO), 60], 89 (12),
77 (20).
(3-Fluoro-6-nitrobenzyl)diphenylphosphine oxide (6c)
The phosphine oxide 6c was prepared from chloromethyl-
diphenylphosphine oxide (5) (1.71 g, 6.83 mmol) and 4-fluoro-
nitrobenzene (1.06 g, 7.52 mmol) in a similar way to the
diphenylphosphine oxide 6a. The phosphine oxide 6c (350 mg,
14%) was obtained as a pale brown solid, mp 189–190 ЊC after
chromatography (silica, 4 : 1, chloroform : ethyl acetate, v/v).
Found: C, 63.9; H, 4.6; N, 4.1; F, 5.3; P, 8.5. C19H15FNO3P
requires C, 64.2; H, 4.3; N, 3.9; F, 5.4; P, 8.7%; Rf 0.63 (silica,
ethyl acetate); νmax (KBr Disc)/cmϪ1 3120 (w), 1620 (md), 1530
(st), 1440 (md), 1350 (st), 1250 (md), 1190 (st), 1125 (md), 965
(md), 830 (md), 700 (st), 610 (md), 520 (st), 490 (md); δH (300
MHz; CDCl3) 4.25 (2H, d, JPH 13.9 Hz, CH2), 6.99–7.06 (1H,
m, aryl), 7.29–7.33 (1H, m, aryl), 7.42–7.57 (6H, m, aryl), 7.65–
7.72 (4H, m, aryl), 7.90 (1H, dd, JHF 5.2 and JHH 9.1 Hz, H5);
m/z (FAB) 356 [(M ϩ H)ϩ, 100%], 340 (3), 309 (10), 201
[(Ph2PO), 32], 183 (8), 107 (5).
[3-Chloro-6-nitro-4-(trifluoromethyl)benzyl]diphenylphosphine
oxide (18)
The phosphine oxide 18 was prepared from chloromethyl-
diphenylphosphine oxide (5) (2.5 g, 9.98 mmol) and 4-chloro-3-
(trifluoromethyl)nitrobenzene (2.48 g, 11.00 mmol) in a similar
way to the diphenylphosphine oxide 6a. The phosphine oxide
18 (3.62 g, 74%) was obtained as cream coloured needles, mp
243–244 ЊC after recrystallisation from isopropanol. Found: C,
54.5; H, 3.1; N, 3.2; F, 12.6; Cl, 8.1; P, 6.8. C20H14ClF3NO3P
requires C, 54.6; H, 3.2; N, 3.2; F, 13.0; Cl, 8.1; P, 7.0%; Rf 0.72
(silica, ethyl acetate); νmax (KBr Disc)/cmϪ1 3000 (w), 1620 (md),
1530 (st), 1440 (md), 1390 (st), 1350 (st), 1310 (st), 1185 (st),
1130 (st), 1000 (w), 950 (md), 835 (md), 725 (st), 650 (md);
δH (300 MHz; CDCl3) 4.26 (2H, d, JPH 13.8 Hz, CH2), 7.45–7.60
(6H, m, aryl), 7.65–7.72 (5H, m, aryl), 8.20 (1H, s, H5); m/z
(FAB) 879 [(2M(35Cl) ϩ H)ϩ, 3%], 442 [(M(37Cl) ϩ H)ϩ, 40], 440
[(M(35Cl) ϩ H)ϩ, 100], 393 (8), 201 [(Ph2PO), 27], 125 (5), 77 (7).
(2,4-Dinitrobenzyl)diphenylphosphine oxide (15) and
(2,6-dinitrobenzyl)diphenylphosphine oxide (14)
The phosphine oxide 15 was prepared from chloromethyl-
diphenylphosphine oxide 5 (500 mg, 2.00 mmol) and 1,3-
dinitrobenzene (370 mg, 2.20 mmol) in a similar way to the
diphenylphosphine oxide 6a. The phosphine oxide 15 (540 mg,
71%) was obtained as a pale brown solid, mp 166–168 ЊC after
chromatography (silica, 1 : 1, chloroform : ethyl acetate, v/v)
and recrystallisation from isopropanol. Found: C, 59.7; H, 4.1;
N, 7.6; P, 7.7. C19H15N2O5P requires C, 59.7; H, 4.0; N, 7.3; P,
8.1%; Rf 0.42 (silica, 1 : 1, chloroform : ethyl acetate, v/v); νmax
(KBr Disc)/cmϪ1 2930 (md), 1715 (w), 1620 (md), 1540 (st),
1440 (md), 1350 (st), 1180 (st), 1150 (md), 1120 (md), 1100 (w),
900 (md), 860 (md), 830 (md), 770 (w), 750 (md), 720 (md), 710
(md), 690 (md), 550 (md), 510 (md); δH (300 MHz; CDCl3) 4.33
(2H, d, JPH 13.9 Hz, CH2), 7.44–7.51 (4H, m, aryl), 7.54–7.59
(2H, m, aryl), 7.64–7.71 (4H, m, aryl), 7.78 (1H, dd, JHH 8.5 Hz,
JPH 2.1 Hz, H6), 8.33 (1H, dd, JHH 2.3, 8.5 Hz, H5), 8.69 (1H, d,
JHH 2.3 Hz, H3); δC (75 MHz; CDCl3) 35.31 (d, JPC 59.3 Hz,
CH2), 120.47 (d, JPC 2.5 Hz, CH, C3), 126.64 (d, JPC 2.0 Hz,
CH, C5), 128.84 (d, JPC 11.7 Hz, CH, m-Ph2PO), 130.51 (d, JPC
101.9 Hz, C, ipso-Ph2PO), 131.86 (d, JPC 9.5 Hz, CH, o-Ph2PO),
132.54 (d, JPC 3.0 Hz, CH, p-Ph2PO), 134.37 (d, JPC 7.5 Hz, C,
C1), 134.69 (d, JPC 4.4 Hz, CH, C6), 146.58 (d, JPC 2.9 Hz, C,
C4), 148.83 (d, JPC 5.4 Hz, C, C2); m/z (FAB) 765 [(2M ϩ H)ϩ,
10%], 383 [(M ϩ H)ϩ, 100], 367 (10), 336 (10), 307 (12), 201
[(Ph2PO), 24]. The phosphine oxide 14 (40 mg, 5%) was
obtained as a brown solid, 143–144 ЊC after chromatography
(silica, 1 : 1, chloroform : ethyl acetate, v/v). Rf 0.45 (silica, 1 : 1,
chloroform : ethyl acetate, v/v); νmax (KBr Disc)/cmϪ1 2930
(md), 1715 (w), 1620 (md), 1540 (st), 1440 (md), 1350 (st), 1180
(st), 1150 (md), 1120 (md), 1100 (w), 900 (md), 860 (md), 830
(md), 770 (w), 750 (md), 720 (md), 710 (md), 690 (md), 550
(md), 510 (md); δH (300 MHz; CDCl3) 4.76 (2H, d, JPH 13.2 Hz,
CH2), 7.42–7.70 (11H, m, aryl), 8.02 (2H, d, J 8.2 Hz, H3 and
H5); found (CI): (M ϩ H)ϩ, 383.0800. C19H16N2O5P requires
(M ϩ H)ϩ, 383.0797; m/z (FAB) 383 [(M ϩ H)ϩ, 100%], 201
[(Ph2PO), 40].
[3-Chloro-4-nitro-6-(trifluoromethyl)benzyl]diphenylphosphine
oxide (19)
The phosphine oxide 19 was prepared from chloromethyl-
diphenylphosphine oxide (5) (2.0 g, 7.98 mmol) and 2-chloro-5-
trifluoromethylnitrobenzene (1.98 g, 8.78 mmol) in a similar
way to the diphenylphosphine oxide 6a. The phosphine oxide
19 (1.61 g, 46%) was obtained as white needles, mp 175–177 ЊC
after chromatography (silica, 4 : 1, chloroform : ethyl acetate,
v/v) and recrystallisation from isopropanol. Found: C, 54.6; H,
3.0; N, 3.1; Cl, 8.0; F, 12.6; P, 7.0. C20H14ClF3NO3P requires C,
54.7; H, 3.2; N 3.2; Cl, 8.1; F, 13.0; P, 7.1%; Rf 0.49 (silica, 4 : 1,
chloroform : ethyl acetate, v/v); νmax (KBr Disc)/cmϪ1 3110 (w),
2920 (md), 1610 (md), 1535 (st), 1490 (md), 1440 (md), 1360
(st), 1310 (st), 1190 (st), 1120 (st), 850 (md), 720 (st), 690 (md),
590 (w); δH (300 MHz; CDCl3) 3.84 (2H, d, JPH 14.0 Hz, CH2),
7.46–7.60 (6H, m, aryl), 7.67–7.73 (4H, m, aryl), 8.12 (1H, s,
H2), 8.13 (1H, s, H5); m/z (FAB) 442 [(M(37Cl) ϩ H)ϩ, 40%],
440 [(M(35Cl) ϩ H)ϩ, 100], 374 (7), 201 [(Ph2PO), 53], 77 (20).
(E )-1-(3Ј-Chloro-6Ј-nitrophenyl)-2-phenylethene (20a)
To a stirred slurry of 3-chloro-6-nitrobenzyldiphenylphosphine
oxide 6a (400 mg, 1.08 mmol) in dry THF (3 cm3), under nitro-
gen at 0 ЊC, was added dropwise n-butyllithium (2.5 M solution
in hexanes, 0.43 cm3, 1.08 mmol). The reaction mixture was
stirred at 0 ЊC for 15 min then a solution of benzaldehyde
(120 mg, 1.13 mmol) in dry THF (2 cm3) was added. The reac-
tion mixture was stirred at rt overnight. Saturated ammonium
chloride solution (10 cm3) was added and the mixture extracted
with dichloromethane (3 × 20 cm3). The combined extracts
were dried (magnesium sulfate) and the solvent removed under
reduced pressure to yield the stilbene 20a (86 mg, 31%) as
J. Chem. Soc., Perkin Trans. 1, 2002, 2260–2267
2265

View Article Online
yellow needles, mp 90–93 ЊC after chromatography (silica, 1 : 1,
hexane : chloroform, v/v) and recrystallisation from hexane.
Found: C, 65.0; H, 3.9; N, 5.6; Cl, 13.4. C14H10ClNO2 requires
C, 64.8; H, 3.9; N, 5.4; Cl, 13.7%; Rf 0.74 (silica, 1 : 1, hexane :
chloroform, v/v); νmax (KBr Disc)/cmϪ1 3030 (w), 1630 (w), 1600
(md), 1570 (md), 1510 (st), 1345 (st), 1300 (w), 1255 (md), 1190
(md), 960 (md), 920 (md), 900 (md), 860 (md), 760 (md), 745
(md), 720 (md), 690 (md); δH (300 MHz; CDCl3) 7.10 (1H, d,
J 16.1 Hz, H2), 7.32–7.43 (4H, m, aryl), 7.54–7.56 (2H, m,
aryl), 7.59 (1H, d, J 16.1 Hz, H1), 7.74 (1H, d, J 2.2 Hz, HЈ),
7.96 (1H, d, J 8.8 Hz, H5Ј); δC (75 MHz; CDCl3) 122.33 (CH),
126.32 (CH), 127.17 (CH), 127.77 (CH), 127.88 (CH), 128.80
(CH), 128.93 (CH), 134.86 (C), 135.01 (CH), 135.94 (C), 139.43
(C), 145.94 (C); m/z (FAB) 262 [(M(37Cl) ϩ H)ϩ, 25%] 260
[(M(35Cl) ϩ H)ϩ, 100].
hexane : chloroform, v/v) and recrystallisation from ethanol.
Found: C, 65.6; H, 4.1; N, 4.9; Cl, 12.6. C15H12ClNO2 requires
C, 65.8; H, 4.4; N, 5.1; Cl, 13.0%; Rf 0.51 (silica, 1 : 1, hexane :
chloroform, v/v); νmax (KBr Disc)/cmϪ1 1600 (md), 1560 (md),
1530 (st), 1345 (st), 1295 (w), 1250 (w), 1190 (w), 1110 (w), 970
(md), 920 (md), 855 (md), 825 (w), 810 (st), 750 (w); δH (300
MHz; CDCl3) 2.38 (3H, s, CH3), 7.07 (1H, d, J 16.1 Hz, H1),
7.20 (2H, d, J 8.1 Hz, H3Љ and H5Љ), 7.34 (1H, dd, J 2.2 and
8.8 Hz, H4Ј), 7.44 (2H, d, J 8.1 Hz, H2Љ and H6Љ), 7.54 (1H, d,
J 16.1 Hz, H2), 7.73 (1H, d, J 2.2 Hz, H2Ј), 7.94 (1H, d, J 8.8
Hz, H5Ј); δC (75 MHz; CDCl3) 21.28 (CH3), 121.45 (CH),
126.28 (CH), 127.11 (CH), 127.49 (CH), 127.69 (CH), 129.50
(CH), 133.20 (C), 135.00 (CH), 139.09 (C), 139.32 (C), 145.87
(C); m/z (FAB) 276 [(M(37Cl) ϩ H)ϩ, 95%], 275 [(M(37Cl)ϩ, 95],
274 [(M(35Cl) ϩ H)ϩ, 55], 273 (M(35Cl)ϩ, 40), 258 (40), 256 (60),
242 (20), 240 (48), 230 (25) 228 (70), 214 (37), 153 (56), 139 (30),
119 (44), 105 (86).
(E )-1-(3Ј-Bromo-6Ј-nitrophenyl)-2-(4Љ-nitrophenyl)ethane (20b)
The stilbene 20b was prepared from 3-bromo-6-nitrobenzyl-
diphenylphosphine oxide 6b (400 mg, 0.96 mmol), n-butyl-
lithium (2.5 M solution in hexanes, 0.40 cm3, 1.00 mmol) and
4-nitrobenzaldehyde (145 mg, 0.96 mmol) in a similar way to
the nitrostilbene 20a. The stilbene 20b (120 mg, 36%) was
obtained as orange crystals, mp 84–86 ЊC after chromatography
(silica, 4 : 1, chloroform : hexane, v/v) and recrystallisation from
ethanol. Found: C, 48.5; H, 2.6; N, 7.9; Br, 22.9. C14H9BrN2O4
requires C, 48.2; H, 2.6; N, 8.0; Br, 22.9%; Rf 0.65 (silica, 4 : 1,
hexane : chloroform, v/v); νmax (KBr Disc)/cmϪ1 1600 (st), 1560
(md), 1515 (st), 1345 (st), 1300 (md), 1250 (w), 1110 (w), 970
(w), 870 (md), 825 (md), 755 (md); δH (300 MHz; CDCl3) 7.11
(1H, d, J 16.1 Hz, H2), 7.61 (1H, dd, J 2.0 and 8.7 Hz, H4Ј),
7.69 (2H, d, J 8.8 Hz, H2Љ and H6Љ), 7.73 (1H, d, J 16.1 Hz,
H1), 7.90 (1H, d, J 2.0 Hz, H2Ј), 7.95 (1H, d, J 8.7 Hz, H5Ј),
8.26 (2H, d, J 8.8 Hz, H3Љ and H5Љ); δC (75 MHz; CDCl3)
124.23 (CH), 126.57 (CH), 127.13 (CH), 127.72 (CH), 128.40
(C), 131.39 (CH), 131.97 (CH), 132.35 (CH), 134.02 (C), 142.25
(C), 146.59 (C), 147.64 (C); m/z (EI) 350 [M(81Br)ϩ, 4%], 348
[M(79Br)ϩ, 4], 333 (8), 331 (8), 259 (8), 257 (8), 197 (100), 176
(90), 150 (70).
(E )-1-(3Ј-Chloro-6Ј-nitrophenyl)-2-(4Љ-chlorophenyl)ethene
(20d)
The stilbene 20d was prepared from chloromethyldiphenyl-
phosphine oxide (5) (1.0 g, 3.99 mmol), 4-chloronitrobenzene
(690 mg, 4.38 mmol) and 4-chlorobenzaldehyde (840 mg, 5.98
mmol), in a similar way to (E)-1-(3Ј-chloro-6Ј-nitrophenyl)-2-
phenylethene 20a. The stilbene 20d (500 mg, 43%) was obtained
as a yellow solid, mp 116–117 ЊC after chromatography (silica,
1 : 1, hexane : chloroform, v/v) and recrystallisation from
hexane. Found: C, 56.9; H, 2.9; N, 4.6; Cl, 24.0. C14H9Cl2NO2
requires C, 57.2; H, 3.1; N, 4.8; Cl, 24.1%; Rf 0.74 (silica, 1 : 1,
hexane : chloroform, v/v); νmax (KBr Disc)/cmϪ1 1640 (w), 1610
(md), 1595 (md), 1560 (md), 1520 (st), 1500 (st), 1360 (st), 1310
(md), 1300 (md), 1250 (md), 1090 (md), 1015 (md), 970 (md),
925 (md), 860 (md), 815 (st); δH (300 MHz; CDCl3) 7.03 (1H, d,
J 16.1 Hz, H1), 7.35–7.39 (3H, m, H3Ј, H5Љ and H4Ј), 7.47 (2H,
d, J 8.5 Hz, H2Љ and H6Љ), 7.56 (1H, d, J 16.1 Hz, H1), 7.71
(1H, d, J 2.2 Hz, H2Ј), 7.97 (1H, d, J 8.7 Hz, H5Ј); δC (75 MHz;
CDCl3) 122.99 (CH), 126.38 (CH), 127.90 (CH), 128.00 (CH),
128.30 (CH), 129.00 (CH), 133.57 (CH), 134.45 (C), 134.55 (C),
134.64 (C), 139.54 (C), 145.90 (C); m/z (FAB) 297 [M(37Cl37-
Cl)ϩ, 10%], 296 [(M(35Cl37Cl) ϩ H)ϩ, 45], 295 [M(35Cl37Cl)ϩ, 85],
294 [(M(35Cl35Cl) ϩ H)ϩ, 80], 293 [M(35Cl35Cl)ϩ, 100], 276 (50),
261 (15), 250 (24), 214 (32), 199 (20), 165 (20), 153 (50), 139
(36).
Stilbenes via one-pot VNS–Horner–Wittig reactions
(E )-1-(3Ј-Chloro-6Ј-nitrophenyl)-2-phenylethene (20a)
Sodium hydride (60% dispersion in oil, 400 mg, 10.00 mmol)
was added to anhydrous DMSO (10 cm3) and the flask flushed
with nitrogen. Chloromethyldiphenylphosphine oxide (5) (1.0 g,
3.99 mmol) and 4-chloronitrobenzene (690 mg, 4.38 mmol)
were dissolved in anhydrous DMSO (10 cm3) and added drop-
wise to the sodium hydride slurry. The mixture was stirred at
ambient temperature for 30 h before benzaldehyde (0.6 cm3,
5.91 mmol) was added and the resulting mixture stirred over-
night at 60–70 ЊC. The reaction was quenched with distilled
water, acidified with hydrochloric acid (1 M solution) and
extracted with chloroform (3 × 20 cm3). The combined extracts
were washed with distilled water (3 × 20 cm3), dried (mag-
nesium sulfate), filtered and the solvent removed under reduced
pressure to yield the stilbene 20a (490 mg, 47%) as yellow
needles, mp 91–93 ЊC after chromatography (silica, 1 : 1, hexane :
chloroform, v/v) and recrystallisation from hexane. The 1H
NMR, mass and infrared spectra were identical to those of the
previously prepared sample.
(E )-1-[3Ј-Chloro-6Ј-nitro-4Ј-(trifluoromethyl)phenyl]-2-phenyl-
ethene (20e) and (E )-1-(3Ј-chloro-6Ј-nitrophenyl)-2-(4Љ-{(2ٞ-p-
methylphenyl)-2ٞ-hydroxyethyl}phenyl)ethene (21)
Sodium hydride (60% dispersion in oil, 200 mg, 5.00 mmol)
was added to anhydrous DMSO (5 cm3) and the flask
flushed with nitrogen. Chloromethyldiphenylphosphine oxide
(5) (500 mg, 2.00 mmol) and 4-chloro-3-trifluoromethylnitro-
benzene (500 mg, 2.22 mmol) were dissolved in anhydrous
DMSO (5 cm3) and added dropwise to the sodium hydride
slurry. The mixture was stirred at ambient temperature for
6 h before benzaldehyde (0.4 cm3, 3.94 mmol) was added
and the resulting mixture stirred overnight at 60–70 ЊC. The
reaction was quenched with distilled water, acidified with
hydrochloric acid (1 M solution) and extracted with chloroform
(3 × 20 cm3). The combined extracts were washed with distilled
water (3 × 20 cm3), dried (magnesium sulfate), filtered and the
solvent removed under reduced pressure to yield the stilbene
20e (210 mg, 32%) as yellow needles, mp 153–155 ЊC after
chromatography (silica, 4 : 1, hexane : chloroform, v/v) and
recrystallisation from hexane. Found: C, 54.9; H, 2.6; N, 4.3; Cl,
10.9; F, 17.3. C15H9ClF3NO2 requires C, 55.0; H, 2.8; N, 4.3; Cl,
10.8; F, 17.4%; Rf 0.47 (silica, 4 : 1, hexane : chloroform, v/v);
νmax (KBr Disc)/cmϪ1 1615 (md), 1580 (w), 1555 (md), 1505
(md), 1450 (w), 1380 (md), 1340 (st), 1300 (st), 1220 (w), 1150
(st), 1130 (st), 1090 (md), 960 (md), 910 (md), 750 (md), 690
(E )-1-(3Ј-Chloro-6Ј-nitrophenyl)-2-(4Љ-methylphenyl)ethene
(20c)
The stilbene 20c was prepared from chloromethyldiphenyl-
phosphine oxide (5) (1.0 g, 3.99 mmol), 4-chloronitrobenzene
(690 mg, 4.38 mmol) and 4-tolylaldehyde (0.5 cm3, 4.25 mmol)
in a similar way to (E)-1-(3Ј-chloro-6Ј-nitrophenyl)-2-phenyl-
ethene 20a. The stilbene 20c (470 mg, 43%) was obtained as a
yellow solid, mp 70–71 ЊC after chromatography (silica, 1 : 1,
2266
J. Chem. Soc., Perkin Trans. 1, 2002, 2260–2267

View Article Online
6 B. Mudryk and M. Makosza, Tetrahedron, 1988, 44, 209.
(md), 665 (md), 500 (w); δH (300 MHz; CDCl3) 7.20 (1H, d,
J 16.3 Hz, H2), 7.35–7.45 (3H, m, aryl), 7.56–7.59 (2H, m,
aryl), 7.63 (1H, d, J 16.3 Hz, H1), 7.92 (1H, s, H2Ј), 8.34 (1H, s,
H5Ј); δC (75 MHz; CDCl3) 120.96 (CH), 121.72 (q, JFC 273.0
Hz, CF3), 124.94 (q, JFC 5.5 Hz, CH), 127.70 (CH), 127.53 (q,
JFC 10.0 Hz, C), 129.00 (CH), 129.68 (CH), 130.85 (CH), 135.46
(C), 137.14 (C), 137.46 (CH), 137.70 (C), 145.14 (C); m/z (FAB)
328 [(M ϩ H)ϩ, 52%], 282 (100). Further elution gave the alco-
hol 21 (78 mg, 10%) as an oil, Rf 0.39 (silica, chloroform); νmax
(KBr Disc)/cmϪ1 3400 (bm), 1600 (st), 1565 (md), 1520 (st),
1340 (st), 1255 (md), 1110 (md), 965 (md), 920 (md), 820 (md);
δH (300 MHz; CDCl3) 1.95 (1H, br s, OH), 2.36 (3H, s, CH3),
3.03 (2H, d, J 6.6 Hz, CH2), 4.88 (1H, t, J 6.6 Hz, CHOH), 7.07
(1H, d, J 16.1 Hz, H1), 7.11–7.32 (6H, m, aryl), 7.35 (1H, dd,
J 2.2 and 8.7 Hz, H4Ј), 7.47 (2H, d, J 8.1 Hz, aryl), 7.55 (1H, d,
J 16.1 Hz, H2), 7.72 (1H, d, J 2.2 Hz, H2Ј), 7.94 (1H, d,
J 8.7 Hz, H5Ј). Found (CI): (M ϩ NH4)ϩ, 411.1488. C23H24-
ClN2O3 requires (M ϩ NH4)ϩ, 411.1475; m/z (CI using
ammonia) 411 [(M(35Cl) ϩ NH4)ϩ, 8%], 411 [(M(35Cl) ϩ
NH4)ϩ, 20%], 393 [(M(35Cl) ϩ H)ϩ, 10], 214 (60), 188 (100).
7 M. Makosza and J. Winiarski, J. Org. Chem., 1984, 49, 1494.
8 V. J. Traynelis and J. V. McSweeney, J. Org. Chem., 1966, 31, 243.
9 M. Makosza and J. Winiarski, Chem Lett., 1984, 1623.
10 (a) P. Beak and V. Snieckus, Acc. Chem. Res., 1982, 15, 306;
(b) H. W. Gschwend and H. Rodriguez, Org. React., 1976, 26, 1.
11 J. Miller, Aromatic Nucleophilic Substitution, Elsevier, New York,
1968.
12 (a) K. M. Brown, N. J. Lawrence, J. Liddle, F. Muhammad and
D. A. Jackson, Tetrahedron Lett., 1994, 35, 6733; (b) N. J. Lawrence
and F. Muhammad, Tetrahedron, 1998, 54, 15345.
13 M. Makosza and J. Golinski, Angew. Chem. Int. Ed. Engl., 1982, 21,
451.
14 N. J. Lawrence, J. Liddle and D. A. Jackson, Tetrahedron Lett., 1995,
36, 8477.
15 J. Wolinsky and K. L. Erickson, J. Org. Chem., 1965, 30, 2208.
16 A. A. Ardakani, N. Maleki and M. R. Saadein, J. Org. Chem., 1978,
43, 4128.
17 M. Matsumoto and K. Kuroda, Tetrahedron Lett., 1980, 21, 4021.
18 G. Kobrich, H. Trapp, K. Flory and W. Drischel, Chem. Ber., 1966,
99, 689.
19 N. J. De’ath, J. A. Miller, M. J. Nunn and D. Stewart, J. Chem. Soc.,
Perkin Trans 1, 1981, 776.
20 M. Makosza and J. Golinski, J. Org. Chem., 1984, 49, 1488.
21 O. Haglund and M. Nilsson, Synthesis, 1994, 242.
22 M. Makosza and A. A. Tomashewskij, J. Org. Chem., 1995, 60,
5425.
23 A. D. Buss, S. Warren, J. S. Leake and G. H. Whitham, J. Chem.
Soc., Perkin Trans. 1, 1983, 2215.
Acknowledgements
We thank the EPSRC (CASE studentship to J. L.), UMIST and
ZENECA for financial support. We also thank the EPSRC
Chemical Database Service at Daresbury.32
24 J.-P. Cheng, B. Liu, Y. Zhao, Z. Wen and Y. Sun, J. Am. Chem. Soc.,
2000, 122, 9987.
25 M. Makosza and A. Tyrala, Synthesis, 1987, 1142.
26 (a) N. J. Lawrence, J. Liddle, S. M. Bushell and D. A. Jackson,
J. Org. Chem., 2002, 67, 457; (b) N. J. Lawrence, O. Lamarche
and N. Thurrab, Chem. Commun., 1999, 689; (c) M. D. Drew,
D. A. Jackson, N. J. Lawrence, J. Liddle and R. G. Pritchard,
Chem. Commun., 1997, 189; (d ) N. J. Lawrence, J. Liddle and
D. A. Jackson, Synlett, 1996, 55.
References
1 R. Taylor, Electrophilic Aromatic Substitution, Wiley, Chichester,
1990.
2 O. N. Chupakhin, V. N. Charushin and H. C. van der Plas,
Nucleophilic Aromatic Substitution of Hydrogen, Academic Press
Inc., London, 1994.
27 G. Kobrich, H. Trapp, K. Flory and W. Drischel, Chem. Ber., 1966,
99, 689.
3 (a) M. Makosza, J. Pol. Chem., 1992, 66, 1; (b) M. Makosza and
J. Winiarski, Acc. Chem. Res., 1987, 20, 282; (c) M. Makosza,
Russ. Chem. Rev., 1989, 58, 747; (d ) M. Makosza and K. Wojcie-
chowski, Heterocycles, 2001, 54, 445; (e) M. Makosza, T. Lemek,
A. Kwast and F. Terrier, J. Org. Chem., 2002, 67, 394.
4 M. Makosza and T. Glinka, J. Org. Chem., 1983, 48, 3860.
5 B. Mudryk and M. Makosza, Synthesis, 1988, 1007.
28 R. N. McDonald and T. W. Campbell, J. Org. Chem., 1959, 24, 1969.
29 N. J. De’ath, J. A. Miller, M. J. Nunn and D. Stewart, J. Chem. Soc.,
Perkin Trans. 1, 1981, 776.
30 R. S. Marmor and D. Seyferth, J. Org. Chem., 1969, 34, 748.
31 M. J. Gallagher, Aust. J. Chem., 1968, 21, 1197.
32 D. A. Fletcher, R. F. McMeeking and D. J. Parkin, J. Chem. Inf.
Comp. Sci., 1996, 36, 746.
J. Chem. Soc., Perkin Trans. 1, 2002, 2260–2267
2267