Reactions of (1-nitroethenyl)sulfonylbenzene, a nitroethene derivative geminally substituted by a second W-group

Article abstract of DOI:10.1002/poc.1482

Nitroaldol reaction of phenylsulfonylnitromethane with formaldehyde affords a mixture of 2, 4-dinitro-2, 4-bis (phe-nylsulfonyl)butan-1-ol and 2, 4-dinitro-2, 4- bis (phenylsulfonyl)pentane-1, 5-diol. Treatment of this mixture with base followed by reacidification affords 1,1′-[(1, 3-dinitro-1, 3-propanediyl)bis (sulfonyl)]bis (benzene) as a mixture of (R^*, R^*) and (R^*, S^*)- diastereomers from which the (R^*, S^*)- diastereomer can be obtained pure. The intermediate in the nitroaldol reaction is (1-nitroethenyl)sulfonylbenzene and, if dienes are present, additional products are also obtained. If either (E)-2-methyl-1, 3-pentadiene or 1-(1-methylethenyl)cyclohexene are present, typical Diels-Alder adducts are obtained with the major isomers explainable by assuming a transition state in which the nitro group is endo. If furan is present, its formal conjugate addition product, 2-[2-nitro-2-(phenylsulfonyl)ethyl]furan, is formed. If cyclooctatetraene is present, it first dimerizes and then affords isomeric Diels-Alder cycloadducts of the dimer. Semiempirical calculations comparing the LUMO energies of (1-nitroethenyl)sulfonylbenzene to the corresponding trans-1,2 isomer are presented to explain relative reactivity of 1, 1- and 1, 2-disubstituted dienophiles. Copyright

Full text of DOI:10.1002/poc.1482

Research Article
Received: 2 October 2008,
Accepted: 16 October 2008,
Published online in Wiley InterScience: 8 January 2009
(www.interscience.wiley.com) DOI 10.1002/poc.1482
Reactions of (1-nitroethenyl)sulfonylbenzene,
a nitroethene derivative geminally
substituted by a second W-group
a
a
a
a
*
Peter A. Wade , James K. Murray , Alma Pipic , Robert J. Arbaugh
and Amutha Jeyarajasingama
Nitroaldol reaction of phenylsulfonylnitromethane with formaldehyde affords a mixture of 2,4-dinitro-2,4-bis(phe-
nylsulfonyl)butan-1-ol and 2,4-dinitro-2,4- bis(phenylsulfonyl)pentane-1,5-diol. Treatment of this mixture with base
followed by reacidification affords 1,1’-[(1,3-dinitro-1,3-propanediyl)bis(sulfonyl)]bis(benzene) as a mixture of (R*, R*)
and (R*, S*)-diastereomers from which the (R*, S*)-diastereomer can be obtained pure. The intermediate in the
nitroaldol reaction is (1-nitroethenyl)sulfonylbenzene and, if dienes are present, additional products are also
obtained. If either (E)-2-methyl-1,3-pentadiene or 1-(1-methylethenyl)cyclohexene are present, typical Diels-Alder
adducts are obtained with the major isomers explainable by assuming a transition state in which the nitro group is
endo. If furan is present, its formal conjugate addition product, 2-[2-nitro-2-(phenylsulfonyl)ethyl]furan, is formed. If
cyclooctatetraene is present, it first dimerizes and then affords isomeric Diels-Alder cycloadducts of the dimer.
Semiempirical calculations comparing the LUMO energies of (1-nitroethenyl)sulfonylbenzene to the corresponding
trans-1,2 isomer are presented to explain relative reactivity of 1,1- and 1,2-disubstituted dienophiles. Copyright ß
2009 John Wiley & Sons, Ltd.
Keywords: Diels–Alder reaction; nitroalkene; nitroaldol; semibullvalene; nitrosulfone
with formaldehyde followed by in situ dehydration of the
INTRODUCTION
resulting nitroaldol 2 (Scheme 1). To generate 3, one simply
warms a solution of 1 containing formalin and acetic acid.
When generation of 3 is carried out in the absence of dienes, a
gummy residue containing polar products not previously
identified, is obtained. The polar products have now been
identified as the bis(nitrosulfone) formaldehyde nitroaldol
adducts 4a–b. Indeed, these are universal side products in
reactions involving generation of nitroalkene 3 from 1 using
excess formaldehyde: they are also formed in the presence of
dienes. In a definitive run, the mono nitroaldol adduct 4a was
present as a 60:40 mixture of diastereomers readily identifiable by
the presence of two 1H NMR signals (two dd) at d 5.84 and 6.31,
respectively, attributable to H4 of the individual diastereomers.
The presence of bis(nitroaldol) adduct 4b is predicated on the
relative intensity of the complex NMR multiplets at d 3.6–3.8 and
4.1–4.7. The d 3.6–3.8 signal is attributable to C3 protons in both
4a and 4b. The d 4.1–4.7 signal is attributable to C4 protons in
both 4a and 4b and also C5 protons of 4b. The signal intensities in
these regions were consistent with a 1:1 mixture of 4a and 4b
under typical reaction conditions. The aryl signal intensity relative
to the d 3.6–3.8 and 4.1–4.7 signals was also consistent with a 1:1
Nitroethene is
a useful, reactive dienophile suitable for
Diels–Alder reactions[1] and also a useful Michael acceptor for
use in conjugate addition reactions.[2] It is sufficiently stable
for isolation and short-term storage[3] although not highly
amenable to commercialization. Geminal substitution with a
second W-group would be expected to enhance the reactivity of
nitroethene in Diels–Alder reactions. In accordance, we have
shown that (1-nitroethenyl)sulfonylbenzene (3), a nitroethene
derivative possessing a geminal phenylsulfonyl group, is both a
powerful dienophile and a powerful Michael acceptor.[4,5] It has
not been possible to isolate the highly reactive nitroalkene 3, but
methods for its generation and in situ use have been previously
1
described. The H NMR spectrum of 3, taken immediately after
generation, has confirmed its existence in solution.[4]
Here we present a number of new reactions involving nitroalkene
3 as an intermediate, further mechanistic information on the
simplest method of generating 3, and calculations rationalizing the
reactivity of 3. The Diels–Alder cycloadducts formed from
nitroalkene 3, secondary a-nitrosulfones, have potential as
substrates in SRN1 reactions as was previously demonstrated.[4]
*
Correspondence to: P. A. Wade, Chemistry Department, Drexel University, 3141
Chestnut Street, Philadelphia, PA 19104, USA.
E-mail: wadepa@drexel.edu
RESULTS AND DISCUSSION
The nitroaldol route to nitroalkene 3
a
P. A. Wade, J. K. Murray, A. Pipic, R. J. Arbaugh, A. Jeyarajasingam
Chemistry Department, Drexel University, 3141 Chestnut Street, Philadelphia,
PA 19104, USA
The simpler of two reported methods for obtaining nitroalkene 3
involves nitroaldol reaction of phenylsulfonylnitromethane (1)
J. Phys. Org. Chem. 2009, 22 337–342
Copyright ß 2009 John Wiley & Sons, Ltd.

P. A. WADE ET AL.
Scheme 2. Isomerization of 5a–b
analyses of isomer pairs have been reported as, for example,
with isomers of 2,4-diphenylpentanedinitrile.[9,10]
The racemic diastereomer 5a interconverts with 5b in the
presence of acid. Trifluoroacetic acid catalyzed conversion of pure
5a to an equilibrium 50:50 mixture of 5a–b. When a sample of
pure 5a was subjected to preparative TLC, a 50:50 mixture of
5a–b also resulted. These acid-catalyzed isomerizations are
thought to proceed through the aci-nitro isomer (Scheme 2).
Most nitro compounds do not protonate as readily as 5a–b. A
likely explanation is that protonation of the nitro group is
enhanced by internal H-bonding with a sulfone O-atom.
Deprotonation from carbon would then afford the planar
aci-nitro isomer which could be protonated on either face.
Similar internal H-bonding was used to explain the ready
interconversion of isomers of 2,5-dinitro-1,6-hexanediol.[11]
The formation of bis(nitrosulfone) 5a–b from reaction of
formaldehyde with nitrosulfone 1 prompted us to reinvestigate
the synthesis of 1 from nitromethane and sodium benzenesulfi-
nate.[8] Variable amounts of bis(nitrosulfone) 5a–b are formed as
a co-crystallizable side product in this synthesis, but the
preparation does not involve formaldehyde as a starting material.
However, formaldehyde might be expected to form during the
synthesis. Work-up involves acidification with mineral acid which
could generate formaldehyde by Nef reaction of the residual
nitromethane anion present. It seems, then, that condensation of
1 with a limited amount of formaldehyde might be responsible
for formation of 5a–b as the side product [Scheme 1, path (a)]. We
now isolate 1 during its preparation by controlled acidification
using saturated aqueous ammonium chloride. Under these
conditions, 5a–b does not form.
Scheme 1. Formation of bis(nitrosulfones)
ratio of 4a and 4b. Presumably more than one stereoisomer of 4b
was present but this was not confirmed.
Two possible pathways for formation of 4a–b present
themselves [paths (a) and (b)]. The anion of 1 could undergo
Michael addition to nitroalkene 3 affording 5a–b subsequently
converted to 4a–b via nitoaldol reactions with formaldehyde
[path (a)]. Alternatively, the anion of nitroaldol 2 could add to 3
giving 4a directly followed by subsequent partial conversion to
4b [path (b)]. Approximately 10% of anions present would be
[6]
derived from 1 (pKa 5.69) in solutions containing acetic acid
[7]
(pKa 4.74). Nitroaldol 2 should have a similar thermodynamic
acidity to 1 but would be very slow to deprotonate. Other primary
nitrosulfones typically require several minutes for a significant
concentration of anion to build up in the presence of hydroxide
ion, far greater basicity than present here.[8] As build-up of 2 has
never been observed in these reactions, it seems unlikely that a
significant concentration of the anion of 2 could form and react
further to give 4a–b. Therefore, the first alternative [path (a)]
involving the anion of 1 is presumably the main one followed.
Treatment of crude 4a–b with aqueous base followed by
acidification gave the bis(nitrosulfone) 5a–b which was isolated
in 82% overall yield from 1. Typically a 50:50 mixture of racemic
and meso diastereomers 5a–b was obtained. However, isomer 5a
crystallizes more readily than 5b so that rapid acidification led to
exclusive deposition of crystalline 5a in some instances. The
racemic diastereomer 5a has been obtained pure whereas the
meso diastereomer 5b was obtained in mixtures containing 5a.
The racemic diastereomer, isomer 5a, is readily identifiable
based on the homotopic methylene protons present on C2. A
single signal (apparent triplet) was observed for the methylene
protons. Conversely, these protons in the meso diastereomer 5b
are diastereotopic and exhibited separate signals. Similar
Generation of nitroalkene 3 in the presence of dienes
Generation of nitroalkene 3 in the presence of reactive dienes
typically affords the Diels–Alder adduct. We have previously
reported[4] formation of cycloadducts from cyclopentadiene,
spiro[2.4]hepta-4,6-diene, 2,3-dimethyl-1,3-butadiene, isoprene,
and 1-methoxy-1,3-butadiene using the nitroaldol method to
generate 3. Here we report Diels–Alder reactions of 3 with
(E)-2-methyl-1,3-pentadiene, 1-(1-methylethenyl)cyclohexene,
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Copyright ß 2009 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2009, 22 337–342

REACTIONS OF (1-NITROETHENYL)SULFONYLBENZENE
the methyl group in 3-methylcyclohexene.[13] Also known is the
equatorial preference of the nitro group in 4-nitrocyclohexene
(ꢀDG8 ¼ 0.25 kcal molꢀ1).[14] Equatorial preference for the phe-
nylsulfonyl group was indirectly estimated because no confor-
mational preference has been reported for sulfonyl groups at the
4-position of cyclohexene. The conformational preference has
been determined for the phenylsulfonyl group on cyclohexane
(ꢀDG8 ¼ 2.7 kcal molꢀ1).[15] Eliel[12] has noted that ꢀDG8 for
equatorial preference at the 4-position of cyclohexenes is
approximately half ꢀDG8 in cyclohexanes (there is only a single
1,3-diaxial interaction). Halving the known value for the
phenylsulfonyl group allows a straightforward estimation of
conformational preference.[16] Thus, placing the sulfonyl group
equatorial at the 4-position and the methyl pseudo-equatorial at
the 3-position should then be favored by roughly 2.1 kcal molꢀ1
(0.97 þ 1.35–0.25 ¼ 2.1 kcal molꢀ1
) over the ring-flip confor-
mation, a strong preference.
*
*
For the R , S diastereomer by contrast, two significantly
populated conformations should exist. The difference in energy
between these two conformations is estimated to be
0.2 kcal molꢀ1
(0.97–1.35 þ 0.25 ¼ ꢀ0.2 kcal molꢀ1).
Contri-
Scheme 3. Diels–Alder reactions
butions from the conformation with the pseudo-axial methyl
group would result in a large coupling constant owing to the
roughly 458 dihedral angle between Ha and Hx.
Reaction of nitroalkene 3 with 1-(1-methylethenyl)cyclohexene
(8) gave diastereomeric cycloadducts 9a–b in 64% yield as an
85:15 isomeric mixture. Based on the assumption of a preferred
transition state with endo-placement of the nitro group, the
major isomer of the reaction should be the R , S diastereomer
9b. However, here it was not possible to confirm the assignment.
The bridgehead proton of the major isomer did exhibit the
higher-field chemical shift, consistent with structure 9b where it
is cis to the sulfone rather than the nitro group. A similar chemical
shift pattern for the proton adjacent to the nitro and sulfone
groups was observed for cycloadducts 6a and 6b.
furan, and cyclooctatetraene (COT). The first two of these
reactions proceeded in straightforward fashion. The third and
fourth reactions took alternate pathways.
Reaction of nitroalkene 3 with (E)-2-methyl-1,3-pentadiene
gave diastereomeric cycloadducts 6a–b in 61% yield as an 80:20
isomeric mixture (Scheme 3). It was anticipated that the major
*
*
*
*
isomer was the R , R diastereomer 6a. This was by analogy with
previously obtained results for cyclopentadiene.[4] Only adduct 7
was obtained, requiring a transition state with endo-placement of
the nitro group. Similar preferred endo-placement of the nitro
group in reaction with (E)-2-methyl-1,3-pentadiene would afford
*
the R , R diastereomer 6a as the major product.
*
Verification of the major product identity was obtained by
1
Generation of nitroalkene 3 in the presence of furan, a
well-recognized diene for Diels–Alder reactions, gave no
detectable cycloadduct. Instead, the furan adduct 10a was
obtained in 51% yield (Scheme 5). This adduct had limited
stability, undergoing substantial decomposition within a day of
preparation. Adduct 10a is formally the conjugate addition
product of 3 and furan. A similar addition product, nitro
compound 10b, has been reported as the sole product from the
reaction of nitroethene with furan.[3] Under very similar
conditions, the cycloadduct isomers 11c–d (mainly 11c) were
also reported as the reaction products of nitroethene with
furan.[17] It was proposed that 10b was formed from the
cycloadduct 11c via the zwitterion 12b.[3] The analogous
zwitterion 12a would be expected to be more stable than
12b owing to the second W-group. Thus, formation of
cycloadduct 11a, ring-opening to the zwitterion 12a, and
analysis of the H NMR spectra of 6a and 6b. The Ja,x coupling
*
constants for 6a–b provide clear evidence for formation of the R ,
*
R diastereomer 6a as the major product (Scheme 4). The major
isomer exhibited a small (1.5 Hz maximum) coupling constant
while the minor isomer exhibited a 5.8 Hz coupling constant.
From the Karplus equation, the 1.5 Hz coupling constant in the
major product would be consistent with one heavily preferred
conformation having a Ha, Hx dihedral angle in the range of
65–1058.
*
*
The R , R isomer should exist as a single conformation with
a Ha, Hx. dihedral angle of approximately 758. This conclusion
assumes a C1,C4 dihedral angle of 158, similar to the angle present
in cyclohexene.[12] Conformational preference can then be
estimated in the following way. From the literature, there is a
0.97 kcal molꢀ1 preference for pseudo-equatorial placement of
Scheme 4. Conformations of cycloadducts 6a and 6b
J. Phys. Org. Chem. 2009, 22 337–342
Copyright ß 2009 John Wiley & Sons, Ltd.
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P. A. WADE ET AL.
As before, a major material and a minor material were present in a
90:10 ratio: these proved to be isomers. From the spectra of the
major isomer, clear evidence for a semibullvalene structure was
apparent. Proton absorptions at d 3.7–4.0 were assigned to the
four equilibrating cyclopropyl/alkenyl protons. Of the several
possible isomeric structures, only the equilibrating valence bond
tautomers 15a–b are consistent with the spectral data. The
structure of COT dimer 13 has been well established, although
assignment of the trans-stereochemistry relies on two indirect
observations. Moore[19] originally proposed the trans-structure
on the basis of the inability of dimer 13 to undergo an
intramolecular Diels–Alder reaction. Crystallographic data pre-
sented by Stezowski[20] on cycloadduct 18, obtained[21] from
reaction of COT with ethylidene carbonate at elevated
temperature, require trans-COT dimer 13 as the precursor. The
COT dimer 14 is known to be unreactive in typical Diels–Alder
reactions.[18]
The 1H NMR spectrum of the major isomer 15 exhibited signals
for the H17,H18 ethenyl bridge protons similar to the signals for
corresponding protons in the 1,3-cyclohexadiene adduct 17a[5] (d
6.1 vs. 6.0 and d 6.44 vs. 6.36, respectively). Proton H3 in 15 (d 3.07)
is in resonance at substantially lower field than the corresponding
protons H3,H8 (d 2.2) in adduct 18 and in reasonable agreement
with the corresponding proton in adduct 17a (d 2.42). This
presumably arises from the proximity of H3 to the phenylsulfonyl
group at C5. The endo-placement of the nitro group in 17a was
firmly based on the observation that 17a as opposed to 17b is
produced from [3,3]-sigmatropic rearrangement of nitronic ester
19.[5] The signal attributed to H4 in isomer 15 (d 3.68) also
exhibited a similar chemical shift to the corresponding signal for
cyclohexadiene adduct 17a (d 3.6).
Scheme 5. Reactions of furan
Assignment of the minor isomer 16 is based on comparison to
cyclohexadiene adduct 17b. The 1H NMR signals for the H17,H18
ethenyl bridge protons have similar chemical shifts to the signals
of corresponding protons in the adduct 17b (d 6.35 vs. 6.28 and d
6.61 vs. 6.47, respectively) and are at lower field than the H17,H18
signals of major isomer 15 or the corresponding signals of adduct
17a. The signal attributed to H4 in isomer 16 (d 3.4) also exhibited
a similar chemical shift to the corresponding signal for adduct
17b (d 3.27).
De Lucchi and coworkers[22] have reported that
(E)-1,2-bis(phenylsulfonyl)ethene, undergoes reaction with COT
monomer to produce cycloadduct 20 in competition with
cycloaddition to the COT dimer. Although less powerfully
substituted (nitro is a stronger W-group than phenylsulfonyl),
(E)-1,2-bis(phenylsulfonyl)ethene was more reactive with COT
than nitroalkene 3. However, (Z)-1,2-bis(phenylsulfonyl)ethene
behaved similar to nitroalkene 3 failing to react with monomeric
COT and giving uncharacterized cycloadducts of COT dimer.
Based on these observations, it would seem that
1,1-disubstitution of W-groups in the dienophile may be
generally less efficient than trans-1,2 disubstitution at activating
Diels–Alder cycloaddition reactions. This would be expected if
the LUMO of the 1,2-disubstituted dienophile were lower in
energy than the LUMO of the corresponding 1,1-disubstituted
isomer. Semiempirical calculations at the PM3 level were
performed on nitroalkene 3 and the known[23] trans-1,2-
disubstituted isomer 21 with the result that, indeed, the
1,2-isomer had the lower LUMO energy. The calculated LUMO
energy levels for 3 and 21 were ꢀ1.22 eV and ꢀ1.68 eV,
respectively. Thus, 21 should be a more powerful dienophile
than 3. Conversely, 1,1-disubstituted dienophiles such as
Scheme 6. COT cycloadducts and structurally related compounds
tautomerization is a likely pathway for the formation of adduct
10a. In the present case, it is not possible to rule out an alternate
route: conjugate addition of furan to the highly reactive double
bond of 3 to give 12a directly. Either route would involve
tautomerization of 12a to afford adduct 10a.
Reaction of COT, a less reactive Diels–Alder diene component,
was also investigated with nitroalkene 3 (Scheme 6). Generation
of 3 from 1, formalin, and acetic acid under moderate heating in
the presence of COT provided a very low yield of cycloadduct,
two materials in a 90:10 ratio being formed. From NMR spectra,
the major cycloadduct consisted of two COT units and one
dienophile unit. It was thought that COT might have dimerized
prior to reaction with 3 to give the known[18] dimer 13 and that
dimer 13 subsequently reacted with 3 to give the observed
cycloadduct. To confirm this conjecture, COT was dimerized at
[18]
¨
1008C by the method of Schroder
and the dimeric material,
used as a mixture of 13 and 14, was then subjected to
cycloaddition. A 47% yield (96% conversion) of the same
cycloadduct obtained from monomeric COT was now obtained.
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Copyright ß 2009 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2009, 22 337–342

REACTIONS OF (1-NITROETHENYL)SULFONYLBENZENE
nitroalkene
1,2-disubstituted dienophiles.
3
are significantly more regioselective than
50:50 hexanes/CH2Cl2). This purified product was an 80:20
mixture of 6a and 6b (found: MHþ, 296.0958; C14H17NO4SþH
requires 296.0957); nmax (film)/cmꢀ1 1550 (NO2), 1331 (NO2, SO2),
.
1146 (SO2) cmꢀ1 13C NMR (CDCl3) d 135.1, 134.9, 134.6, 133.5,
132.7, 131, 130.3, 129.2, 128.9, 123.6, 121.5, 110.6 (CNO2, 6b),
108.9 (CNO2, 6a), 34.3, 29.7, 27.9, 27.4, 25.3, 22.7, 22.6, 21.6 18.9,
18.3.
A portion of the mixture was enriched in the separate isomers
by cutting the single preparative TLC band (eluted with
60:40 CH2Cl2/hexanes) into three fractions. The minor isomer
was somewhat enriched in the top third fraction (67:33, 6a/6b)
and the major isomer was enriched in the bottom third fraction
(90:10, 6a/6b). 1H NMR (CDCl3) obtained for two mixtures of
different concentration d 7.90 (d, 2H of 6a, J ¼ 7.3 Hz), 7.83 (d, 2H
of 6b, J ¼ 7.3 Hz), 7.74 (m, 1H of 6a–b), 7.59 (m, 2H of 6a–b), 5.36
(d, 1H of 6b, J ¼ 5.8 Hz, HA), 5.25 (m, 1H of 6a, all J < 1.5 Hz, HA),
3.67 (quint, 1H of 6b, J ¼ 6.8 Hz, HX), 3.18 (broad s, 1H of 6a, HX),
2.55–2.7 (m), 2.3–2.45 (m), and 2.05–2.25 (m, 4H total), 1.69 (s, 3H
of 6a), 1.57 (s, 3H of 6b), 1.44 (d, 3H of 6b, J ¼ 6.8 Hz), and 1.15 (d,
3H of 6a, J ¼ 6.8 Hz).
EXPERIMENTAL
General
Commercially available reagents were used without further
purification unless otherwise noted. Tetrahydrofuran was distilled
from sodium benzophenone ketyl. NMR spectra were recorded
on a Varian 500 Innova spectrometer at 500 MHz (1H NMR) or
126 MHz (13C NMR). The three aryl absorptions for PhSO2 are
recorded as apparent d, t and t, respectively, although the
AA’MXX’ pattern is non-first order, and does show additional
complexity. Mass spectra were determined on a VG Analytical
70SE magnetic sector instrument. Reactions were routinely run
under a nitrogen atmosphere. 1-(1-Methylethenyl)cylohexene
was prepared from 1-acetylcyclohexene by a published pro-
cedure[24] except that THF at room temperature was employed
rather than refluxing ether. Phenylsulfonylnitromethane (1) was
prepared by the published procedure,[8] except that acidification
during work-up was carried out first with saturated ammonium
chloride to pH 5 followed by aqueous 5% HCl to pH 1–3. PM3
Semiempirical calculations were performed using Hyperchem
release 7.1.
1,2,3,4,6,7,8,8a-Octahydro-5-methyl-8-nitro-8- (phenylsulfonyl)
naphthalene 9
From 0.68 g (5.6 mmol) of 1-(1-methylethenyl)cyclohexene was
obtained 1.19 g (3.6 mmol, 64% yield) of a semi-solid (50:50 hex-
anes/CH2Cl2 eluent). This purified product consisted of an 85:15
mixture of 9b and 9a, respectively. Iterative flash and thin-layer
chromatography (elution with 50:50 hexanes/CH2Cl2) effected
separation of the two isomers. Major isomer 9b was the less
mobile fraction and was recrystallized three times from
benzene-hexanes (found: MHþ, 336.1264; C17H21NO4SþH
requires 336.1270); mp 106–1088C; nmax (KBr)/cmꢀ1 1553
(NO2), 1330 (NO2, SO2), 1151 (SO2); 1H NMR (CDCl3) d 7.88 (d,
2H, J ¼ 7.8 Hz), 7.73 (t, 1H, J ¼ 7.3 Hz), 7.59 (t, 2H, J ¼ 7.3 Hz),
2.7–2.8 (m, 2H), 2.65–2.7 (m, 1H), 2.61 (m, 1H), 2.38 (dt, 1H, J ¼ 8.7,
14.2 Hz), 2.23 (dd, 1H, J ¼ 8.1, 17.6 Hz), 1.79 (m, 2H), 1.69 (s, 3H),
1.45–1.6 (m, 2H), 1.41 (qt, 1H, J ¼ 3.9, 13.2 Hz), 1.2–1.28 (m, 2H);
13C NMR (CDCl3) d 134.8, 134.6, 130.9, 128.8, 128.6, 123.3, 109.6
(CNO2), 43.0, 31.8, 31.2, 29.6, 27.8, 26.5, 23.8, 18.2.
Minor isomer 9a was the more mobile fraction and, after three
recrystallizations from benzene-hexanes, was obtained as a solid
(found: MHþ, 336.1263; C17H21NO4SþH requires 336.1270); mp
178–818C; nmax (KBr)/cmꢀ1 1553 (NO2), 1323 (NO2, SO2), 1147
(SO2); 1H NMR (CDCl3) d 7.81 (d, 2H, J ¼ 7.8 Hz), 7.72 (t, 1H,
J ¼ 7.8 Hz), 7.56 (t, 2H, J ¼ 7.8 Hz), 3.52 (d, 1H, J ¼ 11.7 Hz), 2.71 (d,
1H, J ¼ 11.7 Hz), 2.63 (dd, 1H, J ¼ 1.5, 12.8 Hz), 2.51 (m, 2H), 2.12
(m, 2H), 1.95 (d, 1H, J ¼ 13.7 Hz), 1.86 (dd, 1H, J ¼ 1.5, 12.2 Hz), 1.70
(m, 2H), 1.53 (s) overlapping 1.2–1.6 (m) [6H total]; 13C NMR
(CDCl3) d 135.1, 133.3, 131.6, 130.2, 129.2, 121.5, 110.5 (CNO2),
43.6, 32.4, 31.7, 28.8, 28.4, 26.8, 23.0, 18.0.
General procedure—generation of (1-nitroethenyl)
sulfonylbenzene 3 in the presence of dienes
A mixture of diene (4.7 mmol), phenylsulfonylnitromethane
(2.83 g, 14 mmol), formalin (3.81 g of a 37% solution, 47 mmol
—
of CH2 O), acetic acid (2.8 g, 47 mmol), and THF (20 ml) was
—
heated at 40–508C for 16 h. Volatiles were removed at reduced
pressure and the residue partitioned between water (50 ml)
and CH2Cl2 (extraction with three 40-mL portions). The combined
extracts were washed with water (50 ml), dried over
anhydrous Na2SO4, and concentrated at reduced pressure. Flash
chromatography (various eluents) gave purified product followed
by more polar side products 4a–b which were not routinely
isolated. All reagent quantities were scaled according to the
amount of diene employed.
Preparation of COT dimers 13 and 14
A 2.01 g (19 mmol) portion of freshly distilled COT was heated in a
closed N2-flushed flask at 95–1058C for 69 h. Volatiles were
removed from the crude product at reduced pressure (20–1008C,
15 mm Hg). The residue was subjected to Kugelrohr distillation to
separate tetramers from the dimers. A 23% yield (0.45 g,
2.2 mmol) of distillate (bp 110–1208C, 0.09 mm Hg) consisting
2-[2-Nitro-2-(phenylsulfonyl)ethyl]furan 10a
1
of a 1:1 mixture (based on the H NMR spectrum) of 13 and 14
was obtained.
The general procedure was followed but the reaction tempera-
ture was kept at 20-258c. A 0.41 g (6 mmol) portion of furan was
used as diene. Rapidly performed flash chromatography (CH2Cl2
followed by 98:2 CH2Cl2/MeOH eluents) gave 0.86 g (3.1 mmol,
51% yield) of pure 10a as a solid having limited stability (found:
MNaþ, 304.0252; C12H11NO5SþNa requires 304.0256); nmax (KBr)/
cmꢀ1 1561 (NO2), 1339 (NO2, SO2), 1151 (SO2); 1H NMR (CDCl3) d
7.92 (d, 2H, J ¼ 7.8 Hz), 7.80 (t, 1H, J ¼ 7.6 Hz), 7.65 (t, 2H,
New products formed from nitroalkene 3
(2,4-Dimethyl-1-nitro-3-cyclohexenen-1-yl)sulfonylbenzene 6
From 0.5 g (6.1 mmol) of (E)-2-methyl-1,3-pentadiene was
obtained 1.09 g (3.7 mmol, 61% yield) of an oil (elution with
J. Phys. Org. Chem. 2009, 22 337–342
Copyright ß 2009 John Wiley & Sons, Ltd.
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P. A. WADE ET AL.
J ¼ 7.8 Hz), 7.31 (m, 1H), 6.28 (dd, 1H, J ¼ 2.9, 2.0 Hz), 6.16 (d, 1H,
J ¼ 2.9 Hz), 5.81 (dd, 1H, J ¼ 9.8, 3.9 Hz, X portion of ABX), 3.68 (dd,
J ¼ 3.9, 15.6 Hz) on 3.65 (dd, J ¼ 9.8, 15.6 Hz, total 2H, AB portion
of ABX); 13C NMR (CDCl3) d 145.9, 143.0, 135.6, 134.1, 129.9, 129.6,
110.8, 109.1, 100.1, 26.9.
The crude 4a–b (1.12 g) was taken up in CH2Cl2 (125 ml) and
was extracted into aqueous 5% NaOH (150 ml). The separated
aqueous layer was acidified to pH 2 with saturated aqueous
ammonium chloride followed by 10% aqueous HCl. The product
was extracted with CH2Cl2 (three 50 ml portions). The combined
organic layers were washed with water (20 ml), dried over
anhydrous Na2SO4, and concentrated at reduced pressure. The
resulting 0.86 g (82% yield) portion of off-white solids consisted
of a 1:1 mixture of 5a and 5b in definitive runs, although
considerable variation in the isomer ratio was noted in other runs.
1H NMR (CDCl3) d 7.9–7.95 (m, 4H of 5a and 5b), 7.83 (t, 2H of 5a
and 5b, J ¼ 7.8 Hz), 7.67 (t, 4H of 5a and 5b, J ¼ 7.8 Hz), 5.84 (dd,
2H of 5b, J ¼ 6.3, 7.3 Hz), 5.78 (t, 2H of 5a, J ¼ 6.8 Hz), 3.53 (dt, 1H
of 5b, J ¼ 6.3, 16.1 Hz), 3.45 (t, 2H of 5a, J ¼ 6.8 Hz), 3.33 (dt, 1H of
5b, J ¼ 7.3, 16.1 Hz).
COT dimer cycloadducts 15 and 16
The crude product was obtained from a mixture of COT dimers
(0.13 g, 0.62 mmol) by the general procedure (elution with
50:50 hexanes/CH2Cl2 followed by CH2Cl2). COT dimeric material
(70 mg, 54% recovery, 1:7 mixture of 13 and 14, respectively) was
obtained from the least polar chromatography fractions followed
by cycloadduct (0.12 g, 0.29 mmol, 47% yield, 96% conversion)
and side products 4a–b. The cycloadduct was a 90:10 mixture of
two isomers that overlapped on a TLC plate. Preparative TLC
(three fractions were taken) provided pure 15 and an enriched
sample of 16. The fastest moving fraction was the major isomer
15: it was recrystallized from ethanol, mp 210–2128C. nmax (KBr):
1544 (NO2), 1328 (NO2, SO2), 1150 (SO2) cmꢀ1. 1H NMR (CDCl3) d
7.81 (d, 2H, J ¼ 7.8 Hz), 7.72 (t, 1H, J ¼ 7.4 Hz), 7.57 (t, 2H,
J ¼ 7.8 Hz), 6.44 (t, 1H, J ¼ 7.3 Hz, H18), 6.1 (t, 1H, J ¼ 7.3 Hz, H17),
6.03 (t, 1H, J ¼ 9.6 Hz, H13 or 16), 5.69 (t, 1H, J ¼ 9.8 Hz, H13 or 16),
The less soluble isomer could be readily crystallized from an
ethanol mixture of the isomers to afford pure 5a as a white solid:
mp 165–668C (lit[8] mp 165–668C). 1H NMR (CDCl3) d 7.93 (d, 4H,
J ¼ 7.8 Hz), 7.83 (t, 2H, J ¼ 7.4 Hz), 7.67 (t, 4H, J ¼ 7.4 Hz), 5.77 (t, 2H,
J ¼ 6.8 Hz), 3.45 (t, 2H, J ¼ 6.8 Hz).
Thin layer chromatography (CH2Cl2 eluent) of pure 5a led to
formation of a 1:1 mixture of 5a and 5b. Stirring a CH2Cl2 solution
of 5a containing 1 molar equivalent of trifluoroacetic acid for 4 h
led to formation of a 1:1 mixture of 5a and 5b.
3.68 (dd, J ¼ 3.6, 6.1 Hz, H4) overlapping 3.35–4.05 (m, H11,12,14,15
,
5H total), 3.07 (quint, 1H, J ¼ 4.4 Hz, H3), 2.91 (m, 1H, H7), 2.76 (dd,
1H, J ¼ 3.9, 15.1 Hz, H6), 2.44 (dd, J ¼ 1.5, 15.1 Hz, H6’) overlapping
2.45–2.5 (m, H8, total 2H), 2.17 (m, 2H, H2,9), and 1.9 (m, 2H, H1,10);
13C NMR (CDCl3) d 136.5, 135.0, 134.4, 130.1, 129.4, 129.1, 126.7,
126.5, 111.6 (C5), 41.5, 39.6, 36.8, 36.2, 35.4, 33.2, 29.7, 27.9, 27.5.
Anal. Calcd. for C24H23NO4S: C 68.39, H 5.50, N 3.32. Found: C
68.25, H 5.49, N 3.22.
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The slowest moving fraction from preparative TLC was a
partially purified mixture, containing 76% of the minor isomer 16
with 24% of the major isomer 15 remaining. 1H NMR (CDCl3)
bands attributable to the minor isomer d 7.84 (d, 2H, J ¼ 7.8 Hz),
7.74 (t, 1H, J ¼ 7.3 Hz), 7.60 (t, 2H, J ¼ 7.8 Hz), 6.61 (t, 1H,
J ¼ 7.3 Hz, H18), 6.35 (t, 1H, J ¼ 7.3 Hz, H17), 5.84 (t, 1H,
J ¼ 9.3 Hz, H13
16), 5.64 (t, 1H, J ¼ 9.7 Hz, H13
16), 3.3–4.1,
or
or
(m, 4H, H11,12,14,15), 3.29 (dd, 1H, J ¼ 3.4, 10.3 Hz, H4), 2.93 (m,
1H, H7), 2.79 (dd, 1H, J ¼ 2.4, 15.6 Hz, H6), 2.60 (dd, 1H, J ¼ 3.4,
15.6 Hz, H6’), 2.25 (m, 1H), 2.07 (m, 2H), and 1.88 (m, 2H).
2,4-Dinitro-2,4-bis(phenylsulfonyl)butan-1-ol 4a, 2,4-dinitro-2,
4-bis(phenylsulfonyl)-pentane-1,5-diol 4b, and 1,1’-[(1,3-dinitro-
1,3-propanediyl)bis(sulfonyl)]bis(benzene) 5a–b
A mixture of phenylsulfonylnitromethane (1.0 g, 5 mmol),
—
formalin (4.07 g of a 37% solution, 50 mmol of CH2 O), acetic
—
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qualitative result.
acid (3 g, 50 mmol), and DMSO (50 ml) was heated at 35–408C for
24 h. The crude reaction solution was added to ice water (500 ml)
and the resultant was extracted with CH2Cl2 (three 100 ml
portions). The combined extracts were washed with water (three
75 ml portions), dried over anhydrous Na2SO4, and concentrated
at reduced pressure. The gummy solid crude product (1.12 g)
consisted mainly of 4a–b. nmax (film) 3250–3600 (broad, OH), 1563
(NO2), 1338 (NO2, SO2), 1155 (SO2) cmꢀ1. 1H NMR (CDCl3) d 7.75–8
(m, 3H all aryl), 7.55–7.7 (m, 2H all aryl), 6.31 (dd, 1H 1st isomer of
4a, J ¼ 2.9, 6.8 Hz), 5.84 (dd, 1H 2nd isomer of 4a, J ¼ 2.9, 7.8 Hz),
4.2–4.7 (m, 2H of 4a–b, all CH2 between CNO2), 3.6–3.8 (m, 2H of
4a and 4H of 4b, CH2O).
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Copyright ß 2009 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2009, 22 337–342