Formation by SRN1 reactions and 1H N.M.R. properties of sterically encumbered 2,4,6-triaIkyIphenyl p-nitrobenzyl sulfides

Article abstract of DOI:10.1071/CH99080

Sterically hindered p-nitrobenzylic chlorides (1) and (2) react with the sodium salts of 2,4,6-trialkylbenzenethiols (3a)-(5a) by the S_RN1 reaction to give good yields of the corresponding p-nitrobenzylic aryl sulfides (6)-(10). For example, th

Full text of DOI:10.1071/CH99080

C S I R O P U B L I S H I N G
Australian Journal
of Chemistry
Volume 52, 1999
© CSIRO Australia 1999
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Aust. J. Chem., 1999, 52, 1077–1083
Formation by SRN1 Reactions and 1H N.M.R.
Properties of Sterically Encumbered
2,4,6-Trialkylphenyl p-Nitrobenzyl Sulfides*
Kai LookA and Robert K. NorrisB
A Division of Organic Chemistry, School of Chemistry, The University of Sydney,
N.S.W. 2006.
B The Deanery, Faculty of Science, The University of Wollongong,
N.S.W. 2525. Author to whom correspondence should be addressed.
Sterically hindered p-nitrobenzylic chlorides (1) and (2) react with the sodium salts of 2,4,6-trialkylbenzenethiols
(3a)–(5a) by the SRN1 reaction to give good yields of the corresponding p-nitrobenzylic aryl sulfides (6)–(10). For
example, the reaction of sodium 2,4,6-triisopropylbenzenethiolate (4b) with ␣-t-butyl-␣-methyl-p-nitrobenzyl
chloride (2) gives the sulfide (10) in over 80% yield after 2 h at room temperature in Me2SO. Only in reactions
involving 2,4,6-tri-t-butylbenzenethiol (5a) are low yields or failed reactions encountered. Qualitative examination
of the dynamic nuclear magnetic resonance spectra of the sulfides prepared in these reactions shows that up to three
restricted rotational phenomena can be identified. These are rotation about the benzylic-carbon to p-nitrophenyl
ring bond, rotation about the sulfur to aromatic ring bond, and rotation about the bond joining the t-butyl group to
the benzylic carbon. The last phenomenon produces, in the sulfide (9), the relatively rare and unusual situation
wherein the t-butyl group appears as three distinct methyl resonances at low temperatures.
Introduction
the regiochemistry of the association step involving p-
nitrobenzylic radicals and the anion of 2-nitropropane from
nearly exclusive C-alkylation (␣-hydrogen) to nearly exclu-
sive (␣-isopropyl) or exclusive (␣-t-butyl) O-alkylation (R =
H, Pri, or But, respectively, in Scheme 2).2–4 In the corre-
sponding reactions with other tertiary carbanions, two types
of products were formed, namely C-alkylates (i.e., formation
of a C–C bond between the benzylic carbon and the carbon of
the nucleophile), and ‘reduced’ products, where the nucleo-
fuge on the benzylic carbon is replaced by a hydrogen.5
The reaction of sterically hindered p-nitrobenzylic halides
with nucleophiles by an SRN1 mechanism can lead to the for-
mation of extremely sterically crowded molecules. The
mechanism1 for this reaction with p-nitrobenzylic substrates
is given in generalized terms in Scheme 1 [equations (1)–(4);
Ar = p-O2NC6H4].
It has been shown in our laboratories that the SRN1 reac-
tion is subject to steric limitations. In the reactions of p-
nitrobenzylic substrates with aci-nitronate anions, C- and
O-alkylation products can arise from changes in the regio-
chemistry of the association step [equation (3)]. The anions
of aci-nitronates follow two alternative pathways, namely C-
or O-alkylation processes, and lead ultimately to the differ-
ent products shown in Scheme 2.
For example, replacement of one of the ␣-hydrogens in p-
nitrobenzyl chloride by an isopropyl or t-butyl group changed
* Dedicated to Professors Sever Sternhell and John Pinhey on their retirement from the Division of Organic Chemistry, School of Chemistry, at the
University of Sydney.
Manuscript received 29 June 1999
© CSIRO 1999
10.1071/CH99080
0004-9425/99/111077

1078
K. Look and R. K. Norris
Table 1. Reactions of the sodium salts (3b)–(5b) of the arenethiols
(3a)-(5a) with the p-nitrobenzylic substrates (1) and (2)
Arenethiolate ions have been demonstrated to be powerful
nucleophiles in SRN1 reactions with p-nitrobenzylic substrates.
Kornblum, a pioneer in this field, showed that the reaction of
sodium benzenethiolate with p-nitrocumyl chloride produces
a good yield of the corresponding sulfide.6 Furthermore, the
reaction of the even more sterically hindered ␣-t-butyl-p-
nitrobenzyl chloride (1) with sodium benzenethiolate also pro-
duces the corresponding sulfide in good yield.4
All reactions were performed in Me2SO at 20° under irradiation by white
light unless otherwise stated. The percentage yields were estimated from
the crude reaction mixtures by 1H n.m.r. with 2,4,6-trinitrotoluene
(TNT) as standard and are believed to be reproducible to ±5%
Entry Substrate
Salt
Time
Products and yields
1
(1)
(1)
(1)
(2)
(2)
(2)
(2)
(2)
(3b)
(4b)
(5b)
(3b)
(4b)
(5b)
(3b)
(4b)
5 min
4 min
3 h
(6) 77%
We decided to examine the reaction of sterically hindered
nitrobenzylic chlorides with arenethiolate ions that have
bulky substituents ortho to the nucleophilic sulfur atom, in
order to delineate the steric limitation of this reaction.
2
(7) 88%
3
(8) 19%, (11) 7%
(9) 91%
4
30 min
2 h
5
(10) 81%
6
4 h
(12) 23%, (13) 20%
(2) 36%
7A
8A
30 min
2 h
Results and Discussion
(2) 85%
Steric Limitation of SRN1 Reactions of Chlorides (1) and (2)
A Reaction was performed with oxygen bubbling through the reaction
mixture.
with Arenethiolates
The chlorides (1) and (2) were treated with the sodium
salts (3b)–(5b) of the 2,4,6-trialkylbenzenethiols (3a)–(5a)
and gave S-alkylation products, sulfides (6)–(10), reduced
compounds (11) and (12) and the alkene (13) as summarized
in Table 1. Based on well established precedent involving
less hindered substrates, these reactions producing the sul-
fides (6)–(10) are believed to be SRN1 processes.
Nevertheless, a study of the inhibition of some of these reac-
tions was carried out by performing them under oxygen, a
well established inhibitor of the SRN1 process.7 It was found
that oxygen had a dramatic effect and sulfide formation was
completely inhibited, as seen in the comparison of entry 4
with entry 7 and entry 5 with entry 8 (Table 1). These results
clearly confirm that the reactions of the chlorides (1) and (2)
with the sodium salts (3b)–(5b) proceed by an SRN1 mecha-
nism (see Scheme 1, where RЈ = H or Me, RЈЈ = But, and
Nu– represents the 2,4,6-trialkylbenzenethiolate ions).
good yields, when ortho-methyl (see entries 1 and 4,
Table 1) and ortho-isopropyl groups (see entries 2 and 5,
Table 1) are present, to a very poor yield (see entry 3,
Table 1), when there are ortho-t-butyl groups. When the reac-
tions of the more hindered chloride (2) are considered, it can
be seen that, whilst the yields of the sulfides with the
ortho-methyl or ortho-isopropyl groups are very good (see
entries 4 and 5, Table 1), the reaction times are longer than
those of the anion (3b) and (4b) with the less hindered chlo-
ride (1). In the reaction of the ␣-t-butyl chloride (1) with
2,4,6-tri-t-butylbenzenethiolate (5b) (see entry 3, Table 1), it
can be seen that the steric limit of the SRN1 reaction of the
arenethiolate ions has almost been reached and the yield of
the sulfide has decreased to only 19%. In the case of the reac-
tion of the chloride (2) with the 2,4,6-tri-t-butyl-
benzenethiolate salt (5b), the SRN1 reaction does not take
place at all. Instead, this reaction produced none of the
expected sulfide (14), but gave the ‘reduced’ product (12) in
23% yield and the alkene (13) in 20% yield (see entry 6, Table
1). The product (13) presumably arises from the elimination
of hydrogen chloride from the chloride (2). This result
clearly demonstrates that the reaction of the ␣-t-butyl ␣-
methyl chloride (2) with the anion from tri-t-butyl-
benzenethiol (5a) has exceeded the steric limit of the SRN1
reaction of p-nitrobenzylic substrates with arenethiolate ions.
One possible mechanism that explains the formation of
the reduced product (11) (see entry 3, Table 1) is given in
eqations (5) and (6) (Ar = p-O2NC6H4):
From the results obtained from the reactions of the ␣-t-
butyl chloride (1) with 2,4,6-trialkylbenzenethiolates
(3b)–(5b), it can be seen that on increasing the size of the
ortho-alkyl group, the yield of S-alkylate decreases from
A source of electrons required for the single-electron
transfer process in equation (5) could be the thiolate ion from
the salt (5b) and this possibility is shown in equation (7)
(Ar = p-O2NC6H4):

2,4,6-Trialkylphenyl p-Nitrobenzyl Sulfides
1079
•
␦ 6.81 led to the loss of the Jortho for H 3 (J2,3 8.3 Hz) and the
loss of Jmeta coupling for H6 (J2,6 1.6 Hz) and confirmed that
H 5 is the most downfield proton. The order of resonances of
the protons from high field to low field on the p-nitrophenyl
ring in (6) are H 2 > H 3 > H 6 > H 5*. The assignment of
chemical shifts for the aromatic protons of the p-nitrophenyl
ring in the sulfide (7) also given in Fig. 1 was based on the
very similar values found for the sulfide (6).
In the normal SRN1 reaction, the radical [ArCHCMe3] and
the thiolate ion, 2,4,6-(CMe3)3C6H2S–, would couple and this
process would lead exclusively to formation of the radical
anion of the sulfide (8). Clearly steric hindrance reduces the
degree of sulfur-to-carbon bond formation that would lead to
(8)–• and an alternative competitive electron transfer [equa-
tion (7)] takes place. Alternative sources of ‘electrons’
required in equation (5) may be the radical anion of the chlo-
ride (1), or that of the sulfide (8). The proton source (BH) in
equation (6) could be the solvent (Me2SO), or adventitious
moisture.
The reduced compound (12) formed in the reaction of the
salt (5b) from 2,4,6-tri-t-butylbenzenethiol (5a) with the ␣-t-
butyl ␣-methyl chloride (2) presumably arises by processes
analogous with those shown in equations (5) and (6). In the
reaction of the less hindered chloride (1) with thiolate salt
(5b) discussed above, the sulfur-to-carbon bond formation,
leading to sulfide (8), and the single-electron transfer process
shown in equation (5) are clearly in a more balanced compe-
tition. This latter result clearly demonstrates that the reaction
of the ␣-t-butyl ␣-methyl chloride (2) with the anion from
the thiol (5a) has exceeded the steric limit of the SRN1 reac-
tion of p-nitrobenzylic substrates with arenethiolate ions.
Overall, from the results collected in Table 1 (entries 1–6),
it can be seen that steric effects have a clear influence on sub-
stitution reactions that occur by the SRN1 mechanism. The
rate of reaction is lowered considerably by increasing the
steric bulk of the nucleophile and/or the substrate, and the
overall yield of S-alkylation product decreases. The
decrease in yield of sulfides is accompanied by the appear-
ance of products resulting from either elimination or reduc-
tion processes.
Fig. 1. 1H n.m.r. chemical shift assignments for the aromatic protons
on the p-nitrophenyl ring and the benzylic hydrogen in the sulfides
(6)–(8).
The chemical shifts for the sulfide (8) were significantly
different from those for (6) and (7). Assignment of reso-
nances (as given in Fig. 1) was based on the assumption that
H 2 was most upfield and the remaining resonances were
assigned on the magnitude of coupling constants and con-
firmed by appropriate double-resonance experiments. The
resulting order of the p-nitrophenyl ring protons in the
sulfide (8) was H 2 > H 6 > H 3 > H 5. This result is quite dif-
ferent from that obtained for the sulfides (6) and (7). One
possible explanation for the change in absolute values for the
shifts and their relative order is that the aryl t-butyl groups
add to the steric congestion in (8) and change the conforma-
tion about the aryl sulfur–benzylic carbon bond. The
anisotropic effect of the arylthio ring on the shifts of the
protons on the p-nitrophenyl ring is subsequently altered,
leading to the observed changes in shift values.
The sulfides (9) and (10) containing a methyl group
instead of a hydrogen at the benzylic position were then
studied. N.O.e. experiments were performed on the sulfide
(9) and these led to assignment of the most upfield aromatic
proton on the p-nitrophenyl ring at ␦ 7.21 to H 2. Double-
irradiation experiments and differences in the values of Jmeta
and Jortho led to the assignment of proton resonances for the
sulfide (9), given in Fig. 2. The order of resonances for the
p-nitrophenyl ring protons was H2 > H 3 > H 5 > H 6. The
assignments for the p-nitrophenyl ring protons in the sulfide
(10) were based on those in (9) and are also given in Fig. 2.
The replacement at the benzylic position of the hydrogen
by a methyl group significantly affects the chemical shifts
Dynamic 1H N.M.R. Properties of 2,4,6-Trialkylphenyl
p-Nitrobenzyl Sulfides (6)–(10)
1
The sulfides (6)–(10) show dynamic effects in their H
n.m.r. spectra. The 1H n.m.r. spectra at low temperatures in
CD2Cl2 show that there is an appreciable barrier to rotation8
not only about aryl carbon–benzylic carbon bond, but also
about the aryl carbon–sulfur bond.
At low temperature, the aromatic protons on the p-nitro-
phenyl rings in each of the sulfides (6)–(10) appeared as four
separate non-equivalent resonances and unambiguous
assignment of these resonances was required. Assignment of
resonances in the sulfides (6)–(10) with a benzylic hydrogen
was made first. In the 1H n.m.r. spectrum of the sulfide (6)
at 220 K, irradiation of the benzylic proton (␦ 3.71) gave an
11% n.O.e. enhancement for the most upfield signal at ␦ 6.81
and this chemical shift was assigned to H 2, where H 2 is
defined as the aromatic proton ortho to the benzylic carbon
and syn to the in-plane benzylic proton as represented in the
structures given in Fig. 1. Double-irradiation experiments
and the different values for Jmeta (J2,6 and J3,5) and Jortho (J2,3
and J5,6) confirmed the remaining assignments for sulfide (6)
and these are given in Fig. 1. As examples of the double-irra-
diation experiments performed, irradiation of the signal at
* The symbolism ‘H 2 > H 3’ means that the proton H2 is upfield of proton H 3.

1080
K. Look and R. K. Norris
for the protons H 2, H 3, and H 6 in the sulfides (9) and (10)
relative to those in (6) and (7). Also, the order of resonances,
H 2 > H 3 > H 6 > H 5, for (6) and (7) changes to
H 2 > H 3 > H 5 > H 6 for the sulfides (9) and (10). Clearly,
replacement of the hydrogen by a methyl group can lead to
changes in conformation about the benzylic-carbon to
aryl-carbon bond and the aryl-sulfur to benzylic-carbon
bonds. The methyl group for example may be further away
from the in-plane position in sulfides (9) and (10) than the
position occupied by the benzylic hydrogen in sulfides (6)
and (7).
␦ 1.20). In similar fashion the para-methyl group on the
mesityl ring shifts slightly downfield on warming the solu-
tion from 170 to 330 K (from ␦ 2.07 to 2.15) and the two
ortho-methyl groups on the mesityl ring coalesce over the
same temperature range to their averaged chemical shift
value (observed, ␦ 2.03; calculated on 170 K shifts, ␦ 1.88)
but are still very broad (Fig. 3c).
Fig. 2. 1H n.m.r. chemical shift assignments for the aromatic
protons on the p-nitrophenyl ring in the sulfides (9) and (10).
The spectra of these sulfides (6)–(10) showed some inter-
1
esting variations with temperature on the H n.m.r. time
1
scale. The variations with temperature of the 400 MHz H
n.m.r. spectra for the sulfide (9), for example, in the aliphatic
and aromatic regions, respectively, are shown in Figs 3 and
1
Fig. 3. Temperature variation of the aliphatic region of the 400 MHz
1H n.m.r. spectrum of mesityl 1,2,2-trimethyl-1-(4-nitrophenyl)propyl
sulfide (9) in CD2Cl2.
4. At 170 K and 400 MHz the H n.m.r. spectrum of the
sulfide (9) is consistent with that expected from a species in
which the dynamic exchange effects observable at higher
temperatures are slow on the n.m.r. time scale (see Figs 3a
and 4a). For example, in the methyl region of the spectrum
(Fig. 3a) there are seven methyl resonances. Three sharp sin-
glets arise from the two (different) ortho-methyl groups
(␦ 1.36 and 2.40) and the para-methyl (␦ 2.07) on the mesityl
ring. Four further, broad methyl absorptions are present.
These were assigned to the benzylic methyl group (at
␦ 1.06), and three broad separate absorptions, one for each
of the methyl groups in the t-butyl group (at ␦ 0.46, 1.02 and
1.30). These assignments were confirmed by examination of
the methyl region in the spectra obtained on warming the
solution of sulfide (9) to 220 K (Fig. 3b) and 300 K
(Fig. 3c)*. The three individual methyl groups from the t-
butyl group coalesce on warming to the average chemical
shift of the three individual groups (observed, ␦ 1.05; calcu-
lated from 170 K shifts, ␦ 0.93), the benzylic methyl sharp-
ens slightly and moves downfield slightly (from ␦ 1.06 to
Dynamic 1H n.m.r. effects are also apparent in the aromatic
region of the spectra of sulfide (9) (see Fig 4). At both 170
and 220 K (see Figs 4a and 4b) the protons on the p-nitro-
phenyl ring appear as four distinct, sharp resonances charac-
teristic of an ABMX system and the protons on the mesityl
ring appear as two separate signals (an AX system). The
absorptions in these sharp low-temperature spectra broaden
and, at 300 K, the protons on the p-nitrophenyl ring appear as
a broad doublet (two protons ortho to the nitro group) and a
broad poorly defined absorption (two protons meta to the
nitro group) and the two protons on the mesityl ring have coa-
lesced into a broad singlet (see Fig. 4c). As the temperature
of the system is increased further, these relatively broad
signals sharpen into the normally expected splitting patterns.
The protons on the p-nitrophenyl ring move towards the usual
splitting pattern expected for a para-disubstituted benzene
* Calculated averaged chemical shift values differ by up to 0.15 ppm from observed values since significant chemical shift variations were appar-
ent over the 130 K temperature range between Figs 3a and 3c.

2,4,6-Trialkylphenyl p-Nitrobenzyl Sulfides
1081
stored over type 4Amolecular sieves. Ethyl acetate and light petroleum
(60–80°) were distilled prior to use. 2,4,6-Trinitrotoluene (TNT) was
purified by recrystallization from ethanol. Sodium hydride refers to
material produced from sodium hydride (60% dispersion in oil) by
washing under nitrogen with dry redistilled light petroleum.
‘Chromatography’ refers to the flash chromatography method of
Still9 and all solvents were distilled prior to use.
ring (an AAЈXXЈ pattern) and the protons on the mesityl ring
sharpen further (an A2 pattern).
Unless otherwise stated in the following descriptions of experimen-
tal procedures, the following general workup procedure, referred to as
‘worked up in the usual manner’, was used; the reaction mixture was
diluted with water and the products were extracted threefold into ethyl
acetate. The organic extracts were washed with water and brine, dried
over anhydrous sodium sulfate and the solvent was removed under
reduced pressure.
Preparation of Starting Materials
Mesitylenethiol (3a)
Lithium aluminium hydride (6 g) was placed in a Soxhlet apparatus
whose delivery system was charged with dry glass wool rather than the
usual Soxhlet thimble. A solution of mesitylenesulfonyl chloride (10 g,
46 mmol), prepared by the method of Carten and Huntress,10 in tetrahy-
drofuran (300 ml) was heated under reflux whilst attached to the
Soxhlet system for 3 h. On completion of the reaction the excess of
lithium aluminium hydride was quenched with an ethanol/benzene
solution (50%, 160 ml). The lithium and aluminium salts were dis-
solved in an excess of sulfuric acid (10%), and a further amount of
benzene (40 ml) was added. The reaction mixture was worked up in the
usual manner followed by purification (by distillation) to yield
mesitylenethiol (3a) (4.2 g, 60%) as a colourless oil (Kugelrohr,
73–79°/2 mmHg; lit. b.p.11 109.5–111°/18 mmHg).
2,4,6-Triisopropylbenzenethiol (4a)
Fig. 4. Temperature variation of the aromatic region of the 400 MHz
1H n.m.r. spectrum of mesityl 1,2,2-trimethyl-1-(4-nitrophenyl)propyl
sulfide (9) in CD2Cl2.
Reduction of 2,4,6-triisopropylbenzenesulfonyl chloride with
lithium aluminium hydride by the method used in the preparation of
thiol (3a) produced the thiol (4a) (7.5 g, 75%) as a clear colourless oil
(Kugelrohr, 125–131°/1.5 mmHg; lit.12 b.p. 135–138°/10 mmHg).
The spectra reported in the Experimental section for the
sulfides (6)–(10) were obtained at temperatures where
proton exchange processes in the aromatic region of the p-
2,4,6-Tri-t-butylbenzenethiol (5a)
(a) 1-Bromo-2,4,6-tri-t-butylbenzene
1
nitrophenyl ring protons were slow on the H n.m.r. time
Tri-t-butylbenzene (10.0 g, 40.6 mmol) was dissolved in trimethyl
phosphate (250 ml) and the mixture was heated to 75°. Bromine (3.0
ml, 58.3 mmol) in trimethyl phosphate (50 ml) was slowly added and
the mixture was stirred for 24 h (the colour changed from brown to pale
yellow). A further aliquot of bromine (3.0 ml, 58.3 mmol) in trimethyl
phosphate (50 ml) was added. After 3 days, the mixture was cooled and
then extracted with light petroleum (b.p. 30–40°). The light petroleum
extracts were washed with aqueous sodium sulfite, water and brine,
then dried over anhydrous sodium sulfate and the solvent removed
under reduced pressure. The residue was recrystallized from ethanol to
give 1-bromo-2,4,6-tri-t-butylbenzene (8.96 g, 68%) as white needles,
m.p. 171–173° (lit.13 173–174°).
scale.
Experimental
The following generalizations apply throughout this Experimental.
Melting points were determined on a Reichert melting point stage
and are uncorrected. Boiling points, recorded in the format (Kugelrohr,
x–y°/z mmHg), were determined by distillation in a Buchi GKR-50
Kugelrohr apparatus at the oven temperature and the reduced pressure
specified.
Microanalyses were carried out by the Microanalytical Unit of the
School of Chemistry at the University of New South Wales, Sydney, or
by the Chemical and Micro Analytical Services Pty Ltd, Melbourne.
Ultraviolet spectra were recorded on a Hitachi 150-20 spectropho-
tometer, and infrared spectra were recorded on either a Biorad 20-80
Fourier transform infrared or a Perkin Elmer 1600 spectrophotometer.
1H n.m.r. and 13C n.m.r. spectra were determined on either a Bruker
(b) 2,4,6-Tri-t-butylbenzenethiol (5a)
Butyllithium (2.27 M, 1.1 ml, 2.50 mmol) was added to a solution of
1-bromo-2,4,6-tri-t-butylbenzene (550 mg, 1.69 mmol) in dry tetrahy-
drofuran (8 ml) at –70°. The reaction mixture was stirred for a further
hour and then warmed to room temperature. Sulfur (81 mg, 2.54 mmol)
was added and the reaction mixture was heated under reflux for 2 days.
An excess of lithium aluminium hydride (1 g) was added and the
mixture was heated under reflux for 1 h. The excess of lithium alu-
minium hydride was quenched with water, the lithium and aluminium
salts were dissolved with sulfuric acid (10%) and benzene (20 ml) was
added to the reaction mixture. The mixture was worked up in the usual
manner. The crude mixture contained the thiol (5a) (55%, by g.l.c.) and
starting material (23%, by g.l.c.). The thiol was isolated by flash chro-
matography with light petroleum as an eluent. The solid residue was
recrystallized from ethanol to yield the thiol (5a) as a pale yellow solid
(156 mg, 33%), m.p. 177–180° (lit.14 177°).
1
AMX400 (400 MHz) or a Bruker AC200 (200 MHz) H n.m.r. spec-
trometer with SiMe4 as an internal standard on 10% w/v solutions.
Unless otherwise stated, n.m.r. spectra were recorded in CDCl3 at 300
K at 400 MHz and chemical shifts (␦) are quoted in ppm downfield
from SiMe4; multiplicity: s, singlet; d, doublet; t, triplet; q, quartet; sept,
septet; m, multiplet. Coupling constants (J) are in hertz (Hz).
Mass spectra were determined on an AEI MS902 instrument and are
quoted in the form x (y) where x is the mass-to-charge ratio and y is the
percentage abundance relative to the base peak. Peaks with low inten-
sity are not quoted unless significant.
Dimethyl sulfoxide (Me2SO) was dried by stirring over calcium
hydride for 24 h, followed by distillation under reduced pressure and

1082
K. Look and R. K. Norris
The less polar product on recrystallization from ethanol gave pale
yellow crystals of 2,2-dimethyl-1-(4-nitrophenyl)propyl 2,4,6-tri-t-
butylphenyl sulfide (8) (28 mg, 12%), m.p. 105–107° (Found: M+•
469.3015; C, 74.4; H, 9.1; N, 2.8. C29H43NO2S requires M+• 469.3020;
C, 74.2; H, 9.2; N, 3.0%). ␯max (CHCl3) 2964, 1596, 1519, 1476, 1395,
1346, 1224 cm–1. ␭max (CHCl3) 241 (⑀1.3×104), 282 nm (1.4×104). 1H
n.m.r. (CD2Cl2, 210 K): ␦ 0.95, s, 2×o-CMe3; 1.33, s, p-CMe3; 1.45, s,
benzylic CMe3; 3.98, s, benzylic H; 6.60, br d, J2,3 8.3 Hz, H2; 6.73, br
d, J3´,5´ 1.9 Hz, ArH ortho to the t-butyl; 6.93, br d, J3´,5´ 1.9 Hz, ArH
ortho to the t-butyl; 7.43, dd, J5,6 8.7, J2,6 1.7 Hz, H6; 7.60, dd, J2,3 8.3,
Reactions of 2,4,6-Trialkylthiolates (3b)–(5b) with ␣-Alkylated
p-Nitrobenzylic Halides (1)3 and (2)15
General Procedure
An excess of sodium hydride was added to a solution of the appro-
priate arenethiol (3a)–(5a) (5.0 mmol) in dry dimethyl sulfoxide (10.0
ml) under nitrogen; the solution was stirred for about 5 min, then fil-
tered through sintered glass and the filtrate was deoxygenated (unless
otherwise stated) by passage of nitrogen. The appropriate benzylic
chloride (1) or (2) (2.5 mmol) was then added and the solution was
stirred at 20° under nitrogen in a temperature-controlled water bath,
with exposure to a 500 W G.E. sunlamp placed 10 cm from the reaction
vessel for the time specified in Table 1. The reaction mixture was
diluted with water and extracted with ethyl acetate. The ethyl acetate
extracts were washed with water and brine and then dried (Na2SO4).
The solvent was evaporated under reduced pressure and the products
were purified by flash chromatography. Each reaction mixture was
mixed with a known amount of 2,4,6-trinitrotoluene (TNT), and the
yield of product(s) was estimated by 1H n.m.r. spectroscopy; these esti-
mated yields are recorded in Table 1.
J
3,5 2.0 Hz, H3; 7.87, dd, J5,6 8.7, J3,5 2.3 Hz, H5. m/z 470 (M+1, 2%),
469 (M, 8), 356 (4), 278 (36), 221 (5), 150 (19), 91 (5), 57 (100).
The more polar product eluted from the column was 1-(2,2-
dimethylpropyl)-4-nitrobenzene (11) (9%) as a red oil, identical by t.l.c.
and by 1H n.m.r. spectroscopy with an authentic sample.3
Reaction of 4-(1-Chloro-1,2,2-trimethylpropyl)nitrobenzene (2) with
the Sodium Salt (3b) of Mesitylenethiol (3a) (Table 1, Entry 4)
Workup of the mixture from the reaction of the chloride (2) (118 mg,
0.488 mmol) with the sodium salt (3b) prepared from mesitylenethiol
(3a) (152 mg, 0.618 mmol) in Me2SO (5.2 ml) for 30 min, followed by
recrystallization from ethanol, gave pale yellow crystals of mesityl
1,2,2-trimethyl-1-(4-nitrophenyl)propyl sulfide (9) (104 mg, 60%),
m.p. 201–202° (Found: C, 70.4; H, 7.6; N, 3.9. C21H27NO2S requires
C, 70.6; H, 7.6; N, 3.9%). ␯max (CHCl3) 1603, 1518, 1455, 1341 cm–1.
Isolation and Characterization of Products
Reaction of 1-(1-Chloro-2,2-dimethylpropyl-4-nitrobenzene (1) with
the Sodium Salt (3b) of Mesitylenethiol (3a) (Table 1, Entry 1)
Workup of the mixture from reaction of the chloride (1) (37 mg, 2.33
mmol) with the sodium salt (3b) prepared from mesitylenethiol (3a)
(691 mg, 4.54 mmol) in Me2SO (8 ml), followed by recrystallization
from ethanol, gave 2,2-dimethyl-1-(4-nitrophenyl)propyl mesityl
sulfide (6) (401 mg, 51%) as pale yellow crystals, m.p. 97–98° (Found:
C, 70.1; H, 7.4; N, 3.9. C20H25NO2S requires C, 69.9; H, 7.7; N, 4.1%).
␭
max (CHCl3) 240 (⑀1.39×104), 279 nm (1.17×104) 1H n.m.r. (CD2Cl2,
190 K):␦ 0.49, s, CMeMe2; 1.07, s, CMeMe2; 1.11, s, benzylic Me;
1.34, s, CMeMe2; 1.39, s, o-Me; 2.12, s, p-Me; 2.44, s, o-Me; 6.67, br
s, ArH ortho to Me; 6.97, s, ArH ortho to Me; 7.21, dd, J2,3 8.7, J2,6 2.2
Hz, H2; 8.02, dd, J2,3 8.7, J3,5 2.6 Hz, H3; 8.13, dd, J5,6 8.8, J3,5 2.6 Hz,
H5; 8.35, dd, J5,6 8.8, J2,6 2.2 Hz, H 6. m/z 358 (M+1, 0.2%), 357 (M,
2), 342 (0.7), 301 (3), 300 (7), 152 (100), 150 (45), 119 (10), 91 (6), 77
(3), 57 (6).
␯
(CHCl3) 1597, 1521, 1461, 1348, 853 cm–1. ␭max (CHCl3) 238
max
(⑀ 8.0×103), 268 nm (1.1×104). 1H n.m.r. (CD2Cl2, 220 K): ␦ 1.03, s,
But; 2.08, s, p-Me; 2.20, br s, 2×o-Me; 3.71, s, benzylic H; 6.71, br s,
ArH on mesityl ring; 6.81, dd, J2,3 8.3, J2,6 1.6 Hz, H 2; 7.84, dd, J2,3 8.3,
Reaction of the Chloride (2) with the Sodium Salt (4b) of
2,4,6-Triisopropylbenzenethiol (4a) (Table 1, Entry 5)
J
3,5 2.4 Hz, H3; 7.93, br dd, J2,6 1.6, J5,6 8.7 Hz, H 6; 8.11, dd, J3,5 2.4,
J5,6 8.7 Hz, H5. N.O.e. results: irradiation of the benzylic H (␦ 3.71)
gave an 11.0% enhancement for the signal of H2 (␦ 6.81). m/z 344
(M+1, 5%), 343 (M, 20), 287 (24), 286 (24), 270 (7), 192 (14), 152
(100), 119 (16), 104 (6), 91 (12), 77 (6), 57 (8).
Workup of the mixture from the reaction of the chloride (2) (400 mg,
1.65 mmol) with the sodium salt (4b) prepared from 2,4,6-triisopropyl-
benzenethiol (4a) (728 mg, 3.08 mmol) in Me2SO (6.2 ml) followed by
recrystallization from ethanol gave pale yellow crystals of 2,4,6-triiso-
propylphenyl 1,2,2-trimethyl-1-(4-nitrophenyl)propyl sulfide (10) (589
mg, 81%), m.p. 157–159° (Found: C, 73.4; H, 8.9; N, 2.9. C27H39NO2S
Reaction of the Chloride (1) with the Sodium Salt (4b) of
2,4,6-Triisopropylbenzenethiol (4a) (Table 1, Entry 2)
requires C, 73.4; H, 8.9; N, 3.2%). ␯
(CHCl3) 1597, 1521, 1464,
max
Workup of the mixture from the reaction of the chloride (1) (342
mg, 1.5 mmol) with the sodium salt (4b) prepared from 2,4,6-triiso-
propylbenzenethiol (4a) (690 mg, 2.9 mmol) in Me2SO (5.8 ml) fol-
lowed by recrystallization from ethanol gave pale yellow crystals
of 2,2-dimethyl-1-(4-nitrophenyl)propyl 2,4,6-triisopropylphenyl
sulfide (7) (388 mg, 57%), m.p. 102–104° (Found: C, 73.0; H, 8.6; N,
3.0. C26H37NO2S requires C, 73.0; H, 8.7; N, 3.3%). ␯max (CHCl3)
1595, 1521, 1518, 1464, 1348 cm–1. ␭max (CHCl3) 238 (⑀7.2×103), 269
nm (1.1×104). 1H n.m.r. (CD2Cl2, 170 K): ␦ 0.19, d, J 6.5 Hz,
CHMeMe; 0.83, d, J 6.5 Hz, CHMeMe; 1.02–1.06, m, 15H, But and
2×CHMeMe; 1.10, d, J 6.5 Hz, CHMeMe; 1.29, d, J 6.5 Hz,
CHMeMe; 2.69, sept, J 6.5 Hz, o-CHMe2; 3.30, sept, J 6.5 Hz,
o-CHMe2; 3.46, s, benzylic H; 3.87, sept, J 6.5 Hz, p-CHMe2; 6.67,
br s, ArH ortho to Pri; 6.82, br d, J2,3 8.3 Hz, H 2; 7.06, br s, ArH ortho
to Pri; 7.85, dd, J2,3 8.3, J3,5 2.3 Hz, H 3; 7.95, br d, J5,6 8.7 Hz, H 6;
8.18, dd, J3,5 2.3, J5,6 8.7 Hz, H 5. m/z 428 (M+1, 1.3%), 427 (M, 5),
370 (21), 236 (100), 221 (62), 193 (11), 177 (6), 151 (40), 150 (133),
137 (15), 91 (12), 57 (6), 43 (40).
1348 cm–1. ␭
(CHCl3) 240 (⑀1.31×104), 278 nm (1.12×104).
1H n.m.r. (CD2mCalx2, 190 K): ␦ 0.11, d, J 6.5 Hz, CHMeMe; 0.47, br s,
CMeMe2; 0.76, d, J 6.5 Hz, CHMeMe; 0.98–1.13: m, 15H, benzylic
Me, CMeMe2, 3×CHMeMe; 1.23, d, J 6.5 Hz, CHMeMe; 1.36, br s,
CHMeMe2; 2.71, sept, J 6.5 Hz, p-CHMe2; 2.89, sept, J 6.5 Hz,
o-CHMe2; 4.10, sept, J 6.5 Hz, o-CHMe2; 6.55, d, J3´,5´ 1.5 Hz, ArH
ortho to Pri; 6.95, d, J3´,5´ 1.5 Hz, ArH ortho to Pri; 7.23, dd, J2,3 8.5, J2,6
2.5 Hz, H2; 8.00, dd, J2,3 8.5, J3,5 2.5 Hz, H3; 8.17, dd, J5,6 8.5, J3,5 2.5
Hz, H 5; 8.48, dd, J5,6 8.5, J2,6 2.5 Hz, H6. m/z 442 (M+1, 0.2%), 441
(M, 1), 384 (4), 237 (10), 236 (100), 221 (18), 150 (24), 134 (2), 104
(3), 91 (2), 57 (2), 43 (4).
Reaction of the Chloride (2) with the Sodium Salt (5b) of 2,4,6-Tri-t-
butylbenzenethiol (5a) (Table 1, Entry 6)
Workup of the mixture from the reaction of the chloride (2) (137 mg,
0.49 mmol) with the sodium salt (5b) prepared from 2,4,6-tri-t-butyl-
benzenethiol (5a) (70 mg, 0.36 mmol) in Me2SO (5 ml) failed to
produce any of the corresponding sulfide. The ‘reduced’ compound
1-nitro-4-(1,2,2-trimethylpropyl)benzene (12)15 and the elimination
product 3,3-dimethyl-2-(4-nitrophenyl)but-1-ene (13)16 were shown to
be present by 1H n.m.r. and t.l.c. comparison with authentic samples.
Reaction of the Chloride (1) with the Sodium Salt (5b) of 2,4,6-Tri-t-
butylbenzenethiol (5a) (Table 1, Entry 3)
The sodium salt (5b) prepared from 2,4,6-tri-t-butylbenzenethiol
(5a) (137 mg, 0.49 mmol) in Me2SO (5.0 ml) was added to the chloride
(1) (70 mg, 0.36 mmol) in Me2SO (5 ml). After 3 h, the reaction
mixture was worked up in the usual manner. Chromatography of the
crude reaction mixture with 5% ethyl acetate/light petroleum gave two
components.
Reaction of the Chloride (2) with the Sodium Salt (3b) of
Mesitylenethiol (3a) under Oxygen (Table 1, Entry 7)
Workup of the mixture from reaction of the chloride (2) (72 mg, 0.30
mmol) with the sodium salt (3b) prepared from mesitylenethiol (3a)

2,4,6-Trialkylphenyl p-Nitrobenzyl Sulfides
1083
3
4
(111 mg, 0.75 mmol) in Me2SO (11.4 ml) under oxygen for 30 min
failed to produce any of the sulfide, and only starting material (2) was
recovered.
Norris, R. K., and Randles, D., Aust. J. Chem., 1979, 32, 1487.
Norris, R. K., and Randles, D., J. Org. Chem., 1982, 47, 1047; Aust.
J. Chem., 1982, 35, 1621.
5
6
Jacobs, B. D., Kwon, S.-J., Field, L. D., Norris, R. K., Randles, D.,
Wilson, K., and Wright, T. A., Tetrahedron Lett., 1985, 26, 3495.
Kornblum, N., Davies, T. M., Earl, G. W., Holy, N. L., Manthey, J.
W., Musser, M. T., and Swiger, R. T., J. Am. Chem. Soc., 1967, 89,
725.
Reaction of the Chloride (2) with the Sodium Salt (4b) of
2,4,6-Triisopropylbenzenethiol (4a) under Oxygen (Table 1, Entry 8)
Workup of the mixture from reaction of the chloride (2) (97 mg, 0.40
mmol) with the sodium salt (4b) prepared from 2,4,6-triisopropyl-
benzenethiol (4a) (189 mg, 0.80 mmol) in Me2SO (11.4 ml) under
oxygen for 30 min failed to produce any of the sulfide, and only start-
ing material (2) was recovered.
7
8
Kornblum. N., Angew. Chem., Int. Ed. Engl., 1975, 14, 734.
Sternhell, S., in ‘Dynamic Nuclear Resonance Spectroscopy’ (Eds
L. M. Jackman and F. A. Cotton) p. 170 (Academic: New York
1975).
9
10
11
12
Still, W. C., Kahn, M., and Mitra, A., J. Org. Chem., 1979, 43, 2923.
Carten, F. H., and Huntress, E. H., J. Am. Chem. Soc., 1940, 62, 511.
Truce, W. E., and Norman, O. L., J. Org. Chem., 1953, 75, 6023.
Costanza, A. J., Coleman, R. J., Pierson, R. M., Marvel, C. S., and
King, C., J. Polym. Sci., 1955, 17, 319.
References
1
Kornblum, N., in ‘The Chemistry of the Functional Groups,
Supplement F’ (Ed. S. Patai) Ch. 10 (John Wiley: Chichester 1982);
Norris, R. K., in ‘The Chemistry of Functional Groups, Supplement
D’ (Eds S. Patai and Z. Rappoport) Ch. 16 (John Wiley: Chichester
1983); Rossi R., Pierini, A. B., and Penenory, A. B., in ‘The
Chemistry of Halides, Pseudo Halides and Azides’ Supplement D2
(Eds S. Patai and Z. Rappoport) Ch. 24 (John Wiley: Chichester
1995).
13
Pearson, D. E., Caine, D., and Field, L., J. Org. Chem., 1960, 25,
867.
14
15
Rundel, W., Z. Naturforsch., Teil B, 1960, 15, 546.
Anderson, J. E., J. Chem. Soc., Chem. Commun., 1973, 3, 95; Kwon,
S.-J., Honours Thesis, University of Sydney, 1983, p. 25.
Hamer, G. K., Peat, I. R., and Reynolds, W. F., Can. J. Chem., 1973,
51, 915.
16
2
Norris, R. K., and Randles, D., Aust. J. Chem., 1976, 29, 2621.