Thermolytic decomposition of benzylic dialkoxy disulfides

Article abstract of DOI:10.1016/j.tetlet.2009.07.084

Dialkoxy disulfides have been used as an alkoxy radical source under photolytic conditions. In addition, this class of disulfide thermally decomposes to deliver S₂ to dienes. We examined benzylic dialkoxy disulfides (X-Ph-CH₂-O-S-S-O-CH₂-Ph-X) under thermolytic conditions and observed that the rates of decomposition are related to Swain and Lupton's field constant, F. In addition, the observed non 1:1 ratio of alcohol to aldehyde reaffirms Harpp's-postulated cage mechanism. We have shown that the ratio is dependant upon the substituent present which can enhance the pi-stacking ability with the solvent, and thus favor diffusion out of the solvation cage yielding the non 1:1 ratio observed.

Full text of DOI:10.1016/j.tetlet.2009.07.084

Tetrahedron Letters 50 (2009) 5520–5522
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Thermolytic decomposition of benzylic dialkoxy disulfides
DiAndra M. Rudzinski, Mary P. McCourt, Ronny Priefer *
Department of Chemistry, Biochemistry, and Physics, Niagara University, NY 14109, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Dialkoxy disulfides have been used as an alkoxy radical source under photolytic conditions. In addition,
Received 6 July 2009
Revised 15 July 2009
Accepted 16 July 2009
Available online 21 July 2009
this class of disulfide thermally decomposes to deliver S
2
to dienes. We examined benzylic dialkoxy disul-
fides (X–Ph–CH –O–S–S–O–CH –Ph–X) under thermolytic conditions and observed that the rates of
2
2
decomposition are related to Swain and Lupton’s field constant, F. In addition, the observed non 1:1 ratio
of alcohol to aldehyde reaffirms Harpp’s-postulated cage mechanism. We have shown that the ratio is
dependant upon the substituent present which can enhance the pi-stacking ability with the solvent,
and thus favor diffusion out of the solvation cage yielding the non 1:1 ratio observed.
Ó 2009 Elsevier Ltd. All rights reserved.
In 1895, Lengfield reported the first synthesis of dialkoxy disul-
S
S
R
O
fides by the reaction of an alcohol with sulfur monochloride
S
S
R
R
1
(
S
2
Cl
2
). However, the structure was not unambiguously confirmed
O
O
O
R
2
for over 100 years. Prior to this there was debate as to whether this
1
2
structure existed as a linear molecule, 1, or as the branched thiono-
3
sulfite, 2 (Fig. 1). However in 1997, an X-ray crystal structure study
Figure 1. Structure of dialkoxy disulfide, 1, and thionosulfite, 2.
was carried out and it confirmed the linear dialkoxy disulfide struc-
2
ture, 1. Subsequently, branched thionosulfites have been synthe-
sized, however only when cyclic.4 The dialkoxy disulfide has
unique characteristics; including a short S–S bond length of
and Lupton’s field constant, F,12 was deduced. We now wish to re-
port the thermytic behavior of this series of dialkoxy disulfides.
The synthesis of the library of dialkoxy disulfides was performed
as previously described. {1(H): bis(benzyloxy) disulfide; 1(Me):
bis(p-methylbenzyloxy) disulfide; 1(OMe): bis(p-methoxybenzyl-
5
6
1
.95 Å and a high barrier of rotation of 18 kcal/mol, compared
7
11
to ꢀ2.05 Å and ꢀ8 kcal/mol for simple disulfides, respectively.
These traits have been attributed to electronic modulation of the
S–S
r
-bond where it is believed that a lone pair of electrons from
2
oxy) disulfide; 1(NO ): bis(p-nitrobenzyloxy) disulfide; 1(Cl):
bis(p-chlorobenzyloxy) disulfide; 1(tBu): bis(p-t-butylbenzyloxy)
disulfide; 1(Ph): bis(p-phenylbenzyloxy) disulfide} (Scheme 3).
*
one of the sulfurs donates its electrons to the
r
orbital of the adja-
8
cent S–O bond, hence providing double bond characteristic.
The synthetic use of dialkoxy disulfides have been examined in
two major areas. Lunazzi and Placucci have successfully used this
moiety as an alkoxy radical donor when irradiated.9 In addition,
2
The rate of thermolytic decomposition of 1(NO ) has been previ-
8
ously reported. In that study three solvents, spanning a large range
of polarities were explored. It was determined that in all cases the
8
Harpp has shown that dialkoxy disulfides can donate S
2
, which
rate of decomposition was first order. What we wished to examine
can be trapped in a pseudo Diels–Alder reaction with dienes to form
cyclic di- and tetrasulfides, under thermolytic conditions.10 Thomp-
son had postulated that this latter thermolytic fragmentation went
through a concerted mechanism (Scheme 1).3 However, recently
Zysman-Colman and Harpp have provided an alternate theory on
this, whereby there is an initial homolytic cleavage of the S–O bond,
was how the substitution on the aromatic ring would affect the rate
of decomposition. For our system we examined toluene as the sol-
vent. The dialkoxy disulfides were refluxed in toluene (110 °C),
while being protected from ambient light with aluminum foil. As
followed by liberation of S
2
(Scheme 2).8
R
O
O
R
O
S
S
S
S
We have recently examined the photolytic behavior of a series of
para-substituted benzylic dialkoxy disulfides (1).11 A correlation of
rate of decomposition, to their corresponding alcohols, with Swain
H
R
H
R
O
*
Corresponding author. Tel.: +1 716 286 8261; fax: +1 716 286 8254.
E-mail address: rpriefer@niagara.edu (R. Priefer).
Scheme 1. Thompson’s proposed mechanism of intramolecular thermolytic frag-
mentation of dialkoxy disulfides.3
0
040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.084

D.M. Rudzinski et al. / Tetrahedron Letters 50 (2009) 5520–5522
5521
RCHO
+
S2
S8
+
RCH OH
2
*disporportionated
RCH OSS. OCH R
.
RCH O. S2 .OCH R
2 2
RCH OSS
OCH R
2
2
2
2
2
RCH OH + S2
S8
cage
2
*diffusion
Scheme 2. Harpp’s-proposed cage mechanism of thermolytic decomposition of dialkoxy disulfides.8
S
S
OH
O
O
S Cl , Et N
2
2
3
CH Cl , 0ºC
2
2
X
X
X
X= H
Me
MeO 1(OMe)
NO 1(NO )
1(H)
Cl 1(Cl)
t Bu 1(tBu)
Ph 1(Ph)
1(Me)
2
2
Scheme 3. Library of dialkoxy disulfides synthesized.
5
4
3
2
1
0
1
(Cl)
1(NO2)
d
Figure 3. Rate constant (k ) of a library of para-substituted bis(benzyloxy)
disulfides versus Swain and Lupton’s field constant, F.
y = -0.3448x + 4.7525
R
= 0.9851
homolytic S–O bond cleavages, at which point the alkoxy radical
can either diffuse out of the cage to yield alcohol, or stay within
y = -0.4856x + 4.7758
and disproportionate to a 1:1 ratio of alcohol to aldehyde.8 With
R
= 0.9944
1
2
(NO ), it was reported that alcohol to aldehyde ratios ranged from
8
just under 2:1 up to ꢀ8:1 depending on solvent and temperature.
We also observed a range of ratios (1.09–2.03:1; alcohol to aldehyde)
for our system. This however was not as drastic as in previous stud-
0
1
2
3
4
5
6
7
8
9
Time (hrs)
8
Figure 2. Plot of ln(%dialkoxy disulfide) versus time, illustrates
reaction.
a
first order
ies. Harpp noted that the greatest deviation from the 1:1 ratio was
when the most polar solvent (i.e., DMSO) was used. By employing a
less polar solvent, the ability for the alkoxy radical to diffuse out of
the cage should be hampered, thus a near 1:1 ratio of alcohol to alde-
hyde for 1(tBu) is observed.
Table 1
Rates of reaction compared to Swain and Lupton’s F values
In an effort to understand the experimental ratios of alcohol to
aldehyde we computationally examined the abilities of these com-
pounds to pi-stack using toluene as our model solvent. Starting
with crystallographic structural analysis to determine starting
À1
Compound
F-value
d
Rate constant (k ) hrs
1
1
1
1
1
1
1
(NO
(Cl)
(OMe)
(Ph)
(H)
2
)
1.109
0.69
0.413
0.139
0
À0.3448
À0.4856
À0.4809
À0.4237
À0.3303
À0.3193
À0.2921
13
packing, the benzylic alcohol analogs were modeled with the sol-
vent, toluene, with the pi-systems stacking at 3.0 Å apart from each
other simultaneously minimizing steric interactions. The total
energy of the modeled system was calculated using SYBYL with a
(Me)
(tBu)
À0.052
À0.104
1
4
Tripos force field and MMFF94 charges. The termination gradient
was set to 0.05 kcal/(mol Å) with a non-bonded cutoff of 8 Å. The to-
tal energy of the modeled stacked system was calculated
(Table 2).
with 1(NO
Fig. 2).
The rates of decomposition showed no correlation with Ham-
2 d
), all decompositions were first order (i.e., rate = k [1])
(
11
Table 2
mett’s constants, similar to our photolytic work. We therefore
explored other variables and indeed discovered a relationship
with Swain and Lupton’s field constant, F12 (Table 1). By com-
Experimental ratio of alcohol to aldehyde during thermolytic decomposition of
dialkoxy disulfide (1) and total energy calculated for pi-stacked model systems of
benzylic alcohols with toluene
paring the rate constant (k
parabolic correlation (Fig. 3). This type of relationship to the rate
d
) versus F-values we obtained a
Compound
Ratio of alcohol
to aldehyde
Total energy
(kcal/mol)
1/Total energy
(mol/kcal)
of decomposition with F-values was also observed for
a
photolytic study on the same system.11
2
1(NO )
1.44
2.03
1.39
1.25
1.69
1.85
1.09
22.526
7.772
0.04439
0.1287
1
1
(Cl)
(OMe)
As shown above, there are two competing theories for the
mechanism of decomposition (Schemes 1 and 2). With Thompson’s
mechanism the products formed should be in a 1:1 ratio of alcohol
31.847
52.616
11.004
10.854
318.100
0.03140
0.01901
0.09088
0.09213
0.003144
1(Ph)
1(H)
1(Me)
3
to aldehyde. However, experimentally this is not the case.
1(tBu)
Zysman-Colman and Harpp’s proposal suggests two successive

5
522
D.M. Rudzinski et al. / Tetrahedron Letters 50 (2009) 5520–5522
The energy of stacking for 1(tBu) with toluene was by far the
sition of dialkoxy disulfides. Current studies are underway on the
ortho and meta-substituted bis(benzyloxy) disulfides to see how
their rates and product ratios may be altered.
highest with 318.00 kcal/mol. This can most likely be attributed
to the steric bulk of the tert-butyl group. Similarly, 1(Ph) possesses
a relatively high stacking energy (52.616 kcal/mol) due to the twist
of the biphenyl, increasing the steric interactions of the system.
The lowest stacking energy was observed with 1(Cl) (7.772 kcal/
Acknowledgments
mol), which possesses not only pi-stacking but also a LPCl
–
p
inter-
We thank Niagara University and the Niagara University Aca-
demic Center for Integrated Science for financial support. MPM
would like to thank the National Science Foundation, James Cum-
mings Foundation, and GeNYsis for additional financial support.
1
5
action. Graphing the experimental ratio versus the inverse of the
total energy demonstrates a linear relationship (Fig. 4). This shows
that there is a correlation between pi-stacking and product ratios,
thus supporting Harpp’s cage mechanism model.8
We have examined the thermolytic decay of a range of para-
substituted bis(benzyloxy) disulfides (1). Their rates of decomposi-
tion were all first order, and their rate constants (k ) were corre-
d
lated to Swain and Lupton’s field constant, F. The ratio of
alcohol to aldehyde obtained for this series of compounds provides
further evidence for the cage mechanism of thermolytic decompo-
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