Benzylic Thio and Seleno Newman-Kwart Rearrangements

Article abstract of DOI:10.1021/acs.joc.8b01468

The thermally induced O_Bn → S_Bn and O_Bn → Se_Bn migration reactions facilitate the rearrangement of O-benzyl thio- and selenocarbamates [BnOC(=X)NMe₂] (X = S or Se) into their corresponding S-benzyl thio- and Se-benzyl selenocarbamates [BnXC(=O)NMe₂] (X = S or Se). A series of substituted O-benzyl thio- and selenocarbamates were synthesized and rearranged in good yields of 33-88%. The reaction rates are higher for substrates with electron-donating groups in the 2 or 4 position of the aromatic ring, but the rearrangement also proceeds with electron-withdrawing substituents. The rearrangement follows first-order reaction kinetics and proceeds via a tight ion pair intermediate consisting of the benzylic carbocation and the thio- or selenocarbamate moiety. Computational studies support these findings.

Full text of DOI:10.1021/acs.joc.8b01468

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Article
Benzylic Thio and Seleno Newman-Kwart Rearrangements
Kristina Eriksen, Anne Ulfkjær, Theis Ivan Sølling, and Michael Pittelkow
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01468 • Publication Date (Web): 15 Aug 2018
Downloaded from http://pubs.acs.org on August 15, 2018
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Benzylic Thio and Seleno Newman-Kwart Rearrangements
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Kristina Eriksen, Anne Ulfkjær, Theis I. Sølling, and Michael Pittelkow*
Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen, Denmark
E-mail: pittel@chem.ku.dk
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Table of Contents/Abstract Graphic
ꢀ High conversion
ꢀ Broad substrate scope
ꢀ 14 examples, both S and Se ꢀ Computational chemistry
ꢀ Xꢀray diffraction analysis
ꢀ Mechanistic studies
Abstract
The thermally induced OBn → SBn and OBn → SeBn migration reactions facilitate the rearrangement of O-benzyl
thio- and selenocarbamates [BnOC(=X)NMe2] (X = S or Se) into their corresponding S-benzyl thio- and Se-benzyl
selenocarbamates [BnXC(=O)NMe2] (X = S or Se). A series of substituted O-benzyl thio- and selenocarbamates
were synthesised and rearranged in good yield of 33 – 88 %. The reaction rates are higher for substrates with
electron donating groups in the 2- or 4-position of the aromatic ring but the rearrangement also proceeds with
electron withdrawing substituents. The rearrangement follows first order reaction kinetics and proceeds via a
tight ion pair intermediate consisting of the benzylic carbocation and the thio- or selenocarbamate moiety. Com-
putational studies support these findings.
Introduction
Thiols and selenols play important parts in a range of chemistry, biochemistry, and materials applications.1-6 Their
use as ligands in inorganic chemistry and as components in supramolecular assemblies are two central
examples.7-9 The subtle interplay between the thiol/disulfide and the selenol/diselenide through oxida-
tion/reduction reactions are a defining trait of the chemical properties of these functional groups.10-13 Prominent-
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ly, both the thiol and selenol is part of the chiral amino acids as cysteine and selenocysteine, respectively. Seleno-
cysteine is known as the 21st amino acid,14 and the role of selenocysteine (selenol) and selenocystine (diselenide)
in protein function and structure is becoming increasingly recognized, as is the role of the more common cyste-
ine/cysteine system.12, 14-15 The presence of selenocysteine is known to influence the catalytic properties of en-
zymes and can provide a mean to alter the structural properties of the protein as compared to the corresponding
proteins containing cysteine.12-13, 16 Native chemical ligation with selenocysteine is also known to be highly effec-
tive,17-19 and selenols/diselenides are also efficient in catalysing the disulfide exchange reaction.8
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The thiol functionality can efficiently be introduced via the Newman-Kwart rearrangement which facilitates the
conversion from phenol to thiophenol via the thermal OAr → SAr rearrangement of aromatic thiocarbamates
(Scheme 1, top).20-21 However, the wide spread use of selenols is hampered by their limited synthetic availability.
We have initiated a research program focused at identifying new reactions that make selenols, and also thiols,
readily available. Recently, we described how the conversion of a phenol into the corresponding selenophenol
can be performed effectively by expanding the Newman-Kwart rearrangement from using O-aryl thiocarbamate
substrates to O-aryl selenocarbamate substrates.22 The rearrangement yields Se-aryl selenocarbamates that can
then conveniently be hydrolysed to the arylselenols using aqueous base (Scheme 1, top). Attempts to introduce
aliphatic versions of the Newman-Kwart rearrangement have been hampered by competitive reaction pathways,
especially elimination pathways yielding alkenes instead.23-24 One example describing a derived benzylic version of
the original Newman-Kwart rearrangement has been published. Here, the conversion of O-(o-azidobenzyl) thio-
carbamates into S-(o-azidobenzyl) thiocarbamate was found to proceed as a [1,3]-shift via an uncoupled concert-
ed mechanism.25 Computational studies suggested that the benzylic rearrangement is activated by electron do-
nating groups substituted on the aromatic ring and thereby exhibits the opposite pattern, compared to the OAr →
SAr and OAr → SeAr rearrangements.
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Scheme 1 The original Newman-Kwart rearrangements (top) and the two new benzylic Newman-Kwart rearrangements pre-
sented here (bottom).
In this contribution, we describe the use of benzylic substrates for the Newman-Kwart rearrangement using both
O-benzyl thiocarbamates and O-benzyl selenocarbamates to yield the corresponding S-benzyl thiocarbamates and
Se-benzyl selenocarbamates (Scheme 1, bottom). A fundamental change in mechanism is inevitable when chang-
ing the phenyl group in the original Newman-Kwart rearrangement to a benzyl group. Instead of a nucleophilic
attack on an sp2 hybridised carbon atom, the rearrangement is now initiated via an sp3 hybridised carbon atom.
We present general reaction conditions for both types of conversions and discuss the reaction mechanism based
on reaction scope, kinetics- and computational studies. The reaction mechanism involves a solvated ion-pair, and
the reaction rate is favoured by substituents on the aromatic ring of the benzyl group that aid in the stabilization
of the benzylic carbocation, and is thus favoured by electron donating substituents on the aromatic ring.
Results and Discussion
Synthesis of the carbamates
The starting material for the thiol version of the benzylic Newman-Kwart rearrangement, the O-benzyl thiocar-
bamates, was prepared by reaction of N,N-dimethylthiocarbamoyl chloride with the desired benzyl alcohol in the
presence of sodium hydride in THF giving the products in good yields of 82 to 99 % (Table 1, step 1). The O-benzyl
selenocarbamate equivalents were more arduous to synthesise since the seleno analogue of N,N-
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dimethylthiocarbamoyl chloride, N,N-dimethylselenocarbamoyl chloride, is both air- and moisture sensitive.26 This
makes it unpractical to handle, and we therefore explored S-phenyl N,N-dimethylthioselenocarbamate as a shelf
stable alternative.26-27 This reacts readily with the benzyl alcohols upon addition of sodium hydride in THF to form
the O-benzyl selenocarbamates in excellent yields ranging from 89 to 93 % (Table 1, step 1). All compounds were
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1
characterised by H, 13C, and 77Se NMR spectroscopy (when appropriate) together with a high-resolution mass
spectrometry analysis and the details hereof are presented in the Experimental Section.
Table 1 Overview of synthesised O-benzyl thio- and selenocarbamates 2 and their conversion to the corresponding S-benzyl
thio- and Se-benzyl selenocarbamates 3.[a]
Compound
X
Y
S
S
S
S
S
S
S
S
S
S
S
S
Isolated
yield of 2
97 %
Isolated
yield of 3
48 %
Conversion of
2 after 10 h[f]
100 %[h]
a
b
c
d
e
f
2-OMe
3-OMe
4-OMe
4-OMe[b]
4-OEt
94 %
96 %
98 %
82 %
91 %
87 %
92 %
96 %
98 %
99 %
90 %
59 %
70 %
60 %
54 %
62 %
41 %
33 %
35 %
100 %[h]
100 %[h]
100 %[h]
100 %[h]
75 %
4-OEt[b]
4-Me
g
h
i
4-H
66 %
(rac)-4-H[c]
(R)-4-H[c]
4-Cl
–
–
[d]
[d]
[d]
[d]
j
–
–
k
l
51 %
59 %
45 %
55 %
4-Br
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m
n
4-CO2CH3
4-NO2
4-OMe
4-H
S
83 %
52%
93 %
93 %
97 %
89 %
-
67 %
-
40 %
Trace
S
o
Se
Se
Se
Se
Se
Se
88 %[e]
54 %
100 %[h]
100 %[h]
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p
[d]
[d]
q
(rac)-4-H[c]
4-Br
–
–
r
61 %
100 %[h]
s[g]
t[g]
4-Cl
-
-
-
-
4-NO2
-
[a]
The notation “LGC(=Y)NMe2” corresponds to the reagents N,N-dimethylthiocarbamoyl chloride (used for 2a – 2n) or S-
phenyl N,N-dimethylthioselenocarbamate (used for 2o – 2t).
[b] The carmabate group is the ethyl derivative, N,N-diethylthiocarbamate.
[c] The benzylic position is methylated, i.e. the phenol used is 1-phenylethan-1-ol.
[d] No rearrangement occurs, instead an elimination reaction take place.
[e] The rearrangement was performed at 150 °C.
[f] Monitored by 1H NMR spectroscopy, see supporting information for further information.
[g] The compound is not synthesised and only used for computational studies.
[h] The reaction is complete before 10 hours.
With the O-benzyl thiocarbamates in hand we were ready to investigate whether the various substrates were
prone to rearrange to the corresponding S-benzyl thiocarbamates (Table 1, step 2). The migration reaction was
initially tested in 1-methylpyrrolidin-2-one (NMP), a solvent often used for Newman-Kwart rearrangements,28-29 as
well as N,N-dimethylformamide (DMF) and diphenyl ether, where diphenyl ether was found superior. With the
optimal solvent found the reaction temperature was investigated next. When heating O-(4-methylbenzyl) N,N-
dimethylthiocarbamate (2g) to 150 °C in diphenyl ether for two days no reaction happened and no notable de-
composition was observed. Increasing the temperature to 175 °C some conversion was seen after two days but
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unfortunately together with a non-negligible amount of unwanted by-products. Finally, adjusting the temperature
to 200 °C complete conversion was observed within one day thus showing the importance of a high reaction tem-
perature to overcome the reaction barrier. The desired product 3g was however only isolated in 41 % yield show-
ing how rearrangement and degradation are competing reactions. Most other substrates gave better yields.
The unambiguously proof of the successful benzylic Newman-Kwart rearrangement came by single-crystal X-ray
crystallography where it transpires how the oxygen and sulfur atoms are exchanged during the rearrangement of
2k into 3k (Figure 1a and b).30
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Figure 1 Analytical data supporting the OBn → SBn rearrangement by showing a) single-crystal X-ray structure of 2k, b) single-
crystal X-ray structure of 3k (colour code, S: yellow, O: red, N: blue, Cl: green, C: grey, H: white), c) 1H NMR spectra (500 MHz,
CDCl3, 25 °C) of 2h and 3h. Assignment of the signals is based on the labelling shown on the structures.
The progress of the rearrangement can easily be monitored by 1H NMR spectroscopy as shown in Figure 1c where
1
the H NMR spectra of O-benzyl N,N-dimethylthiocarbamate (2h) and the corresponding rearranged 3h are
shown. Focusing on the signals corresponding to the N,N-dimethylamino group (Hc) it transpires how the two
well-resolved singlets in the reactant merges into one broad singlet in the product. This is a result of a changed
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energy barrier for the internal rotation about the C–N thiocarbamate bond going from reactant to product. In 2h
the rotational energy barrier is sufficiently high to allow slow exchange on the NMR timescale thus showing two
distinctive peaks for the N,N-dimethylamino group whereas the barrier in 3h is lower giving rise to a merger of
the two peaks as the domain of fast exchange is entered. The peak corresponding to the benzylic protons (Hb)
moves 1.34 ppm upfield during the rearrangement showing how the electron density decreases on the benzylic
centre as oxygen is exchanged for sulfur. Similar trends are observed in the corresponding 13C NMR spectra (see
Supporting Information).
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The benzylic Newman-Kwart rearrangement shows great tolerance towards a wide range of functional groups
ranging from methoxy, through alkyl and halogens, to ester substituted O-benzyl thiocarbamates (Table 1, step 2).
Performing the rearrangement with electron donating groups increases the reaction time. For example, the con-
versions of the ethers 2c, 2d, 2e, and 2f were complete within two hours at 200 °C while the halogens 2k and 2l
required 24 hours for complete conversion. The rearrangement also allows substituents in both the 2-, 3-, and 4-
position of the aromatic unit (2a, 2b, 2c) and extending the N,N-dimethylamino group to an N,N-diethylamino
group is also feasible (2d and 2f). The rearrangement is also possible when the electron withdrawing nitro group
is placed in the para position (2s). However, the reaction time is, not surprisingly, very long and the rearrange-
ment was only 50 % complete after heating to 200 °C for 3 days.
In addition, the racemic and enantiomerically pure O-(1-phenylethyl) N,N-dimethylthiocarbamate (2i and 2j, re-
spectively) were tested if feasible for the OBn → SBn rearrangement. It was envisaged that the products of these
could give insight to the stereochemical aspect of the reaction mechanism as whether we would obtain an inver-
sion of the configuration or a racemic mixture of the rearranged product. Analysis of the reaction mixture did not
show the desired rearranged product but instead complete and clean conversion to styrene (Figure 2 and Sup-
porting Information). The presence of a β-proton in similar O-benzyl thiocarbamates are known to facilitate elimi-
nation over rearrangement through a Chugaev-like elimination.23
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Figure 2 Heating O-(1-phenylethyl) N,N-dimethylthiocarbamate does not give the rearranged product but instead styrene and
N,N-dimethylthiocarbamic acid where the latter react further to form carbonyl sulfide and N,N-dimethylamine.
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After the successful rearrangement of the O-benzyl thiocarbamates we were intrigued to investigate whether the
selenium analogues would be just as efficient. The first substrate examined was the O-(4-methoxybenzyl) N,N-
dimethylselenocarbamate (2o) which was found to rearrange just within five minutes when heated to 200 °C.
Comparing this with the sulfur analogue 2c heating for two hours was necessary to obtain same conversion. This
observation, showing how the OBn → SeBn rearrangement proceeds significantly faster than the OBn → SBn rear-
rangement, is also known for the aryl versions of the Newman-Kwart rearrangement.22 The O-benzyl N,N-
dimethylselenocarbamate (2p) and the bromo derivative 2r also smoothly underwent rearrangement and again
with reaction times substantially shorter than their sulfur analogues (Table 1, step 2).
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A single-crystal suitable for X-ray crystallography of the rearranged product 3p was obtained proving the connec-
tivity in the product (Figure 3a).31 Consulting the 1H NMR spectra of the OBn → SeBn rearrangement of substrate 2p
into 3p similar trends are observed as in the OBn → SBn rearrangement (Figure 1c vs Figure 3b). As the rearrange-
ment proceeds the signals corresponding to the N,N-dimethylamino group (Hc) alters from being two well sepa-
rated singlets in 2p to approach each other forming two closely connected broad singlets in 3p. In comparison,
the Hc protons in the sulfur analogue merged completely. This agrees with the reported observation that the rota-
tional barrier increases from amides through thioamides to selenoamides.32-33 Again, the benzylic protons Hb
shifts substantially upfield during the rearrangement but besides increasing the shielding of the Hb protons the
selenium atom also causes the signal to split into a triplet (Figure 3b). Selenium has six naturally occurring iso-
topes from which only 77Se (7.58%) is NMR active having a nuclear spin quantum number of I = 1/2. Therefore, it
is possible in the 1H NMR spectrum of rearranged product 3p to observe a 2JSe–H spin-spin coupling between the Hb
protons and the selenium atom with a strength of 11 Hz, which are in agreement with the literature.34 In compari-
son, no coupling is observed in 2p as the 4JSe–H coupling is too small to observe. Similar observations can be done
in the corresponding 13C NMR spectra (see Supporting Information).
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Figure 3 Analytical data supporting the OBn → SeBn rearrangement by showing a) single-crystal X-ray structure of 3p (colour
code, Se: orange, O: red, N: blue, C: grey, H: white), b) 1H NMR spectra (500 MHz, CDCl3, 25 °C) of 2p and 3p, and c) 77Se NMR
spectra (57 MHz, CDCl3 with a saturated solution of (PhSe)2 in CDCl3 as external standard, 25 °C) of 2p and 3p. The spectra
shows an enlargement of selected 77Se,1H-coupled signals, assignment of the signals is based on the labelling shown on the
structures.
2
The JSe–H spin-spin coupling can also be observed in the corresponding 77Se NMR spectrum (Figure 3c). The non-
rearranged 2p shows a singlet, as expected, at 216 ppm while the signal for the rearranged 3p appears as a triplet
2
at 464 ppm with the equivalent JSe–H spin-spin coupling of 11 Hz between the Hb protons and the selenium atom
(Figure 3c). Besides the spin-spin coupling the 77Se NMR spectrum also gives information on the chemical envi-
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ronment of the selenium atom within the molecule.34 As the rearrangement occurs the signal for the selenium
atom shifts remarkably 248 ppm downfield in the spectrum demonstrating a changed environment for the seleni-
um atom which corresponds well with the change in connectivity within the molecule due to the rearrangement.
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The OBn
→
SeBn rearrangement was also investigated for the (rac)-O-(1-phenylethyl) N,N-
dimethylselenocarbamate (2q), but again, the presence of β-protons favoured a very efficient Chugaev-like elimi-
nation23 thus affording styrene (Figure 2 and Supporting Information).
Hydrolysis of the rearranged products gives access to the corresponding benzyl thiols or selenols (Table 1, step 3).
As representative examples, both the 4-methoxy substituted S-benzyl thio- and Se-benzyl selenocarbamates 3c
and 3o were treated with potassium hydroxide in a methanol/water mixture thus giving the hydrolysed products
4c and 4o, respectively, in quantitative yield. The benzyl selenol 4o was isolated as the diselenide, 1,2-bis(4-
methoxyphenyl)diselane, due to the rapid oxidation of the selenol functionality.
Mechanistic studies
To gain insight to the course of the reaction the kinetics for the OBn → SBn rearrangement of O-(4-methoxybenzyl)
N,N-dimethylthiocarbamate (2c) was studied in detail and compared with previously reported results from the OAr
→ SAr and OAr → SeAr rearrangements. The conversion from 2c into 3c follows clearly first order reaction kinetics
which is similar to the aryl version of the rearrangement. Measuring the conversion at different temperatures the
activation parameters were derived. The enthalpy of activation (ꢀH‡) was calculated to 35.7 kcal/mol while the
entropy of activation (ꢀS‡) was 1.45 cal/molꢁK (see Supporting Information). The OAr → SAr and OAr → SeAr rear-
rangements have both been reported to proceed in a unimolecular concerted manner via a four-membered cyclic
transition state why it would be reasonable to believe that the benzylic version would follow the same route.22, 35
However, the activation parameters obtained from those studies differ substantially from the ones obtained in
this study thus contradicting the mechanistic proposal (ꢀH‡(OAr → SAr) = 28.8 kcal/mol, ꢀS‡(OAr → SAr) = – 10.0
cal/molꢁK and ꢀH‡(OAr → SeAr)= 26.7 kcal/mol, ꢀS‡(OAr → SeAr)= – 11.9 cal/molꢁK, all values obtained for the 4-
nitro substituted derivative).22, 35 The ꢀH‡ value of the OBn → SBn rearrangement is increased greatly compared to
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both aryl rearrangements indicating that the C–O bond breaking in the reactant is more important for the benzylic
rearrangement than the aryl rearrangements. Also, the ꢀS‡ value changes significantly. The large negative values
obtained in the aryl rearrangements correspond well to the strained four-membered cyclic transition state. In
comparison, the ꢀS‡(OBn → SBn) value is small and positive indicating that the transition state is not very con-
strained structurally. The positive ꢀS‡ value point towards a dissociative mechanism, where the bond breaking
has occurred to a higher extend than bond formation in the transition state, with the extreme case being the SN1
reaction mechanism. Comparing the ꢀS‡ values the OBn → SBn rearrangement possess less SN2 character compared
to the aryl version, but has not quite reached the limiting domain of the SN1 mechanism.
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In order to clarify the influence of the substituents on the aromatic ring upon the reaction rate of the benzylic
rearrangement, the kinetics was studied on the different substrates (Table 2 and Supporting Information). The OBn
→ SBn reaction rate shows strong dependency on the nature of the substituent. Substrates with an electron do-
nating group attached, i.e. the ether group in 2c and 2f, accelerates the reaction rate by more than one order of
magnitude compared to the unsubstituted compound 2h. Conversely, the rate constant gets even smaller when
electron withdrawing substituents are attached to the aromatic unit, like the ester 2m, however the reaction still
proceeds. The reaction rate is also influenced by the position of the substituent on the aromatic ring where the 2-
and 4-positions are favoured over the 3-position (2a and 2c vs 2b).
Table 2 Overview of the obtained rate constants (ks) for the rearrangement of substituted O-benzyl thio- and selenocarba-
mates into their corresponding S-benzyl thio- and Se-benzyl selenocarbamates in diphenyl ether (0.4 ) at 200 °C. The values
M
are obtained with 1H NMR spectroscopy analysis unless otherwise stated.
Compound
X
Y
S
S
ks [s–1]
a
b
2-OMe
3-OMe
8.38 ∙ 10–5
1.53 ∙ 10–5
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c
f
4-OMe
4-OEt[a]
4-Me
S
S
S
S
S
S
S
5.03 ∙ 10–4
2.97 ∙ 10–4
3.65 ∙ 10–5
3.59 ∙ 10–5
2.89 ∙ 10–5
2.49 ∙ 10–5
1.42 ∙ 10–5
g
h
k
l
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4-H
4-Cl
4-Br
m
o
p
4-CO2CH3
4-OMe Se 9.25 ∙ 10–3 [b]
Se 8.51 ∙ 10–4 [b,c]
4-H
[a] The carmabate group is the ethyl derivative, N,N-diethylthiocarbamate.
[b] Determined by LC-MS analysis.
[c] Performed in with a substrate concentration of 20 mM.
The substrates for the OBn → SeBn rearrangement have already shown to proceed at lower reaction temperatures
and have faster reaction rates than the corresponding OBn → SBn rearrangements. This is also proven quantitative-
ly, and the reaction rates of the seleno analogues are found to be about two orders of magnitude larger than the
equivalent sulfur analogues, both following first order reaction kinetics (Table 2). Again, electron donating groups
accelerate the rearrangement compared to the unsubstituted analogue (2o vs 2p). The electronic demand in the
OBn → SBn and OBn → SeBn rearrangements is thus found to be completely opposite compared to the OAr → SAr and
OAr → SeAr rearrangements. Here, electron withdrawing substituents increases the rate significantly while elec-
tron donating substituents deter the rearrangement from proceeding.22, 28
In order to elucidate the reaction mechanism a linear free energy relationship study was made on the OBn → SBn
rearrangement. Ordinary Hammett plots were constructed from the obtained rate constants of the substrates in
Table 2 and the tabulated substituent constants σ, σ +, and σ – (see Supporting Information).36 Unfortunately,
none of these gave linear correlations. The plot against the σ + substituent constant presented the best, but still
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not optimal, correlation in agreement with the observation that electron donating substituents increases the re-
action rate. The OAr → SAr rearrangement has previously been analysed successfully with the Yukawa-Tsuno equa-
tion, why we also applied this analytical method on the OBn → SBn rearrangement (see Supporting Information).37-
40
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For a particular substituent the σ value is generally considered constant, however for compounds in which the
transition state bears a nearly full charge, this no longer apply and the Hammett equation becomes invalid. The
Yukawa-Tsuno equation manages to account for the enhanced resonance effects that are present in such reac-
tions with high electron demand. A good linear relationship was obtained with this modified version of the Ham-
mett equation and a value of – 0.44 was obtained for the Hammett reaction constant (ρ) while the Yukawa-Tsuno
constant, the enhanced resonance parameter (r) equals 5.40 (Figure 4).
Figure 4 Yukawa-Tsuno plot used to descibe the OBn → SBn rearrangement in diphenyl ether at 200 °C. The parameters ob-
tained are ρ = – 0.44 and r = 5.40.
The obtained negative ρ value indicates that the reaction rate is favoured by electron donating substituents on
the aromatic ring, due to an accumulation of positive charge in the transition state structure, which is in accord-
ance with the observed reaction rates (Table 2). The greater the magnitude of ρ, the more sensitive the rear-
rangement is to the nature of the substituents. However, the comparison should always be relative to other re-
lated systems. A ρ value of +1.92 was obtained for the OAr → SAr rearrangement (using σ – values).40 According to
this, the reaction mechanism of the OAr → SAr and OBn → SBn rearrangements are not equivalent as the electronic
demand in the transition state in the benzylic version is completely opposite to the aryl version.
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The enhanced resonance parameter r is a measure of the influence of resonance on the reaction. Positive values
show that the reaction is more sensitive to resonance effects than the standard, unsubstituted reaction, while
negative values are less sensitive.41 As stated the r value for the OBn → SBn rearrangement is 5.40 and in compari-
son the OAr → SAr rearrangement has an r value of 1.6 (using σ – values).40 This is in agreement with the proposal
that the mechanism of the OBn → SBn rearrangement possess more SN1 character, i.e. retain more ionic character,
than the OAr → SAr rearrangement and is thereby more stabilised by resonance than the aryl version in which only
partial charges in the transition state structure are present.
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The benzylic Newman-Kwart rearrangement was further investigated by a crossover experiment to examine
whether the rearrangement is inter- or intramolecular. The two similar, but distinguishable, reactants O-(4-
methoxybenzyl) N,N-dimethylthiocarbamate (2c) and its ethyl analogue 2f possess similar reaction rates (Table 2)
and were thus chosen for further investigation. Performing the crossover experiment at high concentrations (1.0
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, diphenyl ether, 200 °C) the two non-crossover rearranged products 3c and 3f formed with comparable rates
together with a minor fraction of the crossover products 3d and 3e as observed by 13C NMR spectroscopy and MS
analysis (Figure 5 and Supporting Information). Thus, under the presented conditions, the rearrangement pro-
ceeds via an ionic reaction mechanism where the substrates rearrange mainly intramolecularly but also to a less
degree intermolecularly. However, a 10-fold decrease in concentration (0.1 , diphenyl ether, 200 °C) gave only
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the products 3c and 3f and none of the crossover products were observed. This indicates that even though the
rearrangement follows an ionic reaction mechanism, the low concentration crossover experiments shows that the
rearrangement has not reached the pure domain of an SN1 mechanism. Instead it proceeds via a tight ion pair
intermediate consisting of the benzylic carbocation and the thiocarbamate moiety.
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Figure 5 Cross-over experiment between 2c and 2f indicating that the benzylic Newman-Kwart rearrangement proceeds via
an ionic mechanism.
Computational studies
A theoretical study was sought to get further insight into the reaction mechanism of the rearrangement. The
study included both O-benzyl thio- and selenocarbamates substituted with electron donating (2c and 2o), neutral
(2h and 2p), halogen (2k and 2s), and electron withdrawing groups (2n and 2t) on the aromatic unit. The fourth
generation composite method referred to as G4MP2 was used as the level of theory with the GAUSSIAN09 suite
of programs.42-43 The G4MP2 is approximating a large basis set CCSD(T) single point calculations on a B3LYP/6-
31G(2df,p) geometry and is incorporating a so-called higher level correction that is derived by a fit to the experi-
mental values in the G3/05 test set with 454 experimental entries. The average absolute derivation from the ex-
perimental test set values is 1.04 kcal/mol.44
A potential energy diagram has been constructed to visualise the mechanism showing the reactant, transition
state, and product for the OBn → SBn and OBn → SeBn conversion of 2h into 3h and 2p into 3p, respectively (Figure 6
and Supporting Information). The local minima on the potential energy surfaces were characterised by real vibra-
tional frequencies while the transition states were characterised by one imaginary frequency corresponding to a
molecular displacement along the reaction coordinate. The nature of the transition state structures was investi-
gated by an intrinsic reaction coordinate (IRC) calculation that showed the transition state to the reactions and
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products without intermediates.45-46 An optimisation of the end-points of the IRC was compared to the optimised
reactants and products and found similar, indicating that the transition state structures are reliable. According to
the IRC, the mechanism contains one transition state and no intermediates.
9
Based on the optimised structures, the activation energies (ꢀEǂ) and reaction energies (ꢀE°), including zero point
vibrational energies, were calculated. The OBn → SBn rearrangement of substrate 2h into 3h gives an ꢀEǂ value of
178.1 kJ/mol and ꢀE° of 56.7 kJ/mol while the corresponding OBn → SeBn rearrangement of 2p into 3p gives values
of 168.7 kJ/mol and 61.6 kJ/mol for ꢀEǂ and ꢀE°, respectively (Figure 6). These values show, in agreement with
the experimental work, how the OBn → SeBn rearrangement proceeds with a lower activation barrier, and thus a
higher reaction rate, compared to the OBn → SBn rearrangement. The ꢀEǂ values of the benzylic rearrangements
are comparable in size to the corresponding aryl versions, which has been calculated to 159 kJ/mol for the OAr →
SAr rearrangement (B3LYP/6-31+G(d,p) level of theory)47 and 142 kJ/mol for the OAr → SeAr rearrangement
(MP2/6-31G(d) level of theory).22
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Figure 6 Schematic potential energy profile comparing the OBn → SBn conversion (2h into 3h, G4MP2 calculated structures are
shown) and OBn → SeBn conversion (2p into 3p). The energies are given in kJ/mol and the reactants for both reactions are set
at 0 kJ/mol with an offset at 50 kJ/mol.
Comparing the energies for all examined substrates it transpires how the activation energy for the rearrangement
generally decreases with electron donating groups attached on the aromatic unit and vice versa for electron
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withdrawing groups (Figure 7). This is in accordance with the experimental results. The activation barrier is, how-
ever, only lowered 6-7 kJ/mol altering the substituent from an electron withdrawing to an electron donating sub-
stituent (2c vs 2n or 2o vs 2t). This makes it possible to rearrange a wider collection of derivatives with different
electronic demands, a possibility which are not feasible for the aryl rearrangements. These results are also con-
firmed experimentally.
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Figure 7 G4MP2 optimised transition state structures for the OBn → SBn conversion (top) and OBn → SeBn conversion (bottom).
Selected bond lengths are shown in angstrom on the structure while the dihedral angle (θ
), the activation energy (ΔEǂ), and
the reaction energy (ΔE°) are given below for each structure. Colour code, S: yellow, Se: orange, O: red, N: blue, Cl: green, C:
grey, and H: white.
Examination of the geometry of the various substituted transition states gives access to more knowledge of the
reaction mechanism for the rearrangement. All eight transition state structures possess two planar units; one
consisting of the benzylic carbocation and one comprising the thio- or selenocarbamate moiety. The two ele-
ments are placed perpendicular to each other in all cases, as seen by the measured dihedral angle (θ) given for
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each structure (Figure 7). Analysis of the bond length distances between the two units gives an indication wheth-
er the structures are connected covalently or through ionic interactions. The average distance between the C–O,
C–S, and C–Se atoms was found to be 2.2 Å, 2.8 Å, and 3.0 Å, respectively. These values are all larger than the
values for a corresponding covalent bond (C–O: 1.4 Å, C–S: 1.8 Å, and C–Se: 2.0 Å)13 thus indicating an ionic inter-
action. The measured distances are, however, still relatively close to the covalent bond lengths, supporting the
proposal of a tight ion pair intermediate consisting of the benzylic carbocation and the thio- or selenocarbamate
moiety. Also, the changes in geometry of the transition states as a function of the different substituents have
been examined (Figure 7). Here it transpire, how both the C–O and the C–S/Se distance between the two ionic
species increases when an electron donating group (2c and 2o) is introduced and similarly decreases upon substi-
tution of an electron withdrawing substituent (2n and 2t). The chlorine atom in 2k and 2s can both donate a lone
pair into the aromatic ring but is also electronegative and can thus withdraw electron density inductively. These
two opposing effects are why a difference in the bond lengths between the chlorine (2k and 2s) and unsubstitut-
ed (2h and 2p) substrates are not observed.
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These computational studies of the benzylic Newman-Kwart rearrangement further support a tight ion pair in-
termediate consisting of the benzylic carbocation and the thio- or selenocarbamate moiety. The electron donating
substituents are able to stabilise the benzylic carbocation to a higher degree than the electron withdrawing deriv-
atives, thus giving rise to a more ionic intermediate, envisaged through longer bond lengths, and thus lower acti-
vation energies.
Conclusion
In this paper we have presented a systematic and in-depth study of the OBn → SBn and OBn → SeBn Newman-Kwart
rearrangements. Synthetic procedures have been shown together with thorough mechanistic studies as well as a
theoretical elucidation of the reaction mechanism. The values obtained from computational chemistry support
the experimental results that the rearrangement proceeds via an ionic reaction mechanism. The rate determining
step is the bond breaking of the Cbenzylic–O bond in the reactant thus forming a tight ion pair intermediate consist-
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ing of a benzylic carbocation and a thio- or selenocarbamate moiety. The ion pair formation is feasible due to the
benzylic stabilisation of charge. This mechanism supports the trend that electron donating groups increases the
rate of the rearrangement and the electronic demand is thereby opposite that of the original aryl version of the
Newman-Kwart rearrangement.
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Experimental Section
General methods
All chemicals, unless otherwise stated, were purchased from commercial suppliers and used as received. Solvents
were HPLC grade and used as received except THF, which was tapped from a Solvent Purification System, Innova-
tive Technology, Inc., and diphenyl ether, which was distilled prior to use. All reactions involving selenium were
carried out under an anhydrous nitrogen atmosphere.
Analytical thin layer chromatography (TLC) was performed on Merck DC-Alufolien SiO2 60 F254 0.2 mm thick pre-
coated TLC plates and visualised under UV light (254 nm). Column chromatography and dry column vacuum
chromatography was performed using SiO2 from ROCC (SI 1721, 60 Å, 40 – 63 μm and SI 1722, 60 Å, 15 – 40 μm
respectively). Melting points (mp.) were determined on a Büchi melting point apparatus and are uncorrected.
1H NMR and 13C NMR spectra were recorded at 500 MHz and 126 MHz, respectively, on a Bruker Ultrashield Plus
500 spectrometer using residual non-deuterated solvent as the internal standard. 77Se NMR spectra were record-
ed on a Bruker spectrometer operating at 57 MHz using a saturated solution of diphenyl diselenide (
δ = 463 ppm)
in CDCl3 at 20 °C in a sealed tube as external standard. All chemical shifts ( ) are quoted in ppm and coupling con-
δ
stants (J) are expressed in Hertz (Hz). The following abbreviations are used for convenience in reporting the mul-
tiplicity for NMR resonances: s = singlet, bs = broad singlet, d = doublet, t = triplet, q = quartet, and m = multiplet.
The NMR data were processed using MestReNova v. 10.0.2. Assignment of all 1H and 13C resonances was achieved
using standard 2D NMR techniques as 1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC.
Standard HPLC analyses were performed on a Dionex UltiMate 3000 system coupled to an UltiMate 3000 diode
array UV/Vis detector. Separations were achieved using a Dionex Acclaim RSLC 120 C18 2.2 μm 120 Å 2.1 × 50 mm
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column maintained at 40 °C. The mobile phase solution was prepared with 0.1 % HCOOH in the solvents. The wa-
ter used as eluent was purified by a Millipore system. LC/MS was carried out on a Bruker MicrOTOF-QII-system
with ESI-source with nebuliser 1.2 bar, dry gas 8.0 L min–1, dry temperature 200 °C, capillary – 4500 V, end plate
offset – 500 V, funnel 1 RF 200.0 Vpp, ISCID energy 0.0 eV, funnel 2 RF 200.0 Vpp, hexapole RF 100.0 Vpp, quad-
rupole ion energy 5.0 eV, low mass 100.00 m/z, collision energy 8.0 eV, collision RF 100.0 Vpp, transfer time
80.0 μs, and pre puls storage 1.0 μs. LC-HRMS samples were calibrated by an automated pre-run internal mass
scale calibration of the individual samples by injecting a sodium formate solution, consisting of 10 mM NaOH(aq) in
i-PrOH:H2O 1:1 v/v (+ 1 % HCOOH). Subsequent calibration was performed based on the calibrator ions. The
LC/MS data were processed using DataAnalysis v. 4.0 SP5. For Se-containing ions in the mass spectrum, only the
main selenium isotope (80Se) is quoted.
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Elemental analyses were performed by the microanalytical service of the Department of Chemistry, University of
Copenhagen, Denmark on a CE Instrument, Flash 1112 series EA.
Experimental procedures for the O-benzyl thio- and selenocarbamates
General procedure. The desired alcohol (1.0 equiv.) and sodium hydride (60 % in mineral oil, 1.2 equiv. for S sub-
strates and 2.2 equiv. for Se substrates) were added to anhydrous, degassed THF under a nitrogen atmosphere.
The reaction mixture was cooled by a water bath and stirred for 10 minutes. N,N-Dimethylthiocarbamoyl chloride
(1.0 equiv., used for S substrates) or S-phenyl N,N-dimethylthioselenocarbamate27 (1.0 equiv., used for Se sub-
strates) was added in situ and the reaction mixture was further stirred for 1 hour at 25 °C. The mixture was con-
centrated in vacuo before CH2Cl2 was added and the solution was filtered through a plug of Celite and concen-
trated in vacuo. If needed, the product was purified by column chromatography.
O-(2-Methoxybenzyl) N,N-dimethylthiocarbamate (2a). 2-Methoxybenzyl alcohol (559 mg, 4.05 mmol) and NaH
(60 % in mineral oil, 194 mg, 4.86 mmol) in anhydrous THF (25 mL) were reacted with N,N-dimethylthiocarbamoyl
chloride (500 mg, 4.05 mmol) following the general procedure. The product was isolated as a white powder
1
(884 mg, 3.92 mmol, 97 %), mp. 37–38 °C. H NMR (500 MHz, DMSO-d6, 25 °C): δ = 7.34 – 7.31 (m, 2H), 7.04 –
7.02 (m, 1H), 6.97 – 6.94 (m, 1H), 5.41 (s, 2H), 3.81 (s, 3H), 3.29 (s, 3H), 3.09 (s, 3H). 13C NMR (126 MHz, DMSO-d6,
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25 °C): δ = 187.0, 156.9, 129.4, 128.8, 123.9, 120.2, 110.8, 67.8, 55.4, 42.3, 37.4. HRMS (ESI-TOF) m/z: [M+H]+
calculated for C11H16NO2S 226.0896; Found 226.0898.
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O-(3-Methoxybenzyl) N,N-dimethylthiocarbamate (2b). 3-Methoxybenzyl alcohol (559 mg, 4.05 mmol) and NaH
(60 % in mineral oil, 194 mg, 4.86 mmol) in anhydrous THF (25 mL) were reacted with N,N-dimethylthiocarbamoyl
chloride (500 mg, 4.05 mmol) following the general procedure. The product was isolated as a light yellow oil
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1
(857 mg, 3.80 mmol, 94 %). H NMR (500 MHz, DMSO-d6, 25 °C): δ = 7.29 (t, J = 8.2 Hz, 1H), 6.99 – 6.94 (m, 2H),
6.90 (ddd, J = 8.2, 2.5, 0.9 Hz, 1H), 5.42 (s, 2H), 3.75 (s, 3H), 3.29 (s, 3H), 3.12 (s, 3H). 13C NMR (126 MHz, DMSO-d6,
25 °C): δ = 186.9, 159.3, 137.8, 129.5, 119.7, 113.3, 113.2, 71.7, 55.0, 42.4, 37.5. HRMS (ESI-TOF) m/z: [M+H]+
calculated for C11H16NO2S 226.0896; Found 226.0900.
O-(4-Methoxybenzyl) N,N-dimethylthiocarbamate (2c). 4-Methoxybenzyl alcohol (559 mg, 4.05 mmol) and NaH
(60 % in mineral oil, 194 mg, 4.86 mmol) in anhydrous THF (25 mL) were reacted with N,N-dimethylthiocarbamoyl
chloride (500 mg, 4.05 mmol) following the general procedure. The product was isolated as a yellow oil (875 mg,
3.88 mmol, 96 %). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.32 (d, J = 8.5 Hz, 2H), 6.89 (d, J = 8.5 Hz, 2H), 5.43 (s, 2H),
3.80 (s, 3H), 3.37 (s, 3H), 3.09 (s, 3H). 13C NMR (126 MHz, CDCl3, 25 °C): δ = 188.1, 159.7, 130.0, 128.3, 114.0, 72.9,
55.3, 42.8, 37.9. HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C11H15NNaO2S 248.0716; Found 248.0723.
O-(4-Methoxybenzyl) N,N-diethylthiocarbamate (2d). 4-Methoxybenzyl alcohol (455 mg, 3.29 mmol) and NaH
(60 % in mineral oil, 158 mg, 3.95 mmol) in anhydrous THF (25 mL) were reacted with N,N-diethylthiocarbamoyl
chloride (500 mg, 3.29 mmol) following the general procedure. The product was isolated as a yellow oil (818 mg,
3.23 mmol, 98 %). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.32 (d, J = 8.7 Hz, 2H), 6.89 (d, J = 8.7 Hz, 2H), 5.44 (s, 2H),
3.84 (q, J = 7.1 Hz, 2H), 3.81 (s, 3H), 3.45 (q, J = 7.1 Hz, 2H), 1.25 (t, J = 7.1 Hz, 3H), 1.12 (t, J = 7.1 Hz, 3H). 13C NMR
(126 MHz, CDCl3, 25 °C): δ = 187.2, 159.7, 130.0, 128.5, 114.0, 72.6, 55.4, 47.9, 43.5, 13.5, 12.1. HRMS (ESI-TOF)
m/z: [M+Na]+ calculated for C13H19NNaO2S 276.1029; Found 276.1019.
O-(4-Ethoxybenzyl) N,N-dimethylthiocarbamate (2e). 4-Ethoxybenzyl alcohol (616 mg, 4.05 mmol) and NaH (60
% in mineral oil, 194 mg, 4.86 mmol) in anhydrous THF (25 mL) were reacted with N,N-dimethylthiocarbamoyl
chloride (500 mg, 4.05 mmol) following the general procedure. The product was isolated as a yellow oil (794 mg,
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3.32 mmol, 82 %). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.31 (d, J = 8.7 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 5.43 (s, 2H),
4.04 (q, J = 7.0 Hz, 2H), 3.38 (s, 3H), 3.10 (s, 3H), 1.41 (t, J = 7.0 Hz, 3H). 13C NMR (126 MHz, CDCl3, 25 °C): δ =
188.2, 159.1, 130.1, 128.2, 114.6, 73.1, 63.6, 42.9, 38.0, 15.0. HRMS (ESI-TOF) m/z: [M+Na]+ calculated for
C12H17NNaO2S 262.0872; Found 262.0873.
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O-(4-Ethoxybenzyl) N,N-diethylthiocarbamate (2f). 4-Ethoxybenzyl alcohol (502 mg, 3.30 mmol) and NaH (60 %
in mineral oil, 158 mg, 3.96 mmol) in anhydrous THF (25 mL) were reacted with N,N-diethylthiocarbamoyl chlo-
ride (408 mg, 3.30 mmol) following the general procedure. The product was isolated as white crystals (802 mg,
3.00 mmol, 91 %), mp. 44–46 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.31 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.6 Hz,
2H), 5.43 (s, 2H), 4.04 (q, J = 7.0 Hz, 2H), 3.84 (q, J = 7.1 Hz, 2H), 3.45 (q, J = 7.1 Hz, 2H), 1.42 (t, J = 7.0 Hz, 3H),
1.25 (t, J = 7.1 Hz, 3H), 1.12 (t, J = 7.1 Hz, 3H). 13C NMR (126 MHz, CDCl3, 25 °C): δ = 187.3, 159.1, 130.0, 128.3,
114.6, 72.7, 63.6, 47.9, 43.5, 15.0, 13.5, 12.1. HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C14H21NNaO2S
290.1185; Found 290.1189.
O-(4-Methylbenzyl) N,N-dimethylthiocarbamate (2g). 4-Methylbenzyl alcohol (494 mg, 4.04 mmol) and NaH (60
% in mineral oil, 194 mg, 4.85 mmol) in anhydrous THF (25 mL) were reacted with N,N-dimethylthiocarbamoyl
chloride (500 mg, 4.04 mmol) following the general procedure. The product was isolated as light yellow needles
(737 mg, 3.52 mmol, 87 %), mp. 33–35 °C. 1H NMR (500 MHz, DMSO-d6, 25 °C): δ = 7.29 (d, J = 8.0 Hz, 2H), 7.18 (d,
J = 8.0 Hz, 2H), 5.40 (s, 2H), 3.28 (s, 3H), 3.08 (s, 3H), 2.30 (s, 3H). 13C NMR (126 MHz, DMSO-d6, 25 °C): δ = 186.9,
137.3, 133.2, 128.9, 127.9, 71.9, 42.3, 37.4, 20.7. HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C11H15NNaOS
232.0767; Found 232.0762.
O-Benzyl N,N-dimethylthiocarbamate (2h). Benzyl alcohol (438 mg, 4.05 mmol) and NaH (60 % in mineral oil,
194 mg, 4.86 mmol) in anhydrous THF (25 mL) were reacted with N,N-dimethylthiocarbamoyl chloride (501 mg,
4.05 mmol) following the general procedure. The product was isolated as a yellow oil (727 mg, 3.72 mmol, 92 %).
1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.42 – 7.28 (m, 5H), 5.50 (s, 2H), 3.38 (s, 3H), 3.12 (s, 3H). 13C NMR (126 MHz,
CDCl3, 25 °C): δ = 188.0, 136.2, 128.5, 128.1, 128.0, 72.9, 42.8, 37.9. HRMS (ESI-TOF) m/z: [M+H]+ calculated for
C10H14NOS 196.0791; Found 196.0795.
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(rac)-O-(1-Phenylethyl) N,N-dimethylthiocarbamate (2i). 1-Phenylethan-1-ol (494 mg, 4.04 mmol) and NaH (60 %
in mineral oil, 194 mg, 4.85 mmol) in anhydrous THF (25 mL) were reacted with N,N-dimethylthiocarbamoyl chlo-
ride (500 mg, 4.04 mmol) following the general procedure. The product was isolated as a light yellow oil (813 mg,
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3.88 mmol, 96 %). H NMR (500 MHz, CDCl3, 25 °C): δ = 7.40 – 7.25 (m, 5H), 6.55 (q, J = 6.6 Hz, 1H), 3.35 (s, 3H),
3.15 (s, 3H), 1.63 (d, J = 6.6 Hz, 3H). 13C NMR (126 MHz, CDCl3, 25 °C): δ = 187.3, 141.8, 128.4, 127.7, 126.2, 78.9,
42.6, 37.8, 22.5. HRMS (ESI-TOF) m/z: [M+H]+ calculated for C11H16NOS 210.0947; Found 210.9050.
(R)-O-(1-Phenylethyl) N,N-dimethylthiocarbamate (2j). (R)-1-Phenylethan-1-ol (494 mg, 4.04 mmol) and NaH (60
% in mineral oil, 194 mg, 4.85 mmol) in anhydrous THF (25 mL) were reacted with N,N-dimethylthiocarbamoyl
chloride (500 mg, 4.04 mmol) following the general procedure. The product was isolated as a light yellow oil
(830 mg, 3.97 mmol, 98 %). 1H NMR (500 MHz, DMSO-d6, 25 °C): δ = 7.43 – 7.34 (m, 4H), 7.37 – 7.25 (m, 1H), 6.40
(q, J = 6.6 Hz, 1H), 3.26 (s, 3H), 3.16 (s, 3H), 1.54 (d, J = 6.6 Hz, 3H). 13C NMR (126 MHz, DMSO-d6, 25 °C): δ = 186.1,
141.8, 128.4, 127.6, 125.9, 78.1, 42.2, 37.5, 22.5. HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C11H15NNaOS
232.0767; Found 232.0767. Elemental analysis (%) calculated for C11H15NOS: C 63.12, H 7.22, N 6.69; Found:
C 63.50, H 7.67, N 5.64.
O-(4-Chlorobenzyl) N,N-dimethylthiocarbamate (2k). 4-Chlorobenzyl alcohol (1.00 g, 7.01 mmol) and NaH (60 %
in mineral oil, 337 mg, 8.42 mmol) in anhydrous THF (50 mL) were reacted with N,N-dimethylthiocarbamoyl chlo-
ride (867 mg, 7.01 mmol) following the general procedure. The product was isolated as white crystals (1.59 g,
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6.92 mmol, 99 %), mp. 36–37 °C. H NMR (500 MHz, CDCl3, 25 °C): δ = 7.37 – 7.29 (m, 4H), 5.48 (s, 2H), 3.39 (s,
3H), 3.13 (s, 3H). 13C NMR (126 MHz, CDCl3, 25 °C): δ = 188.0, 134.9, 134.2, 129.6, 128.9, 72.1, 43.1, 38.1. HRMS
(ESI-TOF) m/z: [M+H]+ calculated for C10H13ClNOS 230.0401; Found 230.0400.
O-(4-Bromobenzyl) N,N-dimethylthiocarbamate (2l). 4-Bromobenzyl alcohol (1.00 g, 5.35 mmol) and NaH (60 %
in mineral oil, 257 mg, 6.42 mmol) in anhydrous THF (50 mL) were reacted with N,N-dimethylthiocarbamoyl chlo-
ride (661 mg, 5.35 mmol) following the general procedure. The product was isolated as dark yellow crystals (1.31
g, 4.79 mmol, 90 %), mp. 54–55 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.49 (d, J = 8.5 Hz, 2H), 7.26 (d, J = 8.5 Hz,
2H), 5.46 (s, 2H), 3.39 (s, 3H), 3.13 (s, 3H). 13C NMR (126 MHz, CDCl3, 25 °C): δ = 188.0, 135.4, 131.8, 129.9, 122.3,
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72.1, 43.1, 38.1. HRMS (ESI-TOF) m/z: [M+H]+ calculated for C10H13BrNOS 273.9896; Found 273.9898. Elemental
analysis (%) calculated for C10H12BrNOS: C 43.81, H 4.41, N 5.11; Found: C 43.98, H 4.40, N 5.11.
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O-(4-Carbomethoxybenzyl) N,N-dimethylthiocarbamate (2m). 4-Carbomethoxybenzyl alcohol (1.00 g, 6.02
mmol) and NaH (60 % in mineral oil, 289 mg, 7.22 mmol) in anhydrous THF (50 mL) were reacted with N,N-
dimethylthiocarbamoyl chloride (744 mg, 6.02 mmol) following the general procedure. The product was isolated
as a light yellow solid (1.27 g, 5.01 mmol, 83 %), mp. 67–69 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 8.04 (d, J = 8.2
Hz, 2H), 7.44 (d, J = 8.2 Hz, 2H), 5.57 (s, 2H), 3.92 (s, 3H), 3.40 (s, 3H), 3.17 (s, 3H). 13C NMR (126 MHz, CDCl3,
25 °C): δ = 188.0, 166.9, 141.5, 130.0, 130.0, 127.6, 72.2, 52.3, 43.2, 38.1. HRMS (ESI-TOF) m/z: [M+Na]+ calculat-
ed for C12H15NNaO3S 276.0665; Found 276.0673.
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O-(4-Nitrobenzyl) N,N-dimethylthiocarbamate (2n). The 4-nitrobenzyl alcohol (501 mg, 3.27 mmol) was dissolved
in anhydrous, degassed THF (50 mL) under a nitrogen atmosphere. The reaction mixture was cooled by a water
bath and potassium tert butoxide (441 mg, 3.93 mmol.) was added slowly in situ to and subsequently stirred for
15 minutes. The reaction mixture turned brown/yellow after 15 min stirring and N,N-dimethylthiocarbamoyl chlo-
ride (404 mg, 3.27 mmol.) was added in situ and the reaction mixture was further stirred for 18 hours at 25 °C.
The mixture was concentrated in vacuo before CH2Cl2 was added and the solution was filtered through a plug of
Celite and concentrated in vacuo. The reaction mixture was purified by column chromatography (ethyl ace-
tate/heptane, 2 % gradient). The product was isolated as yellow needles (409 mg, 1.70 mmol, 52 %), mp. 32–
34 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 8.23 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 8.8, 2H), 5.64 (s, 2H), 3.41 (s, 3H),
3.20 (s, 3H). 13C NMR (126 MHz, CDCl3, 25 °C): δ = 187.7, 147.8, 143.8, 128.3, 124.0, 71.2, 43.3, 38.2. HRMS (ESI-
TOF) m/z: [M+H]+ calculated for C10H12N2O3S 241.06569; Found 241.06555.
O-(4-Methoxybenzyl) N,N-dimethylselenocarbamate (2o). 4-Methoxybenzyl alcohol (283 mg, 2.05 mmol) and
NaH (60 % in mineral oil, 180 mg, 4.51 mmol) in anhydrous THF (25 mL) were reacted with S-phenyl N,N-
dimethylthioselenocarbamate (500 mg, 2.05 mmol) following the general procedure. The product was isolated as
a light yellow oil (518 mg, 1.90 mmol, 93 %). 1H NMR (500 MHz, CDCl3, 25 °C): δ =7.33 (d, J = 8.7 Hz, 2H), 6.88 (d, J
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= 8.7 Hz, 2H), 5.53 (s, 2H), 3.79 (s, 3H), 3.47 (s, 3H), 3.07 (s, 3H).48 13C NMR (126 MHz, CDCl3, 25 °C): δ = 190.5 (d,
JC–Se = 235 Hz), 159.8, 130.1, 127.8, 114.0, 76.5, 55.3, 45.3, 38.2. 77Se NMR (57 MHz, CDCl3, 25° C) δ = 216.2. HRMS
(ESI-TOF) m/z: [M+Na]+ calculated for C11H15NNaO2Se 296.0160; Found 296.0165.
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O-Benzyl N,N-dimethylselenocarbamate (2p). Benzyl alcohol (221 mg, 2.05 mmol) and NaH (60 % in mineral oil,
180 mg, 4.50 mmol) in anhydrous THF (25 mL) were reacted with S-phenyl N,N-dimethylthioselenocarbamate
(500 mg, 2.05 mmol) following the general procedure. The product was isolated as a light yellow oil (461 mg, 1.90
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mmol, 93 %). H NMR (500 MHz, CDCl3, 25 °C): δ = 7.42 – 7.31 (m, 5H), 5.61 (s, 2H), 3.50 (s, 3H), 3.12 (s, 3H).
13C NMR (126 MHz, CDCl3, 25 °C): δ = 190.7 (d, JC–Se = 236 Hz), 135.8, 128.7, 128.4, 128.2, 76.6, 45.4, 38.3.
77Se NMR (57 MHz, CDCl3, 25° C) δ = 216.1. HRMS (ESI-TOF) m/z: [M+H]+ calculated for C10H14NOSe 244.0235;
Found 244.0231.
(rac)-O-(1-Phenylethyl) N,N-dimethylselenocarbamate (2q). 1-Phenylethan-1-ol (250 mg, 2.05 mmol) and NaH
(60 % in mineral oil, 180 mg, 4.50 mmol) in anhydrous THF (25 mL) were reacted with S-phenyl N,N-
dimethylthioselenocarbamate (500 mg, 2.05 mmol) following the general procedure. The product was isolated as
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a yellow oil (508 mg, 1.98 mmol, 97 %). H NMR (500 MHz, DMSO-d6, 25 °C): δ = 7.43 – 7.27 (m, 5H), 6.58 (q, J =
6.6 Hz, 1H), 3.37 (s, 3H), 3.16 (s, 3H), 1.57 (d, J = 6.6 Hz, 3H). 13C NMR (126 MHz, DMSO-d6, 25 °C): δ = 188.3 (d, JC–
= 235 Hz), 141.3, 128.4, 127.7, 126.0, 81.7, 44.6, 37.8, 22.4. 77Se NMR (57 MHz, CDCl3, 25° C) δ = 220.5. HRMS
Se
(ESI-TOF) m/z: [M+H]+ calculated for C11H16NOSe 258.0392; Found 258.0374.
O-(4-Bromobenzyl) N,N-dimethylselenocarbamate (2r). 4-Bromobenzyl alcohol (383 mg, 2.05 mmol) and NaH
(60 % in mineral oil, 180 mg, 4.50 mmol) in anhydrous THF (25 mL) were reacted with S-phenyl N,N-
dimethylthioselenocarbamate (500 mg, 2.05 mmol) following the general procedure. The product was isolated as
a yellow oil (585 mg, 1.82 mmol, 89 %). 1H NMR (500 MHz, DMSO-d6, 25 °C): δ = 7.58 (d, J = 8.4 Hz, 2H), 7.39 (d, J
= 8.4 Hz, 2H), 5.55 (s, 2H), 3.40 (s, 3H), 3.12 (s, 3H). 13C NMR (126 MHz, DMSO-d6, 25 °C): δ = 189.2 (d, JC–Se = 236
Hz), 135.4, 131.4, 130.0, 121.3, 74.3, 44.9, 37.9. 77Se NMR (57 MHz, CDCl3, 25° C) δ = 219.9. HRMS (ESI-TOF) m/z:
[M+H]+ calculated for C10H13BrNOSe 321.9337; Found 321.9341.
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S-(2-Methoxybenzyl) N,N-dimethylthiocarbamate (3a). O-(2-Methoxybenzyl) N,N-dimethylthiocarbamate (132
mg, 586 μmol) was dissolved in Ph2O (0.5 mL) and heated to 200 °C for 4 hours. The reaction mixture was cooled
to 25 °C and the title compound was isolated after column chromatography (SiO2, heptane to CH2Cl2) as a yellow
oil (63.4 mg, 281 μmol, 48 %). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.40 (dd, J = 7.5, 1.8 Hz, 1H), 7.23 (ddd, J = 8.1,
7.5, 1.8 Hz, 1H), 6.89 (td, J = 7.5, 1.1 Hz, 1H), 6.85 (dd, J = 8.1, 1.1 Hz, 1H), 4.19 (s, 2H), 3.86 (s, 3H), 2.98 (bs, 6H).
13C NMR (126 MHz, CDCl3, 25 °C): δ = 168.6, 157.5, 130.8, 128.7, 126.8, 120.7, 110.6, 55.7, 36.8 (2 × C), 29.7.
HRMS (ESI-TOF) m/z: [M+H]+ calculated for C11H16NO2S 226.0896; Found 226.0900.
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S-(3-Methoxybenzyl) N,N-dimethylthiocarbamate (3b). O-(3-Methoxybenzyl) N,N-dimethylthiocarbamate (210
mg, 932 μmol) was dissolved in Ph2O (1 mL) and heated to 200 °C for 20 hours. The reaction mixture was cooled
to 25 °C and the title compound was isolated after column chromatography (SiO2, heptane to CH2Cl2) as a yellow
oil (124 mg, 550 μmol, 59 %). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.21 (t, J = 7.9 Hz, 1H), 6.94 (dt, J = 7.9, 1.1 Hz,
1H), 6.91 (t, J = 2.3 Hz, 1H), 6.78 (ddd, J = 7.9, 2.3, 1.1 Hz, 1H), 4.14 (s, 2H), 3.80 (s, 3H), 3.00 (bs, 6H). 13C NMR
(126 MHz, CDCl3, 25 °C): δ = 167.9, 159.8, 140.0, 129.7, 121.4, 114.5, 112.9, 55.4, 36.9 (2 × C), 35.0. HRMS (ESI-
TOF) m/z: [M+H]+ calculated for C11H16NO2S 226.0896; Found 226.0895.
S-(4-Methoxybenzyl) N,N-dimethylthiocarbamate (3c). O-(4-Methoxybenzyl) N,N-dimethylthiocarbamate (100
mg, 444 μmol) was dissolved in Ph2O (5 mL) and heated to 200 °C for 2 hours. The reaction mixture was cooled to
25 °C and the title compound was isolated after column chromatography (SiO2, heptane to CH2Cl2) as a yellow oil
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(70.0 mg, 311 μmol, 70 %). H NMR (500 MHz, CDCl3, 25 °C): δ = 7.27 (d, J = 8.7 Hz, 2H), 6.83 (d, J = 8.7 Hz, 2H),
4.11 (s, 2H), 3.78 (s, 3H), 3.00 (bs, 6H). 13C NMR (126 MHz, CDCl3, 25 °C): δ = 168.1, 158.9, 130.5, 130.2, 114.1,
55.4, 36.8 (2 × C), 34.5. HRMS (ESI-TOF) m/z: [M+H]+ calculated for C11H16NO2S 226.0896; Found 226.0893.
S-(4-Methoxybenzyl) N,N-diethylthiocarbamate (3d). O-(4-Methoxybenzyl) N,N-diethylthiocarbamate (107 mg,
422 μmol) was dissolved in Ph2O (0.5 mL) and heated to 200 °C for 2 hours. The reaction mixture was cooled to 25
°C and the title compound was isolated after column chromatography (SiO2, heptane to CH2Cl2) as a light yellow
oil (64.1 mg, 253 μmol, 60 %). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.27 (d, J = 8.7 Hz, 2H), 6.83 (d, J = 8.7 Hz, 2H),
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4.11 (s, 2H), 3.78 (s, 3H), 3.37 (m, 4H), 1.16 (m, 6H). 13C NMR (126 MHz, CDCl3, 25 °C): δ = 167.0, 158.8, 130.4,
130.2, 114.1, 55.4, 42.3, 42.1, 34.2, 13.8, 13.4. HRMS (ESI-TOF) m/z: [M+H]+ calculated for C13H20NO2S 254.1209;
Found 254.1211.
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S-(4-Ethoxybenzyl) N,N-dimethylthiocarbamate (3e). O-(4-Ethoxybenzyl) N,N-dimethylthiocarbamate (168 mg,
702 μmol) was dissolved in Ph2O (1 mL) and heated to 200 °C for 2 hours. The reaction mixture was cooled to 25
°C and the title compound was isolated after column chromatography (SiO2, heptane to CH2Cl2) as a light yellow
oil (90.0 mg, 376 μmol, 54 %). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.26 (d, J = 8.6 Hz, 2H), 6.82 (d, J = 8.6 Hz, 2H),
4.11 (s, 2H), 4.00 (q, J = 7.0 Hz, 2H), 2.98 (bs, 6H), 1.39 (t, J = 7.0 Hz, 3H). 13C NMR (126 MHz, CDCl3, 25 °C): δ =
168.2, 158.2, 130.3, 130.2, 114.7, 63.6, 36.8 (2 × C), 34.5, 15.0. HRMS (ESI-TOF) m/z: [M+H]+ calculated for
C12H18NO2S 240.1053; Found 240.1052.
S-(4-Ethoxybenzyl) N,N-diethylthiocarbamate (3f). O-(4-Ethoxybenzyl) N,N-diethylthiocarbamate (78.8 mg, 295
μmol) was dissolved in Ph2O (0.5 mL) and heated to 200 °C for 2 hours. The reaction mixture was cooled to 25 °C
and the title compound was isolated after column chromatography (SiO2, heptane to CH2Cl2) as a light yellow oil
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(49.0 mg, 183 μmol, 62 %). H NMR (500 MHz, CDCl3, 25 °C): δ = 7.26 (d, J = 8.7 Hz, 2H), 6.82 (d, J = 8.7 Hz, 2H),
4.11 (s, 2H), 4.01 (q, J = 7.0 Hz, 2H), 3.37 (m, 4H), 1.39 (t, J = 7.0 Hz, 3H), 1.16 (m, 6H). 13C NMR (126 MHz, CDCl3,
25 °C): δ = 167.0, 158.2, 130.2, 130.2, 114.7, 63.6, 42.3, 42.0, 34.3, 15.0, 13.8, 13.4. HRMS (ESI-TOF) m/z: [M+H]+
calculated for C14H22NO2S 268.1366; Found 268.1365.
S-(4-Methylbenzyl) N,N-dimethylthiocarbamate (3g). O-(4-Methylbenzyl) N,N-dimethylthiocarbamate (144 mg,
688 μmol) was dissolved in Ph2O (3 mL) and heated to 200 °C for 19 hours. The reaction mixture was cooled to 25
°C and the title compound was isolated after column chromatography (SiO2, heptane to CH2Cl2) as a yellow oil
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(59.0 mg, 282 μmol, 41 %). H NMR (500 MHz, CDCl3, 25 °C): δ = 7.24 (d, J = 7.8 Hz, 2H), 7.11 (d, J = 7.8 Hz, 2H),
4.12 (s, 2H), 2.99 (bs, 6H), 2.32 (s, 3H). 13C NMR (126 MHz, CDCl3, 25 °C): δ = 168.1, 136.9, 135.4, 129.4, 129.0,
36.8 (2 × C), 34.7, 21.3. HRMS (ESI-TOF) m/z: [M+H]+ calculated for C11H16NOS 210.0947; Found 210.0951.
S-Benzyl N,N-dimethylthiocarbamate (3h). O-Benzyl N,N-dimethylthiocarbamate (133 mg, 681 μmol) was dis-
solved in Ph2O (1 mL) and heated to 200 °C for 22 hours. The reaction mixture was cooled to 25 °C and the title
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compound was isolated after column chromatography (SiO2, heptane to CH2Cl2) as a yellow oil (44.0 mg, 225
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μmol, 33 %). H NMR (500 MHz, CDCl3, 25 °C): δ = 7.38 – 7.27 (m, 4H), 7.25 – 7.21 (m, 1H), 4.16 (s, 2H), 3.00 (bs,
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6H). 13C NMR (126 MHz, CDCl3, 25 °C): δ = 168.0, 138.5, 129.1, 128.7, 127.2, 36.9 (2 × C), 35.0. HRMS (ESI-TOF)
m/z: [M+H]+ calculated for C10H14NOS 196.0791; Found 196.0788.
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S-(4-Chlorobenzyl) N,N-dimethylthiocarbamate (3k). O-(4-Chlorobenzyl) N,N-dimethylthiocarbamate (232 mg,
1.01 mmol) was dissolved in Ph2O (0.5 mL) and heated to 200 °C for 22 hours. The reaction mixture was cooled to
25 °C and the title compound was isolated after column chromatography (SiO2, heptane to CH2Cl2) as an orange
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solid (119 mg, 518 μmol, 51 %), mp. 40–41 °C. H NMR (500 MHz, CDCl3, 25 °C): δ = 7.32 – 7.23 (m, 4H), 4.11 (s,
2H), 2.99 (bs, 6H). 13C NMR (126 MHz, CDCl3, 25 °C): δ = 167.6, 137.3, 133.0, 130.4, 128.8, 36.9 (2 × C), 34.2. HRMS
(ESI-TOF) m/z: [M+H]+ calculated for C10H13ClNOS 230.0401; Found 230.0410.
S-(4-Bromobenzyl) N,N-dimethylthiocarbamate (3l). O-(4-Bromobenzyl) N,N-dimethylthiocarbamate (324 mg,
1.18 mmol) was dissolved in Ph2O (0.5 mL) and heated to 200 °C for 23 hours. The reaction mixture was cooled to
25 °C and the title compound was isolated after column chromatography (SiO2, heptane to CH2Cl2) as a light yel-
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low solid (190 mg, 693 μmol, 59 %), mp. 37–38 °C. H NMR (500 MHz, CDCl3, 25 °C): δ = 7.41 (d, J = 8.4 Hz, 2H),
7.23 (d, J = 8.4 Hz, 2H), 4.09 (s, 2H), 2.99 (bs, 6H). 13C NMR (126 MHz, CDCl3, 25 °C): δ = 167.6, 137.9, 131.7, 130.8,
121.1, 36.9 (2 × C), 34.3. HRMS (ESI-TOF) m/z: [M+H]+ calculated for C10H13BrNOS 273.9896; Found 273.9888.
S-(4-Carbomethoxybenzyl)
N,N-dimethylthiocarbamate
(3m).
O-(4-Carbomethoxybenzyl)
N,N-
dimethylthiocarbamate (176 mg, 695 μmol) was dissolved in Ph2O (0.5 mL) and heated to 200 °C for 23 hours. The
reaction mixture was cooled to 25 °C and the title compound was isolated after column chromatography (SiO2,
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heptane to CH2Cl2) as a yellow oil (118 mg, 466 μmol, 67 %). H NMR (500 MHz, CDCl3, 25 °C): δ = 7.96 (d, J = 8.0
Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 4.18 (s, 2H), 3.90 (s, 3H), 3.01 (bs, 6H). 13C NMR (126 MHz, CDCl3, 25 °C): δ = 167.4,
167.0, 144.1, 130.0, 129.4, 129.1, 52.2, 36.9 (2 × C), 34.6. HRMS (ESI-TOF) m/z: [M+H]+ calculated for C12H16NO3S
254.0845; Found 254.0855.
S-(4-Methoxybenzyl) N,N-dimethylselenocarbamate (3o). O-(4-Methoxybenzyl) N,N-dimethylselenocarbamate
(204 mg, 749 μmol) was dissolved in Ph2O (0.5 mL) and heated to 150 °C for 2.5 hours. The reaction mixture was
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cooled to 25 °C and the title compound was isolated after column chromatography (SiO2, heptane to CH2Cl2) as a
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yellow oil (179 mg, 659 μmol, 88 %). H NMR (500 MHz, CDCl3, 25 °C): δ = 7.27 (d, J = 8.7 Hz, 2H), 6.81 (d, J = 8.7
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Hz, 2H), 4.16 (s [d, 2JH–Se = 11.5 Hz], 2H), 3.78 (s, 3H), 3.04 (bs, 3H), 2.93 (bs, 3H). 13C NMR (126 MHz, CDCl3, 25 °C):
δ = 165.3 (d, JC–Se = 127 Hz), 158.5, 131.5, 130.0, 114.0, 55.3, 37.3, 36.7, 30.0 (d, JC–Se = 58.1 Hz). 77Se-NMR (57
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MHz, CDCl3, 25° C) δ = 464.4 (t, JSe–H = 11.5 Hz). HRMS (ESI-TOF) m/z: [M+Na]+ calculated for C11H15NNaO2Se
296.0160; Found 296.0157.
S-Benzyl N,N-dimethylselenocarbamate (3p). O-Benzyl N,N-dimethylselenocarbamate (200 mg, 826 μmol) was
dissolved in Ph2O (10 mL) and heated to 200 °C for 6 hours. The reaction mixture was cooled to 25 °C and the title
compound was isolated after dry column vacuum chromatography (SiO2, heptane to ethyl acetate with 4 % gradi-
ent) as a white solid (108 mg, 446 μmol, 54 %), mp. 55–56 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.37 – 7.17 (m,
5H), 4.20 (s [d, 2JH–Se = 11.4 Hz], 2H), 3.04 (bs, 3H), 2.94 (bs, 3H). 13C NMR (126 MHz, CDCl3, 25 °C): δ = 165.3 (d, JC–
= 126 Hz), 139.7, 129.1, 128.7, 127.0, 37.4, 36.9, 30.6 (d, JC–Se = 58.7 Hz). 77Se-NMR (57 MHz, CDCl3, 25° C) δ =
Se
464.3 (t, 2JSe–H = 11.4 Hz). HRMS (ESI-TOF) m/z: [M+H]+ calculated for C10H14NOSe 244.0235; Found 244.0237.
S-(4-Bromobenzyl) N,N-dimethylselenocarbamate (3r). O-(4-Bromobenzyl) N,N-dimethylselenocarbamate (200
mg, 623 μmol) was dissolved in Ph2O (10 mL) and heated to 200 °C for 4 hours. The reaction mixture was cooled
to 25 °C and the title compound was isolated after dry column vacuum chromatography (SiO2, heptane to ethyl
acetate with 4 % gradient) as a yellow oil (122 mg, 380 μmol, 61 %). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.38 (d, J
= 8.4 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 4.11 (s [d, JH–Se = 12.4 Hz], 2H), 3.03 (bs, 3H), 2.91 (bs, 3H). 13C NMR
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(126 MHz, CDCl3, 25 °C): δ = 164.7 (d, JC–Se = 125 Hz), 139.0, 131.7, 130.8, 120.7, 37.3, 36.9, 29.7 (d, JC–Se = 59.5 Hz).
77Se-NMR (57 MHz, CDCl3, 25° C) δ = 472.8 (t, JSe–H = 12.4 Hz). HRMS (ESI-TOF) m/z: [M+H]+ calculated for
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C10H13BrNOSe 321.9337; Found 321.9336.
Experimental procedures for the benzyl thiol and benzyl selenol
4-Methoxybenzenethiol (4c). A solution of S-(4-methoxybenzyl) N,N-dimethylthiocarbamate (53.0 mg, 235 μmol)
in 1.75 M KOH in degassed (N2, 30 minutes) MeOH:H2O (2:1 v/v, 10 mL) was stirred for 21 hours at 25 °C. The
mixture was cooled to 0 °C before concentrated HCl(aq) (3 mL) was added. A white precipitate was formed which
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