Catalytic Production of Isothiocyanates via a Mo(II)/Mo(IV) Cycle for the "soft" Sulfur Oxidation of Isonitriles

Article abstract of DOI:10.1021/acs.organomet.6b00302

In the presence of excess amounts of elemental sulfur, the dimolybdenum dinitrogen complex {CpMo[N(ⁱPr)C(Ph)N(ⁱPr)]}₂(μ-N₂) (4; Cp? = η⁵-C₅Me₅) serves as a precatalyst for the production of isothiocyanates from isonitriles via highly efficient and atom-economical metal-mediated sulfur atom transfer (SAT) under mild conditions. Mechanistic and structural studies support a catalytic cycle for SAT involving initial formation of a Mo(II) bis(isonitrile) complex that then undergoes sulfination to generate a formal "side-bound" Mo(IV) κ ²-(C,S)-isothiocyanate as the key intermediate. This metal-catalyzed SAT process has further been employed for the "on-demand" production of isothiocyanates that are trapped in situ by benzhydrazides to provide thiosemicarbazides, which are useful precursors to biologically active thiadiazoles.

Full text of DOI:10.1021/acs.organomet.6b00302

Article
pubs.acs.org/Organometallics
Catalytic Production of Isothiocyanates via a Mo(II)/Mo(IV) Cycle for
the “Soft” Sulfur Oxidation of Isonitriles
Wesley S. Farrell, Peter Y. Zavalij, and Lawrence R. Sita*
Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States
S
* Supporting Information
ABSTRACT: In the presence of excess amounts of elemental sulfur, the dimolybdenum
dinitrogen complex {Cp*Mo[N(iPr)C(Ph)N(iPr)]}2(μ-N2) (4; Cp* = η5-C5Me5) serves
as a precatalyst for the production of isothiocyanates from isonitriles via highly efficient and
atom-economical metal-mediated sulfur atom transfer (SAT) under mild conditions.
Mechanistic and structural studies support a catalytic cycle for SAT involving initial
formation of a Mo(II) bis(isonitrile) complex that then undergoes sulfination to generate a
formal “side-bound” Mo(IV) κ2-(C,S)-isothiocyanate as the key intermediate. This metal-
catalyzed SAT process has further been employed for the “on-demand” production of
isothiocyanates that are trapped in situ by benzhydrazides to provide thiosemicarbazides,
which are useful precursors to biologically active thiadiazoles.
have now reported the direct synthesis of ITCs through
sulfination of isonitriles (RNC) with S8 using either
transition-metal complexes or, in one example, selenium as a
catalyst.8−12 For transition-metal catalysts, elucidating the steric
and electronic requirements for key sulfur atom transfer (SAT)
processes between S8 and the RNC substrate can potentially
lead to more optimal reaction conditions (e.g., time and
temperature) and higher yields, as well as a larger range of ITCs
and products derived therefrom.
Previously, we have demonstrated that group 6 metal
complexes supported by the monocyclopentadienyl, mono-
amidinate (CPAM) ligand framework are capable of catalyzing
the production of organic isocyanates RNCO from
isonitriles through use of either nitrous oxide (N2O) or carbon
dioxide (CO2) via oxygen-atom transfer (OAT) or, alter-
natively, from organic azides (RN3) through nitrene group
transfer (NGT) to carbon monoxide (CO).13−15 In each case,
the overall catalytic cycle proceeds through a formal midvalent
M(II)/M(IV) redox couple. More recently, we extended these
studies to explore the possibility of developing SAT processes
that can be mediated by CPAM molybdenum complexes.
Gratifyingly, these studies led to the establishment of a
photocatalytic cycle for generation of carbonyl sulfide (S
CO, also known as COS) from CO and S8 under near-
ambient conditions.16 Notably, when the reactions were
conducted in the presence of primary amines, a variety of
symmetric 1,3-disubstituted ureas ((RNH)2CO) were obtained
in excellent yields, thereby validating this system for the “on-
demand” (in situ) generation of COS. Herein, we now report
the successful catalytic synthesis of several ITCs from S8 and
the corresponding isonitriles that proceeds under near-ambient
INTRODUCTION
■
One of the primary tenets of “green” chemistry is to develop
new atom-economical and energy-efficient industrial processes
that contribute to reducing the environmental impact
associated with production of commodity and fine chemicals.1
In this regard, organic isothiocyanates RNCS (ITCs) are a
valuable class of synthetic building blocks for the assembly of
more complex sulfur- and nitrogen-containing molecular
frameworks.2 Methyl isothiocyanate (MITC), which is the
most industrially significant member of this family, is produced
on the multikiloton scale through thermal rearrangement of
methyl thiocyanate, which is obtained itself through methyl-
ation of thiocyanate anion.2,3 Other alkyl and aryl isothiocya-
nates, however, have often been prepared through the
traditional route of reacting an amine with thiophosgene
(Cl2CS).4 In order to avoid use of the latter volatile and toxic
reagent, other synthetic methods have been developed that
involve a variety of different thiocarbonyl transfer reagents.5
Nonetheless, there still remains the need to develop new
synthetic routes to ITCs that (a) offer a broader scope of
functional group tolerance, (b) can be derived from inexpensive
and nontoxic starting materials, and (c) are suitable for being
employed for the “on-demand” in situ generation of ITCs as a
means by which to avoid the large-scale handling and storing of
these compounds, which are also known to pose serious health
and environmental risks. With respect to point b, elemental
sulfur (hereafter referred to as S8) is an intriguing raw material
to consider as a readily available feedstock. since the world’s
annual production is in excess of 70 million metric tons.6 Marks
and co-workers7 have also recently drawn attention to the use
of sulfur as a “soft” oxidant as a strategy for increasing the
selectivity of a chemical process in which more complex
product mixtures arise when molecular oxygen (O2) is
employed instead. Indeed, several groups of investigators
Received: April 14, 2016
© XXXX American Chemical Society
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conditions according to the proposed Mo(II)/Mo(IV) cycle of
Scheme 1, which is supported by the isolation and structural
isonitrile ligands are magnetically and, presumably, chemically
equivalent.19
As illustrated by the stacked plot of partial H NMR spectra
1
displayed in Figure 1, addition of excess equivalents of an
Scheme 1
characterization of key intermediates. Importantly, this catalytic
process is uninhibited by the presence of benzhydrazide
derivatives, which provides access to the one-pot synthesis of
several thiosemicarbazides in high yield through a similar on-
demand generation of ITCs. Thiosemicarbazides are, in turn,
important precursors to a range of biologically active
thiadiazoles.17
1
Figure 1. Partial H NMR (400 MHz, 50 °C, benzene-d6) spectra for
production of tBuNCS (singlet) from tBuNC (triplet) in the presence
of 2 (5 mol %, c = 8.3 mM) and excess S8. Spectra were recorded every
200 min and vertically displayed (t = 0 min at bottom) with a
horizontal offset of 0.02 ppm.
isonitrile and S8 to benzene-d6 solutions of 1−3 (generated in
situ from 4) led to steady generation of the corresponding
ITCs over time. For methyl and tert-butyl isonitrile (MeNC
RESULTS AND DISCUSSION
Catalyst Synthesis and SAT Reactions. As Scheme 2
reveals, the CPAM Mo(II) bis(isonitrile) complexes Cp*Mo-
■
t
and BuNC, respectively), this reaction occurred readily at
room temperature, and it was further accelerated upon heating
(cf. TOF = 1.2 h−1 at 50 °C for BuNC; Figure 1). In the case
t
Scheme 2
of 2,6-dimethylphenyl isonitrile, however, an elevated temper-
ature of 80 °C was essential to observe catalytic turnover.19
Importantly, these isonitrile sulfination reactions were found
to be unaffected by the use of solvents that had not been
previously dried by standard procedures, thereby demonstrating
a tolerance of the catalytic process to trace amounts of
moisture.
Mechanistic Investigations. Due to experimental diffi-
culties in establishing the exact nature of elemental sulfur
speciation and of intermediates that are involved, reports for
metal-mediated SAT processes are oftentimes sparse with
respect to mechanistic details.9,11 With these challenges in
mind, we undertook a series of investigations that would serve
to put the observed catalytic SAT process of Figure 1 onto a
firm mechanistic foundation. Thus, to begin, following the
course of isonitrile sulfination as catalyzed by the complexes 1−
3 showed, in each case, the appearance of only a single new
CPAM-based molybdenum complex. Fortunately, efforts to
structurally characterize this set of new species, hereafter
referred to as complexes 5−7, were successful. More
specifically, as Scheme 3 reveals, addition of S8 to benzene-d6
solutions of 1−3, in the absence of any additional isonitrile,
quantitatively generated previously observed 5−7 as deter-
[N(iPr)C(Ph)N(iPr)](CNR)2 (Cp* = η5-C5Me5; R = Me (1),
tBu (2), 2,6-(CH3)2C6H3 (3)) were conveniently prepared in
high yield through ligand substitution of dinitrogen (N2) in the
dinuclear dinitrogen complex {Cp*Mo[N(iPr)C(Ph)N-
(iPr)]}2(μ-η1:η1-N2) (4)18 by the corresponding isonitriles.19
A solid-state structural characterization of 1 (νCN 2086, 1767
cm−1), achieved through single-crystal X-ray analysis, revealed a
sharp geometric difference between the two methyl isocyanide
ligands, with one bound to the molybdenum center in a nearly
linear fashion and the other being distinctly nonlinearly ligated
(cf. Mo−C−N bond angles of 166.9(2) and 129.6(2)°,
respectively).19 A similar structural feature was previously
reported for a closely related structural analogue of 3,18 and
collectively, these solid-state data support the conclusion that
there exists a substantial degree of π back-bonding20 between
the metal center and the isonitrile ligands in 1−3. Finally, it can
1
mined by H NMR spectroscopy. Unfortunately, subsequent
attempts to isolate these compounds in pure form only resulted
in their decomposition. On the other hand, by switching to
toluene as the solvent, addition of S8 to a solution of 2
t
(generated in situ from 4 and 4 equiv of BuNC), followed by
1
be noted that, in solution, H NMR spectra support a Cs-
immediate removal of solids by filtration, layering the toluene
filtrate with pentane, and cooling to −30 °C, yielded single
symmetric structure for all three compounds in which the
B
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guide for thought, this study provided estimates for the
enthalpy and entropy of activations of ΔH⧧ = 17.8 kcal mol−1
and ΔS⧧ = −13.2 cal mol−1 K−1, respectively, and these values
correspond to a calculated ΔG⧧ = 22.3 kcal mol−1 at a
temperature of 298 K. The negative value for ΔS⧧ also implies
that a more highly ordered transition state for the rate-
determining step (RDS) in the catalytic cycle exists. Since 6 is
the only observed intermediate, one possible scenario is that
this RDS corresponds to a formal associative interchange (IA)
Scheme 3
mechanism22 in which coordination of BuNC to 6 proceeds
t
simultaneously with formal reductive elimination and release of
free BuNCS to regenerate 2.
crystals of compound 6 that were suitable for structure
t
determination by X-ray crystallography.16 Figure 2 presents
The overall proposed SAT catalytic cycle of Scheme 1
proceeds via a formal Mo(II)/Mo(IV) oxidation couple, and
this is in keeping with previous results obtained by us for
catalytic OAT chemistry mediated by similar CPAM group 6
complexes.13−15 It is interesting then to compare the
mechanism of Scheme 1 to that of Bargon and co-workers,11a
who have proposed a different catalytic cycle which is based on
a Mo(IV)/Mo(VI) oxidation couple to account for the
sulfination of isonitriles to ITCs that is mediated by the
Mo(IV) oxo bis(dithiocarbamate) Mo(O)[κ-(S,S)-S2CN(Et2)]2
(I). As proposed by these authors, a key intermediate in the
SAT cycle is reaction of I with S8 to produce the Mo(VI)
persulfido complex Mo(O)(η2-S2)[κ-(S,S)-S2CN(Et2)]2 (II),
which then transfers a sulfur atom to an isonitrile to produce
the Mo(VI) terminal sulfide Mo(O)(S)[κ-(S,S)-S2CN(Et2)]2
(III). Although III must ultimately cycle back to I through
reductive transfer of another sulfur atom to an isonitrile to
generate another 1 equiv of ITC, no mechanistic considerations
were provided to illuminate how this latter step might occur.
Intriguingly, we have also observed and isolated the CPAM
Mo(IV) carbonyl persulfido complex Cp*Mo[N(iPr)C(Ph)N-
(iPr)](CO)(η2-S2) (IV) and the dimolybdenum disulfide
{Cp*Mo[N(iPr)C(Ph)N(iPr)]}2(μ-S)2 (V), which are key
intermediates in the photocatalytic sulfination of CO by S8.16
However, in the present work, no evidence has yet been found
for the corresponding Mo(IV) isonitrile persulfido intermediate
Cp*Mo[N(iPr)C(Ph)N(iPr)](CNR)(η2-S2) (VI) or for the
intermediacy of V.23 Thus, although there are additional details
that could be filled in, the catalytic cycle of Scheme 1 is
attractive for its mechanistic simplicity with respect to sulfur
atom economy and a minimal number of formal metal
oxidation/reduction steps.
Figure 2. Molecular structure (30% thermal ellipsoids) of compound
6. Hydrogen atoms have been removed for the sake of clarity. Selected
bond lengths (Å) and angles (deg): Mo1−S1 2.4976(6), Mo1−C24
2.117(2), S1−C24 1.776(2), C24−N3 1.255(2), N3−C25 1.490(3),
Mo1−C29 2.050(2), C29−N4 1.168(3), N4−C30 1.455(3); S1−
C24−N3 136.91(18), Mo1−C24−N3 143.51(17), C24−N3−C25
125.8(2), Mo1−C29−N4 178.23(17), C29−N4−C30 159.5(2).
the solid-state molecular structure obtained from this analysis,
along with selected geometric parameters, that serve to
establish 6 as being the complex Cp*Mo[N(iPr)C(Ph)N(iPr)]-
(CNtBu)[κ-(S,C)-SCNtBu], depicted in Scheme 3. To the best
of our knowledge, 6 is not only a very rare example of a formal
“side-bound” κ-(S,C)-isothiocyanate transition-metal complex,
but it is the only one that has been obtained through the direct
sulfination of a metal-bound isonitrile ligand and the first to
involve a midvalent Mo(IV) center.21 On the basis of
One curious observation is that the intermediates involved in
the catalytic cycle of Scheme 1 also appear to be impervious to
a steady buildup in concentration of the ITC product, which a
priori one might have thought could productively compete for
coordination to Mo(II) centers. Indeed, as Scheme 4 reveals,
treatment of a toluene solution of 4 with excess amounts of
tBuNCS at the slightly elevated temperature of 65 °C provided
a good yield of the CPAM Mo(IV) dithiocarbonimidate
Cp*Mo[N(iPr)C(Ph)N(iPr)][κ-(S,S)-S2C-(NtBu)] (8) as an
orange crystalline material.19 The solid-state molecular
̀
similarities in NMR data and chemical reactivity, vis-a-vis the
catalytic conversion of RNC to RNCS with S8, it is reasonable
to assume that compounds 5 and 7 share the same structure as
6. Finally, it can be noted that, in solution, 5−7 all appear to
engage in structural dynamics that give rise to a time-averaged
Cs-symmetric molecular structure.19
Additional insight regarding the most probable mechanism
for the sulfination of isonitriles as catalyzed by 1−3 was
1
obtained by a variable-temperature H NMR Eyring analysis
Scheme 4
t
employing 2 as the catalyst for the conversion of BuNC to
tBuNCS under pseudo-first-order conditions with respect to
S8.19 We recognize from the outset that results obtained from
such a study are less than ideal since the exact speciation and
concentration of sulfur in solution, as well as the nature of the
intermediate involved in the intimate transfer of a single sulfur
atom from elemental sulfur to 2, are not known. However, as a
C
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structure of 8 as determined by single-crystal X-ray analysis is
presented in Figure 3, for which the geometric bond length
Table 1. Synthesis of Thiosemicarbazides via in Situ
Generation of Isothiocyanates According to Scheme 5
R1
R2
yield (%)
R1
R2
yield (%)
a
H
Me
tBu
76
69
88
96
97
Me
Ar
95
82
80
91
H
OMe
OMe
OMe
Me
tBu
a
H
Ar
a
Me
Me
Me
tBu
Ar
a
Ar = 2,6-(CH3)2C6H3.
be competent for the analogous production of thiosemicarba-
zides from acyl hydrazides.
CONCLUSIONS
■
In conclusion, the present report serves to establish a new class
of earth-abundant transition-metal catalysts that can be used to
take advantage of inexpensive and abundant elemental sulfur
for the production of synthetically useful ITC compounds.
Through spectroscopic analyses and the isolation and structural
characterization of a key catalytic intermediate, support for the
proposed Mo(II)/Mo(IV) mechanism of Scheme 1 is
presented. Additional studies are currently in progress to
extend the catalytic utility of CPAM group 6 metal complexes.
Figure 3. Molecular structure (30% thermal ellipsoids) of compound
8. Hydrogen atoms have been removed for the sake of clarity. Selected
bond lengths (Å) and angles (deg): Mo1−S1 2.3694(4), Mo1−S2
2.3763(3), S1−C24 1.7963(12), S2−C24 1.7823(12), C24−N3
1.2631(15), N3−C25 1.4850(16); S1−C24−N3 133.89(9), S2−
C24−N3 122.78(9), C24−N3−C25 123.26(10).
EXPERIMENTAL SECTION
values (Å) associated with the κ-(S,S)-S2CNtBu fragment are as
follows: Mo1−S1, 2.3694(4); Mo1−S2, 2.3763(3); S1−C24,
1.7832(12); S2−C24, 1.7963(12); C24−N3, 1.2631(15).24 On
the basis of literature precedent, the most likely mechanism for
formation of 8 involves SAT from initial coordination of
tBuNCS to a Mo(II) center to form a transient formal Mo(IV)
■
General Considerations. All manipulations with air- and
moisture-sensitive compounds were carried out under N2 or Ar
atmospheres using standard Schlenk or glovebox techniques. Et2O and
THF were dried over Na/benzophenone and distilled under N2 prior
to use. Toluene and pentane were dried and deoxygenated by passage
over activated alumina and GetterMax 135 catalyst (purchased from
Research Catalysts, Inc.) and collected under N2 prior to use. Benzene-
d6 was dried over Na/K alloy and isolated by vacuum transfer prior to
use, except when otherwise stated. Celite was oven-dried (150 °C for
several days) before use in the glovebox. Cooling was performed in the
internal freezer of a glovebox maintained at −30 °C. tert-Butyl
isonitrile was purchased from Sigma-Aldrich and degassed by three
“freeze−pump−thaw” cycles prior to use. tert-Butyl isothiocyanate was
dried over CaH2 and isolated by vacuum transfer prior to use. 2,6-
Dimethylphenyl isonitrile, methyl triflate, and all benzhydrazides were
purchased from Sigma-Aldrich and used as received. Elemental sulfur
was purchased from Fischer Scientific and used as received. Methyl
isonitrile27 and compound 418 were prepared according to the
literature in similar yield and purity. 1H NMR spectra were recorded at
400 or 500 MHz. 13C NMR spectra were recorded at 125 MHz.
Elemental analyses were carried out by Midwest Microlab LLC.
Cp*Mo[N(iPr)C(Ph)N(iPr)](CNCH3)2 (1). Methyl isonitrile (0.01
mL, 0.19 mmol) was added via microsyringe to a solution of 4 (0.038
g, 0.04 mmol) in 3 mL of toluene at room temperature. The resulting
red solution was stirred for 1 h, at which point volatiles were removed
in vacuo. The resulting red solid was extracted into pentane and
filtered through a pad of Celite, the volume was reduced in vacuo, and
the resulting solution was cooled to −30 °C overnight, furnishing red
crystals of 1 (0.037 g, yield 85%). Data for 1 are as follows. Anal. Calcd
for C27H40N4Mo: C, 62.76; N, 7.81; H, 10.85. Found: C, 63.09; N,
7.57; H, 10.79. 1H NMR (400 MHz, benzene-d6): 1.07 [6H, d, J = 6.4
Hz, CH(CH3)2], 1.15 [6H, d, J = 6.4 Hz, CH(CH3)2], 1.95 [15H, s,
C5(CH3)5], 3.41 (6H, s, CNCH3), 3.55 [2H, sp, J = 6.4 Hz,
CH(CH3)2], 7.05 (2H, m, C6H5), 7.16 (2H, m, C6H5), 7.23 (1H, d, J
= 7.4 Hz, C6H5). IR (KBr) νCN 2086, 1767 cm−1.
t
terminal sulfide through elimination of BuNC, followed by
t
trapping of this metal sulfide with another 1 equiv of BuNCS
to form the final thermodynamically stable dithiocarbonimidate
product.25 Thus, the fact that 8 is never observed during
t
t
conversion of BuNC and S8 to BuNCS strongly suggests the
absence of competing SAT processes involving the ITC
product that might lead to CPAM MoIV(S) intermediates
during catalysis.
“On-Demand” ITC Production. Given the known
potential hazards of working with isolated quantities of ITCs,
we next sought to apply the new catalytic SAT process for
preparative-scale synthetic purposes. In this regard, trapping of
the ITC intermediate through addition of a benzhydrazide to
form a thiosemicarbazide product according to Scheme 5 is a
Scheme 5
very attractive target.26 Gratifyingly, as Scheme 5 and Table 1
reveal, in refluxing THF, compound 4 is indeed capable of
serving as an efficient precatalyst for the desired coupling
chemistry to provide a number of thiosemicarbazides in
excellent yields.19 Finally, it is important to note that, while it
has been recently reported that thioureas (R1NH)C(S)(NHR2)
can be conveniently synthesized directly by heating a mixture of
elemental sulfur, an amine (R1NH2), and an isonitrile
(R2NC),10d in our hands, this procedure does not appear to
Cp*Mo[N(iPr)C(Ph)N(iPr)](CNtBu)(η2-SCNtBu) (6). To a solution
of 2 (0.06 mmol generated in situ) in 2 mL of toluene was added S8
(0.014 g, 0.06 mmol) at room temperature. The resulting red solution
was stirred for 10 min, at which point solids were removed by filtration
through Celite and volatiles were removed in vacuo to leave a red oil,
which was analyzed by 1H NMR (confirming it to be analogous to the
D
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catalyst resting state; see the Supporting Information). Crystalline 6
was obtained cooling a toluene solution to −30 °C and then layering
pentane on top to diffuse in to yield single crystals suitable for X-ray
analysis (vide infra). Due to its instability, larger amounts of crystalline
material suitable for further analysis of 6 could not be obtained by this
procedure.
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Cp*Mo[N(iPr)C(Ph)N(iPr)](κ-(S,S)-S2CNtBu) (8). To a solution of
4 (0.042 g, 0.05 mmol) in 10 mL of toluene in a 100 mL Schlenk tube
was added tert-butyl isothiocyanate (0.06 mL, 0.47 mmol). The tube
was sealed, and the solution was stirred at 65 °C for 3 days, at which
point volatiles were removed in vacuo. The resulting orange-red oil
was extracted in pentane, filtered through Celite, concentrated, and
cooled to −30 °C to yield orange-red crystals of 8 (0.028 g, 52%
yield). Data for 8 are as follows. Anal. Calcd for C28H43N3S2Mo: C,
1
57.81; N, 7.23; H, 7.46. Found: C, 58.17; N, 7.29; H, 7.39. H NMR
(400 MHz, benzene-d6): 0.93 [3H, d, J = 6.4 Hz, CH(CH3)2], 0.95
[3H, d, J = 6.4 Hz, CH(CH3)2], 1.27 [3H, d, J = 6.4 Hz, CH(CH3)2],
1.27 [3H, d, J = 6.4 Hz, CH(CH3)2], 1.83 [15H, s, C5(CH3)5], 1.84
[9H, s, S2CNC(CH3)3], 3.37 [1H, sp, J = 6.4 Hz, CH(CH3)2], 3.38
[1H, sp, J = 6.4 Hz, CH(CH3)2], 6.94 (4H, m, C6H5), 7.11 (1H, m,
C6H5).
Variable-Temperature NMR Experiments. A representative
procedure is given. In a J. Young NMR tube equipped with a Teflon
valve was added 0.6 mL of benzene-d6 solution consisting of 2
(prepared in situ) (8.6 mM, 5 μmol), tert-butyl isonitrile (171.6 mM,
103 μmol), and durene internal standard (35.9 mM, 22 μmol). S8
(0.026 g, 102 μmol) was added, and the tube was quickly placed into
the NMR probe, which was pre-equilibrated to 50 °C. NMR spectra
were recorded every 10 min until all tert-butyl isonitrile was consumed.
The concentration of tert-butyl isothiocyanate was plotted versus time
and fit with a first-order polynomial, affording the initial rate constant
as the slope.
Synthesis of Thiosemicarbazides through “On-Demand”
Generation of Isothiocyanates. A representative procedure is
given. In 3 mL of THF, 2 (8 μmol) was generated in situ through
addition of 44 equiv of tert-butyl isonitrile (20 μL, 0.177 μmol) with
respect to to 4 (0.004 g, 0.004 μmol). After 30 min, excess S8 (0.040 g,
0.155 μmol) and p-tolylbenzhydrazide (0.020 g, 0.131 μmol) were
added with an additional 5 mL of THF. The solution was heated to 85
°C in a sealed Schlenk tube for 16 h, after which volatiles were
removed in vacuo. The organic product was extracted into ethyl
acetate and then washed with 1 M HCl and 1 M KCl. The organic
layer was isolated and passed through a pad of silica gel supported by a
Kimwipe within a glass pipet. Volatiles were removed in vacuo to
furnish 1-(p-tolylbenzoyl)-4-tert-butylthiosemicarbazide as brown
crystals (0.032 g, 97% yield). Characterization (1H NMR, 13C{1H}
NMR, and ESI-MS) data and yields are provided in the Supporting
Information for all thiosemicarbazides.19
ASSOCIATED CONTENT
* Supporting Information
■
S
(12) For non-metal-catalyzed syntheses of ITCs using S8 and RNC,
see: (a) Fujiwara, S.; Shin-Ike, T. Tetrahedron Lett. 1991, 32, 3503−
3506. (b) Nishikawa, K.; Umezawa, T.; Garson, M. J.; Matsuda, F. J.
Nat. Prod. 2012, 75, 2232−2235.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.6b00302.
Supporting spectra, characterization data, and crystal data
(PDF)
Crystallographic data (CIF)
(13) Yonke, B. L.; Reeds, J. P.; Zavalij, P. Y.; Sita, L. R. Angew. Chem.,
Int. Ed. 2011, 50, 12342−12346.
(14) Reeds, J. P.; Yonke, B. L.; Zavalij, P. Y.; Sita, L. R. J. Am. Chem.
Soc. 2011, 133, 18602−18605.
(15) Yonke, B. L.; Reeds, J. P.; Fontaine, P. P.; Zavalij, P. Y.; Sita, L.
R. Organometallics 2014, 33, 3239−3242.
AUTHOR INFORMATION
Corresponding Author
*E-mail for L.R.S.: lsita@umd.edu.
■
(16) Farrell, W. S.; Zavalij, P. Y.; Sita, L. R. Angew. Chem., Int. Ed.
2015, 54, 4269−4273.
(17) Mukerjee, A. K.; Ashare, R. Chem. Rev. 1991, 91, 1−24.
(18) Fontaine, P. P.; Yonke, B. L.; Zavalij, P. Y.; Sita, L. R. J. Am.
Chem. Soc. 2010, 132, 12273−12285.
Notes
The authors declare no competing financial interest.
(19) Details are provided in the Supporting Information.
(20) (a) Pombeiro, A. J. L.; Chatt, J.; Richards, R. L. J. Organomet.
Chem. 1980, 190, 297−304. (b) Morsing, T. J.; Bendix, J. J. Mol. Struct.
2013, 1039, 107−112.
ACKNOWLEDGMENTS
We thank the National Science Foundation (CHE-1361716)
for financial support of this work.
■
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DOI: 10.1021/acs.organomet.6b00302
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