Kinetic and thermodynamic evaluation of the reversible N-heterocyclic carbene-isothiocyanate coupling reaction: Applications in latent catalysis

Article abstract of DOI:10.1021/jo101850g

Using stopped flow and other spectroscopic techniques, the thermodynamic parameters of the coupling reaction between 1,3-dimesitylimidazolylidene and phenyl isothiocyanate were determined (H^o = -96.1 kJ mol^-1 and ΔS^o = -39.6 J mol^-1 K^-1). On the basis of these data which indicated that the reaction was reversible (K _eq = 5.94 × 10¹⁴ M^-1 at 25 °C; k _f = 252 M^-1 s^-1; k_r = 4.24 × 10^-13 s^-1), the adduct formed from the two aforementioned coupling partners was used as a latent catalyst to facilitate the [2 + 2 + 2] cyclotrimerization of phenyl isocyanate and the polymerization of dl-lactide.

Full text of DOI:10.1021/jo101850g

pubs.acs.org/joc
Contemporary efforts have been directed toward the devel-
Kinetic and Thermodynamic Evaluation of the
Reversible N-Heterocyclic Carbene-Isothiocyanate
Coupling Reaction: Applications in Latent Catalysis
opment of latent catalysts that generate N-heterocyclic
carbenes (NHCs).2 NHCs are a diverse class of reactive species
that are known to catalyze numerous reactions,3 including
the [2 þ 2 þ 2] cyclotrimerization of isocyanates4 and the
polymerization of lactide and other monomers.5 Previous
reports of using NHC adducts as latent catalysts generally
contain either transition metals or carbon dioxide.6,7 While
these adducts are effective, only the NHC component may be
altered to tune the activation temperature, which can influ-
ence the reactivity of the carbene catalyst generated. To
expand the utilities of latent catalysts involving NHCs and to
access adducts which do not involve transition metals, there is
a need to develop other organic coupling partners that rever-
sibly react with NHCs.
Brent C. Norris, Daniel G. Sheppard, Graeme Henkelman,
and Christopher W. Bielawski*
Department of Chemistry and Biochemistry, The University of
Texas at Austin, 1 University Station, A5300, Austin,
Texas 78712, United States
bielawski@cm.utexas.edu
Received September 19, 2010
Recently, we discovered8 that the reaction9,10 between
NHCs and isothiocyanates is thermally reversible and demon-
strated that appropriately functionalized ditopic derivatives
may be used to prepare structurally dynamic polymers. More-
over, we found that the reversibility of the reaction depended
on the structure and electronic properties of the coupling
partners. Building on these results, we reasoned that NHC-
isothiocyanate adducts may find utility as latent catalysts,
and we describe our efforts toward achieving that goal herein.
Since the thermodynamic parameters of the NHC-
isothiocyanate coupling reaction are essential to predicting the
concentration of the carbene catalyst that may ultimately be
generated upon activation, initial efforts were directed toward
studying a reaction involving two prototypical substrates:
1,3-dimesitylimidazolylidene (1) and phenyl isothiocyanate (2).
Using stopped flow and other spectroscopic techniques,
the thermodynamic parameters of the coupling reaction
between 1,3-dimesitylimidazolylidene and phenyl iso-
thiocyanate were determined (Ho = -96.1 kJ mol-1 and
ΔSo = -39.6 J mol-1 K-1). On the basis of these data
which indicated that the reaction was reversible (Keq
=
5.94 ꢀ 1014 M-1 at 25 °C; kf = 252 M-1 s-1; kr = 4.24 ꢀ
10-13 s-1), the adduct formed from the two aforemen-
tioned coupling partners was used as a latent catalyst to
facilitate the [2 þ 2 þ 2] cyclotrimerization of phenyl
isocyanate and the polymerization of DL-lactide.
(3) For excellent reviews on the utilities of NHCs as organocatalysts, see:
(a) Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007, 107, 5606–5655.
ꢀ
´
ez-Gonzalez, S.; Nolan, S. P. Angew. Chem., Int. Ed. 2007,
(b) Marion, N.; Dı
46, 2988–3000.
(4) Duong, H. A.; Cross, M. J.; Louie, J. Org. Lett. 2004, 6, 4679–4681.
€
(5) (a) Connor, E. F.; Nyce, G. W.; Myers, M.; Mock, A.; Hedrick, J. L.
J. Am. Chem. Soc. 2002, 124, 914–915. (b) Culkin, D. A.; Jeong, W.; Csihony,
S.; Gomez, E. D.; Hedrick, J. L.; Balsara, N. P.; Waymouth, R. M. Angew.
Chem., Int. Ed. 2007, 46, 2627–2630. (c) Raynaud, J.; Absalon, C.; Gnanou,
Y.; Taton, D. J. Am. Chem. Soc. 2009, 131, 3201–3209. (d) Lohmeijer,
B. G. G.; Dubois, G.; Leibfarth, F.; Pratt, R. C.; Nederberg, F.; Nelson, A.;
Waymouth, R. M.; Wade, C.; Hedrick, J. L. Org. Lett. 2006, 8, 4683–4686.
(6) (a) Van Ausdall, B. R.; Glass, J. L.; Wiggins, K. M.; Aarif, A. M.;
Louie, J. J. Org. Chem. 2009, 74, 7935–7942. (b) Duong, H. A.; Tekavec,
T. N.; Arif, A. M.; Louie, J. Chem. Commun. 2004, 112–113.
Latent catalysts are generally inert under ambient conditions
but become activated upon the application of an external
stimulus, such as heat or light. They have found utility in a
broad range of applications, including adhesives, photo-
resists (i.e., Novolac), and packaging for “flip chip” circuits.1
(7) For examples of using NHC-CO2 adducts as precursors to metal
complexes, see: (a) Voutchkova, A. M.; Appelhans, L. N.; Chianese, A. R.;
Crabtree, R. H. J. Am. Chem. Soc. 2005, 127, 17624–17625. (b) Tudose, A.;
Demonceau, A.; Delaude, L. J. Organomet. Chem. 2006, 691, 5356–5365.
(c) Sauvage, X.; Demonceau, A.; Delaude, L. Adv. Synth. Catal. 2009, 351,
2031–2038. For examples of using NHC-CO2 adducts as latent catalysts for
the synthesis of cyclic carbonates, see: (d) Zhou, H.; Zhang, W.-Z.; Liu,
C.-H.; Qu, J.-P.; Lu, X.-B. J. Org. Chem. 2008, 73, 8039–8044.
(1) (a) Smith, J. D. B. In Epoxy Resin Chemistry; Bauer, R. S., Ed.;
American Chemical Society: Washington, DC, 1978; Chapter 3. (b) Pappas,
S. P.; Hill, L. W. J. Coat. Technol. 1981, 53, 43–51. (c) Muizebelt, M. J.
J. Coat. Technol. 1985, 57, 43–44. (d) Endo, T.; Sanda, F. Macromol. Symp.
1996, 107, 237–238.
€
(2) (a) Nyce, G. W.; Glauser, T.; Connor, E. F.; Mock, A.; Waymouth,
R. M.; Hedrick, J. L. J. Am. Chem. Soc. 2003, 125, 3046–3056. (b) Nyce,
G. W.; Csihony, S.; Waymouth, R. M.; Hedrick, J. L. Chem. Eur. J. 2004,
(8) Norris, B. C.; Bielawski, C. W. Macromolecules 2010, 43, 3591–3593.
(9) The products obtained from NHC-isothiocyanate coupling have
been shown to engage in 1,3-dipolar additions with alkynes and arynes,
see: (a) Liu, M.-F.; Wang, B.; Cheng, Y. Chem Commun. 2006, 1215–1217.
(b) Zhu, Q.; Liu, M.-F.; Bo, W.; Cheng, Y. Org. Biomol. Chem. 2007, 5, 1282–
1286. (c) Li, J.-Q.; Liao, R.-Z.; Ding, W.-J.; Cheng, Y. J. Org. Chem. 2007,
72, 6266–6269. (d) Cheng, Y.; Liu, M.-F.; Fang, D.-C.; Lei, X.-M. Chem.
;
Eur. J. 2007, 13, 4282–4292. (e) Xue, J.; Yang, Y.; Huang, X. Synlett 2007,
1533–1536.
(10) For early examples of using NHC-isothiocyanate adducts in 1,3-
dipolar cycloaddition reactions, see: (a) Winberg, H. E.; Coffman, D. D.
€
J. Am. Chem. Soc. 1965, 2776–2777. (b) Regitz, M.; Hocker, J.; Schossler,
W.; Weber, B.; Liedhegener, A. Liebigs Ann. Chem. 1971, 748, 1–19.
;
10, 4073–4079. (c) Csihony, S.; Culkin, D. A.; Sentman, A. C.; Dove, A. P.;
Waymouth, R. M.; Hedrick, J. L. J. Am. Chem. Soc. 2005, 127, 9079–9084.
(d) Coulembier, O.; Dove, A. P.; Pratt, R. C.; Sentman, A. C.; Culkin, D. A.;
Mespouille, L.; Dubois, P.; Waymouth, R. M.; Hedrick, J. L. Angew. Chem.,
Int. Ed. 2005, 44, 4964–4968. (e) Coulembier, O.; Lohmeijer, B. G. G.; Dove,
A. P.; Pratt, R. C.; Mespouille, L.; Culkin, D. A.; Benight, S. J.; Dubois, P.;
Waymouth, R. M.; Hedrick, J. L. Macromolecules 2006, 39, 5617–5628.
(f) Arnold, P. L.; Casely, I. J.; Turner, Z. R.; Bellabarba, R.; Tooze, R. B.
Dalton Trans. 2009, 7236–7247. (g) Bantu, B.; Pawar, G. M.; Wurst, K.;
Decker, U.; Schmidt, A. M.; Buchmeiser, M. R. Eur. J. Inorg. Chem. 2009,
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;
DOI: 10.1021/jo101850g
r
Published on Web 12/01/2010
J. Org. Chem. 2011, 76, 301–304 301
2010 American Chemical Society

Norris et al.
JOCNote
FIGURE 1. (Left) Plot of ln kf versus 1/T for the reaction shown
in eq 1. The best-fit line can be described by the equation: y =
-2795.2x þ 14.903 (R2 = 0.995). (Right) Plot of ln kr versus 1/T
for the reaction shown in eq 2. The best-fit line can be described by
the equation: y=-14356x þ 19.661 (R2 =0.997). The data shown
are the average of three separate experiments performed for each
temperature analyzed.
FIGURE 2. NHC-PhNCS adduct 3 facilitated the (top) [2 þ 2 þ 2]
cyclotrimerization of phenyl isocyanate and the (bottom) ring-opening
polymerization of DL-lactide.
and reverse reactions described above. From these data,
the activation energies (Ea) were determined for eqs 1 and 2
using the Arrhenius equation: Ea (eq 1) = 23 kJ mol-1 K-1
and Ea (eq 2) = 119 kJ mol-1 K-1. The kinetics data also
facilitated the determination of the Keq for the reaction of 1
with 2. For example, at 25 °C, the Keq=5.94ꢀ1014 M-1 (kf=
252 M-1 s-1, kr = 4.24 ꢀ 10-13 s-1). Using these data, the
thermodynamic parameters of the reaction were also calculated:
ΔHo =-96.1 kJ mol-1 and ΔSo =-39.6 J mol-1 K-1. The
experimentally measured ΔHo was in reasonable agreement
Preliminary efforts attempted to measure the equilibrium
constant (Keq) between these reagents and their respective
adduct (3) using 1H NMR spectroscopy. However, analysis
of a dilute DMF-d7 solution of 3 ([3]0=70 mM) did not show
the presence of 1 or 2, even at elevated temperatures (120 °C),
which suggested to us that the reaction between 1 and 2 is
highly favored. As such, the equilibrium constant (Keq) was
determined by measuring the rates of the forward (kf) and
reverse (kr) reactions over a range of temperatures and using
the equation Keq = kf/kr.
with the ΔHo predicted from DFT calculations (-111 kJ mol-1
)
(see ESI).13
The forward rate kf was measured by combining toluene
solutions 1 and 2 in a stopped flow reactor, and the concen-
tration of the product 3was measured by continuously monitor-
ing the absorbance signal at λmax=350 nm over time. By
varying the initial concentrations of the starting materials,
the reaction was determined to be first order with respect to
both the free NHC as well as the isothiocyanate (Figures S1
and S2, Supporting Information). Under pseudo-first-order
kinetics conditions, where an excess of 1 (22 equiv) was
employed, the kf was measured over a range of temperatures
(9.9-55 °C); a summary of the data is shown in Figure 1 (left).
The reverse rate kr was also determined over a range of
temperatures (90-120 °C)11 by monitoring toluene solutions
of 3 in the presence of excess sulfur (2.0 equiv), which reacts
irreversibly with 112 to form a known12a thiourea. Aliquots
were periodically removed from the aforementioned solu-
tions, separated via high performance liquid chromatogra-
phy (HPLC; conditions: methanol as eluent, 25 °C), and then
analyzed by UV/vis spectroscopy (λ = 350 nm); a summary
of the data are shown in Figure 1 (right). The reaction was deter-
mined to be first order with respect to the starting material 3
and zero order with respect to sulfur (Figures S3 and S4,
Supporting Information). These results suggested to us that
the dissociation of NHC-isothiocyanate adduct was the
rate-determining step and that the sulfur effectively trapped
the NHC generated in situ without facilitating dissociation.
As shown in Figure 1, linear correlations between the ln k
and the inverse temperature were observed for the forward
Once the kinetic and thermodynamic parameters for afore-
mentioned NHC-isothiocyanate coupling reaction were deter-
mined, our efforts shifted toward exploring the potential
of using 3 as a latent catalyst to facilitate [2 þ 2 þ 2] cyclo-
trimerization reactions. As summarized in Figure 2 (top),
heating a toluene solution of phenyl isocyanate (initial
concentration = 0.42 M) and 3 (20 mol %) at 120 °C for
24 h afforded phenyl isocyanurate in 82% isolated yield after
purification via column chromatography.14 To support the
notion that a catalytically active NHC (i.e., 1) was generated
during the aforementioned reaction, a series of control
(13) DFT calculations were performed using the Perdew-Wang-91 general-
ized-gradient approximation functional. Valence electrons were described with a
plane wave basis set up to a cutoff energy of 250 eV. Frozen core states were
described by pseudopotentials using the projector-augmented wave framework,
as implemented in the VASP code. See: (a) Kresse, G.; Hafner, J. Phys. Rev. B
1993, 47, 558–561. (b) Kresse, G.; Hafner, J. Phys. Rev. B 1994, 49, 14251–14269.
(f) Perdew, J. P. In Electronic Structure of Solids; Ziesche, P., Eschrig, H., Eds.;
Akademie Verlag: Berlin, 1991. (c) Blochl, P. E. Phys. Rev. B 1994, 50, 17953–
17979. (d) Kresse, G.; Furthmuller, J. Comput. Mater. Sci. 1996, 6, 1–50.
(e) Kresse, G.; Furthmuller, , J. Phys. Rev. B 1996, 54, 11169–11186.
(11) The forward reaction (i.e., eq 1) was measured at the full temperature
range of the stopped flow detector (9.9-55 °C). However, the reverse reaction
(i.e., eq 2) was found to be too slow to achieve good kinetic data at these
temperatures, and therefore was studied over the range of 90-120 °C.
(12) (a) Huang, J.; Schanz, H.-J.; Stevens, E. D.; Nolan, S. P.; Capps,
K. B.; Bauer, A.; Hoff, C. D. Inorg. Chem. 2000, 39, 1042–1045. (b) Ramnial,
T.; Taylor, S. A.; Bender, M. L.; Gorodetsky, B.; Lee, P. T. K.; Dickie, D. A.;
McCollum, B. M.; Pye, C. C.; Walsby, C. J.; Clyburne, J. A. C. J. Org. Chem.
2008, 73, 801–812.
(14) Using the data shown in Figure 1, the concentration of 1 at 120 °C
(Keq = 5.09ꢀ 1010 M-1; kf = 2.43 ꢀ 103 M-1 s-1, kr = 4.79 ꢀ 10-8 s-1) was
calculated to be approximately 2 orders of magnitude higher than at 25 °C.
302 J. Org. Chem. Vol. 76, No. 1, 2011

Norris et al.
JOCNote
a polymeric material of comparable molecular weight
(Mn = 3.1 kDa) as described above.
Finally, efforts were directed toward determining if the
identity of the isothiocyanate component of a NHC-
isothiocyanate adduct would influence its activation tem-
perature. Adducts 3-7 (Figure 3, top) were selected for study
because they feature a range of electron-rich and/or bulky
aryl isothiocyanate moieties. These differences were expected
to effect the adduct dissociation process and facilitate cata-
lyst activation at different temperatures. After the synthe-
sis of 3-7, toluene solutions of these adducts (0.05 mol %)
with phenyl isocyanate and cyclooctane as an internal stan-
dard were independently prepared and divided into several
ampules. Following heating at various temperatures for 2 h
to facilitate catalyst activation, the ampules were allowed to
stand at ambient temperature for 8 h to enable the [2þ2þ2]
cyclotrimerization reaction to proceed. Afterward, the am-
pules were opened, and the conversion of phenyl isocyanate
to phenyl isocyanurate was measured via IR spectroscopy
(CH2Cl2) by comparing the integrated signal attributed to
product (υCO = 1700 cm-1) to that assigned to cyclooctane
(υCH = 2845 and 2915 cm-1).
As summarized in Figure 3 (bottom), the activation tem-
perature of the adducts studied appeared to be more dependent
on the electronic properties of the isothiocyanate component
than sterics. The methoxy derivative 6, for example, consist-
ently afforded higher percent conversions of phenyl isocyanate
to phenyl isocyanurate over the range of temperatures and
reaction times studied.18 Surprisingly, 5 appeared to activate
more readily than 3 or 4, which suggested to us that the
NHC-isothiocyanate adducts may require the adoption of
a specific conformation that is aided by electron-donating
groups to dissociate. Although other trends were not apparent,
the data obtained indicated that the catalyst activation
process was dependent on the identity of the isothiocyanate
component of the respective adducts.
In summary, the kinetic and thermodynamic parameters
of the coupling reaction between 1,3-dimesitylimidazolylidene
and phenyl isothiocyanate were evaluated. The reaction was
determined to be reversible, and the adduct formed from the
two aforementioned coupling partners was used as a latent
catalyst to facilitate the [2 þ 2 þ 2] cyclotrimerization of
phenyl isocyanate and the polymerization of DL-lactide.
Furthermore, it was found that the catalyst activation tem-
perature may be modified by varying the structure and elec-
tronic properties of the isothiocyanate component of the
NHC-isothiocyanate adduct. These results effectively expand
the range of organic latent catalysts that generate NHCs
upon thermal activation and provides a method for tuning
the temperature at which catalyst activation occurs without
modifying the NHC component.
FIGURE 3. (Top) Structures of 3-7. (Bottom) Plot of percent
conversion of phenyl isocyanate to phenyl isocyanuranate versus
temperature. Each data point was taken after the respective reaction
was heated for 2 h at the indicated temperature followed by 8 h at
ambient temperature. Conditions: 2:1 phenyl isocyanate/cyclooctane
(as an internal standard), 0.05 mol % catalyst. The cycloaddition
reactions were monitored by IR spectroscopy (see text).
experiments were performed. Heating a toluene solution of
phenyl isocyanate in the presence of 2 (20 mol %) to 120 °C
did not afford the isocyanurate product. Likewise, a toluene
solution of phenyl isocyanate did not undergo spontaneous
cyclotrimerization upon heating to 120 °C for 24 h.
In a separate experiment, neat DL-lactide was treated with
3 (0.7 mol %) and benzyl alcohol (BnOH) as an initiator
([lactide]0/[BnOH]0 = 10,000) at 120 °C (Figure 3, bottom).
After 24 h, 80% of the lactide had been consumed, as deter-
mined by gas chromatography (GC),15 and the resulting
polymer was collected in 70% isolated yield after dissolution
in tetrahydrofuran followed by precipitation from methanol.
The number average molecular weight (Mn) of the polymer
was determined by gel permeation chromatography16 to be
2.1 kDa, which was lower than expected based on the initial
monomer to initiator ratio and monomer conversion. This
discrepancy suggested to us that the polymerization reaction
experienced premature termination.17 Regardless, heating
a solution of DL-lactide with BnOH at 120 °C for 24 h did not
afford polymer, which supported the notion that 3 effectively
catalyzed the polymerization reaction (via the in situ generation
of 1). To probe catalyst latency, a solution of DL-lactide, 3
(20 mol %), and benzyl alcohol ([lactide]0/[BnOH]0 = 10,000)
was stirred at room temperature for 7 d. Although no monomer
consumption was observed, as determined by GC, subsequent
heating of the reaction mixture to 120 °C for 24 h afforded
Experimental Section
Determination of kf. Toluene solutions of 1 (λ=350 nm; ε=
6790 M-1 cm-1) were prepared in a nitrogen filled glovebox and
(18) This result is consistent with previous studies which demonstrated that
NHCs react relatively slowly with electron-rich electrophiles, see: (a) Khramov,
D. M.;Bielawski, C. W. Chem. Commun. 2005, 4958–4960. (b) Khramov, D. M.;
Bielawski, C. W. J. Org. Chem. 2007, 72, 9407–9417. (c) Tennyson, A. G.;
Khramov, D. M.; Varnado, C. D., Jr.; Creswell, P. T.; Kamplain, J. W.; Lynch,
V. M.; Bielawski, C. W. Organometallics 2009, 28, 5142–5147. (d) Coady, D. J.;
Khramov, D. M.; Norris, B. C.; Tennyson, A. G.; Bielawski, C. W. Angew.
Chem., Int. Ed. 2009, 5187–5190.
(15) A predetermined quantity of diglyme (100 mg) was added as an
external standard to each aliquot (100 mg) removed from the reaction
mixture prior to GC analysis.
(16) The molecular weight data are reported relative to polystyrene
standards in DMF.
(17) In support of this conclusion, the polydispersity of the isolated
polymer was broad (PDI=2.8).
J. Org. Chem. Vol. 76, No. 1, 2011 303

Norris et al.
JOCNote
transferred to a stopped flow reactor via nitrogen-flushed syringes.
Separate injections were made with excess 1 ([1]0=2.16 mM; [2]0=
0.100 mM) as well as excess phenyl isothiocyanate ([2]0=1.00mM;
[1]0=0.100 mM) to determine the order of the reaction (Figures S1
and S2, Supporting Information). Under pseudo-first-order kinetics
conditions ([1]0 =2.16 mM; [2]0 =0.100 mM), the reaction was
monitored at various temperatures (9.9, 14, 20, 40, 46, and 55 °C),
and the kf were calculated by plotting ln [1] vs time. The error
was calculated by standard deviation from the average of three,
separate 100 μL injections.
Compound 4: obtained as tan solid (297 mg, 94% yield); mp
259-260 °C. 1H NMR (300 MHz, CDCl3): δ 7.00 (s, 2H), 6.96
(s, 4H), 6.6 (s, 2H), 2.4 (s, 12H), 2.3 (s, 6H), 2.1 (s, 3H), 1.3 (s,
6H). 13C NMR (75 MHz, CDCl3): δ 164.7, 147.0, 146.9, 140.3,
136.1, 131.3, 130.6, 129.1, 128.0, 126.8, 120.4, 20.5, 18.5, 17.0.
HRMS: [M þ Hþ] Calcd for C31H36N3S: 482.2625; Found:
482.2626. Anal. Calcd. (%) for C31H35N3S: C, 77.30; H, 7.32;
N, 8.72; S, 6.66; Found: C, 77.08; H, 7.24 ; N, 8.70; S, 6.66.
Compound 5: obtained as tan solid (272 mg, 84% yield); mp
258-260 °C. 1H NMR (400 MHz, CDCl3): δ 7.01 (s,2H), 6.97 (s,
4H), 6.8 (m, 2H), 6.21 (t, J=7.8 Hz), 2.36 (m, 18H), 1.45 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 165.2, 151.3, 146.7, 140.4,
136.0, 131.4, 129.8, 129.3, 128.3, 126.0, 122.1, 120.6, 119.7, 21.2,
18.5, 17.1. HRMS: [M þ Hþ] Calcd for C29H32N3S: 454.2317;
Found: 454.2309. Anal. Calcd (%) for C29H31N3S: C, 76.78; H,
6.89; N, 9.26; S, 7.07; Found: C, 76.57; H, 6.60; N, 9.33; S, 7.15.
Compound 6: obtained as yellow solid (276 mg, 88% yield);
mp 244-246 °C. 1H NMR (400 MHz, CDCl3): δ 7.02 (s, 2H),
6.94 (s, 4H), 6.91 (d, J=8.8 Hz, 2H), 6.68 (d, J =8.8 Hz, 2H),
3.68 (s, 3H), 2.3 (m, 18H). 13C NMR (100 MHz, CDCl3): δ 163.5,
155.2, 136.7, 144.7, 140.3, 135.7, 131.5, 129.3, 123.1, 113.43, 55.4,
21.2, 18.4. HRMS: [MþHþ] Calcd for C29H32N3OS: 470.2266;
Found: 470.2273. Anal. Calcd (%) for C29H31N3OS: C, 74.17;
H, 6.65; N, 8.95; S, 6.83; Found: C, 74.26; H, 6.90; N, 8.61; S,
6.63.
Determination of kr. In a nitrogen-filled glovebox, a series of
5-mL vials containing 3 A molecular sieves was charged with
various quantities of 1, elemental sulfur, anthracene (as an internal
standard) (400 mM), and toluene. The vials were then placed
in an oil bath and heated to 120 °C. Aliquots (100 μL) were
removed periodically over time and diluted to a total volume of
1 mL with methanol. The aliquots were then separated via HPLC
and analyzed by UV-vis spectroscopy (λ=350 nm). The residual
concentration of 1 was determined by calculating the integral
of the signal attributed to this compound (λ = 350 nm; ε =
6790 M-1 cm-1) with respect to the internal standard (λ=350 nm;
ε=3938 M-1 cm-1). The order of the reaction was determined
by varying the initial concentrations of 1 and sulfur (Figures S3
and S4, Supporting Information). Next, a stock solution of 1
(175.6 mg, 0.400 mmol), sulfur (25.6 mg, 0.800 mmol), anthracene
(71.3 mg, 0.400 mmol), and toluene (100 mL) was prepared in a
100-mL volumetric flask, and kinetic experiments analogous to
those described above were performed using 2-mL portions of
this stock solution at 90, 95, 100, 105, 110, and 120 °C.
General Procedure for the Synthesis of 3-7. In a nitrogen-
filled glovebox, a 5-mL vial was charged with 1 (263 mg, 0.866
mmol), tetrahydrofuran (2 mL), and a stir bar. A solution of aryl
isothiocyanate (1 equiv) in tetrahydrofuran (2 mL) was added at
ambient temperature, and the solvent was immediately removed
under vacuum. The residual solid was purified by silica column
chromatography using acetone/hexanes (0:1 f 1:1 v/v) as the
mobile phase which yielded the desired compound. Isolated
yields and spectroscopic data are reported below.
Compound 7: obtained as white solid (282 mg, 81% yield); mp
282-284 °C. 1H NMR (300 MHz, CDCl3): δ 7.05 (s, 4H), 6.98
(s, 2H), 6.9 (m, 3H), 2.4 (m, 18H), 1.85 (m, 2H), 0.87 (d, J=6.9
Hz, 6H), 0.67 (d, 6.9 Hz, 6H). 13C NMR (75 MHz, CDCl3): δ
167.4, 147.5, 140.7, 138.2, 136.5, 131.7, 129.6, 123.0, 123.0,
120.8, 27.6, 24.7, 24.2, 21.5, 18.8. HRMS: [M þ Hþ] Calcd for
C34H42N3S: 524.3099; Found: 524.3101. Anal. Calcd (%) for
C34H41N3S: C, 77.97; H, 7.89; N, 8.02; S, 6.12; Found: C, 78.24;
H, 7.70; N, 8.12; S, 6.03.
Acknowledgment. We thank the Office of Naval Research
(N00014-08-1-0729), the National Science Foundation (CHE-
0645563), and the Robert A. Welch Foundation (F-1621) for
their generous financial support. We are grateful to Prof.
Kenneth A. Johnson and his group for their assistance with
the stopped flow technique.
Compound 3: obtained as a yellow solid (368 mg, 97% yield);
mp 241-242 °C. 1H NMR (300 MHz, CDCl3): δ 7.09 (t, J=7.3
Hz, 2H), 7.03 (s, 2H), 7.00 (s, 4H), 6.85 (t, J=7.2 Hz, 1H), 6.64
(d, J=3 Hz, 2H), 2.33 (m, 18H). 13C NMR (75 MHz, CDCl3): δ
164.8, 151.6, 146.6, 140.3, 135.7, 131.3, 129.2, 128.1, 122.2, 121.3,
120.1, 21.1, 18.3. HRMS: [MþHþ] Calcd for C28H30N3S:
440.2155; Found: 440.2156. Anal. Calcd (%) for C28H29N3S:
C, 76.50; H, 6.65; N, 9.56; S, 7.29; Found: C, 76.42; H, 6.67; N,
9.55; S, 7.13.
Supporting Information Available: Additional experimental
procedures, integrated UV-vis data, IR spectra, NMR spectra,
and Cartesian coordinates used for the DFT calculations are
available free of charge via the Internet at http://pubs.acs.org.
304 J. Org. Chem. Vol. 76, No. 1, 2011