The curtius rearrangement of cyclopropyl and cyclopropenoyl azides. a combined theoretical and experimental mechanistic study

Article abstract of DOI:10.1021/jo801104t

(Chemical Equation Presented) A combined experimental and theoretical study addresses the concertedness of the thermal Curtius rearrangement. The kinetics of the Curtius rearrangements of methyl 1-azidocarbonyl cycloprop-2-ene-1- carboxylate and methyl 1-azidocarbonyl cyclopropane-1-carboxylate were studied by ¹H NMR spectroscopy, and there is close agreement between calculated and experimental enthalpies and entropies of activation. Density functional theory (DFT) calculations (B3LYP/6-311+G(d,p)) on these same acyl azides suggest gas phase barriers of 27.8 and 25.1 kcal/mol. By comparison, gas phase activation barriers for the rearrangement of acetyl, pivaloyl, and phenyl azides are 27.6, 27.4, and 30.0 kcal/mol, respectively. The barrier for the concerted Curtius reaction of acetyl azide at the CCSD(T)/6-311+G(d,p) level exhibited a comparable activation energy of 26.3 kcal/mol. Intrinsic reaction coordinate (IRC) analyses suggest that all of the rearrangements occur by a concerted pathway with the concomitant loss of N₂. The lower activation energy for the rearrangement of methyl 1-azidocarbonyl cycloprop-2-ene-1-carboxylate relative to methyl 1-azidocarbonyl cyclopropane-1-carboxylate was attributed to a weaker bond between the carbonyl carbon and the three-membered ring in the former compound. Calculations on the rearrangement of cycloprop-2-ene-1-oyl azides do not support π-stabilization of the transition state by the cyclopropene double bond. A comparison of reaction pathways at the CBS-QB3 level for the Curtius rearrangement versus the loss of N₂ to form a nitrene intermediate provides strong evidence that the concerted Curtius rearrangement is the dominant process.

Full text of DOI:10.1021/jo801104t

The Curtius Rearrangement of Cyclopropyl and Cyclopropenoyl
Azides. A Combined Theoretical and Experimental Mechanistic
Study
Vinod Tarwade, Olga Dmitrenko, Robert D. Bach,* and Joseph M. Fox*
Department of Chemistry and Biochemistry, UniVersity of Delaware, Newark, Delaware 19716
rbach@udel.edu; jmfox@udel.edu
ReceiVed May 27, 2008
A combined experimental and theoretical study addresses the concertedness of the thermal Curtius
rearrangement. The kinetics of the Curtius rearrangements of methyl 1-azidocarbonyl cycloprop-2-ene-
1-carboxylate and methyl 1-azidocarbonyl cyclopropane-1-carboxylate were studied by 1H NMR
spectroscopy, and there is close agreement between calculated and experimental enthalpies and entropies
of activation. Density functional theory (DFT) calculations (B3LYP/6-311+G(d,p)) on these same acyl
azides suggest gas phase barriers of 27.8 and 25.1 kcal/mol. By comparison, gas phase activation barriers
for the rearrangement of acetyl, pivaloyl, and phenyl azides are 27.6, 27.4, and 30.0 kcal/mol, respectively.
The barrier for the concerted Curtius reaction of acetyl azide at the CCSD(T)/6-311+G(d,p) level exhibited
a comparable activation energy of 26.3 kcal/mol. Intrinsic reaction coordinate (IRC) analyses suggest
that all of the rearrangements occur by a concerted pathway with the concomitant loss of N2. The lower
activation energy for the rearrangement of methyl 1-azidocarbonyl cycloprop-2-ene-1-carboxylate relative
to methyl 1-azidocarbonyl cyclopropane-1-carboxylate was attributed to a weaker bond between the
carbonyl carbon and the three-membered ring in the former compound. Calculations on the rearrangement
of cycloprop-2-ene-1-oyl azides do not support π-stabilization of the transition state by the cyclopropene
double bond. A comparison of reaction pathways at the CBS-QB3 level for the Curtius rearrangement
versus the loss of N2 to form a nitrene intermediate provides strong evidence that the concerted Curtius
rearrangement is the dominant process.
Introduction
rearrangement invoked the intermediacy of acylnitrenes,2 ex-
perimental studies suggested that the thermal rearrangement is
a concerted process3,4 that occurs with retention of con-
figuration.4b Most notably, extensive experimental studies by
Lwowski and co-workers4c-e failed to intercept pivaloylnitrene
upon pyrolysis of pivaloyl azide. Pivaloylnitrene, generated
photolytically from pivaloyl azide, did not rearrange to pivaloyl
The transformation of an acyl azide into an isocyanatesthe
Curtius rearrangementsis a broadly useful method for the
synthesis of amine derivatives from carboxylic acids (eq 1).1
The mechanism of the Curtius rearrangement has been a
question of longstanding interest. The rearrangement of acyl
azides to isocyanates represents a classic example of a 1,2-
nucleophilic shift where the migrating group carries a pair of
electrons, and the migration terminus is an atom with a formal
open sextet. While early mechanistic proposals for the Curtius
(2) For example, (+)-PhCHMeCOOH may be converted to (-)-PhCHMeNH2
by the Curtius reaction with 99.3% retention of configuration. The correspond-
ingly related Schmidt, Hofmann, Lossen, and Beckman reactions also all proceed
with essentially complete retention of configuration. See: Campell, A.; Kenyon,
J. J. Chem. Soc. 1946, 25.
(3) (a) Stieglitz, J. Am. Chem. J. 1896, 18, 751. (b) Brower, K. R. J. Am.
Chem. Soc. 1961, 83, 4370. For a thorough discussion of early mechanistic
proposals on the Curtius rearrangement, see: (c) Smith, P. A. In Molecular
Rearrangements; de Mayo, P., Ed.; Interscience Publishers: New York, 1963;
pp 457-591.
(1) (a) Curtius, T. Chem. Ber. 1890, 23, 3023. (b) Curtius, T. Chem. Ber.
1894, 27, 778. (c) Smith, P. A. S. Org. React. 1946, 3, 337. (d) L’Abbe´, G.
Chem. ReV. 1969, 69, 345. (e) Lwowski, W. In Azides and Nitrenes; Scriven,
E. F. V., Ed.; Academic Press: New York, 1984; p 205.
10.1021/jo801104t CCC: $40.75
Published on Web 10/01/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 8189–8197 8189

Tarwade et al.
SCHEME 1. Curtius Rearrangements of Cycloprop-1-enoyl
azide 1 and Cyclopropanoyl azide 3
isocyanate, and both singlet and triplet pivaloylnitrene were
excluded as intermediates in both thermal and photoinduced
Curtius rearrangement of pivaloyl azide.4c-e Resonance interac-
tions in phenyl substituents are known to influence the aryl
migration rate. It has also been established that electron-releasing
groups in the meta position of benzoyl azides increase the rate
of rearrangement while all para substituents decrease the rate.1d,5
In theoretical studies,6 Hadad, Platz, and co-workers studied
the Curtius rearrangements of acetyl azide at several levels of
theory (B3LYP/6-31+G**, CCSD(T), and CBS-QB3).7 Acyl
azides can exist as both syn and anti conformations with respect
to the C-N bond. We refer to these conformations as synC-N
and antiC-N, respectively. DFT and CBS-QB3 calculations
suggest that the conformer of MeC(O)N3 with the synC-N
relationship between the carbonyl and azide group is 4.5-4.8
kcal/mol more stable than the antiC-N conformer.7 This is an
important distinction because rearrangements of synC-N acyl
azides have been calculated to proceed by a concerted mech-
anism while the higher energy antiC-N conformers tend to follow
the stepwise pathways that produce acylnitrene intermediates.7,8
It was concluded that the synC-N conformer of acetyl azide
rearranges by a concerted mechanism to methylisocyanate with
a barrier of ∼27 kcal/mol, whereas the calculated barrier for
the formation of acetylnitrene, with the attendant loss of N2,
was calculated to be higher (32 kcal/mol), leading to the
suggestion that a free nitrene is not produced in the pyrolysis
of acetyl azide. However, it was recognized that the relative
barriers for concerted versus stepwise Curtius rearrangement
could be sensitive to the substituent on the carbonyl group. It
was shown that for methoxycarbonyl azide the stepwise process
to generate the free nitrene was favored over concerted
rearrangement, an observation that is consistent with ac-
companying experimental studies of alkoxycarbonyl azides that
do produce trapable nitrenes upon thermolysis.7 Although an
experimental study on acetyl azide is not available for direct
comparison, the calculated barrier for the concerted rearrange-
ment of acetyl azide is in reasonable agreement with the
experimentally determined barriers for thermal Curtius rear-
rangements of other acyl azides.1d,3c,5
A subsequent DFT study on the Curtius rearrangement was
conducted by Zabalov and Tiger at the PBE/TZ2P level of
theory.8 The barriers to concerted rearrangement of several
synC-N and antiC-N acyl azide conformers, versus the loss of
N2 and formation of the corresponding nitrene, were reported
for formyl azide (28.0 vs 34.6 kcal/mol), acetyl azide (32.9 vs
32.9 kcal/mol), and benzoyl azide (34.5 vs 32.3 kcal/mol),
respectively.8 Because of the additional barrier associated with
the subsequent rearrangement of the acylnitrenes to the isocy-
anates (20.9, 18.9, and 13.6 kcal/mol, respectively) in a two-
step process, these authors concluded that overall concerted
pathways would be predominant. Thus, calculated relative
activation barriers suggest that rearrangement of acyl azides by
the one-step concerted mechanism is preferable to the two-step
process involving formation of acylnitrene.8
However, in a more recent computational study at the
Moller-Plesset ((MP2)(full)/6-31G*) level of theory, it was
proposed that the thermal rearrangements of acetyl azide and
benzoyl azide are stepwise processes that proceed via acylnitrene
intermediates.9 The activation energies for the formation of
acetylnitrene was calculated to be 39.2 kcal/mol, and the
transition state for the conversion of the nitrene into methyl-
isocyanate was 55.6 kcal/mol relative to the acyl azide ground
state. Similarly, unusually large activation energies were
calculated for the formation of benzoylnitrene (47.8 kcal/mol)
and phenylisocyanate (64.6 kcal/mol) relative to the benzoyl
azide ground state. By contrast, a single transition state was
located for the rearrangement of formyl azide to isocyanate with
an activation energy of 37.5 kcal/mol.
In light of these conflicting conclusions regarding the thermal
Curtius rearrangement, we considered that a combined theoreti-
cal and experimental study might provide additional insight into
the mechanism. In the course of our studies on the synthesis
and application of cyclopropene R-amino acids,10 we noticed
that acyl azides of cyclopropene biscarboxylic acids undergo
Curtius rearrangement with unusual facility. Thus, cycloprop-
1-enoyl azide 1 undergoes rearrangement to isocyanate 2 to
>90% conversion within 24 h at room temperature, whereas
elevated temperatures have been reported for similar rearrange-
ments of acyl azides derived from malonic acid (Scheme 1).11
As a control, we synthesized the cyclopropane analogue 3 and
noted that a significantly higher reaction temperature was
required for conversion into isocyanate 4 within a similar time
(4) (a) Wentrup, C.; Bornemann, H. Eur. J. Org. Chem. 2005, 4521. (b)
Lwowski, W. Angew. Chem., Int. Ed. Engl. 1967, 6, 897. (c) Linke, S.; Tisue,
G. T.; Lwowski, W. J. Am. Chem. Soc. 1967, 89, 6308. (d) Lwowski, W.; Tisue,
G. T. J. Am. Chem. Soc. 1965, 87, 4022. (e) Tisue, G. T.; Linke, S.; Lwowski,
W. J. Am. Chem. Soc. 1967, 89, 6303. (f) Hauser, C. R.; Kantor, S. W. J. Am.
Chem. Soc. 1950, 72, 4284. (g) Horner, L.; Bauer, G.; Do¨rges, J. Chem. Ber.
1965, 98, 2631. (h) Huisgen, R.; Anselme, J.-P. Chem. Ber. 1965, 98, 2998. (i)
See pp 171-172 in Abramovitch, R. A.; Davis, B. A. Chem. ReV 1964, 64,
149.
(5) (a) The photochemical Curtius rearrangement may take place via concerted
rearrangement of the acyl azide or via a stepwise mechanism that involves an
acylnitrene. For experimental work on the photo-Curtius rearrangement, see refs
1e, 4e, and 4a and references therein. (b) Yukawa, Y.; Tsuno, Y. J. Am. Chem.
Soc. 1957, 79, 5530.
(6) For computations on the Curtius rearrangements of acylnitrenes, see refs
4a, 6, and (a) Sigman, M. E.; Autrey, T.; Schuster, G. B. J. Am. Chem. Soc.
1988, 110, 4297. (b) Yokoyama, K.; Takane, S.-Y.; Fueno, T. Bull. Chem. Soc.
Jpn. 1991, 64, 2230. (c) Mebel, A. M.; Luna, A.; Lin, M. C.; Morokuma, K.
J. Chem. Phys. 1996, 105, 6439. (d) Shapley, W.; Backskay, G. B. J. Phys.
Chem. A 1999, 103, 6624. (e) Gristan, N. P.; Pritchina, E. A. MendeleeV Commun.
2001, 94. (f) Faustov, V. I.; Baskir, E. G.; Biryukov, A. A. Russ. Chem. Bull.
2003, 52, 2328.
(9) Abu-Eittah, R. H.; Mohamed, A. A.; Al-Omar, A. M. Int. J. Quantum
Chem. 2006, 106, 863.
(10) Zhang, F.; Fox, J. M. Org. Lett. 2006, 8, 2965.
(11) (a) Yamada, S.; Ninomiya, K.; Shioiri, T. Tetrahedron Lett. 1973, 26,
2343. (b) Wheeler, T. N.; Ray, J. A. Synth. Commun. 1988, 18, 141. (c) Izquierdo,
M. L.; Arenal, I.; Bernabe, M.; Alvarez, F. Tetrahedron 1985, 41, 215. (d)
Baldwin, J. E.; Adlington, R. M.; Rawlings, B. J. Tetrahedron Lett. 1985, 26,
481.
(7) Liu, J.; Mandel, S.; Hadad, C. M.; Platz, M. S. J. Org. Chem. 2004, 69,
8583.
(8) Zabalov, M. V.; Tiger, R. P. Russ. Chem. Bull. 2005, 54, 2270.
8190 J. Org. Chem. Vol. 73, No. 21, 2008

Mechanism of the Curtius Rearrangement
TABLE 1. Kinetic Measurements on Curtius Rearrangements of 1
and 3
SCHEME 2. Synthesis of Acyl Azides 1 and 3
frame. An intriguing explanation for the accelerated rearrange-
ment of 1 relative to 3 would invoke π-stabilization of the
transition state(s) for rearrangement of the former by involve-
ment of the π-bond of the highly strained alkene. Alternatively,
a simpler explanation would invoke the differing C-C bond
strengths12 of the acyl bonds to cyclopropenes and cyclopro-
panes as discussed below. An accurate theoretical method should
be capable of affirming the origin of this reactivity trend.
Given the unusual reactivity of 1, we considered that this
rearrangement might deviate from the generic Curtius rear-
rangement pathway. Herein, it is shown that the activation
energies calculated by density functional theory (DFT) are in
close agreement with experimentally measured free energies of
activation for the rearrangements of 1 (23.8 kcal/mol by
experiment; 25.1 kcal/mol by calculation) and 3 (25.5 kcal/mol
by experiment; 27.8 kcal/mol by calculation). In both rear-
rangements, small entropies of activation were measured (0.3
and 0.2 cal/mol·K for 1 and 3, respectively). These measure-
ments are consistent with the calculated entropies (3.1 cal/mol ·K
for 1, 3.7 cal/mol ·K for 3) and the location of early transition
states in which N2 bond breakage is not far advanced. Calcula-
tions were also carried out on the rearrangements of acetyl azide,
benzoyl azide, and pivaloyl azide. In each case, concerted
rearrangement to the isocyanate was observed with barriers of
27.6, 30.0, and 27.4 kcal/mol, respectively.
a The sample standard deviation is listed in parentheses.
ppm) were integrated, depending on the rate of rearrangement,
every 20 to 144 s over the entire course of the reaction. This in
situ method allows for the collection of many data points, as is
desired for accurate rate determination. First-order rate constants
were measured in duplicate runs by monitoring the disappear-
ance of 1 at 30, 40, and 50 °C and the disappearance of 3 at
50, 61, and 71 °C. The Arrhenius equation was used to calculate
the activation energies, and Eyring analyses were used to
determine the free energies of activation, the enthalpies of
activation, and the entropies of activation for the Curtius
rearrangements of 1 and 3. The kinetic data are summarized in
Table 1.
The Curtius rearrangements of 1 and 3 proceed in high yield
as determined by analysis of the crude NMR spectra: 3 and 4
are both formed in >95% purity. The free energy of activation
for the rearrangement of 1 was measured to be 23.8 kcal/mol.
The free energy of activation energy for the rearrangement of
3 was 25.5 kcal/mol. Small, positive entropies of activations
(0.2-0.3 cal/mol ·K) were measured for the rearrangements of
both 1 and 3. At 50 °C, the relative rates of Curtius rearrange-
ments for 1 and 3 could be directly compared: the rearrangement
of 1 is 14 times faster than that of 3.
Theoretical Results. In order to establish reliable theoretical
activation barriers for the Curtius rearrangement of 1 and 3,
we first revisited the calculated activation barriers for several
more simple acyl azides. In this manner, it was possible to
establish the accuracy of our DFT calculations relative to the
earlier studies described above.7-9 The calculated DFT activa-
tion barrier (Figure 1) for the concerted Curtius rearrangement
on acetyl azide was 27.6 kcal/mol [B3LYP/6311+G(d,p)]. This
barrier is comparable to that reported earlier for synC-N acetyl
azide at CBS-QB3 (27 kcal/mol) and significantly lower than
the reported barrier for the formation of the corresponding
nitrene (32 kcal/mol).7
Results and Discussion
Experimental Results. Acyl azide 1 was prepared from
dimethyl diazomalonate as shown in Scheme 2. Dimethyl
cycloprop-2-ene-1,1-biscarboxylic ester was synthesized with
a modification of Gevorgyan’s protocol,13 and subsequent
conversion into 1 was accomplished with a modified version
of Wheeler and Ray’s procedure.14 Analogously, acyl azide 3
was prepared from dimethyl cyclopropane-1,1-biscarboxylic
ester (Scheme 2).
Kinetic Measurements. NMR spectroscopy was used to
monitor reactions for the disappearance of 1 and 3. The peaks
assigned to the methyl esters of 1 (3.38 ppm) and of 3 (3.34
(12) (a) Bach, R. D.; Dmitrenko, O. J. Am. Chem. Soc. 2004, 126, 4444. (b)
Bach, R. D.; Dmitrenko, O. J. Org. Chem. 2002, 67, 2588, and references therein.
(13) Rubina, M.; Rubin, M.; Gevorgyan, V. J. Am. Chem. Soc. 2003, 125,
7198.
These Curtius rearrangement barriers did not change signifi-
cantly with a higher degree of electron correlation. The
(14) Wheeler, T. N.; Ray, J. J. Org. Chem. 1987, 52, 4875.
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Tarwade et al.
FIGURE 1. Transition structures for the Curtius rearrangement on
synC-N conformers of acetyl azide, pivaloyl, azide and benzoyl azide.
Transition structures were optimized at the B3LYP/6-311+G(d,p) level
of theory. (A) ∆(E + ZPVE)q )27.6 kcal/mol. (B) ∆(E + ZPVE)q
)27.4 kcal/mol. (C) ∆(E + ZPVE)q )30.0 kcal/mol.
FIGURE 3. Snapshots along the reaction pathway from the transition
state to product for the Curtius reaction of benzoyl azide.
weakly bound to the developing NCO central carbon atom as
depicted in Figure 2 for the CCSD surface. Along the 1,2-methyl
migration pathway, the N-C-C bond angle in the transition
state (Figure 2, 99.7°) contracts to about 70° as the 1,2-methyl
migration to nitrogen takes place. At no point on the PES is
expansion of the N-C-C angle observed, as would be required
for formation of a singlet nitrene (141.5°). Similarly, the
N-C-O angle in the transition state (136.0°) continues to
expand as it approaches 180° and shows no sign of contracting
to the 86.6° in acylnitrene.
DFT calculations were also performed for a series of model
cyclopropyl compounds that are related to those that were
examined experimentally. The simplest cyclopropanoyl azide
can exist as four basic conformers [B3LYP/6-311+G(d,p)] that
include both syn and anti relationships of the carbonyl oxygen
with respect to the azide group and the cyclopropyl ring. These
stereochemical relationships are referred to as synC-N/antiC-N
and synC-C/antiC-C, respectively. The current study was re-
stricted to the synC-N conformation that is required for concerted
Curtius rearrangement. Calculations were performed for both
synC-C and antiC-C conformations. The synC-N, synC-C con-
former 5a is 1.06 kcal/mol lower in energy than synC-N, antiC-C
FIGURE 2. Activation barrier for concerted acetyl azide rearrangement
at the CCSD(T)/6-311+G(d,p) level. Total reaction exothermicity for
the formation of methylisocyanate is ∆E ) -53.9 kcal/mol.
CCSD(T)/6-311+G(d,p) activation energy for this concerted
exothermic (∆E ) 53.9 kcal/mol) loss of N2 from acetyl azide
was ∆Eq ) 26.3 kcal/mol (Figure 2).
Steric factors do not seem to play a measurable role in the
Curtius reaction because concerted 1,2-migration of the t-butyl
group in pivaloyl azide (Figure 1) had essentially the same
barrier as that for CH3 migration with the acetyl group. A
slightly larger activation energy was calculated for phenyl
migration (30.0 kcal/mol). A possible reason for the higher
barrier is that the phenyl and the carbonyl groups of benzoyl
azide are conjugated in the ground state but not in the transition
state of the rearrangement where the benzene ring is essentially
orthogonal to the CdO group.5 An IRC analysis supports the
concerted rearrangement mechanism with bonding of the
benzene ipso-carbon atom to the nitrogen atom at the migration
terminus with concomitant loss of N2 as suggested by several
snapshots along the reaction pathway (Figure 3). Examination
of the molecular orbitals in this transition state also shows a
definite overlap of the ipso-carbon atomic p-orbital overlapping
with both the carbonyl carbon and the nitrogen terminus in the
HOMO-3 orbital ( N1-C1-C2-C3 ) 93.4°, Figure 1). Thermal
decomposition of benzoyl azide in toluene and in n-heptane
exhibited enthalpies of activation of 27.1 and 31.6 kcal/mol1d
in excellent agreement with our gas phase calculations.
Additional evidence that these are indeed concerted rear-
rangements comes from an analysis of the potential energy
surface (PES) for acetyl azide. Concerted rearrangement is
evidenced by an IRC calculation (DFT) that proceeds from the
transition state down to methylisocyanate with the N2 molecule
conformer 5b (Figure 4). Similarly, the concerted TS-5(synC-N
synC-C) for the Curtius rearrangement is 2.2 kcal/mol lower in
energy than TS-5(synC-N, antiC-C) (not shown). TS-5(synC-N
,
,
synC-C) exhibits an activation barrier with ZPE corrections of
29.3 kcal/mol (νi ) 468.7i cm-1), a barrier that is 1.7 kcal/mol
higher than that calculated for the simplest acyl azide, acetyl
azide.
In an effort to better understand the origin of the more facile
Curtius rearrangement attributed to the presence of a carbon-
carbon double bond in 1, we next calculated rearrangement
barriers with the corresponding cyclopropene derivatives. The
synC-N, synC-C isomer of the parent cycloprop-1-enoyl azide
6a is slightly more stable (0.26 kcal/mol) than the synC-N
,
antiC-C isomer 6b (Figure 5). The synC-N, synC-C activation
barrier of 29.0 kcal/mol (νi ) 561.6i cm-1) for this cyclopropene
derivative is 0.9 kcal/mol higher than TS-6(synC-N, antiC-C
(νi ) 606.7i cm-1).
)
If there is any π-stabilization of TS-6(synC-N, antiC-C) by
the cyclopropene double bond, it is only a modest effect. In
TS-6(synC-N, antiC-C), the distance to N1 appears to be too
great for extensive interaction with the π-bond. More impor-
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Mechanism of the Curtius Rearrangement
FIGURE 6. HOMO orbitals for (A) TS-5(synC-N, synC-C) and (B)
TS-6(synC-N, antiC-C).
FIGURE 4. Minima of the (synC-N, synC-C) and (synC-N, antiC-C
)
conformers of cyclopropanoyl azide (5a and 5b), and TS-5(synC-N
,
synC-C) (∆Eq )29.3 kcal/mol) optimized at the B3LYP/6-311+G(d,p)
level of theory.
FIGURE 7. Structures of 1 and 3 minima and their corresponding
transition structures,TS-1 and TS-3, optimized at the B3LYP/6-
311+G(d,p) level of theory.
synC-C) and TS-6(synC-N, antiC-C) that clearly evidence an
overlap of the migrating carbon atom and the nitrogen atom of
the migration terminus (Figure 6).
In order to examine the effect of the ester group on the
reaction rate, we also carried out calculations on the Curtius
reactions for 1 and 3 (Figure 7). The activation barrier for
saturated cyclopropyl derivative, TS-3 (27.8 kcal/mol, νi )
534.8i cm-1), was reduced by 1.5 kcal/mol relative to that of
the parent cyclopropanoyl TS-5(synC-N, synC-C) as a conse-
quence of adding the ester functionality. More importantly, the
barrier for the unsaturated cycloprop-1-enoyl ester (TS-1) was
2.65 kcal/mol lower than that of the saturated ester (TS-3), in
good agreement with the experimental energy difference (∆Ea
) 1.7 kcal/mol). When the role of solvent (toluene) was
examined using the CPCM (Cosmo) solvent model, we observed
a comparable ∆∆Eq ) 2.53 kcal/mol for these two transition
states. An IRC analysis starting from both transition states in
the forward direction clearly showed migration of the cyclo-
propyl carbon to the migration terminus (nitrogen) with the
concomitant loss of N2, while the reverse IRC pathway
generated ground-state acyl azides. We also examined TS-1 and
TS-3 with a different DFT variant (mPW1PW/6-31G(d)) that
has been reported to treat both covalent and noncovalent
interactions quite satisfactorily.18 We again found a comparable
∆∆Eq ) 2.86 kcal/mol for the two transition states (see
Supporting Information).
FIGURE 5. Minima of the (synC-N, synC-C) and (synC-N, antiC-C
)
conformers of cycloprop-1-enoyl azide (6a and 6b) and the corre-
sponding transition structures [TS-6(synC-N, synC-C)sa second-order
saddle point and TS-6(synC-N, antiC-C)] optimized at the B3LYP/6-
311+G(d,p) level of theory.
tantly, the effect of the alkene results in only a 1.2 kcal/mol
reduction in activation energy relative to that of cyclopropyl
TS-5(synC-N, synC-C). Attempts to locate a syn-syn TS, where
the geometry precludes π-stabilization, resulted in a second-
order saddle point that is only 0.9 kcal/mol higher in energy
than that of first-order saddle point, TS-6(synC-N, antiC-C).
Reoptimization of the second-order saddle point TS-6(synC-N
,
synC-C) (Figure 5) led to TS-6(synC-N, antiC-C), with a dihedral
angle between the CdC bond and the N-CdO fragment of
essentially zero (<C-C-N-O ) 0.92°). On the basis of these
observations, it is plausible that the CdC π-bond of TS-
6(synC-N, antiC-C) may offer a small stabilization to the
N-CdO π-system by a through-space interaction. Nonetheless,
we conclude that the energetics simply do not support a
meaningful π-interaction in the transition state. Additional
support for a concerted Curtius rearrangement for synC-N acyl
DFT calculations support the conclusions reached thus far
about the concerted nature of the Curtius rearrangement of
azides comes from plotting the HOMO orbitals for TS-5(synC-N
,
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Tarwade et al.
FIGURE 9. Minimum [6b(synC-N, antiC-C)] and transition structure
[TS-6b(synC-N, antiC-C)] for the Curtius rearrangement, and the
transition state for loss of N2 (TS-7) to form cycloprop-2-enoylnitrene
at the CBS-QB3 level of theory.
FIGURE 8. Cycloprop-2-enoyl antiC-C singlet nitrene (A), synC-C
triplet nitrene (B), and antiC-C triplet nitrene (C) at the CBS-QB3 level
of theory.
ring with respect to the carbonyl group being preferred by 0.31
kcal/mol. More importantly, at the CBS-QB3 level, the antiC-C
singlet nitrene is predicted to be the ground state (∆E ) 2.50
kcal/mol) as suggested by earlier calculations by Platz and co-
workers7 on related nitrenes. These data provide confidence that
the above transition structures on the singlet surface are
adequately represented by DFT theory.
synC-N acyl azides. To support these conclusions, energy
refinement calculations were carried out on selected key acyl
azides at the CBS-QB3 level of theory. Platz and co-workers
used this method to check the ground-state electronic config-
uration of several acylnitrenes because DFT theory sometimes
improperly assigned singlet versus triplet ground states for
acylnitrenes.7 If acylnitrenes could potentially form along the
reaction pathway, then the correct assignment for the electronic
state is of primary importance. Additionally, the CBS-QB3
method provides a level of accuracy comparable to that of G3
theory that typically provides geometries within experimental
accuracy.20
Studies were focused on the rearrangement of cycloprop-2-
enoyl azide 6. This acyl azide was chosen for study because it
rearranges with the lowest barrier and might therefore be most
likely to deviate from a concerted mechanism. A striking
observation is that the synC-C-cycloprop-1-enoylnitrene [cor-
responding to 6a (Figure 5)] does not exist as a minimum on
the singlet surface. The synC-C singlet nitrene immediately
rearranges to the corresponding isocyanate, precluding the
formation of a discrete singlet nitrene intermediate from this
conformer on the PES. The antiC-C singlet nitrene (Figure 8a)
exhibits the relatively closed N-C-O angle (87.6°) alluded to
above. That same angle for the triplet nitrenes is much wider.
On the triplet surface, both synC-C and antiC-C nitrenes exist
as minima, with the synC-C arrangement of the cyclopropenoyl
Interestingly, the antiC-N, antiC-C conformer of cycloprop-
1-enoyl azide (not shown) does not exist as a minimum but
rotates about the C-C bond to produce synC-N/antiC-C
cycloprop-1-enoyl azide 6b. We have therefore located the
transition state for the Curtius rearrangement of the synC-N
-
,
antiC-C isomer of cycloprop-1-enoyl azide 6b at the CBS-QB3
level of theory (Figure 9). Again, it was observed that the
N-C-O fragment was twisted by nearly 90° in TS-6b(synC-N
,
antiC-C) (<H9-C3-C4-O5 ) -91.6°), and the activation
barrier (∆Eq ) 29.3 kcal/mol) was quite comparable to that at
the DFT level (Figure 5). Perhaps of more relevance to the
primary question at hand, the degree of concertedness of the
rearrangement, animation of the single imaginary frequency (Vi
) 617.4i cm-1) for TS-6b(synC-N, antiC-C) clearly evidenced
involvement of the cycloprop-1-enoyl moiety including the vinyl
hydrogens. The migration terminus nitrogen (N6) was oscillating
between the cyclopropene carbon (C3) and the departing nitrogen
(N7). Although the largest contribution to the vector comes from
breaking the N6-N7 bond, the C3-C4-N6 and C3-C4-O5 bond
angles were clearly involved. It is concluded that this is a
concerted process with alkyl migration in concert with the loss
of N2 and formation of the isocyanate.
For comparison, we also located the transition state for loss
of N2 from 6b to form the cycloprop-2-enoylnitrene that
provided further support for the concerted nature of the Curtius
rearrangement. Although the TS-7 (synC-N, antiC-C) (Figure 9)
was only 2.9 kcal/mol higher in energy than the Curtius
transition state [TS-6b(synC-N, antiC-C], there is a mechanistic
difference between the two pathways. Animation of the single
(15) (a) Frisch, M. J. Gaussian 98, revision A.7; Gaussian, Inc.: Pittsburgh,
PA, 1998. (b) Gaussian 03, revision B.05 (SGI64-G03RevB.05); Gaussian, Inc.:
Pittsburgh, PA, 2003. See the Supporting Information for the full list of authors.
(16) Schlegel, H. B. J. Comput. Chem. 1982, 3, 214.
(17) (a) Becke, A. D. Phys. ReV. A 1988, 38, 3098. (b) Lee, C.; Yang, W.;
Parr, R. G. Phys. ReV. B 1988, 37, 785. (c) Stevens, P. J.; Devlin, F. J.;
Chabalowski, C. F.; Frisch, M. J. J. Phys. Chem. 1994, 98, 11623.
(18) Adamo, C.; Barone, V. J. Chem. Phys. 1998, 108, 664.
(19) (a) McLean, A. D.; Chandler, G. S. J. Chem. Phys. 1980, 72, 5639. (b)
Krishnan, R.; Binkley, J. S.; Seeger, R.; Pople, J. A. J. Chem. Phys. 1980, 72,
650.
imaginary frequency for this transition state (νi ) 460.1i cm-1
)
showed that it contained essentially no contribution from the
cyclopropene moiety and was composed largely of N6-N7 bond
breaking and a modest contribution from the N6-C4-O5 angle
that disclosed a wagging of the carbonyl oxygen as the N2
(20) (a) Montgomery, J. A.; Frisch, M. J.; Ochterski, J. W.; Petersson, G. A.
J. Chem. Phys. 2000, 112, 6532. (b) Montgomery, J. A.; Frisch, M. J.; Ochterski,
J. W.; Petersson, G. A. J. Chem. Phys. 1999, 110, 2822. (c) Klamt, A.;
Schu¨u¨rmann, G. J. Chem. Soc., Perkin Trans. 2 1993, 799. (d) Barone, V.; Cossi,
M.; Tomasi, J. J. Comput. Chem. 1998, 19, 404.
8194 J. Org. Chem. Vol. 73, No. 21, 2008

Mechanism of the Curtius Rearrangement
FIGURE 11. Curtin-Hammett equilibrium between 8(antiC-N, synC-C
)
(which leads to nitrene formation) and 8(synC-N, synC-C) (which gives
concerted Curtius rearrangement). Because TS8a(antiC-N, synC-C) is
3.9 kcal/mol higher in energy relative to TS8(synC-N, synC-C), it is
the concerted rearrangement to isocyanate that is favored.
TABLE 2. C-C Bond Dissociation Energies of Selected
Compounds
compound
experimental
90.412b
calculated
method
G2
CBS-APNO
CBS-APNO
C2H6
90.812b
Me-cyclopropane
Me-cyclopropene
Me-Phe
99.5a
90.7a
87.622
78.723
neopentane
87.7a
G3
a Bond dissociation energy calculated in the present study.
to TS-8(synC-N, synC-C), it is the concerted rearrangement to
isocyanate that is favored.
Animation of the single imaginary frequencies for the above
TSs (Figure 10) closely mirrored those for the cycloprop-1-
enoyl transition states (Figure 9). The vectors for Curtius
rearrangement TS-8 had a large contribution from the cyclo-
propane ring that was essentially absent from TS-8a that largely
involved N-N bond breaking attending the loss of N2. In TS-8
and TS-8a, the H9-C3-C4O5 dihedral angles are 180°. This
stands in contrast to TS-6b (Figure 9), where the H9-C3-C4O5
dihedral angle is -91.6°. This observation reinforces the earlier
comment that the double bond of the cyclopropene does exert
an influence on the geometry of the Curtius transition state, but
not necessarily on the energetics of the transition state.
From this series of calculations on the Curtius reaction, it is
evident that both the alkene and the ester functionalities each
make a small contribution to the rate enhancement noted for 1
relative to 3. However, calculations suggest that it is unlikely
that the primary role of the alkene is π-stabilization by the CdC
in the transition state. A more likely explanation lies in the
differing strengths of C-C bonds to cyclopropane and to the
allylic position of cyclopropene. The bond dissociation energy
(BDE) of the C-C single bond in methylcyclopropane is 8.8
kcal/mol higher than the corresponding bond in 3-methylcy-
clopropene (Table 2). Analogously, we feel that the lower barrier
for the rearrangement of 1 relative to 3 is attributable to a weaker
bond between the carbonyl carbon and the three-membered ring
in the former compound.
FIGURE 10. Conformers of cyclopropanoyl azides: 8(synC-N, synC-C
)
and 8(synC-N, antiC-C), 8(antiC-N, synC-C) and 8(antiC-N, antiC-C),
TS-8(synC-N, synC-C) for Curtius rearrangement, and TS-8a(antiC-N
synC-C) for the loss of N2 to produce cyclopropanoylnitrene.
,
departed. The <H9-C3-C4-O5 dihedral angles (180.0 and
-91.6°) for these two transition states also clearly distinguish
the two mechanisms.
A very similar picture emerged when we examined the
transition structures for rearrangement versus loss of N2 from
the cyclopropanoyl azides at the CBS-QB3 level. First, we
provide the relative energies of four of the potential conformers
involved in the rearrangement. The ground-state conformer of
cyclopropanoyl azide 8(synC-N, synC-C) undergoes the Curtius
rearrangement with an activation barrier of 28.9 kcal/mol, a
value very close to that predicted above at the DFT level for
TS-5 (∆Eq ) 29.3 kcal/mol). The loss of N2 from an acyl azide
requires the anti orientation of the azide functionality with
respect to the CdO group. The cyclopropanoyl azide 8(antiC-N
,
synC-C) is 4.5 kcal/mol lower in energy than the more sterically
hindered antiC-N, antiC-C conformer (Figure 10), and its barrier
for loss of N2 from 8(antiC-N, synC-C) to produce the cyclo-
propanoyl nitrene is actually 0.7 kcal/mol lower in energy (∆Eq
) 28.2 kcal/mol) than the Curtius transition state. However,
8(antiC-N, synC-C) is 4.6 kcal/mol higher in energy than
8(synC-N, synC-C), and this is a classic Curtin-Hammett
equilibration where the barrier for ground-state rotation is much
lower than either activation barrier (Figure 11). Because TS-
8a(antiC-N, synC-C) is 3.9 kcal/mol higher in energy relative
(21) Dooley, R. K.; Milfeld, K.; Guiang, C.; Pamidighantam, S.; Allen, G.
J. Grid Computing 2006, 4, 195.
(22) Kandel, R. J. J. Chem. Phys. 1954, 22, 1496.
(23) Eckstein, B. H.; Scherga, H. A.; Van Artsdalen, E. R. J. Chem. Phys.
1954, 22, 28.
J. Org. Chem. Vol. 73, No. 21, 2008 8195

Tarwade et al.
of dimethyl diazomalonate24 (15.48 g, 97.95 mmol) dissolved in
trimethylsilylacetylene (3 mL) was added by a syringe pump (0.5
mL/h) to a suspension of Rh2(OAc)4 (267 mg, 0.604 mmol, 0.6
mol%) in trimethylsilylacetylene (52 mL) at room temperature.
After the addition was complete, the reaction mixture was allowed
to stir at room temperature overnight. The majority of unreacted
trimethylsilylacetylene was recovered by short path distillation from
the reaction mixture at atmospheric pressure. The residue was
passed through a short plug of silica gel (7′′ × 6′′). Ethyl acetate
was used as the eluent, and filtrate was again concentrated under
reduced pressure. The crude product was dissolved in THF (100
mL), and the solution was cooled by ice-water bath (0 °C) and
allowed to stir. To this solution was added dropwise 160 mL of an
aqueous solution of K2CO3 (16.24 g, 117.5 mmol). After the
addition was complete, the solution was allowed to warm to room
temperature and stir for 1 h. The reaction mixture was concentrated
under reduced pressure. The aqueous phase was extracted with ethyl
acetate (4 × 150 mL). The combined organic layers were dried
(MgSO4), filtered, and concentrated under reduced pressure. Flash
column chromatography (5-20% EtOAc in hexane) furnished 10.54
g (67.50 mmol, 69%) of dimethyl cycloprop-2-ene-1,1-dicarboxylate
as pale brown oil along with 1.27 g (5.56 mmol, 5.7%) of
2-methoxy-3-methoxycarbonyl-4-trimethylsilyl furan as pale brown
oil. Spectroscopic data for these compounds (1H, 13C NMR)
matched those described previously.13
Of course, BDE is not the only consideration that determines
the activation energy for the Curtius rearrangement. For
example, the BDE for Ph-CH3 in toluene (∼90 kcal/mol) is
relatively weak (Table 2), but the activation energy for the
Curtius rearrangement of benzoyl azide (30.0 kcal/mol) is higher
than that of an alkyl group. As explained earlier, stereoelectronic
factors can influence the high barrier for the transformation of
benzoyl azide to phenylisocyanate. However, we feel that the
comparison of BDE’s is appropriate for structurally similar
systems, as is the case for the acyl azides of cyclopropene and
cyclopropane.
Conclusions
In summary, we conclude on the basis of theoretical studies
that the Curtius rearrangements of a series of syn-acylazides
are concerted in nature. The kinetics of the Curtius rearrange-
ments of methyl 1-azidocarbonyl cycloprop-2-ene-1-carboxylate
(1) and methyl 1-azidocarbonyl cyclopropane-1-carboxylate (3)
were studied by 1H NMR spectroscopy, and there is close
agreement between calculated and experimental enthalpies and
entropies of activation. The lower activation energy for the
rearrangement of 1 relative to 3 was attributed to a weaker bond
between the carbonyl carbon and the three-membered ring in
the former compound. The calculations on 1 are not consistent
with π-stabilization of the transition state by the CdC bond of
the alkene. A comparison of reaction pathways at the CBS-
QB3 level for the Curtius rearrangement versus the loss of N2
to form a nitrene intermediate provides strong evidence that
the concerted Curtius rearrangement is the dominant process.
This combined study places the concerted mechanism of the
thermal Curtius reaction and very likely the closely related
Schmidt, Hofmann, Lossen, and Beckman reactions on a sound
mechanistic basis corroborating both earlier experimental1d,3-5
and theoretical studies.7
Methyl 1-azidocarbonyl-cycloprop-2-ene-1-carboxylate (1).
Note: In one preparation, a sample of 1 decomposed violently.
Although the preparation below describes the isolation of 1, we
strongly recommend that 1 should be handled only in solution.
Methyl cyclopropene-1,1-dicarboxylate was prepared from dimethyl
cycloprop-2-ene-1,1-dicarboxylate by the procedure of Wheeler and
Ray.14
A solution of methyl cyclopropene-1,1-dicarboxylate (0.82 g,
5.8 mmol) in THF (50 mL) was cooled by a cold bath (acetone/
dry ice, -35 °C). The solution was allowed to stir, and triethylamine
(1.23 mL, 8.66 mmol) was added dropwise. After ca. 10 min,
methyl chloroformate (0.67 mL, 8.7 mmol) was added dropwise.
The reaction mixture was allowed to stir while warming to 0 °C
over a period of 2.5 h in the same cold bath. Acetone/dry ice bath
was then replaced by an ice/water bath. Sodium azide (1.13 g, 17.3
mmol) was dissolved in H2O (5 mL) and added dropwise. After
the addition was complete, the reaction mixture was allowed to
stir at 0 °C for 40 min. The crude reaction mixture was concentrated
on the rotary evaporator. Water was added, and the mixture was
extracted with ethyl acetate (3 × 70 mL). The combined organics
were dried (MgSO4), filtered, and concentrated under reduced
pressure to provide 0.82 g (4.9 mmol, 85%) of 1 as pale brown
oil. By the time an NMR spectrum was acquired, 10% of 1 had
rearranged to isocyanate 2. As the Curtius rearrangement took place
at room temperature, it was not possible to obtain a sample of 1
Computational Methods
Quantum chemistry calculations were carried out using the
Gaussian98 and Gaussian03 program15 utilizing gradient geometry
optimization.16 The Becke three-parameter hybrid functional com-
bined with the Lee, Yang, and Parr (LYP) correlation functional,
denoted B3LYP,17 was employed in the calculations using density
functional theory (DFT). In some calculations, we used the hybrid
meta-RMPW1PW9118 DFT method. In this study, we used
6-31G(d) and 6-311+G(d,p) basis sets.19 Selected geometries were
optimized at the CCSD(T)/6-31G(d) and CCSD(T)/6-311+G(d,p)
levels to further check the relative energies of potential TSs versus
intermediates. Zero-point energy corrections are not possible in the
CCSD calculations because analytical frequencies are not yet
available for this method in Gaussian. Additionally, we used The
CBS-QB3 method, which utilizes a B3LYP/6-31G* geometry
optimization and zero-point energy. Energy refinements include
single-point corrections at MP2/6-311+G(3d2f,2df,2p) with CBS
extrapolation:MP4(SDQ)/6-31+G(d(f),p)andQCISD(T)6-31+G′.20a,b
Corrections for solvation and optimizations in dielectric medium
with the toluene dielectric constant (ε ) 2.379) were made using
the CPCM model20c,d implemented in Gaussian03. Most of calcula-
tions were performed using GridChem computational resources and
services, Computational Chemistry Grid (www.gridchem.org).21
1
that was free of the isocyanate: H NMR (CDCl3, 400 MHz, δ)
6.89 (s, 2H), 3.74 (s, 3H); 13C NMR (CDCl3, 100 MHz, δ) 177.8
(C), 170.3 (C), 102.2 (CH), 52.6 (CH3), 32.0 (C); IR (neat, cm-1
)
2143, 1730, 1712, 1437, 1282, 1214, 1133, 1008, 773, 710, 639.
Methyl 1-isocyanato-cycloprop-2-ene-1-carboxylate (2). In a
10 mL round-bottomed flask fitted with a reflux condenser, methyl
1-azidocarbonyl-cycloprop-2-ene-1-carboxylate (190 mg, 1.14 mmol)
was dissolved in anhydrous benzene (3 mL). The solution was
heated to reflux for 30 min. The reaction mixture was then
concentrated under reduced pressure to provide 142 mg (1.02 mmol,
90%) of 2. Compound 2 was further characterized by reaction with
tBuOH (Ti(iOPr)4, reflux, 50%) to give methyl 1-[(tert-butoxycar-
bonyl)amino]cycloprop-2-enecarboxylate, which was spectroscopi-
cally identical to that reported by Wheeler and Ray.14 Spectral
properties of 2: 1H NMR (CDCl3, 400 MHz, δ) 7.12 (s, 2H), 3.73
(s, 3H); 13C NMR (CDCl3, 100 MHz, δ) 172.7 (C), 126.3 (C), 108.7
Experimental Section
Dimethyl cycloprop-2-ene-1,1-dicarboxylate. The following is
(24) Wyatt, P.; Hudson, A.; Charmant, J.; Orpen, A. G.; Phetmung, H. Org.
Biomol. Chem. 2006, 4, 2218.
a modification of a procedure described by Gevorgyan.13 A solution
8196 J. Org. Chem. Vol. 73, No. 21, 2008

Mechanism of the Curtius Rearrangement
(CH), 53.4 (CH3), 38.8 (C); IR (neat, cm-1) 2244, 1730, 1439, 1280,
1215, 1051, 754.
Methyl 1-azidocarbonyl-cyclopropane-1-carboxylate (3). Note:
Low molecular weight acyl azides present explosion hazards (see
preparation of 1). Although compound 3 was isolated in the
preparation below, we recommend that 3 should not be isolated in
pure form and should only be handled in solution.
dissolved in toluene-d8. Analyses of 1 were carried out at 303, 313,
and 323 K. Analyses of 3 were carried out at 323, 334, and 344 K.
Each kinetic run consisted of 90-220 1H NMR experiments, with
2-4 scans in each experiment and a time interval of 20-144 s
between two successive experiments. All reactions were monitored
to 75% conversion except for the reaction of 3 at 323 K, which
was carried out to 52% conversion. After all the experiments in a
kinetic run were finished, they were all integrated serially at the
same time. The singlet corresponding to the methoxy group in the
starting material in the first experiment of the series was normalized
to 100%. The singlet peak appearing at the same chemical shift in
the following experiments was measured against the one that was
normalized to 100% in the first experiment. The residual solvent
peaks from toluene-d8 served as an internal standard for this
analysis: the combined integrals for the product and starting material
methoxy singlets were constant relative to the toluene-d8 methyl
group over the course of the reaction.
Integration values were plotted against time to create a curve
that indicated the disappearance of the starting material as the time
progressed. The first-order rate constants (k) were obtained from a
plot of time versus ln [integration]. Error analysis was conducted
by plotting the combined data from duplicate runs: a straight line
was fit to each plot using the Origin software package. The sample
standard deviation for each rate constant was calculated from the
standard error of the mean associated with each line fit. The error
from the rate was propagated in straightforward fashion for the
calculations of ∆Hq, ∆Gq, and Ea. The values for ∆Sq reported in
Table 1 are averages from the solutions of the Erying equation at
three temperatures. The variance in ∆Sq was estimated by sum of
squares analysis.
A solution of methyl cyclopropane-1,1-dicarboxylate25 (1.15 g,
8.0 mmol) in THF (35 mL) was cooled by a cold bath (acetone/
dry ice, -35 °C). The solution was allowed to stir, and triethylamine
(1.36 mL, 9.6 mmol) was added dropwise. After ca. 10 min, methyl
chloroformate (0.74 mL, 9.6 mmol) was added dropwise. The
reaction mixture was allowed to stir while warming to 0 °C over a
period of 2.5 h in the same cold bath. The acetone/dry ice bath
was then replaced by an ice/water bath. Sodium azide (1.56 g, 23.9
mmol) was dissolved in H2O (5 mL) and added dropwise. After
the addition was complete, the reaction mixture was allowed to
stir at 0 °C for 1 h. The crude reaction mixture was concentrated
on the rotary evaporator. Water was added, and the mixture was
extracted with ethyl acetate (3 × 70 mL). The combined organic
layers were dried (MgSO4), filtered, and concentrated under reduced
pressure. Flash column chromatography (3-5% diethyl ether in
hexane) furnished 1.13 g (6.68 mmol, 84%) of 3 as colorless oil:
1H NMR (CDCl3, 400 MHz, δ) 3.75 (s, 3H), 1.57-1.54 (m, 4H);
13C NMR (CDCl3, 100 MHz, δ) 176.4 (C), 169.4 (C), 52.8 (CH3),
30.1 (C), 18.2 (CH2); IR (neat, cm-1) 2145, 1730, 1712, 1695, 1334,
1298, 1130, 1063, 1015.
Methyl 1-isocyanato-cyclopropane-1-carboxylate (4). In a 10
mL round-bottomed flask fitted with reflux condenser, methyl
1-azidocarbonyl- cyclopropane-1-carboxylate (100 mg, 0.59 mmol)
was dissolved in anhydrous benzene (2 mL). The solution was
heated to reflux for 50 min. The reaction mixture was then
concentrated under reduced pressure to provide 73 mg (0.52 mmol,
87%) of the title compound: 1H NMR (C7D8, 400 MHz, δ) 3.26 (s,
3H), 1.07-1.04 (m, 2H), 0.71-0.68 (m, 2H); 13C NMR (C7D8,
100 MHz, δ) 171.8 (C), 52.5 (CH3), 36.9 (C), 16.8 (CH2); IR (neat,
cm-1) 2262, 1731, 1441, 1328, 1230, 1196, 1069, 1040, 747, 730;
HRMS-CI (NH3) m/z [M + H], calcd for C6H7NO3, 142.0504;
found 142.0504.
Acknowledgment. This work was supported by NIH Grant
GM068640-01, and by National Computational Science Alliance
under CHE050085 and CHE050039N and utilized the NCSA
IBM P690 and NCSA Xeon Linux Supercluster. GridChem is
also acknowledged for computational resources (www.grid-
chem.org) (see ref 21).
Supporting Information Available: Total energies and
Cartesian coordinates. This material is available free of charge
via the Internet at http://pubs.acs.org.
NMR Kinetic Experiments. NMR studies were carried out in
duplicate with 20 mg sample of acyl azides 1 and 3 that were
(25) Westermann, J.; Schneider, M.; Platzek, J.; Petrov, O. Org. Process
Res. DeV. 2007, 11, 200.
JO801104T
J. Org. Chem. Vol. 73, No. 21, 2008 8197