Experimental and theoretical analysis of the photochemistry and thermal reactivity of ethyl diazomalonate and its diazirino isomer. The role of molecular geometry in the decomposition of diazocarbonyl compounds

Article abstract of DOI:10.1021/ja047824r

The photochemical or thermal decomposition of ethyl diazomalonate (1) or ethyl 3,3-diazirinedi-carboxylate in methanol solutions yields the O-H insertion product 6, while products of the Wolff rearrangement were not detected in both cases. The analysis of temperature-dependent ¹³C NMR spectra and the results of DFT B3LYP/6-311+G(3df,2p) and MP2/aug-cc-pVTZ//B3LYP/6-311+G(3df,2p) calculations allow us to conclude that diazodiester 1 predominantly exists in the Z,Z-conformation. In contrast, photolysis of the cyclic isopropylidene diazomalonate (3), which also has a Z,Z-configuration of the diazodicarbonyl moiety, results in a clean Wolff rearrangement. These observations allow us to conclude that the direction of the photodecomposition of diazomalonates is not controlled by the ground-state conformation. The quantum-mechanical analysis of the potential energy surfaces for the dediazotization of 1 and 3 suggests that the formation of a carbene as a discrete intermediate is controlled by the ability of the latter to adopt a conformation in which carbonyl groups are almost orthogonal to the carbene plane. The outcome of the photolysis of ethyl diazomalonate depends on the wavelength of irradiation. Irradiation with 254 nm light results in the loss of nitrogen and the formation of dicarboethoxycarbene (5, Φ₂₅₄ = 0.31), while at longer wavelengths, diazirine 2 becomes an important byproduct (Φ₃₅₀ = 0.09). This observation suggests that the formation of carbene 5 and isomerization to diazirine proceed from different electronically excited states of ethyl diazomalonate.

Full text of DOI:10.1021/ja047824r

Published on Web 08/20/2004
Experimental and Theoretical Analysis of the Photochemistry
and Thermal Reactivity of Ethyl Diazomalonate and Its
Diazirino Isomer. The Role of Molecular Geometry in the
Decomposition of Diazocarbonyl Compounds
Aneta Bogdanova and Vladimir V. Popik*
Contribution from the Center for Photochemical Sciences, Bowling Green State UniVersity,
Bowling Green, Ohio 43403
Received April 15, 2004; E-mail: vpopik@bgnet.bgsu.edu
Abstract: The photochemical or thermal decomposition of ethyl diazomalonate (1) or ethyl 3,3-diazirinedi-
carboxylate in methanol solutions yields the O-H insertion product 6, while products of the Wolff
rearrangement were not detected in both cases. The analysis of temperature-dependent 13C NMR spectra
and the results of DFT B3LYP/6-311+G(3df,2p) and MP2/aug-cc-pVTZ//B3LYP/6-311+G(3df,2p) calcula-
tions allow us to conclude that diazodiester 1 predominantly exists in the Z,Z-conformation. In contrast,
photolysis of the cyclic isopropylidene diazomalonate (3), which also has a Z,Z-configuration of the
diazodicarbonyl moiety, results in a clean Wolff rearrangement. These observations allow us to conclude
that the direction of the photodecomposition of diazomalonates is not controlled by the ground-state
conformation. The quantum-mechanical analysis of the potential energy surfaces for the dediazotization of
1 and 3 suggests that the formation of a carbene as a discrete intermediate is controlled by the ability of
the latter to adopt a conformation in which carbonyl groups are almost orthogonal to the carbene plane.
The outcome of the photolysis of ethyl diazomalonate depends on the wavelength of irradiation. Irradiation
with 254 nm light results in the loss of nitrogen and the formation of dicarboethoxycarbene (5, Φ254
)
0.31), while at longer wavelengths, diazirine 2 becomes an important byproduct (Φ350 ) 0.09). This
observation suggests that the formation of carbene 5 and isomerization to diazirine proceed from different
electronically excited states of ethyl diazomalonate.
Scheme 1
Introduction
Photochemically or thermally induced extrusion of nitrogen
from R-diazocarbonyl compounds usually leads to the formation
of products formed by trapping of two different reactive
intermediates, that is, ketenes and R-carbonylcarbenes (Scheme
1). Ketenes react with nucleophiles to produce carboxylic acid
derivatives, and this overall process is known as the Wolff
rearrangement.1,2 R-Carbonylcarbenes, on the other hand, under-
go an O-H or C-H insertion, add to π- bonds, or form ylides.3
The factors that direct the decomposition of R-diazocarbonyl
compounds into a ketene or carbene pathway are still not well
understood. It has been observed that cyclic diazoketones usually
produce high or quantitative yields of ketenes, while in the case
of their acyclic analogues, the Wolff rearrangement is often
accompanied or even completely suppressed by carbene reac-
tions.4,5 The low-temperature NMR experiments unequivocally
proved that R-diazocarbonyl compounds exist as an equilibrium
of two conformations with s-Z and s-E arrangement of diazo
and carbonyl groups.6,7 The s-Z isomer usually predominates
in the equilibrium, unless steric repulsions of substituents R and
R′ destabilize it in favor of the s-E form.1,8
(1) Kirmse, W. Eur. J. Org. Chem. 2002, 2193.
(2) Meier, H.; Zeller, K.-P. Angew. Chem., Int. Ed. Engl. 1975, 14, 32. (b)
Regitz, M.; Maas, G. Diazo Compounds; Academic Press: Orlando, FL,
1986. (c) Ye, T.; McKervey, A. M. Chem. ReV. 1994, 94, 1091. (d) Doyle,
M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic
Synthesis with Diazo Compounds; Wiley-Intersciences: New York, 1998;
pp 487-534. (e) Zeller, K.-P.; Meier, H.; Muller, E. Tetrahedron 1972,
28, 5831.
(3) Toscano, J. P. In AdVances in Carbene Chemistry; Brinker, U. H., Ed.;
JAI Press: Greenwich, CT, 1998; Vol. 2, pp 216-245. (b) Jones, M.; Moss,
R. A. Carbenes; Wiley: New York, 1973. (c) Zollinger, H. Diazo chemistry,
2. Aliphatic, inorganic, and organometallic compounds; VCH Publishers:
New York, 1995; pp 305-357. (d) Kirmse, W. Carbenes and the O-H
bond. In AdVances in Carbene Chemistry; Brinker, U. H., Ed.; JAI Press
Inc.: Greenwich, CT, 1994; pp 1-57. (e) Miller, D. J.; Moody, C. J.
Tetrahedron 1995, 40, 10811.
Based on the differences in the reactivity of 3,3,6,6-
tetramethyl-2-diazocyclohexanone, which is locked in the s-Z
configuration, and 2,2,5,5-tetramethyl-4-diazo-3-hexanone,5,9
which is forced to adopt the s-E conformation by bulky tert-
butyl substituents, Kaplan postulated that s-Z conformers of
9
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J. AM. CHEM. SOC. 2004, 126, 11293-11302
11293

A R T I C L E S
Bogdanova and Popik
Figure 1. Conformational energy profile for methyl diazomalonate (1′) obtained using the relaxed scan of PES at the B3LYP/6-31+G(d,p) level. The
geometries of three stable conformations of methyl diazomalonate (1′) and the transition states for the rotation around CO-CN2 bonds (1q) were optimized
at the B3LYP/6-311+G(3df,2p) level of theory.
R-diazocarbonyl compounds undergo a concerted Wolff rear-
rangement to ketenes, whereas the s-E form loses nitrogen to
produce R-carbonylcarbene. The latter can undergo isomeriza-
tion into ketenes or be trapped by external reagents. While this
hypothesis has been adopted by other authors,3a,10 some
established s-E diazo ketones produce ketenes with ease.11
One of the most impressive examples of the structural control
of the Wolff rearrangement is found in the family of diazoma-
lonic acid esters. Cyclic isopropylidene diazomalonate (diazo
Meldrum’s acid, 3) undergoes an efficient Wolff rearrangement
both thermally12 and photochemically,12,13 while acyclic diaz-
omalonates, such as 1, produce only carbenic products in
solution.14,15 The conventional explanation for this phenomenon
is based on the assumption that the irradiation of conforma-
tionally flexible acyclic R-diazoesters produces carbalkoxycar-
benes, which do not rearrange due to the low migratory aptitude
of oxygen.2a The excitation of Z,Z-locked diazo Meldrum’s acid,
on the other hand, results in the concerted Wolff rearrangement
that bypasses the R-carbonyl carbene step.
We have recently reported experimental and theoretical
evidence supporting the concerted mechanism for the Wolff
rearrangement of the diazo Meldrum’s acid. However, the
corresponding R,R′-dicarbonylcarbene, which is apparently
produced in the photolysis of diazirine 4, smoothly rearranges
to ketene with virtually no activation barrier.12 To get a better
understanding of the structural influence on the reactivity of
R-diazocarbonyl compounds, we undertook a detailed investiga-
tion of the photo- and thermal chemistry of conformationally
flexible acyclic ethyl diazomalonate (1) and the corresponding
diazirine 2.
(4) Horner, L.; Korobitsyna, I. K.; Rodina, L. L.; Sushko, T. P. Zh. Org. Khim.
1968, 4, 175. Timm, U.; Zeller, K. P.; Meier, H. Tetrahedron 1977, 33,
453. Tomioka, H.; Okuno, H.; Izawa, Y. J. Org. Chem. 1980, 45, 5278.
Rau, H.; Bokel, M. J. Photochem. Photobiol., A 1990, 53, 311. Hadel, L.
M.; Maloney, V. M.; Platz, M. S.; McGimpsey, W. G.; Scaiano, J. C. J.
Phys. Chem. 1986, 90, 2488. Tomioka, H.; Hirai, K.; Tabayashi, K.; Murata,
S. J. Am. Chem. Soc. 1990, 112, 7692. Chiang, Y.; Kresge, A. J.; Pruszynski,
P.; Schepp, N. P.; Wirz, J. Angew. Chem., Int. Ed. Engl. 1991, 30, 1366.
Charette, A. B.; Wurz, R. P.; Ollevier, T. HelV. Chim. Acta 2002, 85, 4468.
Tippmann, E.; Holinga, G.; Platz, M. S. Org. Lett. 2003, 5, in press.
(5) Kaplan, F.; Mitchell, M. L. Tetrahedron Lett. 1979, 9, 759.
(6) Kaplan, F.; Meloy, G. K. Tetrahedron Lett. 1964, 2427. Kaplan, F.; Meloy,
G. K. J. Am. Chem. Soc. 1966, 88, 950. Kessler, H.; Rosenthal, D.
Tetrahedron Lett. 1973, 393. Curci, R.; DiFuria, F.; Lucchini, V. Spectrosc.
Lett. 1974, 7, 211. Lichter, R. L.; Srinivasan, P. R.; Smith, A. B., III; Dieter,
R. K.; Denny, C. T. Chem. Commun. 1977, 366. Dickert, F. L.; Soliman,
F. M.; Bestmann, H. J. Tetrahedron Lett. 1982, 23, 2639.
(7) Nikolaev, V. A.; Rodina, L. L.; Korobitsyna, I. K. Zh. Org. Khim. 1974,
10, 1555. (b) Lauer, W.; Krause, V.; Wengenroth, H.; Meier, H. Chem.
Ber. 1988, 121, 465. (c) Nikolaev, V. A.; Popik, V. V. Zh. Org. Khim.
1989, 25, 1014.
(8) Sorriso, S. In The Chemistry of Diazonium and Diazo Groups; Patai, S.,
Ed.; Wiley: Chichester, 1978; pp 95-136. Goodman, J. M.; James, J. J.;
Whiting, A. J. Chem. Soc., Perkin Trans. 2 1994, 109.
Results and Discussion
Conformational Analysis. The DFT/MP2 analysis of the
structure and reactivity of ethyl diazomalonate (1) was con-
ducted on the example of methyl diazomalonate (1′, Figure 1).
Ethyl groups in 1′ were replaced with methyl groups to simplify
calculations. In our opinion, this modification should not
significantly disturb the relative energies of the species involved
in the transformations of 1.
There are three relatively stable conformations of the R-diazo-
â,â-dicarbonyl fragment in acyclic diazomalonates: Z,Z; Z,E;
(9) Geometry optimization of this diazo compound, that we conducted at the
b3lyp/6-311+G(3df,2p) level of theory, produced the planar s-E conforma-
tion.
(13) Nikolaev, V. A.; Khimich, N. N.; Korobitsyna, I. K. Khim. Geterotsikl.
Soedin. 1985, 321. Lippert, T.; Koskelo, A.; Stoutland, P. O. J. Am. Chem.
Soc. 1996, 118, 1551. Winnik, M. A.; Wang, F.; Nivaggioli, T.; Hruska,
Z.; Fukumura, H.; Masuhara, H. J. Am. Chem. Soc. 1991, 113, 9702.
Stevens, R. V.; Bisacchi, G. S.; Goldsmith, L.; Strouse, C. E. J. Org. Chem.
1980, 45, 2708. Kammula, S. L.; Tracer, H. L.; Shelvin, P. B.; Jones, M.,
Jr. J. Org. Chem. 1977, 42, 2931.
(14) Wang, J.-L.; Toscano, J. P.; Platz, M. S.; Nikolaev, V.; Popik, V. J. Am.
Chem. Soc. 1995, 117, 5477. (b) Jones, M., Jr.; Ando, W.; Hendrick, M.
E.; Kulczucki, A.; Howley, P. M.; Hummel, K. F.; Malament, D. S. J. Am.
Chem. Soc. 1972, 94, 7469.
(10) Tomioka, H.; Okuno, H.; Izawa, Y. J. Org. Chem. 1980, 45, 5278. Tomioka,
H.; Kondo, M.; Izawa, Y. J. Org. Chem. 1981, 46, 1090. Marfisi, C.;
Verlaque, P.; Davidovics, G.; Pourcin, J.; Pizzala, L.; Aycard, J.-P.; Bodot,
H. J. Org. Chem. 1983, 48, 533. Tsuda, M.; Oikawa, S.; Nagayama, K.
Chem. Pharm. Bull. 1987, 35, 1. Tsuda, M.; Oikawa, S. Chem. Pharm.
Bull. 1989, 37, 573. Torres, M.; Gosavi, R. K.; Lown, E. M.; Piotrkowski,
E. J.; Kim, B.; Bourdelande, J. L.; Font, J.; Strausz, O. P. Stud. Phys. Theor.
Chem. 1992, 77, 184. Toscano, J. P.; Platz, M. S.; Nikolaev, V.; Popik, V.
J. Am. Chem. Soc. 1994, 116, 8146.
(11) Zeller, K. P. Chem. Ber. 1979, 112, 678. Fenwick, J.; Frater, G.; Ogi, K.;
Strausz, O. P. J. Am. Chem. Soc. 1973, 95, 124. Torres, M.; Ribo, J.;
Clement, A.; Strausz, O. P. Can. J. Chem. 1983, 61, 996.
(15) In the absence of trapping reagent, for example, in cryogenic matrix or in
the gas phase, dicarbalkoxycarbene can undergo Wolff rearrangement:
Visser, P.; Zuhse, R.; Wong, M. W.; Wentrup, C. J. Am. Chem. Soc. 1996,
118, 12598.
(12) Bogdanova, A.; Popik, V. V. J. Am. Chem. Soc. 2003, 125, 14153.
9
11294 J. AM. CHEM. SOC. VOL. 126, NO. 36, 2004

Thermal Reactivity of Ethyl Diazomalonate
A R T I C L E S
Figure 2. Temperature-dependent 13C spectra of diethyl diazomalonate.
Table 1. Relative Energies and Main Geometrical Parameters of the Equilibrium and Transition Structures Obtained at the B3LYP/
6-311+G(3df,2p)//B3LYP/6-311+G(3df,2p) and MP2 (full) aug-cc-pVTZ//B3LYP/6-311+G(3df,2p) (in Parentheses) Levels
q
q
1′ZZ
1′ZE
1′EE
1 ZZfZE
1 ZEfEE
2′
a
Erel
0.35
0.00
0.55
7.59
7.63
24.17
ZPVE corrected
(kcal/mol)
(0.02)
(0.82)
(8.32)
(9.81)
(20.73)
C1-N6 distanceb/Å
1.326
1.110
134.5
180.0
180.0
1.322
1.110
129.6
180.0
0.0
1.318
1.110
124.9
0.0
1.302
1.120
124.7
-87.6
177.1
1.301
1.120
120.7
-3.5
1.506
1.200
124.5
-12.7
162.9
N
-
6-N7 distance/Å
C2C1C3/deg
-
-
C3C1C2O4/deg
C2C1C3O5/deg
0.0
-86.4
a Energy difference between 1′Z,E and the corresponding structure. b The numbering of atoms in structures 1′, 1q, and 2′ is shown in Figure 1.
and E,E. The DFT optimized geometry of these conformers, as
well as the geometries of the transition states for Z,Z f Z,E
and Z,E f E,E interconversions, are shown in Figure 1. The
electronic energies and representative structural parameters of
these structures, as well as those of dimethyl 3,3-diazirinedi-
carboxylate (2′), are summarized in Table 1. Energies shown
in the text and in the figures correspond to B3LYP/
6-311+G(3df,2p) calculations, while values in parentheses were
obtained using the MP2(full)/aug-cc-pVTZ//B3LYP/6-311+G-
(3df,2p) method. It is interesting to note that all three conformers
were calculated to be perfectly planar, which indicates the
absence of substantial steric interactions. The E,E-conformer
is predicted to be the least stable one, while Z,Z and Z,E have
similar energies. The preference for the Z-arrangement of diazo
and carbonyl functionalities is usually explained by the Cou-
lombic attraction between the positively charged nitrogen of
the diazo group and the negatively charged carbonyl oxygen
atom.8 The barrier for the interconversion between conforma-
tions was predicted to be in the range of 7.6-9.8 kcal/mol (Table
1). In the transition state from Z,Z to Z,E, as well as for the Z,E
to E,E transformation, the carbonyl group that has the same
arrangement in both conformers stays virtually coplanar with
the diazo group, while the other carbonyl fragment is almost
orthogonal to the CdN2 plane.16 The conformational energy
profile shown in Figure 1 was obtained by conducting a relaxed
scan of the potential energy surface starting from the Z,E-
conformer and following the dihedral angle between diazo and
one of the carbonyl groups.
Similar changes are observed in the methylene region of the
spectrum, where splitting of the signal is observed below -70
°C. The coalescence temperature for the carbonyl signals, Tcoal
) -60 °C, and for methylene signals, Tcoal ) -70 °C, allows
us to evaluate the barrier for the conformational interconversion.
For both temperatures, we have obtained identical values of
activation energy ∆Gq
) ∆Gq
) 9.3 kcal/mol, which
213K
203K
are in a good agreement with DFT/MP2 results (Table 1). From
the shape of the NMR signals observed at conditions of slow
exchange (Figure 2), we can conclude that diethyl diazomalonate
exists in solution as a rapid equilibrium of two conformations.
The major conformer, ca. 85%, should be a symmetrical one
as it has only one set of signals in the 13C spectrum. Quantum-
mechanical calculation (vide supra), as well as the known
predominance of the Z,Z-conformer in sterically unhindered
2-diazo-1,3-diketones,7 allows us to assign Z,Z-structure to this
conformer. The alternative symmetrical conformation, E,E, is
predicted to be higher in energy than Z,Z and Z,E by all
quantum-mechanical models, from semiempirical AM1 to
density functional b3lyp and to correlative MP2. In fact, the
E,E-conformer was observed only as a minor component of the
equilibrium mixture in diazodicarbonyl compounds with bulky
substituents.7,17 Additional support for this assignment comes
from the fact that the carbonyl signal of the s-E carbonyl group
in diazodicarbonyl compounds is usually observed at lower
fields than the s-Z signal.7,17 The assignment of a minor
component is more difficult. The signal at 163.25 ppm can
represent both carbonyl groups of a symmetrical E,E-conforma-
tion or E-fragment of the Z,E-conformer, while signals of the
Z-part overlap with an intense peak of the major Z,Z-form. On
the basis of the experimental and theoretical results discussed
above, we favor Z,E-assignment.
Low-temperature NMR experiments allowed us to observe
the conformational equilibrium of ethyl diazomalonate in
solutions. At room temperature, the 13C spectrum of 1 contains
only one set of signals for all carbons. At ca. -30 °C, the signal
of the carbonyl group becomes broad and splits in two below
-60 °C (Figure 2).
In the diazirine 2, the central carbon atom (C1) is formally
sp3 hybridized, and rotation of the carbonyl fragments around
(16) The optimized geometries for the species discussed in the paper are provided
in the Supporting Information.
(17) Nikolaev, V. A.; Popik, V. V.; Korobitsyna, I. K. Zh. Org. Khim. 1991,
27, 505.
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A R T I C L E S
Bogdanova and Popik
C(dO)-C1 should be virtually free. In fact, DFT calculations
predict the barrier for such a rotation in 2′ to be in the order of
2 kcal/mol. The conformational analysis found three relatively
stable rotamers, which are very close in energy: ∆∆E° values
are 0 and 1.1 kcal/mol correspondingly. The geometrical
parameters for the rotamer with the lowest energy are shown
in Table 1.16 In other words, irradiation of 2 should result in
the excitation of a broad spectrum of ground-state conforma-
tions.
Thermal Reactions of the Ethyl Diazomalonate (1) and
Ethyl 3,3-Diazirinedicarboxylate (2). Diazomalonate (1) is a
relatively stable compound; for example, virtually no decom-
position was observed in aqueous or methanolic solutions at
80 °C for 24 h. Due to the high stability of this diazo compound,
little is known about products resulting from its thermal
decomposition. We found that heating ethyl diazomalonate (1)
at 150 °C in neat methanol for 6 h results in quantitative
formation of ethyl 2-methoxymalonate (6), the apparent product
of carbene 5 insertion into the O-H bond of a solvent (Scheme
2). The latter was independently prepared by rhodium-catalyzed
decomposition of ethyl diazomalonate in the presence of
methanol (see Experimental Section). Formation of the insertion
product in the thermolysis of 1 is in sharp contrast with the
thermolysis of cyclic analogue 3, which produces only Wolff
rearrangement products.
Figure 3. Temperature rate profiles for the decomposition of diazirine 2
in aqueous (circles) and dioxane (hexagons) solutions. The lines shown
were drawn using parameters obtained by least-squares fitting of the Eyring
equation.
Scheme 2
Figure 4. UV spectra of ca. 0.00015 M solutions of ethyl diazomalonate
(1, -) and of ca. 0.003 M solutions of ethyl 3H-diazirine-3,3-dicarboxylate
(2, - - -) in methanol.
The isomeric diethyl 3,3-diazirinedicarboxylate (2), on the
other hand, is rather labile and undergoes slow decomposition
even at room temperature with k25°C ) (3.7 ( 0.3)*10-5 s-1 in
methanol. Mild heating of 2 in a methanol solution results in
the rapid decomposition and formation of the O-H insertion
product 6. The isomerization into the diazo compound, which
is the only process observed in the case of cyclic diazirine 4,12
produced only trace amounts (ca. 2%) of ethyl diazomalonate
(1, Scheme 3).
It is interesting to note that the activation parameters for the
decomposition of bis-carboethoxydiazirine (2) in dioxane are
almost identical to the values reported for the cyclic diazirino
Meldrum’s acid (4, ∆Hq ) 22.2 kcal M-1 and ∆Sq ) -10.2 (
2.4 cal M-1 K-1).12 In aqueous solution, the situation is
drastically different: enthalpy of activation for the decomposi-
tion of acyclic diazirine 2 is very close to the dioxane value,
while cyclic diazirine 4 decays in water with a substantially
lower ∆Hq ) 12.6 kcal M-1. This difference can be explained
by the different polarity of transition states for the reactions of
2 and 4. The latter undergoes isomerization from nonpolar
diazirine to a very polar diazodicarbonyl compound 3. The
transition state for this process is, therefore, more polar than
reagent and is better stabilized by a polar solvent. Ethyl 3,3-
diazirinedicarboxylate (2), on the other hand, loses nitrogen to
produce carbene 5, which has a polarity similar to the starting
material. Thus, the dipole moment of the most stable rotamer
of diazirine 2′ is 2.34 D, which is exactly the same as the dipole
moment predicted for the most stable conformer of singlet
carbene 5 (vide infra). The changes in polarity of the substrate
along the reaction coordinate are small, and the enthalpy of
activation should be less dependent on solvent polarity.
Scheme 3
Rates of the decomposition of diazirine 2 were measured in
aqueous and dioxane solutions in the temperature range from
30 to 70 °C. The progress of the reaction was followed by the
decrease in absorbance of 2 at 291 nm. The data so obtained
are summarized in Tables S1-S2 and are displayed as a
temperature rate profile in Figure 3.
The decomposition of 2 is 2-4 times faster in water than in
dioxane, and this rate difference increases with temperature,
indicating a substantial difference in the entropy of activation.
In fact, least-squares fitting of the data gives the following
activation parameters: ∆Hq ) 24.9 ( 0.6 kcal M-1 and ∆Sq )
2.8 ( 1.6 cal M-1 K-1 in aqueous solutions; and ∆Hq ) 22.2
( 0.6 kcal M-1 and ∆Sq ) -7.4 ( 1.8 cal M-1 K-1 in dioxane.
Photochemistry of Ethyl Diazomalonate (1) and Diethyl
3,3-Diazirinedicarboxylate (2). The UV spectrum of diazoma-
lonate 1 has a strong absorbance at 251 nm and a much weaker
band at 344 nm (Figure 4). No fluorescence or phosphorescence
was detected at room temperature in solutions of 1 using 254
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11296 J. AM. CHEM. SOC. VOL. 126, NO. 36, 2004

Thermal Reactivity of Ethyl Diazomalonate
A R T I C L E S
Scheme 4
Scheme 5
Table 2. Results of Low Conversion Photolyses of Ethyl
Diazomalonate (1) in Methanol at Different Wavelengths
Table 3. Results of Low Conversion Photolyses of Ethyl
3H-3,3-Diazirinedicarboxylate (2) in Methanol at Different
Wavelengths
wavelength of irradiation λ (nm)
product
254
300
350
355a
sensb
wavelength of irradiation (nm)
fraction in reaction mixture
product
254
300
350
6
2
7
0.90
0.10
>0.01
0.83
0.17
>0.01
0.68
0.32
>0.01
0.67
0.33
>0.01
0
0
1
fraction in product mixture
6
1
0.99
0.01
0.81
0.19
0.99
0.01
quantum
yield
0.31
0.09
a Monochromatic irradiation using the frequency up-converted output
of the Nd:YAG laser. b Sensitized photolysis was conducted at 254 nm in
2-propanol using a 10-fold excess of benzophenone as a sensitizer.
of diazomalonate 1 should be very fast, in the order of 1012
s-1, to compete with the internal conversion. The much higher
quantum yield of photolysis at 254 nm than that at 350 nm
provides an argument against the formation of a carbene from
“hot” S1 molecules.
Irradiation into a weak long-wavelength band of ethyl
diazomalonate results in a higher fraction of molecules populat-
ing the lowest excited-state S1. This state undergoes an efficient
thermal deactivation to the ground state, which is evident from
a low quantum yield (Φ350 ) 0.09) of phototransformation of
1 at 350 nm, as well as the absence of fluorescence or
phosphorescence of 1. A small fraction of S1 population
undergoes isomerization into diazirine 2.
Benzophenone-sensitized photolysis apparently populates the
lowest triplet excited state of 1, which loses nitrogen to produce
a triplet carbene 5T. The latter undergoes a double hydrogen
abstraction to give ethyl malonate (7). Traces of 7 found in direct
photolyses are apparently due to the low efficiency intersystem
crossing, which yields a triplet excited state of 1. It is interesting
to note that the product of singlet carbene 5S insertion into the
O-H bond of methanol, ethyl 2-methoxymalonate (6), was not
detected in the triplet-sensitized photolyses of ethyl diazoma-
lonate in methanol. This observation indicates that the abstrac-
tion of hydrogen from the solvent by the triplet state of
dicarboethoxycarbene (5T) is much faster than the intersystem
crossing to a singlet state.
and 350 nm excitation light, indicating fast nonradiative
depopulation of excited states. The UV spectrum of isomeric
diazirine 2 is very different: it shows a weak band at 291 nm
and a shoulder on the tail of the short-wavelength band at ca.
244 nm (Figure 4). The spectral characteristics of compounds
1 and 2 are very close to their cyclic counterparts 3 and 4.12
Direct photolysis of the methanol solution of ethyl diazoma-
lonate (1) results in the formation of two major products: ethyl
2-methoxymalonate 6, the product of the O-H insertion reaction
of dicarbethoxycarbene (5), and diazirine 2, the product of
isomerization of the starting diazo compound (Scheme 4). Trace
amounts of ethyl malonate (7) were also detected in the reaction
mixtures. As was mentioned in the Introduction, the photo-
chemical behavior of the cyclic diazomalonate 3 is very different
as it produces mostly Wolff rearrangement products under
similar conditions.
The triplet sensitized photolysis of 1 in methanol results in a
quantitative formation of the malonic ester (7). The triplet
reactivity of the diazomalonate 1, therefore, is similar to that
of diazo Meldrum’s acid (3) and is in line with the accepted
mechanism of the photochemical reduction of R-diazocarbonyl
compounds through a triplet carbonylcarbene intermediate.1,2a
The product ratio of direct photolysis depends on the
wavelength of irradiation: shorter wavelengths favor the forma-
tion of the O-H insertion product 6, while isomerization to
diazirine 2 becomes a prominent process at λirr > 300 nm. Table
2 shows the relative yield of compounds 2, 6, and 7 formed in
photolysis of ethyl diazomalonate (1) at different wavelengths.
Product ratios were measured at a low conversion (ca. 10%) to
ensure that these values were not affected by secondary
photochemistry.
The photochemical behavior of ethyl 3,3-diazirinedicarboxy-
late (2) is similar to that of its diazo isomer: UV irradiation of
2 results in the formation ethyl 2-methoxymalonate (6) ac-
companied by minor diazirine to diazo isomerization (Scheme
5).
The results of low conversion photolyses (ca. 10%, Table 3)
of diazirine 2 allow us to conclude that the O-H insertion
product 6 is formed directly from diazirine 2, rather than from
initially formed diazodiester 1. The molar absorptivity of
dicarboethoxydiazirine (2) at 300 nm (ꢀ300 ) 86 M-1 cm-1) is
more than 6 times higher than that of ethyl diazomalonate (1,
ꢀ300 ) 13 M-1 cm-1). Low conversion photolysis of diazirine
2 at this wavelength should not result in the decomposition of
the diazo compound formed by isomerization of the starting
material. At 254 and 350 nm, the situation is reversed, and a
low yield of ethyl diazomalonate is apparently due to secondary
photochemistry.
The wavelength dependences of the dediazotization to
isomerization product ratio and of the quantum yield are similar
to the photochemical behavior of cyclic diazodiester 3,12
although they are less pronounced. The short-wavelength
irradiation of 1 apparently populates the higher excited state.
About one-third of the molecules at this level lose nitrogen to
give carbene 5. The rest of the molecules undergo an internal
conversion to S1, the participation of which is evident from the
formation of small amounts of diazirine 2, and then onto the
ground-state surface. The loss of nitrogen from the excited state
Theoretical Analysis of the Decomposition of Ethyl Dia-
zomalonate (1). The geometries of the structures discussed
9
J. AM. CHEM. SOC. VOL. 126, NO. 36, 2004 11297

A R T I C L E S
Bogdanova and Popik
Figure 5. B3LYP/6-311+G(3df,2p) optimized geometries of syn-(5SZ) and anti-(5SE) conformers of the singlet carbene, the E,E rotamer of a triplet carbene
(5TEE), transition states for the dediazotization of Z,Z-methyl diazomalonate (1qZZ), and for the Wolff rearrangement of the anti-(5qE) and syn-(5q
)
Z
dicarbomethoxycarbene.
Table 4. Relative Energies and Main Geometrical Parameters of the Equilibrium and Transition Structures Obtained at the B3LYP/
6-311+G(3df,2p)//B3LYP/6-311+G(3df,2p) and MP2 (full) aug-cc-pVTZ//B3LYP/6-311+G(3df,2p) (in Parentheses) Levels
q
q
q
q
q
c
c
c
1 ZZ
1 ZE
1 EE
5SE
5SZ
5 E
5 Z
5TZZ
5TZE
5TEE
a,b
Erel
38.8
36.1
35.5
29.5
(46.0)
31.75
(48.3)
37.6
(52.1)
36.7
(49.7)
34.0
(50.4)
32.1
(49.1)
31.0
(48.7)
ZPVE corrected
(kcal/mol)
C1-N6 distance/Å
2.280
1.090
122.8
100.5
-100.5
2.200
1.090
125.4
74.4
115.9
2.190
1.090
125.1
65.57
-65.57
N6-N7 distance/Å
-
-
-
C2C1C3/deg
122.6
94.9
94.9
123.9
80.3
-80.3
124.0
82.2
90.8
127.3
79.8
-90.0
143.9
149.2
149.1
137.0
-12.5
-130.8
133.9
-31.2
-31.2
C3C1C2O4/deg
C2C1C3O5/deg
a Energy difference between 1′ZE and the corresponding structure. b Energies of various forms of carbene 5 and transition states 5q are corrected by the
addition of energy of a free nitrogen molecule (-109.5176551 (-109.3936875); ZPVE ) 3.513 kcal/mol). c Conformations of the triplet dicarbomethoxym-
ethylene are labeled as the conformers of 1′ having similar arrangements of carbon and oxygen atoms in the molecule.
below were preoptimized at the B3LYP/6-31+G(d,p) level and
then reoptimized using the extended triple-ú 6-311+G(3df,2p)
basis set. The energies of the resulting structures were also
calculated at the full MP2 level using a correlation-consistent
Dunning basis set aug-cc-pVTZ.18 The quantum-mechanical
analysis of the mechanism of diazomalonate decomposition is
complicated by the presence of several conformations of the
species involved.16 The conformational structure of methyl
diazomalonate 1′ and diazirine 2′ is discussed above (Figure 1,
Table 1). The electronic energies and representative structural
parameters for the anti-(5SE) and syn-(5SZ) conformers of the
the π-system of the carbonyl groups. All three relatively stable
rotamers of a triplet dicarbomethoxymethylene (5T), on the other
hand, are predicted to be closer to planarity. Similar differences
in geometry were reported for the cyclic analogue of 5,12 and
for acyclic R-carbonylcarbenes.19 It is interesting to note that
both the DFT and the MP2 calculations predict the singlet state
(5S) of the dicarbomethoxycarbene to be lower in energy than
the triplet (5T), although the energy gap is relatively small (Table
4).
The extrusion of nitrogen from three conformations of diazo-
malonate 1′ proceeds through three different transition states
(1qZZ, 1qZE, and 1qEE) and leads to the formation of a singlet
carbene 5S (Table 4, Figure 6). The geometry of the transition
state corresponding to the loss of nitrogen from the Z,Z-
conformer of methyl diazomalonate (1qZZ) is shown in Figure
singlet carbene and three rotamers of a triplet carbene (5T
,
ZZ
5TZE, 5TEE), as well as the transition states for deazotization of
three conformers of methyl diazomalonate (1qZZ, 1qZE, 1q
)
EE
and the Wolff rearrangement of the anti-(5q ) and syn-(5q )
E
Z
5. It is interesting to note that the C1-N6 bond in 1q is very
dicarbomethoxycarbene, are summarized in Table 4. The
ZZ
B3LYP/6-311+G(3fd,2p) optimized geometries of 5SE, 5S
5TEE, 1qZZ, 5q , and 5q are also shown in Figure 5.
,
Z
long (2.28 Å) and the geometry resembles carbene 5S with a
central atom (C1) located above the plane of the carbonyl groups.
The transition state for the decomposition of the E,E-
conformer of methyl diazomalonate 1′ has the lowest potential
energy. This observation suggests that products produced in the
thermal decomposition of acyclic diazomalonates are mostly
formed from the E,E-conformer. It is interesting to note that
the loss of nitrogen from the E,E- and Z,Z-conformers of 1′
results in the formation of syn- dicarbomethoxycarbene (5SZ),
while the Z,E-conformation produces the anti-form of 5S.
In contrast with the cyclic diazomalonate 3,12 we were unable
to locate saddle points on the potential energy surface that
connects 1′ with the corresponding ketene, that is, the transition
state for the concerted Wolff rearrangement of methyl diaz-
omalonate. The rearrangement of syn-(5SZ) or anti-(5SE) dicar-
bomethoxymethylene to form a ketene, on the other hand, is a
E
Z
The loss of nitrogen from the methyl diazomalonate (1′)
results in the formation of a singlet dicarbomethoxycarbene (5S),
which exists in two relatively stable conformations with anti-
(5SE) and syn-(5SZ) orientations of the carbonyl groups (Figure
5). The anti-isomer is predicted to be 2.3 kcal/mol lower in
energy, and the barrier for the 5S to 5S interconversion is
E
Z
12.5-13.2 (8.7-9.5) kcal/mol. These results indicate that the
rotation of the carbonyl fragment in the singlet dicarbomethoxy-
carbene 5S is apparently slower than its reaction with methanol,
which is known to be a diffusion-controlled process.14a Both
carbonyl groups in 5S and 5S are almost orthogonal to the
E
Z
plane of the carbene (C2-C1-C3, Figure 5). In our opinion,
such geometry provides a better overlap of the orbital containing
an unshared pair of electrons localized on the carbene atom with
(18) Kendall, R. A.; Dunning, T. H., Jr.; Harrison, R. J. J. Chem. Phys. 1992,
96, 6796.
(19) Scott, A. P.; Platz, M. S.; Radom, L. J. Am. Chem. Soc. 2001, 123, 6069
and references therein.
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11298 J. AM. CHEM. SOC. VOL. 126, NO. 36, 2004

Thermal Reactivity of Ethyl Diazomalonate
A R T I C L E S
Figure 6. Schematic potential energy profiles for the decomposition of three conformers of methyl diazomalonate 1′.
feasible process, proceeding via transition states 5q and 5q
Z
E
correspondingly (Figure 5, Table 4). While a cyclic dicar-
balkoxycarbene rearranges to ketene with virtually no activation
barrier,12 the rearrangement of carbene 5S has a sizable barrier,
which is higher for the anti-conformer (8.1 (6.1) kcal/mol) than
for the syn-conformer (5.0 (1.4) kcal/mol). These results agree
well with experimental observations on the photochemical
reactivity of the ethyl diazomalonate as the photolysis of 1 in
methanol solution produces only carbene trapping products. The
irradiation of 1′ isolated in a cryogenic matrix, where carbene
has nothing to react with, was reported to result in the Wolff
rearrangement.20 It is also interesting to note that barriers for
the Wolff rearrangement of 5S and 5S are lower than the
Z
E
activation barrier for the syn- to anti-interconversions. In other
words, the rearrangement or intramolecular reactions of dicar-
bomethoxycarbene 5S are faster than the conformational inter-
conversion.
Figure 7. Contour plot of the potential energy surface for the extrusion of
nitrogen from the Z,Z-conformer of methyl diazomalonate 1′. Values shown
on the isoergic lines represent the relative energy in kcal/mol. The values
of the C3C1C2O4 dihedral angle and the bond angle of the carbonyl group
are shown for representative points on the reaction trajectory.
The Structural Control of the Diazomalonate Reactivity.
The photochemically or thermally induced deazotization of the
diazo Meldrum’s acid (3), which is locked in the Z,Z-
conformation, results in a clean Wolff rearrangement via a
concerted pathway.12 The photolysis of the diazirine isomer 4
apparently produces the corresponding R,R-dicarbonylcarbene
carbene, which rearranges to the ketene faster than it reacts with
the solvent. The photolysis of ethyl diazomalonate (1), which
also exists predominantly in the Z,Z-form, results in the
formation of carbene 5 and gives no Wolff rearrangement
products. The loss of nitrogen from the excited state of 1 is so
fast (k ≈ 1012 s-1) that it does not allow enough time for the
conformational changes after the excitation event. The same
product (6) is formed in the thermal decomposition of 1, which
we believe proceeds mostly through the E,E-conformation (vide
supra). These observations apparently contradict the notion of
the conformational control of the reactivity of this class of
diazocarbonyl compounds.
To analyze the effect of structural factors on the thermal
decomposition of cyclic and acyclic diazomalonates, we have
conducted the 2-D relaxed potential energy surface (PES) scans
for the decomposition of methyl diazomalonate (1′) and diazo
Meldrum’s acid (3). These scans were conducted at the B3LYP/
6-31+G(d,p) level of theory in terms of C1-N6 and C1-O8
(atom migrating in Wolff rearrangement) distances (Figures 7
and 8). The bottom-left corner on the contour plots corresponds
to the energy of the starting diazo compound. The extension of
the C1-N6 bond without explicitly changing the C1-O8 distance
Figure 8. Contour plot of the PES for the Wolff rearrangement of the
diazo Meldrum’s acid (3). Values shown on the isoergic lines represent the
relative energy in kcal/mol. The values of the C3C1C2O4 dihedral angle
and the bond angle of the carbonyl groups are shown for representative
points on the reaction trajectory.
leads to the formation of the carbene (5, bottom-right corner),
while the elongation of the C1-N6 bond accompanied by the
shortening of the C1-O8 distance leads to a ketene (upper-right
corner).
The PES plot for the decomposition of 1′, shown in the Figure
7, allows us to conclude that the concerted Wolff rearrangement
(20) Visser, P.; Zuhse, R.; Wong, M. W.; Wentrup, C. J. Am. Chem. Soc. 1996,
118, 12598. McCluskey, A.; Dunkin, I. R. Aust. J. Chem. 1995, 48, 1107.
9
J. AM. CHEM. SOC. VOL. 126, NO. 36, 2004 11299

A R T I C L E S
Bogdanova and Popik
a relatively deep energy well for these species (ca. 7 kcal mol-1
Table 4). The elongation of the C1-N bond beyond 2.3 Å in
methyl diazomalonate 1′ is, therefore, accompanied by an
increase of the dihedral angle between the C3C1C2 plane and
the planes of the carbonyl group and results in an energy
reduction, leading the system to the formation of a carbene
(Figure 7).
is an unfavorable process for this substrate as the synchronous
cleavage of the C-N bond and the migration of the methoxy
group result in a steep rise in energy. The valley on the PES
follows the elongation of the C1-N6 bond, eventually reaching
the energy plateau at ca. 2.3 Å. At this point, there is a
substantial downhill gradient leading the system toward the
formation of a carbene 5S, while the migration of the substituent
is still an uphill process. This shape of PES explains our failure
to locate the transition state for the concerted Wolff rearrange-
ment of 1′ using various algorithms.
,
In the case of a cyclic diazomalonate 3, this orthogonal
geometry and resulting stabilization cannot be achieved, and
the energy well corresponding to the cyclic dicarbalkoxycarbene
is very shallow (<1 kcal/mol).12 As a result, the elongation of
the C1-N bond beyond 2.45 Å requires additional energy, while
the migration of a substituent from that point on PES is an
exoergic process. In other words, diazo Meldrum’s acid (3) is
predicted to undergo a concerted Wolff rearrangement.
The elongation of the C1-N6 bond is accompanied by
substantial changes in the geometry of the molecule, as the
carbon atom of diazo group (C1) moves out of the plane of two
carbonyl groups. These changes are illustrated in Figure 7 by
the C3C1C2O4 dihedral angles for several representative struc-
tures along the reaction path. The highest point of this path
Singlet-Triplet Equilibrium of Dicarboethoxycarbene 5.
The thermolysis or direct photolyses of ethyl diazomalonates
(1) and diazirine 2 produce no, or minor traces of, ethyl malonate
(7). The triplet-sensitized irradiation of ethyl diazomalonate (1),
on the other hand, results in a quantitative formation of 7. These
observations indicate that a singlet-triplet equilibration of
dicarbomethoxycarbene 5 is substantially slower than the
intermolecular reactions of the respective states. The singlet
corresponds to the transition state 1q (Figure 5). The C2-
ZZ
C1-C3 plane in this structure is almost orthogonal to the plane
of carbonyl groups, resembling the geometry of the singlet
carbene 5SZ (Table 4, Figure 5). The bond angle of the carbonyl
groups is also getting smaller with the increased C-N distance
(Figure 7). This change results in a slight shortening in the
distance between C1 and the oxygen atoms of methoxy groups.
The carbonyl bond angle, however, relaxes back to ca. 116°
after passing the saddle point. This observation apparently
indicates that the oxygen atoms of methoxy groups, while not
migrating themselves, still provide some level of anchimeric
assistance for the extrusion of nitrogen.
carbene 5S reacts with methanol at 1.5 × 109 s-1 M-1 14a
.
This
value allows us to estimate the lower limit for the activation
energy of 5S f 5T intersystem crossing (ISC) at 4-5 kcal/mol.
The rate of the hydrogen abstraction by triplet carbenes from
methanol is usually in the order of 1-5 × 106 M-1 s-1, which
puts the barrier for the reverse ISC (5T f 5S) in the range of at
least 6-7 kcal/mol.
The landscape of PES surrounding diazo Meldrum’s acid (3,
Figure 8) is very similar to that of methyl diazomalonate (1′,
Figure 7). In fact, the synchronous cleavage of the C-N bond
as well as the migration of the substituent is still an unfavorable
process as it is characterized by a sharp uphill energy gradient.
The extrusion of nitrogen from 3 initially proceeds by the
elongation of the C1-N bond, while the C1-O8 distance remains
virtually unchanged. This process is also accompanied by the
shift of the carbon atom of the diazogroup (C1) up from the
plane of carbonyl groups. The energy plateau is reached at a
C1-N distance of ca. 2.45 Å. The structure corresponding to
this point is very close to the one calculated previously for the
concerted Wolff rearrangement transition state of 3 and re-
sembles the boat-shaped geometry of the singlet carbene.12 The
gradients felt by the system on this energy plateau, however,
are very different from the methyl diazomalonate (1′) case. The
further elongation of the C1-N bond leading to the carbene
formation is still an uphill process. The migration of the oxygen
atom O,8 on the other hand, has a negative energy gradient,
and the system collapses to ketene without formation of a
carbene intermediate.
The substantial height of the ISC barriers of 5 can be
explained by the necessity for geometrical changes accompany-
ing the singlet to triplet interconversions. Carbonyl groups in
major rotameric forms of the triplet carbene (5T) are almost
coplanar with the carbene (C2C1C3 fragment), while the singlet
carbene (5S) has orthogonal geometry (vide supra). We scanned
the conformational energy surface of 5S and 5T in a search for
the intersection. This was done by stepwise changing the
geometry of the singlet carbene 5S from orthogonal to planar
Z
and by rotating the carbonyl fragments in 5TEE and 5TZE to the
orthogonal geometry of a singlet carbene. The dihedral angles
between carbonyl groups and the carbene plane were fixed in
steps, while the other degrees of freedom were fully optimized
at the B3LYP/6-31+G(d,p) level. The results of these scans
are presented in Figure 9.
The energy of the triplet dicarbomethoxycarbene (triangles
for 5T and hexagons for 5TZE, Figure 9) is substantially less
EE
dependent on the geometry than the energy of the singlet carbene
(circles, Figure 9). The intersections between singlet and triplet
surfaces are, therefore, located much closer to the stable
conformation of the singlet carbene 5SZ than to its triplet form.
The analysis of the data represented in Figure 9 allows us to
estimate the activation energy of ISC for the syn-conformer of
the singlet carbene (5SZ) at ca. 3 kcal/mol and slightly higher,
and at ca. 4 kcal/mol for the anti-conformer 5SE. The activation
barrier for the reverse ISC (5T f 5S) is ca. 4.5-5 kcal/mol. In
fact, these estimates of ISC activation barriers should be
increased somewhat as we did not take into account another
structural parameter, which is different for the 5S and 5T, the
Comparison of the PES plots for the dediazotization of methyl
diazomalonate (1′, Figure 7) and diazo Meldrum’s (3, Figure
8) allows us to suggest an explanation for the difference in the
reactivity of these two compounds. Both processes start by the
extension of the C1-N bond accompanied by the out-of-plane
shift of C1 until the system reaches the energy plateau at a C1-N
distance in the range of 2.3-2.45 Å. The direction of further
transformation, the formation of a carbene versus concerted
Wolff rearrangement, depends on the relative stability of the
corresponding dicarbalkoxycarbene. The acyclic carbene 5SZ can
adopt the favorable orthogonal conformation, which results in
9
11300 J. AM. CHEM. SOC. VOL. 126, NO. 36, 2004

Thermal Reactivity of Ethyl Diazomalonate
A R T I C L E S
methanol results in the solvent trapping of dicarboethoxycarbene
(5). The major conformer of ethyl diazomalonate (1) has the
same Z,Z-geometry as its cyclic analogue, diazo Meldrum’s acid
(3). Despite this structural similarity, cyclic diazomalonate 3
shows a very different reactivity, producing Wolff rearrangement
products on photolysis in methanol. This observation suggests
that ground-state conformation is not the major factor controlling
the direction of the decomposition of diazomalonates. DFT
analysis of the PES for the loss of nitrogen from cyclic (3) and
acyclic (1′) diazomalonates allows us to conclude that the
mechanism of the Wolff rearrangement is controlled by the
relative stability of the corresponding carbene, which in turn
depends on the rigidity of the molecule. Acyclic carbonyl
carbenes adopt a conformation in which the carbonyl group is
orthogonal to the carbene plane. This geometry helps reduce
the energy of the singlet carbene by conjugative stabilization
of its unshared pair. The carbonyl carbene incorporated into a
six-membered or a smaller cycle cannot achieve such geometry
and is, therefore, unstable directing the Wolff rearrangement
into a concerted pathway.
Figure 9. The dependence of the potential energy of the singlet (5S, circles)
and triplet (5TEE, hexagons; and 5TEZ, triangles) carbenes on the dihedral
angle between the plane of the carbene and carbonyl groups (The energy is
plotted versus the averaged value for the O4C2C1C3 and O5C3C1C2 angles.)
The wavelength dependence of the ethyl diazomalonate
photochemistry, as well as the wavelength dependence of the
quantum yield, allows us to conclude that the isomerization of
diazoester 1 to diazirine 2 takes place from the lowest singlet
excited state, while the loss of nitrogen originates from the
higher excited state. The rate of the diazo group C-N bond
cleavage in the latter should be in the order of 1012 s-1 to be
able to compete with internal conversion.
The singlet dicarbomethoxycarbene (5S) exists in two rela-
tively stable conformations with syn- or anti-arrangement of
the carbonyl groups. The interconversion between these forms
is predicted to be slower than the intermolecular reactions of 5.
Figure 10. The dependence of the relative energy of the singlet (circles)
and triplet (triangles) states of carbene 8 on the dihedral angle between the
carbene and carbonyl planes.
bond angle at the carbene carbon (C1). It is well-known that
this angle is larger in a triplet carbene.2,19
Experimental Section
General Procedures. NMR spectra were recorded on a Varian Unity
+ 400 MHz or a Varian Gemini 200 MHz spectrometer. All NMR
spectra were recorded in CDCl3 and referenced to TMS. The low-
temperature NMR experiments were carried out in carbon disulfide
containing 20% v/v of CDCl3. FT-IR spectra were recorded on a
ThermoNicolet IR200 spectrometer. UV-vis spectra were obtained on
a Cary-300 Bio spectrophotometer. Melting points are uncorrected.
Purification of products by column chromatography was performed
using 40-63 µm silica gel. Tetrahydrofuran was distilled from sodium/
benzophenone ketyl; dioxane, ether, and hexanes were distilled from
sodium. Ethoxyamine as a free base was obtained by distillation of the
corresponding hydrochloride over solid potassium hydroxide at 65 °C.
Other reagents were obtained from Aldrich and were used as received
unless otherwise noted.
The direct and sensitized photolysis of a cyclic diazomalonate
3 and its diazirine isomer 4 in methanol also did not produce
any evidence of the ISC between the triplet and singlet
dicarbalkoxycarbene 8 (Figure 10).12 Thus, the barrier for the
triplet to singlet conversion can be estimated at 6-7 kcal/mol.
The quantum-mechanical analysis of this system, in contrast to
the dicarbomethoxycarbene (5), predicts that the ground state
of the carbene 8 is a triplet. The relaxed scan of the PES
following the dihedral angle between the carbene plane and the
plane of the carbonyl groups in singlet and triplet states of 8 is
shown in Figure 10.
The intersection between the triplet and singlet energy
surfaces is located very close to the most stable conformation
of a singlet carbene 8, and there is virtually no barrier for ISC
to a triplet state (Figure 10). Therefore, the absence of a triplet
carbene-derived product in the direct photolysis of 3 provides
an additional support for the concerted mechanism of the photo-
Wolff reaction of diazo Meldrum’s acid (3). The reverse triplet
to singlet interconversion is predicted to require ca. 7 kcal mol-1
of activation energy. This value agrees well with experimental
estimates.12
Photolytic Experiments. Analytical photolyses were performed by
the irradiation of ca. 10-4 M solutions of diazo compound 1 or diazirine
2 in a 1 cm quartz cell using a RMR-600 Rayonet photochemical reactor
equipped with a carousel and three sets of eight lamps with λmax values
of emission at 254, 300, or 350 nm. Monochromatic irradiations at
355 nm were conducted using a frequency tripled output of a
Q-switched Nd:YAG laser. Reaction mixtures were analyzed by HPLC.
Pure samples of 1, 2, 6, and ethyl malonate (7) were used as references
and for calibration of the HPLC detector. Preparative photolyses were
conducted by the irradiation of methanolic solutions of ca. 100 mg of
substrates using a 16 lamp (with λemission ) 254 or 350 nm) Rayonet
photochemical reactor and a quartz vessel equipped with an immersible
cooling finger. The consumption of starting material was followed by
TLC. Determination of a quantum yield was performed using a
Conclusions
The photochemical or thermal decomposition of ethyl diaz-
omalonate (1) and ethyl 3,3-diazirinedicarboxylate (2) in
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J. AM. CHEM. SOC. VOL. 126, NO. 36, 2004 11301

A R T I C L E S
Bogdanova and Popik
1
ferrioxalate chemical actiniometer.21 The triplet sensitized photolyses
of 1 were conducted using benzophenone as a sensitizer in thoroughly
degassed 2-propanol solutions. The concentration of benzophenone was
adjusted to achieve a 10 times higher absorbance of the sensitizer than
that of the substrate at 254 nm.
Kinetics. Rate measurements were performed using a Carry-300 Bio
UV-vis spectrometer equipped with a thermostatable cell holder.
Substrate concentrations in the reacting solutions were ca. 10-4 M, and
the temperature of these solutions was controlled with 0.05 °C accuracy.
Reactions were monitored by following the changes in absorbance of
ethyl 3H-3,3-diazirinedicarboxylate (2) at 291 nm. Observed first-order
rate constants were calculated by least-squares fitting of a single-
exponential function.
Theoretical Procedures. Quantum-mechanical calculations were
carried out using the Gaussian 98 program.22 The levels of theory
examined ranged from hybrid B3LYP23 density functional theory
calculations with the 6-311+G(3df,2p)24 basis sets to the high level
composite procedure MP2(full)/aug-cc-pVTZ//B3LYP/6-311+G(3df,2p).
For all of the density functional theory calculations, zero-point
vibrational energy (ZPVE) corrections, required to correct the raw
relative energies to 0 K, were obtained from B3LYP/6-31+G(d,p)
method. Analytical second derivatives were computed to confirm each
stationary point to be a minimum by yielding zero imaginary vibrational
frequencies for the intermediates and one imaginary vibrational
frequency for each transition state. These frequency analyses are known
to overestimate the magnitude of the vibrational frequencies. Therefore,
we scaled the corresponding ZPVE by 0.9772.25 Initial geometry
optimization, IRC calculations for transition states, and relaxed scans
of potential energy surfaces were conducted at the B3LYP/6-31+G(d,p)
level. In the PES scans, the C1-O8 and C1-N6 coordinates were fixed
in steps, while the other degrees of freedom were fully optimized. Each
of the two potential energy surfaces consisted of about 160 points
corresponding to different values of C1-O8 and C1-N6 distances.
Materials. Ethyl diazomalonate (1) was prepared in 64% yield by
the diazotransfer reaction2b from N-p-acetamidobenzenesulfonyl azide
to ethyl malonate. H NMR (200 MHz, CDCl3, δ/ppm): 1.31 (3H, t,
J ) 7.4 Hz), 4.31 (2H, q, J ) 7.4 Hz). 13C NMR (100 MHz, CDCl3,
δ/ppm): 14.29, 61.67, 161.04. IR (neat, cm-1): 2984 (m), 2123 (s),
1758 (s), 1732 (vs). MS/DIP (relative intensity, %): 186 (M+, 45),
141 (40), 69 (100). UV (MeOH, λmax, nm/log ꢀ): 251/3.9, 344/1.34
(lit.26).
Ethyl Diazirine-3,3-dicarboxylate (2).27 Ethoxyamine (0.4 mL, 5.7
mmol) was added dropwise to a stirred solution of ethyl O-tosylisoni-
trosomalonate28 (660 mg, 1.9 mmol) in 3 mL of acetonitrile under argon
at -10 °C over 30 min. After 3 h at this temperature, the reaction
mixture was left overnight at 4 °C. The reaction mixture was diluted
with 10 mL of ether, and the resulting white crystals were removed.
The solvent was removed in a vacuum, and the residue was redissolved
in 2 mL of methanol. The colorless crystals of 2 precipitated from
methanolic solution at -78 °C and were immediately sublimed at room
1
temperature to give 140 mg (40%) of the desired product. H NMR
(200 MHz, CDCl3, δ/ppm): 1.30 (3H, t, J ) 7.2 Hz), 4.26 (4H, q, J )
7.4 Hz). 13C NMR (100 MHz, benzene-d6, δ/ppm): 14.28, 63.16,
163.80. IR (neat, cm-1): 2986 (m), 1755 (s), 1730 (vs). UV (MeOH,
max, nm/log ꢀ): 291/1.94.
Ethyl 2-Methoxymalonate (4). Rhodium tetraacetate (3 mg) was
added to a solution of 1 (0.372 g, 2 mmol) in 5 mL of dichloromethane,
followed by 0.41 mL (10 mmol) of methanol. The reaction mixture
was stirred at 50 °C under an argon atmosphere for 12 h. The solvent
was removed, and the reaction mixture was separated on the silica gel
column (hexanes:ether, 25:1), giving 370 mg (98%) of 4 as a colorless
λ
1
oil. H NMR (200 MHz, CDCl3, δ/ppm): 1.31 (6H, t, J ) 7.4 Hz),
3.51 (3H, s), 4.31 (4H, q, J ) 7.4 Hz), 4.41 (1H, s). 13C (100 MHz,
CDCl3, δ/ppm): 13.98, 58.58, 61.98, 80.45, 166.25. IR (neat, cm-1):
1739 (vs). MS/DIP (relative intensity, %): 132 (14), 117 (48), 90 (55),
72 (22), 61 (100) (lit.29).
Acknowledgment. We are grateful to the National Institutes
of Health for partial support of this project (NIH R15 CA91856-
01A1). A.B. thanks the McMaster Endowment for a research
fellowship.
(21) Murov, S. L.; Carmichael, I.; Hug, G. L. Handbook of Photochemistry;
Marcel Dekker: New York, 1993; p 299.
Supporting Information Available: Tables S1 and S2 of rate
data and Gaussian 98 output files for quantum-mechanical
calculations. This material is available free of charge via the
Internet at http://pubs.acs.org.
(22) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M.
A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratmann,
R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin,
K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi,
R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.;
Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.;
Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz,
J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.;
Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng,
C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.;
Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon,
M.; Replogle, E. S.; Pople, J. A. Gaussian 98; Gaussian, Inc.: Pittsburgh,
PA, 2001.
JA047824R
(26) Green, G.M.; Peet, N. P.; Metz, W. A. J. Org. Chem. 2001, 66, 2509.
(27) The procedure we employed for the preparation of diazirine 2 was adopted
with some modifications from: Shustov, G. V.; Tavakalyan, N. B.;
Pleshkova, A. P.; Kostyanovskii, R. G. Khim. Geterotsik. Soed. 1981, 810.
(28) Biehler, J. M.; Fleury, J. P.; Perchais, J.; Regent, A. Tetrahedron Lett. 1968,
4227.
(23) Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
(24) Hehre, W. J.; Radom, L.; Schleyer, P. v. R.; Pople, J. A. Ab Initio Molecular
Orbital Theory; John Wiley & Sons: New York, 1986.
(29) Hannah, J.; Tolman, R. L.; Karkas, J. D.; Liou, R.; Perry, H. C.; Field, A.
K. J. Heterocycl. Chem. 1989, 26, 1261.
(25) Scott, A. P.; Radom, L. J. Phys. Chem. 1996, 100, 16502.
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11302 J. AM. CHEM. SOC. VOL. 126, NO. 36, 2004