Experimental and Theoretical Investigation of Reversible Interconversion, Thermal Reactions, and Wavelength-Dependent Photochemistry of Diazo Meldrum's Acid and Its Diazirine Isomer, 6,6-Dimethyl-5,7-dioxa-1,2-diaza-spiro[2,5]oct-1-ene-4,8-dione

Article abstract of DOI:10.1021/ja037637d

The photochemical or thermal decomposition of diazo Meldrum's acid (1) in methanolic solutions yields ketoester 3a, the product of the Wolff rearrangement, while products produced from the singlet carbene were not detected. This observation, combined with the analysis of activation parameters for the thermal decomposition of 1, as well as with the results of DFT B3PW91/6-311+G(3df,2p) and MP2/aug-cc-pVTZ//B3PW91/6-311+G(3df,2p) calculations, allows us to conclude that the Wolff rearrangement of 1 is a concerted process. The outcome of the photolysis of diazo Meldrum's acid depends on the wavelength of irradiation. Irradiation with 254 nm light results in an efficient (Φ₂₅₄ = 0.34) photo-Wolff reaction, while at 355 nm, the formation of diazirine 2 becomes the predominant process (Φ ₃₅₀ = 0.024). This unusual wavelength selectivity indicates that Wolff rearrangement and isomerization originate from different electronically excited states of 1. The UV irradiation of diazirine 2 leads to the loss of nitrogen and the Wolff rearrangement, apparently via a carbene intermediate. This process is accompanied by a reverse isomerization to diazo Meldrum's acid. Triplet-sensitized photolysis of both isomers results in the formation of Meldrum's acid, the product of a formal reduction of 1 and 2. Mild heating of diazirine 2 produces quantitative yields of diazo Meldrum's acid. The activation parameters for thermal reactions of diazo 1 and diazirino 2 isomers were determined in aqueous and dioxane solutions.

Full text of DOI:10.1021/ja037637d

Published on Web 10/22/2003
Experimental and Theoretical Investigation of Reversible
Interconversion, Thermal Reactions, and
Wavelength-Dependent Photochemistry of Diazo Meldrum’s
Acid and Its Diazirine Isomer,
6,6-Dimethyl-5,7-dioxa-1,2-diaza-spiro[2,5]oct-1-ene-4,8-dione1
Aneta Bogdanova and Vladimir V. Popik*
Contribution from the Center for Photochemical Sciences, Bowling Green State UniVersity,
Bowling Green, Ohio 43403
Received July 30, 2003; E-mail: vpopik@bgnet.bgsu.edu
Abstract: The photochemical or thermal decomposition of diazo Meldrum’s acid (1) in methanolic solutions
yields ketoester 3a, the product of the Wolff rearrangement, while products produced from the singlet carbene
were not detected. This observation, combined with the analysis of activation parameters for the thermal
decomposition of 1, as well as with the results of DFT B3PW91/6-311+G(3df,2p) and MP2/aug-cc-pVTZ//
B3PW91/6-311+G(3df,2p) calculations, allows us to conclude that the Wolff rearrangement of 1 is a
concerted process. The outcome of the photolysis of diazo Meldrum’s acid depends on the wavelength of
irradiation. Irradiation with 254 nm light results in an efficient (Φ254 ) 0.34) photo-Wolff reaction, while at
355 nm, the formation of diazirine 2 becomes the predominant process (Φ350 ) 0.024). This unusual
wavelength selectivity indicates that Wolff rearrangement and isomerization originate from different
electronically excited states of 1. The UV irradiation of diazirine 2 leads to the loss of nitrogen and the
Wolff rearrangement, apparently via a carbene intermediate. This process is accompanied by a reverse
isomerization to diazo Meldrum’s acid. Triplet-sensitized photolysis of both isomers results in the formation
of Meldrum’s acid, the product of a formal reduction of 1 and 2. Mild heating of diazirine 2 produces
quantitative yields of diazo Meldrum’s acid. The activation parameters for thermal reactions of diazo 1 and
diazirino 2 isomers were determined in aqueous and dioxane solutions.
Introduction
application of the Wolff rearrangement is found in photolithog-
raphy, a process used in the production of electronic microchips
and integrated circuit boards.8 Diazo Meldrum’s acid, discussed
in this report, is currently under investigation as a potential
component of deep-UV photoresists9 and mass transfer imaging
materials.10
Mechanistically, the Wolff rearrangement is a complex
process that involves several short-lived intermediates.11,12 The
irradiation or thermolysis of the R-diazocarbonyl compound
usually leads to the loss of nitrogen and the formation of an
R-carbonylcarbene. This key intermediate in the Wolff rear-
rangement can exist in two different electronic states, that is,
The Wolff reaction, the thermal or photochemical transforma-
tion of R-diazocarbonyl compounds into carboxylic acid deriva-
tives, is a key step in many laboratory methods, such as the
Arndt-Eistert homologation of carboxylic acids,2 synthesis of
small strained ring systems by ring contraction,2a,f,3 preparation
of â-ketoacid derivatives,4 photoaffinity labeling,5 DNA pho-
tocleaving,6 and nanomachining.7 The most important industrial
(1) Preliminary communication: Bogdanova, A.; Popik, V. V. J. Am. Chem.
Soc. 2003, 125, 1456-7.
(2) (a) Regitz, M.; Maas, G. Diazo Compounds; Academic Press: Orlando,
FL, 1986. (b) Maas, G. In Methoden der Organischen Chemie (Houben-
Weyl); Regitz, M., Ed.; ThiemeVerlag: Stuttgart, 1989; Vol. 19b/2, p 1022.
(c) Ye, T.; McKervey, A. M. Chem. ReV. 1994, 94, 1091. (d) Meier, H.;
Zeller, K.-P. Angew. Chem., Int. Ed. Engl. 1975, 14, 32. (e) Jones, M.;
Moss, R. A. Carbenes; Wiley: New York, 1973. (f) Doyle, M. P.;
McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic Synthesis
with Diazo Compounds; Wiley-Interscience: New York, 1998; pp 487-
534.
(6) Nakatani, K.; Maekawa, S.; Tanabe, K.; Saito, I. J. Am. Chem. Soc. 1996,
118, 10635. Saito, I.; Nakatani, K. Bull. Chem. Soc. Jpn. 1996, 69, 3007.
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1999, 121, 10832.
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5857-5860. (b) Ghosh, A.; Banerjee, U. K.; Venkateswaran, R. V.
Tetrahedron 1990, 46, 3077. (c) Lawton, G.; Moody, C. J.; Pearson, C. J.
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C. D. AdV. Alicyclic Chem. 1971, 3, 125.
(4) (a) Cossy, J.; Belotti, D.; Thellend, A.; Pete, J. P. Synthesis 1988, 720. (b)
Korobitsyna, I. K.; Nikolaev, V. A. Zh. Org. Khim. 1976, 12, 1251. (c)
Wentrup, C.; Heilmayer, W.; Kollenz, G. Synthesis 1994, 1219.
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Med. Chem. 1996, 39, 2860. Somack, R.; Nordeen, S. K.; Eberhardt, N. L.
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9
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J. AM. CHEM. SOC. 2003, 125, 14153-14162
14153

A R T I C L E S
Bogdanova and Popik
Scheme 1
Scheme 2
singlet or triplet.13-15 Direct photolysis of R-diazocarbonyl
compounds is usually dominated by the chemistry of singlet
carbenes. R-Carbonylcarbene might also exist in equilibrium
with an elusive oxirene.16 Carbenes are very reactive species
and in the presence of water or alcohols undergo rapid O-H
insertion reaction.17 Depending on the electronic properties of
the substituent R, this process proceeds via an enol18 or
carbocation19 intermediate. Alternatively, the R-carbonylcarbene
can rearrange to form a ketene. The latter can also be formed
directly from the diazo compound by the simultaneous loss of
nitrogen and the migration of the substituent X, that is, by the
concerted Wolff rearrangement.11,20 Ketenes react with nucleo-
philes to produce corresponding enols, which then rapidly
ketonize to yield the final product, carboxylic acid derivatives21
(Scheme 1).
cal reactivity. There are some indications that the yield of R-
carbonyl diazirines depends on the wavelength of irradiation
of the parent diazo compound,22a,23 and they might undergo ther-
mal or photochemical22a,e,f reverse isomerization into the parent
diazo compound or lose nitrogen to give an R-carbonyl-
carbene.22a,c,f
Here, we would like to report the experimental and theoretical
investigation of a reversible isomerization of diazo Meldrum’s
acid (1) into the corresponding diazirine, 6,6-dimethyl-5,7-dioxa-
1,2-diaza-spiro[2,5]oct-1-ene-4,8-dione (2), as well as a com-
parison of their photochemical and thermal reactivity.
The chemistry and properties of the species shown in Scheme
1 have been investigated in detail as their reactivity is a key to
understanding and predicting the outcome of reactions of
R-diazocarbonyl compounds. One intermediate or byproduct of
the Wolff reaction, however, has escaped scrutiny. Thus,
R-carbonyldizirines, cyclic isomers of R-diazocarbonyl com-
pounds, are sometimes isolated in the photolysis of the latter22,23
(Scheme 2).
Surprisingly, little is known about the conditions of R-carbo-
nyldizirines formation, as well as their thermal and photochemi-
This pair of structural isomers also provides an insight into
the unusual reactivity of diazo Meldrum’s acid (1). Most of the
R-diazoesters, for example, closely related diazomalonates, pro-
duce either a very low yield or no Wolff rearrangement products
on photolysis,23,24 while for 1, formation of the corresponding
ketene was reported to be the major process in photochemical
decomposition.24,25 The conventional explanation for this
(13) Wang, J. L.; Likhtvorik, I. R.; Platz, M. S. J. Am. Chem. Soc. 1999, 121,
2883. Likhtvorik, I. R.; Zhu, Z.; Tae, E. L.; Tippmann, E.; Hill, B. T.;
Platz, M. S. J. Am. Chem. Soc. 2001, 123, 6061.
(14) Scott, A. P.; Platz, M. S.; Radom, L. J. Am. Chem. Soc. 2001, 123, 6069
and references therein.
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H.-P. J. Am. Chem. Soc. 1985, 107, 7597. Novoa, J. J.; McDouall, J. J.
W.; Robb, M. A. J. Chem. Soc., Faraday Trans. 2 1987, 83, 1629.
(16) Lewars, E. Can. J. Chem. 2000, 78, 297 and references therein. Sung, K.
S. Can. J. Chem. 2000, 78, 562. Vacek, G.; Galbraith, J. M.; Yamaguchi,
Y.; Schaefer, H. F.; Nobes, R. H.; Scott, A. P.; Radom, L. J. Phys. Chem.
1994, 98, 8660. Nobes, R. H.; Schaefer, H. F., III; Radom, L. J. Am. Chem.
Soc. 1994, 116, 10159. Lewars, E. G. Chem. ReV. 1983, 83, 519. Torres,
M.; Lown, E. M.; Gunning, H. E.; Strausz, O. P. Pure Appl. Chem. 1980,
52, 1623-1643. Tomioka, H.; Okuno, H.; Kondo, S.; Izawa, Y. J. Am.
Chem. Soc. 1980, 102, 7123. Zeller, K.-P. Angew. Chem., Int. Ed. Engl.
1977, 16, 781.
(17) 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. Hadel, L. M.; Maloney, V. M.; Platz, M. S.; McGimpsey, W. G.;
Scaiano, J. C. J. Phys. Chem. 1986, 90, 2488. Chiang, Y.; Kresge, A. J.;
Pruszynski, P.; Schepp, N. P.; Wirz, J. Angew. Chem., Int. Ed. Engl. 1991,
30, 1366.
(18) Chiang, Y.; Kresge, A. J.; Schepp, N. P.; Xie, R. Q. J. Org. Chem. 2000,
65, 1175. Chiang, Y.; Jefferson, E. A.; Kresge, A. J.; Popik, V. V.; Xie,
R.-Q. J. Phys. Org. Chem. 2000, 13, 461. Chiang, Y.; Jefferson, E. A.;
Kresge, A. J.; Popik, V. V.; Xie, R. Q. J. Phys. Org. Chem. 1998, 11, 610.
(19) Schepp, N. P.; Wirz, J. J. Am. Chem. Soc. 1994, 116, 11749.
(20) Tidwell, T. T.; Ketenes, J. Wiley: New York, 1976; pp 84-100.
(21) Kresge, A. J. Chem. Soc. ReV. 1996, 25, 275-280.
(22) (a) Rau, H.; Bokel, M. J. Photochem. Photobiol. A 1990, 53, 311. (b)
Ulbricht, M.; Thurner, J. U.; Siegmund, M.; Tomaschewski, G. Z. Chem.
1988, 28, 102. (c) Torres, M.; Raghunathan, P.; Bourdelande, J. L.; Clement,
A.; Toth, G.; Strausz, O. P. Chem. Phys. Lett. 1986, 127, 205. (d) Laganis,
E. D.; Janik, D. S.; Curphey, T. J.; Lemal, D. M. J. Am. Chem. Soc. 1983,
105, 7457. (e) Miyashi, T.; Nakajo, T.; Mukai, T. Chem. Commun. 1978,
442. (f) Voigt, E.; Meier, H. Angew. Chem. 1975, 87, 109. (g) Franich, R.
A.; Lowe, G.; Parker, J. J. Chem. Soc., Perkin Trans. 1 1972, 2036.
(23) (a) Livinghouse, T.; Stevens, R. V. J. Am. Chem. Soc. 1978, 100, 6479.
(b) Nikolaev, V. A.; Khimich, N. N.; Korobitsyna, I. K. Khim. Geterotsikl.
Soedin. 1985, 321.
(24) (a) Wang, J.-L.; Toscano, J. P.; Platz, M. S.; Nikolaev, V.; Popik, V. J.
Am. Chem. Soc. 1995, 117, 5477-83. (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.
(25) (a) Lippert, T.; Koskelo, A.; Stoutland, P. O. J. Am. Chem. Soc. 1996,
118, 1551. (b) Winnik, M. A.; Wang, F.; Nivaggioli, T.; Hruska, Z.;
Fukumura, H.; Masuhara, H. J. Am. Chem. Soc. 1991, 113, 9702. (c)
Stevens, R. V.; Bisacchi, G. S.; Goldsmith, L.; Strouse, C. E. J. Org. Chem.
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M., Jr. J. Org. Chem. 1977, 42, 2931.
9
14154 J. AM. CHEM. SOC. VOL. 125, NO. 46, 2003

Investigation of Diazo Meldrum’s Acid
A R T I C L E S
Figure 1. B3PW91/6-311+G(3df,2p) optimized geometries of cyclic diazoester 1′, diazirine 2′, singlet 4S, and triplet carbene 4T, as well as transition states
for the concerted Wolff rearrangement 8 and diazo to diazirine isomerization 9.
Scheme 3
Scheme 4
phenomenon is based on the assumption that the irradiation of
acyclic R-diazoesters produces R-carbalkoxycarbenes, which do
not rearrange due to a low migratory aptitude of oxygen.26 The
excitation of diazo Meldrum’s acid, on the other hand, results
in the concerted Wolff rearrangement that bypasses the carbo-
nylcarbene step (Scheme 1). Diazirines are well-known photo-
chemical precursors of carbenes,27 and the photolysis of R,R′-
dicarbonyldiazirine 2 is expected to produce the corresponding
carbene.
to the formation of R,R′-dicarbonylcarbene 4 followed by the
migration of one of the ring oxygen atoms to the carbene carbon
to form R-carbonylketene 5 (Scheme 4). The latter can be also
formed in a concerted way directly from 1. The fact that the
carbene insertion product, that is, the 3-methoxy Meldrum’s
acid, has not been detected in the reaction mixture seems to
support the concerted mechanism of the thermal Wolff rear-
rangement of diazodiester 1.
Theoretical analysis of the thermal Wolff rearrangement
of diazo Meldrum’s acid (1) was conducted at the B3PW91/
6-311+G(3df,2p)//B3PW91/6-311+G(3df,2p) and MP2(full)/
aug-cc-pVTZ//B3PW91/6-311+G(3df,2p) levels of theory on
the example of 5-diazo-1,3-dioxane-4,6-dione (1′, Figure 1).
Methyl groups in 1′ were replaced with hydrogen atoms to
simplify calculations. In our opinion, this modification should
not significantly disturb the relative energies of the species
involved in the decomposition of 1. The optimized geometries
of diazodiester 1′, diazirine 2′, singlet (4S), and triplet (4T) states
of R,R′-dicarbonylcarbene 4′, transition states for the concerted
Wolf rearrangement (8), and diazirine isomerization (9) are
shown in Figure 1. The electronic energies and representative
structural parameters of these structures, as well as those of
R-carbonylketene 5′, transition states for the carbene formation
(6), and carbene to ketene isomerization (7), are summarized
in Table 1.
Results and Discussion
Thermal Reactions of Diazo Meldrum’s Acids (1). Diazo
Meldrum’s acid (1) is a relatively stable compound; for example,
it melts with an apparent decomposition above 95 °C. We have
found that in methanol, water, or 1,4-dioxane solutions, a very
slow decomposition of 1 can be observed starting at 60 °C.
Because of the high stability of this diazo compound, little is
known about products of the thermal decomposition of 1. The
only report known to the authors describes the high temperature
pyrolysis of neat diazo Meldrum’s acid which resulted in the
formation of only the following gaseous products: nitrogen,
carbon monoxide, and acetone.25d We found that heating of 1
above 80 °C in neat methanol or in dioxane-methanol mixtures
results in the quantitative formation of methyl 2,2-dimethyl-5-
oxo-1,3-dioxalane-4-carboxylate (3a), the apparent product of
the Wolff rearrangement (Scheme 3).
The key feature of the stepwise mechanism of the Wolff
rearrangement is the formation of the R,R′-dicarbonylcarbene
4′. The singlet dicarbonylcarbene 4S was found to be a real
intermediate at the B3PW91/6-311+G(3df,2p) level of theory
as it is characterized by the minimum on the potential energy
surface (PES) and has no imaginary frequencies. Surprisingly,
this species is not planar with the carbene carbon located above
the plane of the ring in a boatlike conformation (Figure 1). In
The dediazotization of 1, in accordance with the general
scheme discussed in the Introduction (Scheme 1), could lead
(26) Meier, H.; Zeller, K.-P. Angew. Chem., Int. Ed. Engl. 1975, 14, 32. Regitz,
M.; Maas, G. Diazo Compounds; Academic Press: London, 1986; pp 166-
198.
(27) Moss, R. A. Acc. Chem. Res. 1989, 22, 15. Liu, M. T. H.; Stevens, I. D.
R. In Chemistry of Diazirines; Liu, M. T. H., Ed.; CRC Press: Boca Raton,
FL, 1987; Vol. 1, pp 111-160. Doyle, M. P. In Chemistry of Diazirines;
Liu, M. T. H., Ed.; CRC Press: Boca Raton, FL, 1987; Vol. 2, pp 33-76.
9
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A R T I C L E S
Bogdanova and Popik
Table 1. Relative Energies and Main Geometrical Parameters of the Equilibrium and Transition Structures Obtained at B3PW91
6-311+G(3df,2p)//B3PW91 6-311+G(3df,2p), MP2 (full) aug-cc-pVTZ //B3PW91 6-311+G(3df,2p) (in Parentheses), and MP2 (full)
aug-cc-pVTZ //MP2 (full) 6-311+(d,p) [in Brackets] Levels
1′
4S + N a
4T + N a
5′ + N a
6
7+ N a
8
2′
23.23
(22.46)
9
2
2
2
2
Erelb (kcal/mol)
ZPVE corrected
0.00
49.19
(56.86)
[56.70]
N/A
40.90
(56.97)
[55.39]
N/A
-5.88
(-3.86)
49.27
(55.78)
49.46
(57.30)
47.84
(48.39)
[48.05]
2.217
53.62
(60.10)
C1-N9
1.319
1.110
N/A
N/A
3.672
1.095
N/A
N/A
1.498/1.498
1.190
1.540/2.080
1.120
distance/Å
N9-N10
N/A
N/A
1.090
distance/Å
a Energy of the corresponding structure plus energy of a free nitrogen molecule (-109.5176551 (-109.3936875), [-109.39431750] hartree; ZPVE )
3.513 kcal/mol). b Energy difference between 1′ and the corresponding structure.
1′-9 is shown in Figure 1) in 6 is 3.7 Å, while the saddle point
on the free energy surface corresponds to a shorter C1-N9
distance of 2.8 Å.
The barrier for the rearrangement of the singlet carbene 4S
to the ketene 5′ is predicted by both DFT and MP2 calculations
to be very low: below 1 kcal M-1. In accordance with this
finding, the geometry28 of the transition state for the rearrange-
ment reaction (7) is very close to that of the singlet carbene 4S.
The only difference is the slight shift of the migrating oxygen
atom O.6 The C1-O6 distance in 7 is 2.1 Å, while in the starting
carbene it is 2.28 Å. We can conclude that R,R′-dicarbonylcar-
Figure 2. Schematic potential energy profile for the two-step Wolff
rearrangement of diazodiester 1′. (-) represents electronic energy, and (])
represents free energy changes.
bene 4S, if ever formed, is an extremely short-lived intermediate
with a subpicosecond lifetime immediately collapsing to the
ketene 5. This very rapid rearrangement of carbene 4S predicted
by the quantum-mechanical calculations is a noteworthy result.
The low yield of the Wolff rearrangement products in the
thermal or photochemical decomposition of R-diazoesters is
usually explained by the low migratory aptitude of the oxygen
atom in an intermediate carbene.2d,11 Our results show that there
is no intrinsic barrier for the migration of the oxygen atom, at
least in the cyclic carbene 4′.
our opinion, such a geometry provides better overlap of the
orbital containing an unshared pair of electrons localized on
the carbene atom with the π-system of the carbonyl groups.
The triplet state of this carbene (4T) is predicted to be planar
and is 8.3 kcal mol-1 more stable than 4S. Similar differences
in geometry were reported for acyclic R-carbonylcarbenes: in
the triplet state, these carbenes are planar, while in the singlet
state, the carbonyl group is nearly orthogonal to the carbene
plane.14 It is interesting to note that the correlation-corrected
MP2(full) method predicts a much smaller energy gap between
the triplet and the singlet state of the carbene 4′ than do the
density functional calculations (Table 1).
The energy well on the potential energy surface (PES), which
corresponds to the singlet carbene 4S, is very shallow at the
B3PW91/6-311+G(3df,2p) level. There is virtually no potential
energy barrier for the addition of nitrogen to the carbene. In
fact, the single-point energy calculations on MP2 level predict
that this carbene is higher in electronic energy than transition
state 6 (Figure 2). (Energies shown in the text and in figures
correspond to B3PW91/6-311+G(3df,2p) calculations, while
values in parentheses were obtained using MP2 (full)/aug-cc-
pVTZ //B3PW91/6-311+G(3df,2p) and values in square brack-
ets were obtained using the MP2 (full)/aug-cc-pVTZ //MP2(full)/
6-311+G(d,p) method.)
However, the actual activation barrier for the reverse reaction,
which includes an entropy term, is much higher; for example,
∆Gq is 7 kcal mol-1 at 0 °C. A free energy profile for 0 °C
calculated at the B3PW91/6-311+G(3df,2p) level for the
stepwise Wolff reaction of 1′ is shown in Figure 2. It is also
interesting to note that the optimized geometry of the transition
state, which corresponds to the saddle point on the potential
energy surface, is somewhat different from the structure that
corresponds to the saddle point on the free energy surface. For
example, the C1-N9 distance (numbering of atoms in structures
The relaxed PES scan, which follows the shortening of the
O7-C1 distance in cyclic diazodiester 1′, predicts that the
concerted Wolff rearrangement, that is, formation of the ketene
5′ directly from diazodiester 1′, is also a feasible process. The
geometry of transition state 8 (Figure 1) shows that the concerted
Wolff rearrangement of 1′ is an asynchronous process. The
cleavage of the C1-N9 bond in 8 is almost complete (lC-N
)
2.22 Å, Table 1), and the C1 carbon is shifted from the plane
of the molecule similar to carbene 4S. On the other hand, the
C1-O6 distance (1.98 Å) indicates less progress in new bond
formation.
The potential energy barrier for the Wolff rearrangement of
1′ is 47.8 (48.4) [48.1] kcal mol-1 lower than the barrier for
the carbene formation (Figures 2 and 3). In fact, all three
methods used in this work, that is, DFT, MP2/DFT, and MP2,
place the transition state for the concerted Wolff rearrangement
(8) lower in energy than carbene 4′. It has to be noted, however,
that frequency calculations predict 6 (carbene formation) to have
ca. 16 eu higher entropy than 8. It means that, above a certain
temperature, formation of carbene might become the predomi-
nant pathway for the deazotization of diazo Meldrum’s acid
(1). Using the difference in electronic energy between these two
states obtained by MP2(full) calculations (ca. 7 kcal/mol), we
can estimate this temperature to be ca. 200 °C. The change of
(28) Z-matrices for the species 1′-9 are presented in the Supporting Infor-
mation.
9
14156 J. AM. CHEM. SOC. VOL. 125, NO. 46, 2003

Investigation of Diazo Meldrum’s Acid
A R T I C L E S
Scheme 5
than that in dioxane. The interesting feature of the thermal Wolff
rearrangement in both solvents is the substantial negative entropy
of activation, which is rather unusual for the deazotization
reaction. This observation favors the concerted mechanism for
the reaction as migration of the O6 atom puts substantial
constraints on the ring vibrations in transition state 8, which
lowers its vibrational entropy by ca. 15 eu relative to 6. The
negative value of the entropy of activation is abated in aqueous
solution due to the higher polarity of the solvent. The polar
initial state puts more constraints on the orientation of the dipoles
in the solvent shell that are relaxed in the less polar transition
state. To check whether strong hydrogen bonding between the
partially negatively charged carbonyl oxygen of 1 and water
molecules affects the reaction in aqueous solution, we have
measured the rate of the decomposition of diazo Meldrum’s
acid in deuterium oxide at 80 and 90 °C (Table S129). The
solvent isotope effect was found to be kH/kD ) 1.30. The small
value of solvent isotope in the normal direction testifies against
involvement of strong hydrogen bonds as these bonds become
weaker in the transition state and should result in an inverse
isotope effect.
Figure 3. Schematic potential energy profile for the concerted Wolff
rearrangement of the diazodiester 1′.
Figure 4. Temperature rate profile for decomposition of 1 in aqueous
(circles) and dioxane (hexagons) solutions. The lines shown were drawn
using parameters obtained by least-squares fitting of the Eyring equation.
The experimental and theoretical results allow us to conclude
that the thermal Wolff rearrangement of diazo Meldrum’s acid
(1) is a concerted, albeit asynchronous, process.
mechanism from concerted to stepwise would be difficult to
observe experimentally due to a very low energy barrier
separating carbene 4S from ketene 5′ (Figure 2). Thus, we were
not able to trap carbene 4S apparently generated by the
photolysis of the diazirine 2 in methanol, but we isolated Wolff
rearrangement products instead (vide infra).
Thermal Reactions of Diazirino Meldrum’s Acids (2). The
thermal stability of 6,6-dimethyl-5,7-dioxa-1,2-diaza-spiro[2,5]-
oct-1-ene-4,8-dione, the diazirino Meldrum’s acid (2), is
substantially lower than that of diazo isomer 1. Mild heating of
2 results in quantitative isomerization into diazo Meldrum’s acid
(Scheme 5).31
Kinetics of the Thermolysis of Diazo Meldrum’s Acids
(1). The decomposition rates of diazo compound 1 were
measured in aqueous and dioxane solutions in the temperature
range from 50 to 95 °C. The decay of the substrate was followed
by the decrease in absorbance at 250 nm. The data so obtained
are summarized in Tables S1 and S229 and are displayed as the
temperature rate profile in Figure 4.
The elongation of the C1-N9 bond that leads to eventual loss
of nitrogen and formation of the ketene 5 (or carbene 4S) is
accompanied by the reduction of conjugation between diazo and
carbonyl groups and makes transition state 8 (or 6) substantially
less polar than initial diazo compound 1. Surprisingly, the rate
of decomposition of diazo Meldrum’s acid in water is faster
than that in less polar dioxane. Analysis of the temperature
dependence of the rate of this reaction explains this apparent
discrepancy. Least-squares fitting of the data to the Eyring
equation30 gives the following activation parameters: ∆Hq )
21.81 ( 0.13 kcal M-1 and ∆Sq ) -18.67 ( 0.33 cal M-1
K-1 in aqueous solutions; and ∆Hq ) 15.2 ( 1.7 kcal M-1 and
∆Sq ) -37.8 ( 4.1 cal M-1 K-1 in dioxane. The enthalpy of
activation for the decomposition of 1 in water is, in fact, higher
The theoretical analysis of the reactivity of diazirine 2′
(analogue of 2 without methyl groups in 6-position) showed
that the lowest energy barrier leads to reverse isomerization into
diazodiester 1′. We were unable to locate a saddle point on PES
that links 2′ with carbene 4′. In the example of simpler
R-carbonyl diazirine, the 2-diazirinoacetic acid, we have
conducted a relaxed 3-D PES scan in terms of both C-N
distances32 and found that any process other than isomerization
proceeds through a much higher energy barrier. The progress
of the 2′ f 1′ isomerization was explored by both the restricted
and the unrestricted DFT method. No intermediates in this
reaction were found in either case.
The optimized geometries of diazirine 2′ and the transition
state for isomerization reaction (9) are shown in Figure 1, with
corresponding energies presented in Table 1. It is interesting to
note that the ring opening of diazirine proceeds with a
nonequivalent elongation of both C-N bonds. In the transition
(31) This process is so efficient that it was used to develop TLC plates. Diazirine
2 has virtually no absorbance at 254 nm and is therefore invisible on TLC
plates with conventional fluorescent indicator. Heating the plate in an oven
at ca. 100 °C for 1 min converts 2 into diazo Meldrum’s acid (1), which
gives an intense dark spot under UV lamp.
(32) Bogdanova, A.; Popik, V. Abstracts of Papers, 224nd ACS National
Meeting, Boston, MA, August 18-22, 2002.
(29) Supporting Information; see paragraph at the end of this paper regarding
availability.
(30) The nonlinear least-squares fitting calculations were conducted using Origin
6.0 by Microcal. The transmission coefficient in the Eyring equation was
set to unity.
9
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A R T I C L E S
Bogdanova and Popik
Figure 5. Schematic potential energy profile for the isomerization of R,R-
dicarbonyldiazirine 2.
Figure 7. UV spectra of ca. 0.0001 M solutions of diazo Meldrum’s acid
(1, solid line) and diazirine 2 (dotted line) in methanol.
Scheme 6
M-1 K-1 in aqueous solutions; and ∆Hq ) 22.20 ( 0.98 kcal
M-1 and ∆Sq ) -10.2 ( 2.4 cal M-1 K-1 in dioxane.
The isomerization of diazirine 2 into diazo Meldrum’s acid
is accompanied by a substantial increase in the polarity of the
molecule. For example, the ESP charge on the N9 atom
calculated by the DFT method rises from -0.001 in the starting
diazirine 2 to +0.226 in the transition state 9, and then to +0.529
in the diazo isomer. Stabilization of the polar transition state in
water results in a 10 kcal M-1 lower enthalpy of activation than
that in less polar dioxane. The negative entropy of activation
of the isomerization reaction is probably due to the solvent
effects. In fact, DFT calculations predict an insignificant entropy
of activation for this reaction in the gas phase, that is, below
1.0 cal mol-1 K-1. Apparently, the increased charge separation
in the transition state requires a substantial reorganization of
the solvent shell, thus resulting in a negative entropy of
activation. This effect is stronger in an aqueous solution due to
the higher polarity of solvent molecules.
Photochemistry of Diazo (1) and Diazirino Meldrum’s
Acids (2). The UV spectrum of diazo Meldrum’s acid (1) has
a strong absorbance at 248 nm and a much weaker band at 329
nm (Figure 7). The position of these absorbance bands is
virtually independent from the polarity of the solvent. No
fluorescence or phosphorescence could be detected at room
temperature in solutions of 1 using 254 and 330 nm excitation
light. This fact indicates that a fast nonradiative depopulation
of excited states takes place. The UV spectrum of isomeric
diazirine 2 is very different; it shows only two weak shoulders
on the tail of the short-wavelength band at ca. 244 nm and at
ca. 284 nm (Figure 7).
Figure 6. Temperature rate profiles for the isomerization of dizirine 2
aqueous (circles) and dioxane (hexagons) solutions. The lines shown were
drawn using parameters obtained by least-squares fitting of the Eyring
equation.
state for the isomerization reaction (9), corresponding lengths
are 1.54 and 2.08 Å versus 1.50 Å in diazirine 2′ and 1.32 Å in
diazo compound 1′. This fact might be considered as evidence
of diazirine to diazo isomerization occurring via formation of
the carbene followed by the reaction of the latter with N2. The
geometry of the transition state for the isomerization reaction
9, however, is very different from that of carbene 4′; that is, C1
lies in the plane of the ring (compare 9 with 8 and 4S). The
potential energy barrier for the diazirine isomerization in the
gas phase is predicted to be 30.4 (37.6) kcal/mol (Figure 5).
The barrier for the reverse reaction, isomerization of the diazo
compound 1′ into diazirine, is 53.6 (60.1) kcal/mol, which is
much higher than the activation energy of the Wolff rearrange-
ment. This observation allows us to conclude that the thermal
isomerization of diazo Meldrum’s acid (1) to diazirine (2) cannot
compete with the loss of nitrogen.
Kinetics of the Thermal Isomerization of Diazirino Mel-
drum’s Acids (2). Rates of the isomerization of diazirine 2 were
measured in aqueous and dioxane solutions in the temperature
range from 45 to 70 °C in water and from 60 to 90 °C in
dioxane. The progress of this reaction was followed by an
increase in absorbance at 250 nm due to the formation of diazo
Meldrum’s acid (1). The data so obtained are summarized in
Tables S3 and S429 and are displayed as the temperature rate
profile in Figure 6.
Direct photolysis of the methanolic or aqueous solution of
diazo Meldrum’s acid (1) results in the formation of two major
products: ketoacid 3b or a corresponding ester 3a, the product
of the Wolff rearrangement, and diazirine 2, the product of
isomerization of the starting diazo compound (Scheme 6). Small
amounts of Meldrum’s acid (10) were also detected in the
reaction mixtures.
The polarity of the solvent has a profound effect on the rate
of this reaction. The isomerization of the diazirine 2 is more
than 10 times faster in water than in dioxane. Least-squares
fitting of the data gives the following activation parameters:
∆Hq ) 12.58 ( 0.52 kcal M-1 and ∆Sq ) -34.3 ( 1.4 cal
The triplet-sensitized photolysis of 1 in methanol, on the other
hand, results in the quantitative formation of Meldrum’s acid
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Investigation of Diazo Meldrum’s Acid
A R T I C L E S
Table 2. Results of Low Conversion Photolyses of Diazo Meldrum’s Acid (1) and Diazirine (2) in Methanol at Different Wavelengths
a Monochromatic irradiation using the frequency up-converted output of the Nd:YAG laser; 20-30% conversion. b Traces. c Not detected. d In 2-propanol.
Figure 8. Frontier molecular orbitals of diazo Meldrum’s acid (1).
(10). This observation is in line with the accepted mechanism
of the photochemical reduction of R-diazocarbonyl compounds
through a triplet carbonylcarbene intermediate.11 The Wolff
rearrangement-to-isomerization product ratio strongly depends
on the wavelength of irradiation. Table 2 shows the relative
yield of compounds 2, 3a, and 10 formed in the photolysis of
diazo Meldrum’s acid at different wavelengths. Product ratios
were measured at low conversion (ca. 10%) to ensure that these
values were not affected by secondary photochemistry.
UV irradiation of diazo Meldrum’s acid (1) with the
wavelength close to λmax of the major absorbance band results
mostly in the Wolff rearrangement and formation of ketoester
3a. At longer wavelengths, isomerization of 1 into diazirine 2
becomes more pronounced, and at 350 nm diazirine becomes
the major product. The wavelength dependence of diazo
Meldrum’s acid photoreactions becomes even more evident
when a source of monochromatic light is employed. Thus,
irradiation of 1 in methanol with the frequency tripled output
of the Nd:YAG laser (355 nm) produces diazirine 2 in high
yield, and only traces of ketoester 3a were observed. The 254
and 350 nm photolyses of diazo Meldrum’s acid differ not only
in the major photoproduct but also in the quantum yields (Table
2). Irradiation into the major absorbance band of 1 results in a
chemical transformation 14 times more efficiently than irradia-
tion into the weaker band.
of 1 to the lowest singlet excited state (S1) by HOMO f LUMO
transition. The HOMO of diazo Meldrum’s acid (1) is a p-type
orbital, which is mainly localized on the carbon of the
diazogroup and is orthogonal to the plane of the diazodicar-
bonyl fragment. The LUMO is a π* orbital of NtN bond,
which lies in that plane (Figure 8). Thus, HOMO to LUMO
transition is a forbidden process due to poor orbital overlap.
The TD-B3PW91/6-311++G(3df,2p) calculations support this
conclusion, predicting that the HOMO f LUMO transition
occurs at λmax ) 353 nm in the gas phase and is, in fact,
forbidden. The low extinction coefficient of the 329 nm band
in the UV spectrum of diazo Meldrum’s acid agrees well with
this assignment.
The short-wavelength photolysis of diazo Meldrum’s acid
results in the formation of a higher excited state, most probably
S2. The major component of the latter excitation, according to
time-dependent DFT calculations, is the HOMO-1 f LUMO
transition. The HOMO-1 is a nonbonding orbital, which has
its largest coefficients on carbonyl oxygens and lies in the plane
of the diazocarbonyl fragment. This orbital has an efficient in-
phase overlap with LUMO (Figure 8). A good quantum yield
(Φ254 ) 0.34) observed in 254 nm photolysis of 1 indicates
that a higher excited state of diazo Meldrum’s acid undergoes
an extremely rapid loss of nitrogen. For the latter reaction to
compete efficiently with an internal conversion, it should
proceed at a rate of 1012 s-1 or faster.33 The laser flash photolysis
The most long-wave absorbance band in the UV spectrum
of diazo Meldrum’s acid apparently corresponds to the excitation
9
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A R T I C L E S
Bogdanova and Popik
Figure 10. Formation of diazo Meldrum’s acid (1) in 300 nm photolysis
of diazirine 2 in methanol.
Scheme 7
Figure 9. Schematic diagram of process involved in the photochemistry
of diazo Meldrum’s acid.
of 1 conducted at 248 nm using a KrF laser demonstrated that
the formation of a corresponding ketene was complete during
the laser pulse (ca. 20 ns).34 This allows us to estimate the lower
equilibration of triplet carbene 4T proceeds much slower than
its reaction with methanol. The rate of hydrogen abstraction by
triplet carbenes from methanol is usually on the order of 1-5
rate limit for the photo-Wolff rearrangement of 1 at 108 s-1
.
The summary of processes involved in the photochemistry
of diazo Meldrum’s acid is represented in Figure 9. The short-
wavelength irradiation of 1 populates mainly the S2 excited state.
One-third of the molecules at this level lose nitrogen and
eventually form the Wolff rearrangement products. The rest of
the molecules undergo an internal conversion to S1, participation
of which is evident from the formation of small amounts of
diazirine 2, before falling onto the ground state surface. The
much higher quantum yield of 254 nm photolysis than that of
350 nm provides an argument against the formation of a Wolff
rearrangement product from “hot” S1 molecules.
× 106 M-1 s-1 35
.
This value allows us to estimate the lower
limit of the activation barrier for intersystem crossing of 4T into
4S as 6-7 kcal/mol. Such a rather high barrier can be explained
by the necessity for geometrical changes accompanying inter-
conversion.
UV irradiation of diazirino Meldrum’s acid (2) results in
processes similar to that observed in the photolysis of its diazo
isomer: Wolff rearrangement producing ketoester 3a, isomer-
ization to diazo Meldrum’s acid (1), and formal reduction to
10 (Scheme 7).
Irradiation into a weak long-wavelength band of diazo
Meldrum’s acid populates the lowest excited state S1. The fact
that no fluorescence or phosphorescence was observed suggests
that thermal deactivation of the lowest singlet excited state to
the ground state is a very rapid process. This conclusion agrees
with a low quantum yield (Φ350 ) 0.025) of phototransformation
of 1 at 350 nm, indicating that only a small fraction of S1
population, below 3%, undergoes isomerization into diazirine
2. We believe that diazirine formation occurs from the S1 excited
state rather than from the “hot” ground state as a thermal reaction
of 1 does not produce diazirine 2, and DFT calculations predict
isomerization to be much slower than the Wolff rearrangement
(vide supra). Benzophenone-sensitized photolysis apparently
populates the lowest triplet excited state of 1, which loses
nitrogen to produce a triplet carbene. The latter undergoes
double hydrogen abstraction to give Meldrum’s acid (10). Traces
of 10 found in direct photolyses of 1 are apparently due to the
low efficiency intersystem crossing yielding a triplet excited
state of 1.
The composition of product mixtures in the photolysis of
diazirine 2 also depends on the wavelength of irradiation. This
dependence, however, is less pronounced: the ketoester 3a is
always the major product, while the yield of diazo compound
1 increases at longer wavelength (Table 2). The results of low
conversion photolyses (ca. 10%) of diazirino Meldrum’s acid
(2) allow us to conclude that ketoester 3a is formed directly
from R,R′-dicarbonyl diazirine 2, rather than from initially
formed 1. The results of photolysis at 300 nm are especially
indicative as diazirine 2 and diazo Meldrum’s acid (1) have
similar extinction coefficients (19 and 23 M-1 cm-1 correspond-
ingly) at this wavelength. The decomposition of the diazo
compound formed by isomerization of starting diazirine becomes
noticeable only at conversions above 30% (Figure 10). Forma-
tion of ketoester 3a early in the reaction indicates that this
product is formed directly from diazirine 2.
The Wolff rearrangement of diazirine 2 apparently proceeds
via a dicarbonyl carbene. The absence of O-H insertion
products, on the other hand, indicates an extremely short lifetime
of this intermediate, which agrees well with the results of
quantum-mechanical calculations (vide supra). The rate of
reaction of structurally similar dicarbomethoxycarbene with
Singlet-Triplet Equilibrium of r,r-Dicarbonyl Carbene
4. DFT and MP2 calculations discussed above show that a
singlet carbene 4S has virtually no barrier for the rearrangement
into ketene 5. The complete absence of the Wolff rearrangement
products in sensitized photolysis thus indicates that spin
methanol is 1.5 × 109 M-1 s-1 24a
.
This value allows us to
estimate the lower rate limit for the Wolff rearrangement of
(33) Turro, N. J. Modern molecular photochemistry; Benjamin/Cummings Pub.
Co.: Menlo Park, CA, 1978.
(34) Kresge, A. J.; Popik, V. V. ECTOC-1, June, 1995.
(35) Hadel, L. M.; Maloney, V. M.; Platz, M. S.; McGimpsey, W. G.; Scaiano,
J. C. J. Phys. Chem. 1986, 90, 2488.
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Investigation of Diazo Meldrum’s Acid
A R T I C L E S
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 of absorbance of
diazo Meldrum’s acid (1) at 250 nm. Observed first-order rate constants
were calculated by least-squares fitting of a single-exponential function.
At temperatures above 60 °C, where isomerization of 2 was ac-
companied by a very slow but pronounced decomposition of product
1, the double exponential function was used.
Theoretical Procedures. Quantum-mechanical calculations were
carried out using the Gaussian 98 program.37 Levels of theory examined
range from hybrid B3PW9138,39 density functional theory calculations
with the 6-311+G(3df,2p)40 basis sets to high level composite proce-
dures including MP2(full)/aug-cc-pVTZ //B3PW91/6-311+G(3df,2p)
and MP2(full)/aug-cc-pVTZ //MP2(full)/6-311+G(d,p). 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 the B3PW91/6-311+G(3df,2p) method. Analyti-
cal second derivatives were computed to confirm each stationary point
as 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 0.9772.41 Initial geometry optimization, IRC
calculations for transition states, and relaxed scans of potential
energy surfaces were conducted at the B3PW91/6-31+G(d,p) level.
The vertical excitation energies were evaluated using the random phase
approximation for a time-dependent DFT calculation method,42 at the
TD-B3PW91/6-311++G(3df,2p) level.
the cyclic dicarbonyl carbene at 1011 s-1. We also cannot
exclude the possibility that photochemical isomerization of
diazirine 2 produces “hot” molecules of diazo Meldrum’s acid,
which then undergo thermal Wolff rearrangement.
Conclusions
The unique wavelength selectivity of the diazo Meldrum’s
acid photochemistry, as well as the wavelength-dependence of
quantum yield, allows us to conclude that isomerization of 1 to
diazirine 2 takes place from the lowest singlet excited state,
while the Wolff rearrangement originates from the higher excited
state. The rate of the diazo group C-N bond cleavage in the
latter should be on the order of 1012 s-1 to be able to compete
with internal conversion. The experimental data and quantum-
mechanical calculations indicate that the Wolff rearrangement
of diazo Meldrum’s acid is a concerted process. The UV
irradiation of R,R-diazirine 2 also results in the Wolff rear-
rangement, apparently via the singlet dicarbonylcarbene inter-
mediate 4S. According to density functional and MP2 calcula-
tions, the carbene-to-ketene isomerization proceeds with
insignificant activation energy. Thermolysis of the diazirine 2
results in a smooth electrocyclic ring opening and isomerization
to the diazo form.
Experimental Section
General Procedures. NMR spectra were recorded on a Varian
Unity+ 400 (200 MHz for 1H and 100 MHz for 13C) or Varian Gemini
Materials. 5-Diazo-2,2-dimethyl-1,3-dioxane-4,6-dione (diazo Mel-
drum’s acid, 1) was prepared in 54% yield by the diazotransfer
reaction2a from N-p-acetamidobenzenesulfonyl azide to Meldrum’s acid.
Mp 93-95 °C (lit.43 92-93 °C). 1H NMR (200 MHz, CDCl3, δ/ppm):
1.79 (s). 13C (50 MHz, CDCl3, δ/ppm): 26.6, 106.9, 156.2. IR (CCl4,
cm-1): 2145 (s), 1733 (vs). UV (MeOH, λmax, nm/log ꢀ): 248/4, 329/
1.42.
1
200 (200 MHz for H and 50 MHz for 13C) spectrometer. All NMR
spectra were recorded in CDCl3 and referenced to TMS. 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. Reagents were obtained from Aldrich and used
as received unless otherwise noted.
6,6-Dimethyl-5,7-dioxa-1,2-diaza-spiro[2,5]oct-1-ene-4,8-dione (Di-
azirino Meldrum’s Acid, 2). A solution of 1 g (5.9 mmol) of diazo
compound 1 in 140 mL of a THF-water mixture (8:1) was irradiated
at 8 °C for 24 h in a Rayonet photoreactor equipped with 16 350 nm
lamps. THF was removed in a vacuum at 0 °C, and colorless crystals
precipitated from water. Crystalline product (480 mg) was dissolved
in chloroform, washed twice with saturated sodium carbonate and water,
dried over MgSO4, and solvent was removed in a vacuum at room
temperature to give 322 mg (32%) of diazirine 2. Mp 85 °C (lit.23a
Photolytic Experiments. Analytical photolyses were performed by
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 of
emission at 254, 300, or 350 nm. Monochromatic irradiations at 266
and 355 nm were conducted using frequency tripled or quadrupled
output of a Q-switched Nd:YAG laser. Reaction mixtures were then
analyzed by HPLC. Pure samples of 1, 2, 3a, and Meldrum’s acid (10)
were used as a reference and to calibrate 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 quartz vessel equipped
with an immersible cooling finger. The consumption of starting material
was followed by TLC. Determination of the quantum yield was
performed using a ferrioxalate chemical actiniometer.36 The triplet-
sensitized photolyses of 1 and 2 were conducted using benzophenone
as a sensitizer in thoroughly degassed solutions in methanol or
2-propanol. The concentration of benzophenone was adjusted to achieve
sensitizer absorbance at 254 nm 10 times higher than that of the
substrate. The sample of diazirine 2 was purified using preparative
HPLC before every photolytic experiment. This treatment was necessary
to remove minor impurities of diazo Meldrum’s acid accumulated
during storage.
1
82-84 °C). H NMR (200 MHz, CDCl3, δ/ppm): 1.99 (s). 13C (100
MHz, CDCl3, δ/ppm): 27.9, 107.6, 161.5.
Methyl 2,2-Dimethyl-5-oxo-1,3-dioxalane-4-carboxylate (3a). A
solution of 300 mg (1.8 mmol) of 1 in 50 mL of methanol was irradiated
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A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratmann,
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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,
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PA, 2001.
(38) Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
(39) Burke, K.; Perdew, J. P.; Wang, Y. In Electronic Density Functional
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Y. Phys. ReV. 1992, B45, 13244.
Kinetics. Rate measurements were performed using a Carry-300 Bio
UV-vis spectrometer equipped with a thermostatable cell holder.
(40) Hehre, W. J.; Radom, L.; Schleyer, P. v. R.; Pople, J. A. Ab Initio Molecular
Orbital Theory; John Wiley & Sons: New York, 1986.
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1998, 108, 4439.
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A R T I C L E S
Bogdanova and Popik
1
at 10 °C in a mini-Rayonet photoreactor equipped with 254 nm lamps
for 4 h. Solvent was removed under vacuum, and the residue was
redissolved in ether and washed with saturated sodium carbonate
solution. The organic layer was dried over MgSO4, and solvent was
removed in a vacuum. The reaction mixture was separated using
preparative TLC on silica gel to give 171 mg (67%) of ester 3a as
colorless oil. 1H NMR (200 MHz, CDCl3, δ/ppm): 1.64 (s, 3H), 1.71
(s, 3H), 3.87 (s, 3H), 4.98 (s, 1H), lit.23
The same compound was also obtained by thermolysis of the
methanolic solution of 1 in a pressure vessel overnight at 120 °C. The
1H NMR spectrum of reaction mixture obtained after removal of solvent
showed the presence of only 3a.
chloride and dried over Na2SO4. The H spectrum of crude product
showed that it contained mainly target ketoacid 3b with ca. 10%
impurity of Meldrum’s acid (10). Preparative TLC purification of the
crude product gave 144 mg (77%) of pure 3b as colorless oil, which
1
slowly crystallizes on standing. H NMR (200 MHz, CDCl3, δ/ppm):
1.68 (s, 3H), 1.71 (s, 3H), 5.00 (s, 1H), 9.05 (broad s), lit.23 UV (H2O,
λmax, nm/log ꢀ): 270/3.1.
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 research
fellowship.
2,2-Dimethyl-5-oxo-1,3-dioxalane-4-carboxylic acid (3b). A solu-
tion of 200 mg (1.2 mmol) of 1 in 50 mL of a THF-water mixture
(5:1) was irradiated at room temperature in a Rayonet photoreactor
equipped with 254 nm lamps until complete decomposition of diazo
compound was achieved (ca. 40 min). THF and water were removed
in a vacuum at 30-40 °C, and the residue was redissolved in methylene
Supporting Information Available: Tables S1-S4 of rate
data and Gaussian 98 output files for quantum-mechanical
calculations (PDF). This material is available free of charge via
the Internet at http://pubs.acs.org.
JA037637D
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14162 J. AM. CHEM. SOC. VOL. 125, NO. 46, 2003