2-pyridylnitrene and 3-pyridazylcarbene and their relationship via ring-expansion, ring-opening, ring-contraction, and fragmentation

Article abstract of DOI:10.1021/jo902570d

(Figure Presented) Photolysis of triazolo[1,5-b]pyridazine 8 isolated in Ar matrix generates diazomethylpyridazines 9Z and 9E and diazopentenynes 11Z and 11E as detected by IR spectroscopy. ESR spectroscopy detected the 3-pydidazylcarbene 10 as well as pent-2-en-3-yn-l-ylidene 12 formed by loss of one and two molecules of N₂, respectively. Further photolysis caused rearrangement of the carbenes to 1,2-pentadien-4-yne 13 and 3- ethynylcyclopropene 14. Flash vacuum thermolysis (FVT) of 8 at 400-500 °C with Ar matrix isolation of the products yielded 13, 14, and 1,4-pentadiyne 15. At higher temperatures, glutacononitriles 27Z and 27E were formed as well together with minor amounts of 2- and 3-cyanopyrroles 28 and 29. Tetrazolo[1,5-a]pyridine/2-azidopyridine 22T/22A yields 2-pyridylnitrene 19 as well as the novel open-chain cyanodienylnitrene 23 and the ring-expanded 1,3-diazacyclohepta-l,2,4,6-tetraene 21 on short wavelength photolysis. Nitrenes 19 and 23 were detected by ESR spectroscopy, and cumulene 21 by IR and UV spectroscopy. FVT of 22T/22A also affords 2-pyridylnitrene 19 and diazacycloheptatetraene 21, as well as glutacononitriles 27Z,E and 2- and 3-cyanopyrroles 28 and 29. Photolysis of 21 above 300 nm yields the novel spiroazirene 25, identified by its matrix 1R spectrum. The reaction pathways connecting the four carbenes (10Z,E and 12Z,E) and three nitrenes (19, 23EZ, and 23ZZ) in their open-shell singlet and triplet states are elucidated with the aid of theoretical calculations at DFT, CASSCF, and CASPT2 levels. Three possible mechanisms of ring-contraction in arylnitrenes are identified: (i) via ring-opening to dienylnitrenes, (ii) concerted ring-contraction, and (iii) via spiroazirenes 25, whereby (i) is the energetically most favorable.

Full text of DOI:10.1021/jo902570d

pubs.acs.org/joc
2-Pyridylnitrene and 3-Pyridazylcarbene and Their Relationship via
Ring-Expansion, Ring-Opening, Ring-Contraction, and Fragmentation
David Kvaskoff, Pawel Bednarek,† and Curt Wentrup*
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Qld 4072,
Australia. †Present address: Universiteꢀ de Fribourg, Fribourg, Switzerland.
wentrup@uq.edu.au
Received December 4, 2009
Photolysis of triazolo[1,5-b]pyridazine 8 isolated in Ar matrix generates diazomethylpyridazines 9Z
and 9E and diazopentenynes 11Z and 11E as detected by IR spectroscopy. ESR spectroscopy
detected the 3-pydidazylcarbene 10 as well as pent-2-en-3-yn-1-ylidene 12 formed by loss of one
and two molecules of N2, respectively. Further photolysis caused rearrangement of the carbenes to
1,2-pentadien-4-yne 13 and 3-ethynylcyclopropene 14. Flash vacuum thermolysis (FVT) of 8 at
400-500 °C with Ar matrix isolation of the products yielded 13, 14, and 1,4-pentadiyne 15. At higher
temperatures, glutacononitriles 27Z and 27E were formed as well together with minor amounts of
2- and 3-cyanopyrroles 28 and 29. Tetrazolo[1,5-a]pyridine/2-azidopyridine 22T/22A yields
2-pyridylnitrene 19 as well as the novel open-chain cyanodienylnitrene 23 and the ring-expanded
1,3-diazacyclohepta-1,2,4,6-tetraene 21 on short wavelength photolysis. Nitrenes 19 and 23 were
detected by ESR spectroscopy, and cumulene 21 by IR and UV spectroscopy. FVT of 22T/22A also
affords 2-pyridylnitrene 19 and diazacycloheptatetraene 21, as well as glutacononitriles 27Z,E and
2- and 3-cyanopyrroles 28 and 29. Photolysis of 21 above 300 nm yields the novel spiroazirene 25,
identified by its matrix IR spectrum. The reaction pathways connecting the four carbenes (10Z,E
and 12Z,E) and three nitrenes (19, 23EZ, and 23ZZ) in their open-shell singlet and triplet states are
elucidated with the aid of theoretical calculations at DFT, CASSCF, and CASPT2 levels. Three
possible mechanisms of ring-contraction in arylnitrenes are identified: (i) via ring-opening to
dienylnitrenes, (ii) concerted ring-contraction, and (iii) via spiroazirenes 25, whereby (i) is the
energetically most favorable.
Introduction
tetrazolo[1,5-a]pyridazine/3-azidopyridazine 1T/1A, under-
goes an analogous ring-opening to a diazonium ylide, viz. the
diazo compound 3, under both thermal and photochemical
conditions. Flash vacuum thermolysis (FVT) of 1 produced 3
and the products of N2 elimination (Scheme 2).3 The same
products were also obtained on matrix photolysis,4,5 and a
weak signal ascribed to nitrene 2 was detected by ESR
In recent papers we have demonstrated the occurrence of
two types of ring-opening reactions of (hetero)aromatic
nitrenes and carbenes, Type I and Type II (Scheme 1).
Type I ring-opening generates nitrile ylides exemplified by
3-pyridylcarbene, 3-pyridylnitrene,1 and 2-pyrazinylnitrene/
4-pyrimidylnitrene.2 Pyridazinylnitrene 2, generated from
(3) Wentrup, C.; Crow, W. D. Tetrahedron 1970, 26, 4915.
(4) Hill, B. T.; Platz, M. S. Phys. Chem. Chem. Phys. 2003, 5, 1051.
(5) Torker, S. Diploma Thesis, The University of Queensland (Australia)
and Technical University of Graz (Austria), 2003.
(1) Bednarek, P.; Wentrup, C. J. Am. Chem. Soc. 2003, 125, 9083.
(2) Addicott, C.; Wong, M. W.; Wentrup, C. J. Org. Chem. 2002, 67,
8538.
1600 J. Org. Chem. 2010, 75, 1600–1611
Published on Web 02/04/2010
DOI: 10.1021/jo902570d
r
2010 American Chemical Society

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SCHEME 1. Type I and Type II Ring-Openings
SCHEME 2. 3-Pyridazylnitrene and Its Reactions
SCHEME 3. 3-Pyridazylcarbene Ring-Opening and Fragmen-
tation on Photolysis and Thermolysis
spectroscopy of Ar matrices.6 The formation of diazo com-
pound 3 can be described as a Type I ring-opening reaction of
the nitrene 2.
Type II ring-opening generates diradicals or vinylnitrenes
(Scheme 1). The ring-opening of 2-pyridylnitrene is the
subject of detailed discussion in this paper. Type II ring-
openings in 2-quinoxalylnitrene and 1-isoquinolylnitrene
have been reported previously.6,7
Phenylnitrene 5a and 2-pyridylcarbene 7a can intercon-
vert via 1-azacyclohepta-1,2,4,6-tetraene 6a (eq 1).8 2-Pyr-
idylnitrene 5b/7b undergoes a degenerate interconversion
with 1,3-diazacycohepta-1,2,4,6-tetraene 6b,9 and 2-pyrazi-
nylnitrene 5c and 4-pyrimidylnitrene 7c interconvert via
ring-expansion to 1,3,5-triazacycloheptatetraene 6c (eq 1).2
unchanged triazole (Figure S1 in the Supporting Informa-
tion shows the IR and UV spectra), but a small amount of the
diazo valence tautomer 9Z,E is formed on gentle FVT at
500 °C (see below). Photolysis of the matrix-isolated triazole
8 at 222 or 254 nm resulted in ring-opening to the diazo
compound 9 with a UV maximum at ca. 460 nm and IR
peaks at 2094 (vs), 1586 (m), 1446 (s), 1373 (w), 1222 (vw),
801 (w), and 671 (w) cm-1 (Figure 1). Further photolysis
resulted in increased intensity of an additional peak at
2097 cm-1 as well as a smaller doublet at 2070-2075 cm-1
accompanied by a C-H stretching band at 3321 cm-1. The
double peak at 2094 (2093)-2097 cm-1 is ascribed to the s-Z
and s-E conformers of 9. The new peaks at 2070-2075 and
3321 cm-1 indicate the presence of a second, acetylenic,
diazo compound, viz. diazopentenynes 11Z and 11E
(Figure 2). Good agreement with the calculated IR spectra
(Figure 2) supports the assignments. Difference spectra show
that, as 9 is photolyzed, 11 is formed (Scheme 3 and in the
Supporting Information Figure S2).
These reactions motivated us to investigate the potential
interconversion of 3-pyridazinylcarbene 10 and 2-pyridylni-
trene 19. The results are described herein.
Results and Discussion
3-Pyridazylcarbene by Photolysis of Triazolo[1,5-b]-
pyridazine. We first describe the formation of diazo com-
pounds and carbenes (Scheme 3). Triazole 8 was prepared by
oxidation of the hydrazone of 3-pyridazinecarboxaldehyde
with active MnO2. The compound exists exclusively in the
triazole form in the solid state at room temperature, and
codeposition with Ar at 25 K also produced very largely the
Photolysis of an Ar matrix of triazolopyridazine 8 in the
ESR spectrometer gave rise to three sets of carbene signals
(Figure 3), which are ascribed to pyridazylcarbene 10 and the
s-E and s-Z conformers of pentenynylidene, 12E and 12Z, on
the basis of their zero field splitting (ZFS) parameters. After
45 s of photolysis at 308 nm only 10 and one conformer of 12
(6) Kvaskoff, D.; Bednarek, P.; George, L.; Waich, K.; Wentrup, C.
J. Org. Chem. 2006, 71, 4049.
(7) Addicott, C.; Reisinger, A.; Wentrup, C. J. Org. Chem. 2003, 68, 1470.
(8) (a) Wentrup, C. Top. Curr. Chem. 1976, 62, 175. (b) Chapman, O. L.;
Sheridan, R. S.; LeRoux, J.-P. J. Am. Chem. Soc. 1978, 100, 6245.
(9) (a) Winter, H.-W.; Wentrup, C. J. Am. Chem. Soc. 1980, 102, 6159.
(b) McCluskey, A.; Wentrup, C. J. Org. Chem. 2008, 73, 6265.
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FIGURE 2. IR spectrum of triazolopyridazine 8 in Ar matrix after
photolysis at 254 nm for 2 min, showing peaks of diazo compounds
9 and 11 (9Z, 9E and 11Z, 11E). (a) Calculated spectrum of diazo
compound 9E. (b) Calculated spectrum of diazo compound 9Z;
(c) photolysis at 254 nm, 2 min (the negative peaks are the spectrum
of 8 before photolysis). (d) Calculated spectrum of diazo compound
11Z. (e) Calculated spectrum of diazo compound 11E. The shoulders
indicating the presence of the s-Z and s-E geometrical isomers of 9
and 11 are shown in the inset. All calculations are at the B3LYP/
6-311G** level, with wavenumbers scaled by a factor of 0.967.
FIGURE 1. (a) UV difference spectrum of 3-pyridazyldizomethane 9
(major conformer at 2094 cm-1) in Ar matrix, obtained by photolysis
of 8 in Ar matrix at 254 nm for 1 min (200 mA, 50 W low-pressure Hg
lamp). (b) The corresponding IR spectrum. (For the matrix UV and
IR spectra of 8, see Figure S1 in the Supporting Information)
(12E) were detectable (Figure S3, SI). After 60 s at 308 nm all
three species were obtained (Figure 3). Only one conformer
of 10 was detected at all times. The spectra become more
intense but also more complicated at longer photolysis times
with small amounts of other, unidentified triplet species
being formed (see below). ZFS parameters for 10: D/hc =
0.5440 cm-1; E/hc = 0.0254 cm-1. This D value fits the
correlation with calculated natural spin densities on the
carbene carbon in aryl- and heteroarylcarbenes.10 Vinylcar-
benes have significantly smaller D values. ZFS parameters
for 12E: D/hc = 0.3360 cm-1, E/hc = 0.0208 cm-1, E/D =
0.0619; 12Z:D/hc = 0.3798 cm-1, E/hc = 0.0162 cm-1, E/D=
0.0427. For comparison, the ZFS parameters for the parent
vinylcarbene in MTHF solution at 6 K are the following:11
(s-E)-vinylcarbene: D/hc = 0.4093 cm-1, E/hc = 0.0224 cm-1
,
E/D=0.0547; (s-Z)-vinylcarbene: D/hc=0.4578 cm-1, E/hc=
0.0193 cm-1, E/D = 0.0422. The lower D values for 12Z,E are
FIGURE 3. ESR spectrum showing three carbenes after photolysis
of 8 at 308 nm for 60 s. 10: D/hc = 0.5440 cm-1; E/hc = 0.0254
cm-1; Z1 = 2330 G; X2 = 5128 G; Y2 = 6188 G; Z2 = 9243 G. E-
12: D/hc = 0.3360 cm-1; E/hc = 0.0208 cm-1; X2 = 4550 G; Y2 =
5341 G. Z-12: D/hc = 0.3798 cm-1; E/hc = 0.0162 cm-1; X2 = 4795
G; Y2 = 5425 G. Microwave frequency 9.7278 GHz. H0 = 3471 G.
(10) Kvaskoff, D.; Bednarek, P.; George, L.; Pankajakshan, S.; Wentrup,
C. J. Org. Chem. 2005, 70, 7947.
(11) Hutton, R. S.; Manion, M. L.; Roth, H. D.; Wasserman, E. J. Am.
Chem. Soc. 1974, 96, 4680.
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in accord with the extended conjugation, and the E/D ratios
for 12Z,E follow the same trend as those for the parent
vinylcarbenes.
In addition to the carbene signals described above, two
triplet species are formed in the matrix photolyses of 8,
particularly at 222 nm (Figure S4, Supporting Information).
The strongest of these signals (D = 0.636 cm-1; E = 0.0007
cm-1) is indicative of a highly conjugated nitrene or an
(almost) linear carbene. None of these unassigned signals
match the cyanovinylnitrene 23, which is formed from
2-pyridylnitrene as described below. Some candidates for
one or more of the unassigned triplet species are indicated in
Scheme S1 in the Supporting Information. The same triplet
signal is also obtained on photolysis or pyrolysis (FVT) of
the isosteric tetrazolo[1,5-a]pyridazine 1T (D = 0.637 cm-1
,
E = 0.0009 cm-1). The signal looks very much like that of
propynylidene, HCCCH,12 but it is too weak for a secure
identification.
Photolysis of 8 at 254 or 222 nm in the IR cryostat gave, in
addition to the peaks due to the diazo compounds 9 and 11
described above, new peaks at 3333 (m), 1955 (w), 889 (m),
852 (m), and 644 (m) cm-1 and another set at 3338 (w), 2125
(vw), 1661 (m), 986 (s), 945 (m), 613 (s), 605 (vw), and 516 (m)
cm-1, as well as a single, weak peak at 1988 cm-1 not
belonging to any of the other sets of peaks (Figure 4 and in
the Supporting Information Figures S5-S7). The resulting
IR spectrum is interpreted as a composite of two secondary
photolysis products, derived from the carbene 12 (Scheme 3;
Figure 4). The first set of absorptions is assigned to
1,2-pentadien-4-yne 13, and the second set to 3-ethynylcy-
clopropene 14. The peaks due to 13 appeared first. Com-
pounds 13 and 14 were identified by comparison with
literature data13 and with the calculated spectra shown in
the Supporting Information (see Figure S7). IR difference
spectra show that 9 photolyzes to 11, 13, and 14 at 222 and
254 nm (Figures S2 and S5). Both 9 and 11 photolyze to 13
and 14 at 281 nm (Figure S6, Supporting Information).
Compounds 13 and 14 were also isolated from the prepara-
tive FVT described below.
FIGURE 4. IR difference spectrum showing the characteristic
absorptions of the final photoproducts 1,2-pentadien-4-yne 13
and 3-ethynylcyclopropene 14 after continued photolysis in Ar
matrix at 254 nm for 120 min. Negative peaks are due to the
spectrum obtained at 254 nm for 60 min (mainly a mixture of
8, 9Z,E, and 11Z,E). The acetylenic C-H stretching region at
3325-3333 cm-1 is shown in the inset. Allene 13 appears at
1955 cm-1. For the peaks at 1988 and 2042 (K) cm-1 see the text.
glutacononitriles 27Z,E, which are formed on FVT (see
below). The ketenimine 39 described below is another possi-
bility, but this compound should not form at 254 nm.
FVT of Triazolo[1,5-b]pyridazine. Triazolopyridazine 8
was subjected to FVT at 500-700 °C, with the products
being deposited together with Ar at 25 K to form a matrix.
The IR spectrum recorded at 10 K showed that, at an FVT
temperature of 500 °C much unchanged triazole was recov-
ered. At 700 °C the conversion to products was nearly
complete.
Photolysis of the matrix containing the mixture of diazo
compounds at λ > 405 nm caused the intensities of the
triazole peaks to increase, thereby indicating that a portion
of the diazo compounds 9Z,E reverted back to triazole 8,
while another portion was converted to products 13 and 14.
Additional weak peaks appeared during the photolysis at
254 nm; the weak, single peak at 1988 cm-1 (Figure 4 and in
the Supporting Information Figure S5 and S7) does not
belong to either 12 or 13. The most likely assignment is the
1,3-diazacycloheptatetraene 21 (see Scheme 4 and the dis-
cussion below), but the weakness prevented the observation
of any other peaks belonging to 21; therefore, any assign-
ment of the carrier must remain tentative.
Throughout the temperature range 600-700 °C, peaks
corresponding to the two photoproducts described above,
1,2-pentadien-4-yne 13 and 3-ethynylcyclopropene 14, were
observed, as well as new absorptions at 3319 (s), 2140 (w),
1417 (m), 1300 (w), and 605 (w) (Figure S8, Supporting
Information). The new species was identified as 1,4-penta-
diyne 15, formed by thermal rearrangement of 14 and/or 13
(Scheme 3);14 the same three products were isolated in
1
preparative FVT experiments and identified by H NMR
spectroscopy.
In addition to the peaks due to the three products 13, 14,
and 15, new peaks were observed at 2275, 2235, and 2260
cm-1 in the products of FVT at 600-700 °C (Figure S9,
Supporting Information). Absorptions in this region are
typical of nitriles, and these absorptions were readily as-
signed to the known Z- and E-glutacononitriles9,15 27Z,E
(2275 and 2235 cm-1), 2-cyanopyrrole9 28 (2235 cm-1), and
A signal labeled K at 2042 cm-1 in Figure 4 may be due to
cyanovinylketenimine 26, one of the possible precursors of
(12) (a) Bernheim, R. A.; Kempf, R. J.; Gramas, J. V.; Skell, P. S. J. Chem.
Phys. 1965, 43, 196. (b) Seburg, R. A.; Patterson, E. V.; McMahon, R. J.
J. Am. Chem. Soc. 2009, 131, 9442. The matrix site effects reported by these
authors were not observed. The weak Z1 and Z2 transitions were not
observable in our spectrum. (c) The 5956-5986 G transition in our spectra is
very similar to that described in: DePinto, J. T. Ph.D. Thesis, University of
Wisconsin, 1993.
(14) Haley, M. M.; Biggs, B.; Looney, W. A.; Gilbertson, R. D. Tetra-
hedron Lett. 1995, 36, 3457.
(15) Boate, D. R.; Hunter, D. H. Org. Magn. Reson. 1984, 22, 167.
(13) (a) Maier, G.; Endres, J. J. Mol. Struct. 2000, 556, 179. (b) Jones,
E. R. H.; Lee, H. H.; Whiting, M. C. J. Chem. Soc. 1960, 341.
J. Org. Chem. Vol. 75, No. 5, 2010 1603

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SCHEME 4. Further Rearrangements of 3-Pyridazylcarbene 10 and 2-Pyridylnitrene 19
3-cyanopyrrole9 29 (2260 cm-1) (Scheme 4 and in the
Supporting Information Figure S9). The presence of
these compounds was confirmed by GC-MS and 1H NMR
spectroscopy and comparison with samples prepared
from tetrazolo[1,5-a]pyridine 22T (see below).9 Very weak
1
peaks due to 27Z,E were visible in the H NMR spectrum
already at 500 °C, along with 13-15 as the main pro-
ducts, but the cyanopyrroles were not detectable at this
temperature.
2-Pyridylnitrene. The formation and photochemistry of
2-pyridylnitrene are now described. 2-Pyridylnitrene 19 is
easily detected by its Ar matrix ESR spectrum when gener-
ated by FVT of tetrazolo[1,5-a]pyridine/2-azidopyridine
22T/22A (see Scheme 4).9b Photolysis of matrix-isolated
2-azidopyridine 22A at 254 nm also affords a strong ESR
signal due to triplet 2-pyridylnitrene 19 (Figure 5). However,
a second signal at ca. 5000 G has the typical appearance of
the X2Y2 transition of a strongly delocalized nitrene with a
nonzero E value (D/hc = 0.425 cm-1; E/hc = 0.006 cm-1
)
(Figure 5).
FIGURE 5. ESR spectrum obtained after mild FVT of tetrazolo-
pyridine 22T at 200 °C to generate 2-azidopyridine 22A, isolation
of the products in Ar matrix at 15 K, and photolysis at 254 nm.
Signal at X2 = 7025 G, Y2 = 7126 G: D/hc = 1.073 cm-1; E/hc =
0.002 cm-1 (assigned to 2-pyridylnitrene 19). Signal at X2 = 5055 G,
Y2 = 5281 G: D/hc = 0.425 cm-1; E/hc = 0.006 cm-1 (assigned
to 23).
The D value of 0.425 cm-1 is too low to be due to an
aliphatic or aromatic nitrene but would fit a conjugated
vinylnitrene. This signal is ascribed to the ring-opened
cyanodienylnitrene 23.
documented in the matrix photolyses of several substituted
tetrazolo/azidopyridines.7,16
2-Pyridylnitrene undergoes facile ring-expansion to the
cyclic carbodiimide 21 on both photolysis and FVT as
observed by IR spectroscopy.9 Thus photolysis of 22T/22A
in an Ar matrix at 254 nm affords a very clean IR spectrum of
21 in very good agreement with the calculated spectrum
(Figure 6): 1989 (vs), 1318 (m), 978 (m), 975 (m), 747 (m), 551
(m) cm-1. The UV spectrum of 21 has a maximum at 328 nm
(Figures S11-S12, Supporting Information), and the com-
pound therefore undergoes secondary photolysis in the
300-400 nm range.
This assignment is supported by the calculated natural spin
density F on the nitrene-N in 23 (1.2486), which makes this
nitrene fit very well on our D-F correlation diagram6 (see
Figure S10, Supporting Information). Nitrene 23 is the
expected precursor of glutacononitriles 27Z,E described
below. The formation of open-chain ketenimines has been
(16) Addicott, C.; Wentrup, C. Aust. J. Chem. 2008, 61, 592.
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Most interestingly, further photolysis of 21 at 308 or 365 nm
(using a 310-390 nm interference filter) leads to a new
compound, the IR spectrum of which agrees very well with
the calculated spectrum of the spiroazirene 25 (Scheme 4,
Figure 7, and in the Supporting Information Figure S13).
In contrast, very poor agreement was found with the
calculated IR spectra of a number of alternative structures,
including cyanovinylazirenes 30 and isocyanovinylazirenes.
The CdN stretching vibration of spiroazirene 25 appears
at 1688 cm-1. 1-Azaspiro[2.4]hepta-1,4,6-triene 31 (eq 2) has
been prepared by photolysis of 6-azidofulvene
and is reported to absorb at 1676 cm-1 in CCl4 solution.17
The formation of spiroazirene 25 has precedent in the all-
carbon series, where the analogous spirocyclopropene is
postulated as a key intermediate in the thermal carbon
scrambling in phenylcarbene (Scheme 5).18 Such a spirocy-
clopropene can actually be isolated in the indene series.19 The
photochemical formation of 25 would be a logical conse-
quence of an electrocyclic process yielding 24 (Scheme 4).
FIGURE 6. (a) Calculated IR spectrum of carbodiimide 21 at the
B3LYP/6-311G** level, wavenumbers scaled by 0.967, and (b) Ar
matrix IR spectrum resulting from photolysis of tetrazolopyridine/
2-azidopyridine 22T/22A at 222 nm for 30 min. Peaks due to 21:
1989 (vs), 1318 (m), 978 (m), 975 (m), 925 (w), 890 (w), 747 (m), 551
(m) cm-1. The same spectrum is obtained on photolysis of 22T/22A
at 254 nm.
SCHEME 5. Phenylcarbene Rearrangements18
of 2-aminopyridine (formed from triplet 2-pydidylnitrene by
H-abstraction, in yields of 1-10% depending on conditions)
and Z- and E-glutacononitriles 27Z,E (ca. 10%).9 2-Cyano-
pyrrole 28 appears first, but since 2- and 3-cyanopyrroles
interconvert by means of a series of 1,5-H and 1,5-CN shifts,
a mixture of 28 and 29 inevitably forms at elevated tempera-
tures.9 The cyclization of dienylnitrene 23 and a concerted
ring-contraction of 2-pyridylnitrene 19 are attractive mecha-
nisms of formation of the cyanopyrroles (see several routes
to cyanopyrroles in Schemes 4, 6, and 7). Although spiroa-
zirene 25 is a photochemical product, and the cyanopyrroles
are not obtained in any significant quantities on photolysis,
the question has to be asked whether 25 could be a precursor
of the cyanopyrroles in FVT reactions. The analogous
spiroazirene 31 (eq 2) rearranges to isocyanocyclopentadiene
on both photolysis and thermolysis, and on FVT above
420 °C only cyanocyclopentadiene was obtained.17 A similar
reaction could be the source of weak isocyanide absorptions
seen at 2127-2133 cm-1 in IR spectra of the photolyses of
22. The question of involvement of 25 in cyanopyrrole
formation will be considered in the Computational Method
section.
Relationship between 3-Pyridazylcarbene and 2-Pyridylni-
trene. The high-temperature formation of compounds
27-29 from 8 could suggest the possible isomerization of
3-pyridazylcarbene to 2-pyridylnitrene as illustrated in
Scheme 4. This reaction would have to pass through mole-
cules or transition structures resembling the cyclopropene
16, the seven-membered ring ketenimine 17 (a ketene hydra-
zone; not observed experimentally; see Figure S14 in the
Supporting Information), and the formally antiaromatic
diazirene 18 (Scheme 4). The 2-pyridylnitrene energy surface
Either a concerted 1,5-shift or ring-opening to a vinylnitrene
and reclosure leads to 25. This process is considered further
in the Computational Method section below. The weak
absorption at 2042 cm-1 in Figure 7 and in the Supporting
Information Figure S13 may be due to the ketenimine 26
(Schemes 4 and 6) or 39 (Scheme 7, described below). The
weakness of this signal does not permit a distinction.
FVT of 22T/22A affords the cyclic carbodiimide 21 as the
main product at temperatures below ca. 500 °C.9 At higher
temperatures, 21 gradually disappears, to be replaced by
2- and 3-cyanopyrroles 28 and 29 along with minor amounts
€
€
(17) Banert, K.; Kohler, F.; Kowski, K.; Meier, B.; Muller, B.; Rademacher,
P. Chem.;Eur. J. 2002, 8, 5089.
(18) Wong, M. W.; Wentrup, C. J. Org. Chem. 1996, 61, 7022. Wentrup,
€
C.; Wentrup-Byrne, E.; Muller, P. Chem. Commun. 1977, 210.
(19) Wentrup, C.; Benedikt, J. J. Org. Chem. 1980, 45, 1407.
J. Org. Chem. Vol. 75, No. 5, 2010 1605

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FIGURE 7. (a) Calculated spectrum of spiroazirene 25 at the B3LYP/6-311G** level, wavenumbers scaled by 0.967, and (b) difference IR
spectrum obtained after photolysis of tetrazolopyridine 22T at 222 nm for 30 min to generate 21 (negative spectrum), followed by 308 nm for
30 min to generate 25 (positive spectrum). The weak signal at 2042 cm-1 may be due to ketenimine 26 or 39.
is usually accessed from tetrazopopyridine/2-azidopyridine
22T/22A.9 However, the ratio of yields of glutacononitriles
27E,Z and cyanopyrroles 28 and 29, [27E,Z]:[28 þ 29] is
much higher from 8 than from 22 (ratio ∼6:1 from triazole 8
at 600 °C; ratio ∼1:7 from tetrazole 22T). This suggests that
the unobserved seven-membered-ring ketenimine 17 can
undergo Type II ring-opening to cyanodienylnitrene 23, thus
leading to an excess of glutacononitriles when proceeding
from the pyridazine side (see Scheme 4). Moreover, no
2-aminopyridine was detectable by either GC-MS or NMR
spectroscopy of the products of FVT of 8, whereas this
compound is always formed as a minor product (1-10%,
depending on conditions) from (triplet) 2-pyridylnitrene.9
Instead, 3-methylpyridazine was formed on FVT of 8, a
characteristic (triplet) carbene H-abstraction product.10
Conversely, when 2-pyridylnitrene is generated from 22,
there is no formation of either 3-methylpyridazine or the
low molecular weight compounds derived from triazolopyr-
idazine, viz. 13-15. 2-Pyridylnitrene 19 is easily detected by
its Ar matrix ESR spectrum when generated by FVT9b of 22,
but FVT of 8 with Ar matrix isolation in the ESR cryostat
affords at best a trace of a triplet ESR signal, which may be
due to 2-pyridylnitrene 19, but it is too weak to assign it with
any degree of certainty. As described above, 2-pyridylnitrene
undergoes facile ring-expansion to the cyclic carbodiimide 21
on both photolysis and FVT; 21 is detectable by its strong
absorption at 1988-1989 cm-1 in the IR spectrum
(Figure 6). A weak band was observed at 1988 cm-1 in the
photolyses of 8 (Figure 4 and in the Supporting Information
Figures S5 and S14), but it was too weak for any secure
assignment; none of the other absorptions belonging to 21
were detectable. Thus, if 3-pyridazylcarbene rearranges to
2-pyridylnitrene, this leads at best to trace amounts of
nitrene 19 and carbodiimide 21 being observable.
peak was observable in the experimental spectra (see Figure
S14, Supporting Information). A rearrangement of 17 to
2-pyridylnitrene 19 would be possible via the diazirene 18 as
an intermediate or transition state (see the Computational
Method section below). Rearrangements via 1,3-diazirenes
have been invoked in other, similar ring-expansions of
hetarylnitrenes such as 2-pyrimidyl-,5 2-quinazolyl-,6 and
s-triazolylnitrenes.20
When the reaction proceeds from 2-pyridylnitrene 19, type
II ring-opening to 26 and 27 is a minor process under both
thermal9,21 and photochemical16,22 conditions, whereas for-
mation of the cyanopyrroles 28 and 29 is the major process
under FVT conditions.9,21 FVT of 3-azidopyridine also leads
to a mixture of 2- and 3-cyanopyrroles as end products,
but no glutacononitrile is formed. Here, 3-cyanopyrrole
is probably formed via the open-chain nitrile ylide in a
Type I ring-opening-ring-closure.1 The reaction paths will
now be discussed in more detail in light of theoretical
calculations.
Calculations. For further insight, the thermal reaction
paths were explored by calculating the relative energies of
most of the species of interest at the B3LYP/6-31G* level of
theory. The ground state of 2-pyridylnitrene 19 is the triplet
(3A00), which is the reference point for all the energies in
Scheme 6. It is now well-known that singlet nitrenes have an
open shell electronic structure;23 therefore a detailed ex-
ploration of the reaction path 18 f 19 requires CASSCF
and CASPT2 calculations, the results of which are reported
in Scheme 6. It is possible to make reasonable estimates for
open-shell singlet species at the B3LYP/6-31G* level with
use of the Cramer-Ziegler sum method.24 The latest value
(20) Bucher, G.; Ziegler, F.; Wolf, J. J. Chem. Commun. 1999, 2113.
(21) Crow, W. D.; Wentrup, C. Chem. Commun. 1969, 1387.
(22) Reisinger, A.; Bernhardt, P. V.; Wentrup, C. Org. Biomol. Chem.
2004, 2, 245.
(23) Karney, W. L.; Borden, W. T. J. Am. Chem. Soc. 1997, 119, 1378.
(24) Johnson, W. T. G.; Sullivan, M. B.; Cramer, C. Int. J. Quantum
Chem. 2001, 85, 492.
There was no direct spectroscopic evidence for the cyclic
7-membered-ring ketenimine 17 in the photolyses or thermo-
lyses of 8. The calculated frequency for this compound at the
B3LYP/6-31G* level of theory is 1898 cm-1; no matching
1606 J. Org. Chem. Vol. 75, No. 5, 2010

Kvaskoff et al.
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SCHEME 6. Calculated Reaction Pathsa
aEnergies of minima and transition structures relative to triplet 2-pyridylnitrene 19 T0 at the CASSCF (CASPT2) level, with values in italics at the
(U)B3LYP/6-31G* level in kcal/mol. A QCISD(T)/6-31G* single point calculation yielded TS for 16 f 17 1.3 kcal/mol above that for 16.
for the energy gap between the triplet and the open-shell
singlet (OSS) phenylnitrene is ca. 15 kcal/mol,25 whereas a
value of ca. 18 kcal/mol has been assumed previously.23 We
calculate the T0-S1 gap (3A00 - 1A00) in 19 as 18.6 (19.7) kcal/
mol at the CASSCF (CASPT2) levels, and 16.2 kcal/mol at
the B3LYP/6-31G* level using the Cramer-Ziegler correc-
tion.24 Thus, were it to occur, the overall carbene-nitrene
rearrangement reaction, 10 (1A0) f 19 (1A00) would be
exothermic by about 39-48 kcal/mol. The calculated
activation energy for N2 loss from diazo compound 9 is 41
kcal/mol (B3LYP/6-31G*). The cyclization of 10E to the
cyclopropene 16 requires a very modest energy barrier
(Scheme 6), and its rearrangement to the seven-membered-
ring 17 is strongly exothermic. The activation energy for
16 f 17 at the CASPT2 level is seemingly below the energy of
16. The problem stems from the fact that the CASPT2 energy
is calculated at the CASSCF geometry. The correctness of
the CASSCF TS was confirmed by IRC calculations in both
directions. A QCISD(T)/6-31G* single point calculation
(a method with a higher degree of electron correlation)
confirmed that the barrier is very low, with the transi-
tion state for 16 f 17 lying 1.3 kcal/mol above 16. The
further isomerization of ketenimine 17 to diazirene 18 is
approximately thermoneutral or modestly endothermic. Dia-
zirene 18 was optimized as an energy minimum at the B3LYP
level, but it is a transition state for the reaction 17 f 19 at the
CASSCF level. The ring-opening of 18 to 19 (OSS) has a
calculated barrier of ca. 2 kcal/mol at the B3LYP/6-31G* level.
The cyclic carbodiimide 21 has been the subject of prior
calculations, and its energy is close to that of the triplet nitrene
19.26 The bicyclic azirene 20 lies 10-13 kcal/mol above 21.
The ring-opened species 23 may be described as a resonance
hybrid of a nitrene (23N) and a diradical (23R). The calculated
bond lengths indicate that the dienylnitrene canonical structure
23N has higher weight than the diradical structure 23R in
agreement with the experimental observation that the species
is a nitrene. Note, however, that suitable benzannelation can
cause the diradical character to predominate.27
However, two different conformers of 23, namely 23EZ and
23ZZ (Scheme 6), are formed from cyclic ketenimine 17 and
(26) Evans, R. E.; Wong, M. W.; Wentrup, C. J. Am. Chem. Soc. 1996,
118, 4009.
€
(27) Vosswinkel, M.; Luerssen, H.; Kvaskoff, D.; Wentrup, C. J. Org.
Chem. 2009, 74, 1171.
(25) Wijeratne, N. R.; DaFonte,M.; Ronemus, A.; Wyss, P. J.;Tahmassebi,
D.; Wenthold., P. G. J. Phys. Chem. A 2009, 113, 9467.
J. Org. Chem. Vol. 75, No. 5, 2010 1607

Kvaskoff et al.
SCHEME 7. Spiroazirene Route to Cyanopyrrolesa
JOCArticle
pyridylnitrene 19, respectively. The two conformers can
interconvert via a small barrier (5-10 kcal/mol at the
B3LYP/6-31G* level) in both the singlet and triplet states.
It is important to note that, although the barrier is low, there
is no reason to expect that thermally equilibrated intermedi-
ates are formed.28 Therefore, reaction dynamics can cause
the formation of different products or product ratios from 17
and 19. The geometry of 23ZZ could not be optimized at the
CASSCF level, because the species undergoes ring-closure to
2-cyano-2H-pyrrole 32 (Scheme 6).
The Type II ring-opening of cyclic ketenimine 17 to the
open shell singlet state (OSS) of 23EZ is analogous to the
ring-opening of 2-quinazolylnitrene, which has been exam-
ined by CASSCF and CASPT2 calculations previously,
when it was found to have a barrier of ca. 20 kcal/mol.6 An
activation barrier of 30-40 kcal/mol was calculated for 17 f
23EZ (OSS) (Scheme 6), and the reaction is exothermic.
Therefore, on thermodynamic grounds, the ring-opening
17 f 23EZ appears to be a very favorable pathway. There
will be enough energy in high-temperature FVT reactions to
overcome the activation barriers. The reaction 17 f 23EZ,
then, is the likely source of the glutacononitriles 27 found in
the FVT reactions of diazomethylpyridazine 9.
The calculated barrier for the Type II ring-opening of
triplet 2-pyridylnitrene 19 to triplet 23ZZ is ca. 30 kcal/mol
(Scheme 6); the corresponding S1-S1 reaction has a slightly
lower barrier. Both reactions are endothermic (Scheme 6).
A transition state for the concerted ring-contraction of
2-pyridylnitrene 19 (OSS, S1) to 2-cyano-2H-pyrrole 32
(ca. 49 kcal/mol) could only be located at the B3LYP
level. Corresponding TS values have been located for the
ring-contractions of phenylnitrene10 and 1-naphthylnit-
rene29 to 5-cyanocyclopentadiene and 1-cyanoindene, res-
pectively.
A transition state was located for the direct ring-contrac-
tion 19 (S1) f 1-cyanopyrrole 33, but this barrier is high
(47-68 kcal/mol; Scheme 6). Previous substituent and
15N-labeling work has established that 2-pyridylnitrenes do
not undergo ring-contraction via 1-cyanopyrroles such as
33.30 Similarly, 2-quinolyl- and 1-isoquinolylnitrenes do not
undergo ring-contraction to 1-cyanoindole; the products
are formed via ring-opening to o-cyano-β-styrylnitrene.7
Remarkably, 4- and 2-pyrimidylnitrenes do undergo ring-
contraction to 1-cyanoimidazoles and 1-cyanopyrazoles,
respectively, but these reactions, too, may proceed via ring-
opening.2,3,6,8a
Thus, the computational data for the ring-contraction of
2-pyridylnitrene 19 (Scheme 6) clearly indicate that the ring-
opening-recyclization route 19 f 23ZZ f 32 f 28 is
energetically preferred over the concerted ring-contractions
to 2-cyano-2H-pyrrole 32 and the nonobserved 1-cyanopyr-
role 33. The barrier for the 1,5-H shift in 2-cyano-2H-pyrrole
32 to 2-cyanopyrrole 28 is ca. 30 kcal/mol, and for the
1,5-CN shift to 3-cyano-3H-pyrrole 34 it is ca. 35 kcal/mol,
in agreement with the observation that 2-cyanopyrrole is
usually observed prior to 3-cyanopyrrole on FVT.9
aEnergies in italics in kcal/mol relative to 2-oyridylnitrene 19 T0
(Scheme 6) at the (U)B3LYP/6-31G* level.
The reaction 19 f 23f 27 (Scheme 6) explains the
formation of glutacononitriles in the thermolyses of the
precursors of 2-pyridylnitrene 19. There are three possible
routes to glutacononitriles 27: (i) a 1,4-H shift in 23EZ, (ii) a
1,2-H shift in 23ZZ, and (iii) a 1,2-H shift in 23EZ to afford
the ketenimine 26Z, which can isomerize to 27 in a 1,5-H shift
through a small barrier (Scheme 6). As mentioned above, a
weak band at 2042 cm-1 in many photolysis IR spectra
indicates the presence of an open-chain ketenimine. An
alternative carrier of this signal is the azafulvenimine 39
described in Scheme 7.
Spiroazirene Route to Cyanopyrroles. Formation of cya-
nopyrroles from 2-pyridylnitrene via spiroazirene 25
(Schemes 4 and 7) will now be considered. The electrocyclic
process forming 24 from 21 is calculated to be endothermic
by 12-18 kcal/mol, but the spiroazirene 25 is e4 kcal/
mol above 21 (Scheme 7). The reactions summarized in
Scheme 7 indicate that rearrangement of diazacycloheptate-
traene 21 to diazabicyclo[3.2.0]heptadiene 24 and spiro-
azirene 25 constitutes a feasible route to cyanopyrroles,
which is competitive with the concerted ring-contraction of
(28) Baldwin, J. E.; Leber, P. A. Org. Biomol. Chem. 2008, 6, 36.
Carpenter, B. K. In Reactive Intermediate Chemistry; Moss, R. A., Platz,
M. S., Jones, M., Jr., Eds.; Wiley-Interscience: Hoboken, NJ, 2004; p 925.
(29) Kvaskoff, D.; Mitschke, U.; Addicott, C.; Finnerty, J.; Bednarek, P.;
Wentrup, C. Aust. J. Chem. 2009, 62, 275.
(30) Harder, R.; Wentrup, C. J. Am. Chem. Soc. 1976, 98, 1259.
1608 J. Org. Chem. Vol. 75, No. 5, 2010

Kvaskoff et al.
JOCArticle
2-pyridylnitrene 19, but not with ring-contraction via cyano-
dienylnitrenes 23 (Scheme 6). The activation energy for the
first step, 21 f 24, is high (ca. 47 kcal/mol), but the reaction
would be achievable under high-temperature FVT condi-
tions.
SCHEME 8. Calculated Energies for Ring-Opening and Frag-
mentation of 3-Pyridazylcarbenea
Thus, in summary, we have identified three potential
routes to cyanopyrroles: (i) ring-opening-ring-closure via
dienylnitrene 23 (Scheme 6); (ii) concerted ring-contraction
of 2-pyridylnitrene 19 to 2-cyano-2H-pyrrole 32 (Scheme 6;
not likely here, but possible in other arylnitrenes); and
(iii) electrocyclic rearrangement of diazacycloheptatetraene
21 via spiroazirene 25 (Scheme 7). The latter pathway is
actually followed in the phenylcarbene rearrangement.18
While we have no experimental evidence for the spiroazirene
route to cyanopyrroles (Scheme 7), it will be necessary
to consider it in future work. It may well be that different
routes of ring-contraction will be followed in different
systems. Strong evidence for the ring-opening-ring-closure
pathway has been adduced for other systems.2,6,27,29 The
existence of several potential pathways can also provide an
explanation for the different product ratios obtained from
pyridazine 8 and pyridine 22. The ring-opening-ring-closure
mechanism (i) is fully consistent with the results of 15N-
and substituent labeling of 2-pyridylnitrenes.30 The spiroazir-
ene mechanism (iii) can explain the products obtained from
6-substituted tetrazolo[1,5-a]pyridine, but does not explain
the major product obtained from 8-substituted tetrazolo-
[1,5-a]pyridine.30
The potential formation of the azafulvenylnitrene 38
(Scheme 7) as a rearrangement product of diazacyclohepta-
tetraene 21 makes it necessary to consider this nitrene as an
alternative to the cyanodienylnitrene 23 as carrier of the low-
field nitrene signal (5000-5300 G) in the ESR spectrum
(Figure 5). This ESR spectrum was obtained by photolysis
of tetrazole/azide 22T/22A at 254 nm. Under the same
photolysis conditions, diazacycloheptatetraene 21 is formed
cleanly as observed by IR spectroscopy (Figure 6). Com-
pound 21 is stable at this wavelength and rearranges to 25
on irradiation at 308 or 365 nm. Thus, nitrene 38 should not
be formed at 254 nm. Hence, the evidence supports cyano-
dienylnitrene 23 as the carrier of the low-field triplet ESR
signal.
aB3LYP/6-31G* in kcal/mol relative to 19 T0 = 0.
SCHEME 9. Unobserved Ring-Expansions of 3-Pyridazylcar-
bene 10a
Further Reactions of the Pyridazylcarbenes. We will now
consider the remaining reactions of the pyridazylcarbenes 10
(Schemes 8 and 9). The barriers for isomerization of carbene
12E to allene 13 and cyclopropene 14 are only ca. 4 and
2 kcal/mol, respectively. These are the first reactions to take
place on FVT. The isomerization of ethynylcyclopropene 14
to pentadiyne 15 is exothermic by ca. 14 kcal/mol, but that
of pentadienyne 13 to pentadiyne 15 would be endothermic
by ca. 11 kcal/mol (Scheme 8).
The alternative cyclization of carbene 10Z to azirene 42
has a calculated barrier of 14 kcal/mol, and 10E can form the
same product with a barrier of ca. 11 kcal/mol. The seven-
membered ring allene 43 is ca. 12 kcal/mol higher in energy
that the cyclic ketenimine 17, and ca. 37 kcal/mol above
cyclic carbodiimide 21. There was no experimental evidence
for the formation of 43 (Scheme 9 and in the Supporting
Information Figure S14).
Two isomers of 17, viz. the cyclic nitrile ylide 170 and
diazacycloheptatrienylidene 1700, were also considered
(Scheme 9). There was no experimental evidence for these
aCalculations at the CASSCF (CASPT2) and B3LYP/6-31G* levels in
kcal/mol relative to 19 T0 = 0.
species. The calculated energy of 170 and the activation
barrier for the reaction 16 f 170 are too high for their likely
involvement.
J. Org. Chem. Vol. 75, No. 5, 2010 1609

Kvaskoff et al.
JOCArticle
Conclusion
CASSCF34 optimizations and single-point CASPT2 calcula-
tions35 were performed for open-shell and related systems, and
were carried out with the MOLCAS suite of programs,36 using
the 6-31G* basis set. The CASSCF calculations used an
8-electron, 8-orbital active space, e.g. for 19: 3π, 3π*, and the
2 p-AOs on the nitrene-N atom. The reference weights of the
CASSCF wave function remained stable in the range 77-80%.
Cartesian coordinates, energies, vibrational frequencies, and
details of the correlated orbitals in the CASSCF active space
are listed in the Supporting Information.
The isomeric 3-pyridazylcarbene 10 and 2-pyridylnitrene
19 were investigated. There is little evidence for interconver-
sion of these two isomers, but each has a rich chemistry. Mild
FVT of triazolopyridazine 8 generates the diazomethyl
valence tautomer 9, which on either matrix photolysis or
flash vacuum thermolysis (FVT) gives rise to 3-pyridazyl-
carbene 10. The carbene was detected by ESR spectroscopy
in the photolysis reaction. Matrix photolysis with IR
observation reveals ring-opening of the carbene to diazoalk-
enyne 11, which again loses N2 to generate a new carbene,
pent-2-en-4-yn-1-ylidene 12; this too was detected by ESR
spectroscopy, and it rearranges to pentadienyne 13, ethynyl-
cyclopropene 14, and, at elevated temperatures, 1,4-penta-
diyne 15.
Photolysis of matrix-isolated tetrazolo[1,5-a]pyridine/
2-azidopyridine 22T/22A yields both triplet 2-pyridylnitrene
19 and its ring-opened isomer, the cyanodienylnitrene 23,
which are detected by ESR spectroscopy. 1,3-Diazacyclo-
heptatetraene 21 is formed cleanly on matrix photolysis as
observed by IR spectroscopy. It is also a major product of
FVT of 22T/22A under mild conditions. Photolysis of 21
above 300 nm causes its rearrangement to the spiroazirene
25, identified by its Ar-matrix IR spectrum.
FVT of 8/9 causes formation of Z- and E-glutacononitriles
27Z,E and minor amounts of 2- and 3-cyanopyrroles 28 and
29 in addition to 13-15. FVT of tetrazolopyridine/2-azido-
pyridine 22T/22A also affords compounds 27-29, but the
ratios of yields of these products are very different in the two
systems.
Calculations support the postulate that both 3-pyridazyl-
carbene (via 1,7-diazacycloheptatetraene 17) and 2-pyridyl-
nitrene 19 can undergo ring-opening to vinylnitrene 23, but
they can lead to different conformers of 23; one, 23EZ, is
predominantly a precursor of glutacononitriles 27; the other,
23ZZ, is a precursor of 2- and 3-cyanopyrroles via 2-cyano-
2H-pyrrole 32. Another potential route to cyanopyrroles
proceeds via electrocyclization of 1,3-diazacycloheptate-
traene 21 to diazabicyclo[3.2.0]heptatriene 24 and spiroazir-
ene 25. The ring-opening-reclosure reaction via dienyl-
nitrene 23 emerges as the energetically most favorable
mechanism of ring-contraction in 2-pyridylnitrenes.
Experimental Section
General procedures have been published.16,27,29 In matrix
isolation for IR spectroscopy, Ar gas and sample vapor were
codeposited on a CsI target maintained at 25 K. The Ar flow rate
was maintained at ca. 4 mbar per min to obtain a thin,
transparent matrix. After depositing the matrix for ca. 30 min,
the CsI target was cooled to 10 K, and IR spectra were recorded
with 1 cm-1 resolution. For ESR spectroscopy a similar cryostat
was used, where the sample and Ar were condensed on a Cu rod
at ca. 15 K. Photolyses were carried out with use of a 1000 W
high-pressure Xe/Hg lamp equipped with a monochromator
and appropriate cutoff and interference filters, a 75 W low
pressure Hg lamp (254 nm), or excimer lamps operating at 222
(25 mW/cm2) and 308 nm (50 mW/cm2).
FVT experiments with matrix isolation employed a 10 cm
long, 0.7 cm i.d. electrically heated quartz tube suspended in a
vacuum chamber (2.0 ꢀ 10-6 mbar) directly flanged to the
cryostat cold head, with a wall-free flight path of ca. 3 cm
between the exit of the quartz tube and the CsI or Cu targets.
The temperatures used for FVT experiments ranged from 500
to 700 °C
In preparative FVT experiments, the sample was placed in a
sublimation tube and sublimed into a 20 ꢀ 2 cm quartz pyrolysis
tube. The FVT unit was evacuated with an oil diffusion pump
capable of a vacuum of 10-5-10-4 mbar. The pyrolysis pro-
ducts were collected on a coldfinger cooled with liquid nitrogen
(ca. 77 K). After the end of the experiment, the collected product
was dissolved in CDCl3, and NMR and GC-MS analyses were
carried out.
GC-MS analysis used a ZB-5 Zebron GC column (30 m,
0.32 mm i.d., 0.25 μm film thickness), He carrier gas at a flow
rate of 3.7 mL/min, column head pressure 100 kPa, inlet
temperature 200 °C, and GC-MS interface 250 °C. The tempera-
ture program started at 85 °C for 2 min, followed by a ramp of
12 deg/min up to 250 °C.
[1,2,3]Triazolo[1,5-b]pyridazine 8. 3-Pyridazinecarboxalde-
hyde37 was synthesized from furfuryl acetate38 and converted
to its hydrazone.39 The hydrazone (500 mg, 4 mmol) was
dissolved in 50 mL of chloroform, and activated manganese
dioxide (460 mg, 8 mmol, Fluka) was added slowly. The solution
was stirred for 3 h at rt and filtered over Celite, then the solvent
was removed in vacuum. The solid so obtained was purified by
sublimation (70-75 °C, 4 ꢀ 10-5 mbar) to yield colorless
crystals, 348 mg (71%), mp 132-133 °C (lit.39 mp 132-133 °C);
1H NMR (CDCl3) 8.47 (dd, J = 4.3, 1.8 Hz, 1 H), 8.18 (s, 1 H),
8.14 (dd, J = 9.0, 1.8 Hz, 1 H), 7.12 (dd, J = 9.0, 4.3 Hz, 1 H).
Computational Method
Calculations of all species were performed with the B3LYP
method,31 as implemented in the Gaussian 03 suite of pro-
grams,32 with the 6-31G* basis set for geometry and transition
state optimizations. Energies of open-shell S1 nitrenes at the
(U)B3LYP/6-31G* level were estimated with use of the Cra-
mer-Ziegler method.24 Reported energies include zero-point
vibrational energy corrections. All transition states were con-
firmed by intrinsic reaction coordinate calculations. Harmonic
vibrational frequencies were computed with use of the 6-311G**
basis set, and a scaling factor of 0.967 was applied.33 Additional
(35) Andersson, K.; Roos, B. O. CASPT2. In Modern Electronic Struc-
ture Theory; World Scientific Publ. Co.: Singapore, 1995; Vol. 2, Part 1, p 55
˚
(36) (a) Karlstrom, G.; Lindh, R.; Malmqvist, P.-A.; Roos, B. O.; Ryde,
€
U.; Veryazov, V.; Widmark, P.-O.; Cossi, M.; Schimmelpfennig, B.;
(31) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (b) Lee, C.; Yang, W.;
Parr, R. G. Phys. Rev. B 1988, 37, 785.
ꢀ
(32) Frisch, M. J., et al. Gaussian 03, Revision E.01; Gaussian, Inc.,
Wallingford, CT, 2004. (For the complete reference, see the Supporting
Information.)
Neogrady, P.; Seijo, L. Comput. Mater. Sci. 2003, 28, 222. (b) Andersson,
K., et al. MOLCAS, version 7.2; University of Lund: Lund, Sweden, 2008. (For
the complete reference, see the Supporting Information.)
(33) Irikura, K. K.; Johnson, R. D.; Kacker, R. N. J. Phys. Chem. A 2005,
109, 8430. Wong, M. W. Chem. Phys. Lett. 1996, 256, 391. Scott, A. P.;
Radom, L. J. Phys. Chem. 1985, 100, 16502.
(37) Heinisch., G.; Mayrhofer, A. Monatsh. Chem. 1977, 108, 213.
(38) Klauson-Kaas, N.; Limborg, F. Acta Chem. Scand. 1947, 1, 613.
(39) Maury, G.; Meziane, D.; Srairi, D.; Paugam, J. P.; Paugam, R. Bull.
Soc. Chim. Belg. 1982, 91, 153.
(34) Roos, B. O. Adv. Chem. Phys. 1987, 69, 399.
1610 J. Org. Chem. Vol. 75, No. 5, 2010

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JOCArticle
1
Anal. Calcd for C5H4N4: C, 50.00; H, 3.36; N, 46.65. Found: C,
50.25; H, 3.33; N, 46.56.
2-Cyanopyrrole 27:9,41 IR (Ar, 10 K) 2235 cm-1; H NMR
(CDCl3, 500 MHz) 9.37 (br, 1H), 6.94 (m, 1H, apparent J = 3.5,
2.7, and 1.4 Hz), 6.84 (m, 1H, apparent J = 3.8, 2.5, and 1.4 Hz),
6.25 (dt, 1H, J = 3.8 and 2.7 Hz); 13C NMR (CDCl3) 123.9,
120.1, 114.8, 109.8, 100.1.
Matrix Isolation and Photolysis of Triazolo[1,5-b]pyridazine.
Triazolo[1,5-b]pyridazine 8 was sublimed at 65-70 °C under
vacuum (2.0 ꢀ 10-6 mbar) and codeposited with Ar on a CsI
target at 25 K. The IR spectrum recorded at ca. 10 K showed the
main triazole peaks at 1544 (m), 1494 (m), 1403 (m), 1321 (s), 1307
(m), 1256 (m), 957 (m), 815 (s), and 734 (m) cm-1 (see Figure S1 in
the Supporting Information for the IR and UV spectra).
Preparative FVT of Triazolopyridazine. Preparative FVT of 8
(150 mg) was carried out at 500-700 °C. The collected products
1
3-Cyanopyrrole 28:9,42 IR (Ar, 10 K) 2260 cm-1; H NMR
(CDCl3, 500 MHz) 8.96 (br, 1H), 7.30 (m, 1H, apparent J = 3.3
and 1.9 Hz), 6.78 (m, 1H, apparent J = 2.7, 2.1, and 0.7 Hz),
6.47 (m, 1H, apparent J = 2.6 and 1.3 Hz).
Ratios of 13, 14, 15, 26Z, 26E, 27, and 28 formed by FVT of
triazolopyridazine 8 and determined by GC and NMR. GC
retention times Rt = 3.1, 4.2, 5.6, and 8.3 min. Ratio
13:14:15:26Z:26E:27:28 at 500 °C: 12:40:40:3.5:3.5:0:0 (27
and 28 not detectable). Ratio 13:14:15:26Z:26E:27:28 at
600 °C: 31:20:22:12.5:10:2:2. Triazole 8 was recovered
in ca. 20% yield, and 3-methylpyridazine was formed in
ca. 4% yield. Ratio 13:14:15:26Z:26E:27:28 at 700 °C:
18:15:35:12:12:4:4.
Ratios of Z- and E-Glutacononitriles 26Z, 26E, 27, and 28
formed by FVT of tetrazolo[1,5-a]pyridine 19T. Ratio 26Z:26E:
27:28 at 500 °C: 6:4:38:35. Ratio 26Z:26E:27:28 at 600 °C:
6:4:45:41. Ratio at 700 °C: 9:9:41:38.
1
were examined by H NMR (CDCl3; 500 MHz) and GC-MS.
Data are presented below.
2-Ethynylcyclopropene 14:13a,14 IR (Ar, 10 K) 3338 (w), 2125
(vw), 1661 (m), 986 (s), 945 (m), 613 (s), 605 (vw), and 516 (m)
cm-1; 1H NMR (CDCl3, 500 MHz) 7.10 (dd, 2H, J = 1.65 and
0.3 Hz), 1.95 (dt, 1H, J = 1.65 and 1.35 Hz), 1.65 (d, 1H, J =
1.35 Hz) (unresolved coupling, ca. 0.3 Hz also present).
Penta-1,2-dien-4-yne 13:13 IR (Ar, 10 K) 3333 (m), 1955 (w),
889 (m), 852 (m), 644 (m) cm-1; H NMR (CDCl3, 500 MHz)
1
5.35 (td, 1H, J = 7.0 and 2.6 Hz), 5.02 (dd, 2H, J = 7.0 and 1.6
Hz), 2.87 (dt, 1H, J = 2.6 and 1.6 Hz).
1,4-Pentadiyne 15:14,40 IR (Ar, 10 K) 3319 (s), 2140 (w), 1417
(m), 1300 (w), and 605 (w); 1H NMR (CDCl3, 500 MHz) 3.15 (t,
1H, J = 2.75, 2.07 Hz).
Acknowledgment. This research was supported by the
Australian Research Council and the Centre for Computa-
tional Molecular Science at The University of Queensland.
We thank Dr. Lisa George and Mr. Sreekumar Pankajakshan
for preliminary experiments.
Z-Glutacononitrile 26Z:9,15 1H NMR (CDCl3, 500 MHz)
6.47 (dt, 1H, J = 7.0 and 10.8 Hz), 5.65 (dt, 1H, J = 10.3 and 1.7
Hz), 3.35 (dd, 1H, J = 6.8 and 1.7 Hz); 13C NMR (CDCl3)
(mixture of Z and E isomers) 141.1, 140.7, 115.4, 114.2, 105.4,
104.9, 21.2, 19.6; IR (Ar, 10 K) 2275 and 2235 cm-1 (mixture of
Z and E isomers).
Supporting Information Available: Ar matrix IR, UV, and
ESR spectra and relevant calculated IR spectra and Cartesian
coordinates and calculated energies of key intermediates, transi-
tion states, and reaction paths. This material is available free of
charge via the Internet at http://pubs.acs.org.
E-Glutacononitrile 26E:9,15 1H NMR (CDCl3, 500 MHz)
6.59 (dt, 1H, J = 5.0 and 16.25 Hz), 5.80 (dt, 1H, J = 16.25 and
2.1 Hz), 3.50 (dd; 2H, J = 6.7 and 1.65 Hz); 13C NMR (CDCl3)
see data for mixture under Z-glutacononitrile.
(40) Verkruijsse, H. D.; Hasselaar, M Synthesis 1979, 29.
(41) Anderson, H. J. Can. J. Chem. 1959, 37.
(42) den Hertog, H. J.; Martan, R. J.; van der Plas, H. C.; Bon, J.
Tetrahedron Lett. 1966, 4325.
J. Org. Chem. Vol. 75, No. 5, 2010 1611