Comparative study of the photochemistry of the azidopyridine 1-oxides

Article abstract of DOI:10.1021/jo8001936

(Chemical Equation Presented) The photochemistry of azidopyridine 1-oxides was studied using an array of glass and matrix isolation techniques. As with room temperature, the photochemistry of 4-azidopyridine 1-oxide is dominated by triplet nitrene chemistry. However, in the case of the 3-azide, matrix photolysis indicates the formation of diazabicyclo[4.1.0]hepta-2,4,6-triene N-oxide and diazacycloheptatetraene N-oxide intermediates as well as triplet nitrene.

Full text of DOI:10.1021/jo8001936

Comparative Study of the Photochemistry of the Azidopyridine
1-Oxides
Kyle N. Crabtree,† Katherine J. Hostetler,† Tamara E. Munsch,‡ Patrik Neuhaus,‡
Paul M. Lahti,§ Wolfram Sander,‡ and James S. Poole*,†
Department of Chemistry, Ball State UniVersity, Muncie, Indiana 47306, Lehrstuhl für Organische Chemie
II, Ruhr-UniVersität Bochum, D-44780 Germany, and Department of Chemistry, UniVersity of
Massachusetts, Amherst, Massacusetts 01003
jspoole@bsu.edu
ReceiVed January 31, 2008
The photochemistry of azidopyridine 1-oxides was studied using an array of glass and matrix isolation
techniques. As with room temperature, the photochemistry of 4-azidopyridine 1-oxide is dominated by
triplet nitrene chemistry. However, in the case of the 3-azide, matrix photolysis indicates the formation
of diazabicyclo[4.1.0]hepta-2,4,6-triene N-oxide and diazacycloheptatetraene N-oxide intermediates as
well as triplet nitrene.
SCHEME 1. Photochemistry of Phenyl Azide
Introduction
The chemistry of aryl azides has received a great deal of
attention due to their ability to undergo 1,3-dipolar cycloaddition
reactions and their ability to act as thermo- and photochemical
precursors of aryl nitrene species. Much of aryl nitrene chemistry
has been concerned with the utilization of such species as
bioaffinity labels1 or as potential conductor materials,2 although
these nitrenes may also be synthetically useful in the formation
of azepine3 and carbazole4 systems. The photochemistry of
simple aryl azides is now well-established and has been the
subject of recent reviews by Platz et al.5,6 Using phenyl azide
† Ball State University.
as an exemplar, the salient features of aryl nitrene photochem-
istry are shown in Scheme 1.
‡ Ruhr Universität Bochum.
§ University of Massachusetts.
(1) (a) Meisenheimer, K. M.; Koch, T. H. Crit. ReV. Biochem. Mol. Biol.
1997, 32, 101. (b) Schnapp, K. A.; Platz, M. S. Bioconjugate Chem. 1993, 4,
178. (c) Schnapp, K. A.; Poe, R.; Leyva, E.; Soundararajan, N.; Platz, M. S.
Bioconjugate Chem. 1993, 4, 172.
Photodecomposition of the aryl azide yields a singlet nitrene
species 2S, which at room temperature undergoes a ring-closure/
ring-expansion sequence to yield the didehydroazepine 4, for
which a significant body of experimental evidence exists. The
(2) Meijer, E. W.; Nijhuis, S.; van Vroonhoven, F.C.B.M. J. Am. Chem. Soc.
1998, 110, 7209.
(3) Doering, W.; Odum, R. A. Tetrahedron 1966, 22, 81.
(4) (a) For example, see: Swenton, J.; Ikeler, T.; Williams, B. J. Am. Chem.
Soc. 1970, 92, 3103. (b) Tsao, M-L.; Gritsan, N. P.; James, T. R.; Platz, M. S.;
Hrovat, D. A.; Borden, W. T. J. Am. Chem. Soc. 2003, 125, 9343.
(5) PlatzM.J.InReactiVeIntermediateChemistry;Moss,R.A.,Platz,M.S.,Jones,M.,
Jr., Eds.; John Wiley & Sons:Hoboken, NJ,2004; pp 522–546..
(6) Gritsan, N. P.; Platz, M. S. Chem. ReV. 2006, 106, 3844.
10.1021/jo8001936 CCC: $40.75
Published on Web 04/10/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 3441–3451 3441

Crabtree et al.
TABLE 1. Summary of Calculated Data for 4-Nitrenopyridine 1-Oxide and Photoproducts
method
geometry
B3LYP/6-31G*
B3LYP/6-31G*
ZPEa
CASSCF(8,8)/6-31G*
CASSCF(8,8)/6-31G*
CASSCF(10,9)/6-31G*
CASSCF(8,8) MP2/6-31G*
CASSCF(8,8)/6-31G*
CASSCF(8,8)/6-31G*
b
d
d
d
energy
(hartree)
Erel,0K
energy
Erel,0K
energy
Erel,0K
energy
Erel,0K
species
(hartree) (kcal/mol)
(hartree)
ZPEc(hartree) (kcal/mol)
(hartree)
(kcal/mol)
(hartree)
(kcal/mol)
7T
7S
-377.5166 0.08422
-377.5010f 0.08429f
-9.8
0.0e,f
24.2
19.9
26.9
14.4
-375.3795
-375.3706
-375.3314
-375.3344
-375.2945
-375.3338
0.08874
0.08852
0.08751
0.08870
0.08696
0.088587
-5.4
0.0e
24.0
22.9
46.8
23.2
-375.3849
-375.3744
-375.3371
-375.3393
-375.3015g
-375.3388
-6.5
0.0e
22.7
22.1
44.7g
22.4
-376.3426
-376.3294
-376.3031
-376.3065
-376.2689
-376.3096
-8.2
0.0e
15.9
14.5
37.0
12.5
TS (7S-8) -377.4614 0.08328
8
TS (8-9)
9
-377.4691 0.08419
-377.4564 0.08251
-377.4780 0.08432
a Unscaled ZPE energies, b Determined using ZPE scaled by the factor recommended by Scott and Radom, ref 23. c Unscaled ZPE energies calculated
at CAS(8,8)/6-31G*level of theory. d Determined using unscaled ZPE corrections calculated at CASSCF(8,8)/6-31G*level of theory. e Energies for each
species are determined relative to the energy of the singlet nitrene 7S (relative energy defined as 0). f Energies of singlet nitrenes are estimated from
DFT calculations using the sum method described by Johnson et al., ref 16. g See the Supporting Information.
TABLE 2. Summary of Calculated Data for 3-Nitrenopyridine-1-Oxide and Photoproducts
method
geometry
B3LYP/6-31G*
B3LYP/6-31G*
ZPEa
CASSCF(8,8)/6-31G*
CASSCF(8,8)/6-31G*
CASSCF(10,9)/6-31G*
CASSCF(8,8) MP2/6-31G*
CASSCF(8,8)/6-31G*
CASSCF(8,8)/6-31G*
energy
(hartree)
Erel,0K
energy
(hartree)
ZPEc
Erel,0K
(hartree) (kcal/mol)
energy
Erel,0K
energy
Erel,0K
b
d
d
d
species
(hartree) (kcal/mol)
(hartree)
(kcal/mol)
(hartree)
(kcal/mol)
12T
12S
-377.5004
0.08359 -16.4
-375.3659 0.08754
-375.3375 0.08660
-375.3257 0.08683
-375.3266 0.08672
-375.3339 0.08898
-375.3426 0.08976
-375.2965 0.08708
-375.2994 0.08723
-375.3368 0.08897
-375.3316 0.08824
-17.2
0.0e
7.5
7.0
3.7
-1.2
26.0
24.3
1.9
-375.3706
-375.3429
-375.3314
-375.3320
-375.3394
-375.3484
-375.3019
-375.3046
-375.3430
-375.3354
-16.8
0.0e
7.4
6.9
3.7
-1.5
26.1
24.4
1.4
-376.3274
-376.3019
-376.2949
-376.2932
-376.3077
-376.3146
-376.2759
-376.2825
-376.3117
-376.3033
-15.4
0.0e
-377.4741e,f 0.08330e,f
0.0e,f
TS (12S-13a) -377.4483g
TS (12S-13b)
0.08325g
16.1g
4.6
5.5
13a
13b
-377.4713
-377.4840
0.08441
0.08491
0.08283
0.08277
0.08460
0.08403
2.4
-5.3
6.8
6.1
-6.3
-0.1
-2.1
-6.0
16.6
12.6
-4.7
0.1
TS (13a-14a) -377.4627
TS(13b-14b)
14a
14b
-377.4638
-377.4853
-377.4749
4.7
5.7
a Unscaled ZPE energies, b Determined using ZPE scaled by the factor recommended by Scott and Radom, ref 23. c Unscaled ZPE energies calculated
at CAS(8,8)/6–31G* level of theory, d Determined using unscaled ZPE corrections calculated at CASSCF(8,8)/6–31G* level of theory. e Energies for
each species are determined relative to the energy of the singlet nitrene 12S (Rel. energy defined as 0). f Energies of singlet nitrenes are estimated from
DFT calculations using the sum method described by Johnson et al., ref 19. g The transition state found can serve both reaction paths as the imaginary
frequency corresponds to an out-of-plane N vibration. However, given the nature of the computational method it cannot necessarily be described as a
true bifurcation point, and the CASSCF calculations bear this out.
compounds as antitumor agents.10 In terms of the nitrene
SCHEME 2. Potential Photoproducts of 4-Azidopyridine
1-Oxide (6)
chemistry of such compounds, the presence of the N-oxide group
would be expected to enhance the water solubility of these
prospective bioaffinity agents, and provide opportunities for
novel photochemistry from the N-oxide moiety, which is known
to be photoreactive. Earlier product studies of the simplest of
these compounds, the azidopyridine N-oxides, found that in the
case of 2-azidopyridine 1-oxide, ring contraction to yield
cyanopyrrole derivatives was particularly facile, and had
demonstrable synthetic potential.11 On the other hand, product
studies following thermal and photochemical decomposition of
3- and 4-azidopyridine 1-oxide in organic solvents indicated
that the products were predominantly polymeric and unchar-
acterizable in nature, and the majority of isolable and charac-
terizable material could not be unambiguously identified as being
derived from nitrene chemistry.12
benzazirine 3 has not been observed for phenylnitrene6 but has
been observed in polycyclic arylnitrenes.7 The ketenimine 4 is
susceptible to nucleophilic attack, and this reaction may be used
synthetically to yield amino- and alkylthioazepines.3,8 At low
temperatures (<165 K), intersystem crossing to the ground-
state triplet is dominant,9 and azobenzene (5) is observed as
the dominant product.
In a recent paper, the photochemistry of 4-azidopyridine
1-oxide (6) was studied using transient spectroscopic techniques
A subclass of the aryl azides, the azidoheteroaryl N-oxides,
has also received attention due to the potential of these
(9) (a) For examples, see: Gritsan, N. P.; Godmundsdottir, A. D.; Tigelaar,
D.; Platz, M. S. J. Phys. Chem. A 1999, 103, 3458. (b) Gritsan, N. P.; Tigelaar,
D.; Platz, M. S. J. Phys. Chem. A 1999, 103, 4465.
(7) (a) Tsao, M.-L.; Platz, M. S. J. Phys. Chem. A 2004, 108, 1169. (b)
Dunkin, I. R.; Thomson, P. C. J. Chem. Soc., Chem. Commun. 1980, 499. (c)
Schrock, A. K.; Schuster, G. B. J. Am. Chem. Soc. 1984, 106, 5234. (d)
Motawietz, J.; Sander, W. J. Org. Chem. 1996, 61, 4351.
(10) (a) Itai, T.; Kamiya, S. Chem. Pharm. Bull. 1961, 9, 87. (b) Itai, T.;
Kamiya, S. Chem. Pharm. Bull. 1963, 11, 348. (c) Itai, T.; Kamiya, S. Chem.
Pharm. Bull. 1963, 11, 1059.
(11) (a) Abramovitch, R. A., Jr J. Org. Chem. 1973, 38, 173. (b) Abramovitch,
R. A., Jr J. Am. Chem. Soc. 1976, 98, 1478.
(8) (a) DeGraff, B. A.; Gillespie, D. W.; Sundberg, J. Am. Chem. Soc. 1974,
96, 7491. (b) Carroll, S. E.; Nay, B.; Scriven, E. F. V.; Suschitzky, H.; Thomas,
D. R. Tetrahedron Lett. 1977, 3175.
(12) Abramovitch, R. A.; Bachowska, B.; Tomasik, P. Pol. J. Chem. 1984,
58, 805.
3442 J. Org. Chem. Vol. 73, No. 9, 2008

Photochemistry of Azidopyridine 1-Oxides
FIGURE 1. Reaction profile for 4-nitrenopyridine 1-oxide (7) calculated at various levels of theory. All energies are calculated at 0 K, relative to
the energy of the nitrene S1 state. ZPE corrections are employed.
(Scheme 2).13 The authors reported that even at room temper-
ature, the photochemistry of this compound was dominated by
triplet nitrene chemistrysthe only observed product was 4,4′-
azobis(pyridine 1-oxide), 10, and no evidence of products
derived from 9 was found.
The explanation for this behavior was a selective stabilization
of the S1 state of the nitrene (7S), leading to enhanced rate of
intersystem crossing to the triplet (7T) and a significant increase
intheenergeticbarrierforcyclizationto3,7-diazabicyclo[4.1.0]hepta-
2,4,6-triene 3-oxide, 8. In the same way, it is sometimes
convenient to consider 2S as a biradical species, so it may also
be useful to consider 7S as an iminyl-aminoxyl biradical
species. The aminoxyl character is a stabilizing influence:
aminoxyls themselves have long been known to be stable (or
persistent) free radicals,14 and similar stabilizing effects may
be used to explain the “super-stabilizing” effect the 4-(pyridine
1-oxide) group has on radical species, as demonstrated by
Creary.15
allow the “super-stabilizing” effect, and we might anticipate
that these nitrenes would exhibit chemical behavior qualitatively
similar to 2S/T.
In this contribution, we report on a combined computational
and low-temperature spectroscopic study of the photochemistry
of 6 and 11.
Results and Discussion
Theoretical Calculations. Summaries of calculated energies
for critical points along the reaction paths of 4-nitrenopyridine
1-oxide (7) and 3-nitrenopyridine 1-oxide (12) are shown in
Tables 1 and 2 respectively, and graphical representations of
the various reaction paths are shown in Figures 1 and 2.
Each of the methods used in this study have their strengths
and weaknesses, which have been alluded to in previous
studies.16,17 The DFT methodology, as utilized in GAUSSIAN,
cannot readily calculate the properties of open shell singlet
statessit is necessary to use approximate sum methods to predict
the energy of aryl nitrene S1 states because of this fact. In
addition, the transition states for cyclization to the benzazirine
analogues are likely to retain a significant amount of open-shell
character, so we cannot expect DFT methods to perform well
In the case of 3-azidopyridine 1-oxide (11) and its resultant
nitrenes (12S/T), the positioning of the two groups does not
(13) Hostetler, K. J.; Crabtree, K. N.; Poole, J. S. J. Org. Chem. 2006, 71,
9023.
(14) (a) Mahoney, L. R.; Mendenhall, G. D.; Ingold, K. U. J. Am. Chem.
Soc. 1973, 95, 8610. (b) Lebedev, Y. A.; Rozantsev, E. G.; Kalashnikova, L. A.;
Lebedev, V. P.; Neiman, M. B.; Apin, A. Y. Dokl. Akad. Nauk SSSR (Engl.)
1966, 40, 460.
(16) Johnson, W. T. G.; Sullivan, M. B.; Cramer, C. J. Int. J. Quantum Chem.
2001, 85, 492.
(15) Creary, X. Acc. Chem. Res. 2006, 39, 761.
(17) Karney, W. L.; Borden, W. T. J. Am. Chem. Soc. 1997, 119, 1378.
J. Org. Chem. Vol. 73, No. 9, 2008 3443

Crabtree et al.
FIGURE 2. Reaction profile for 3-nitrenopyridine 1-oxide (12) calculated at various levels of theory. All energies are calculated at 0 K, relative
to the energy of the nitrene S1 state. ZPE corrections are employed.
for these transition states, and the CI approach of CASSCF
calculations might be expected to be superior.
kcal/mol depending on method used) relative to the analogous
value for phenylnitrene (19.1 kcal/mol, calculated at CASPT2/
6-31G*),17 both favoring the triplet. This will lead to the
enhanced rate of ISC observed experimentally.13 In addition,
the cyclization reaction to 8 is energetically unfavorable; it has
a large barrier to cyclization and a very small barrier to ring
opening. While cyclization of aryl nitrenes to benzazirines is
generally endoergic, what is interesting about this system is that
1,4-diazacyclohepta-2,4,5,7-tetraene 1-oxide (9), formed by ring
expansion, is also an energetically unfavorable product. It is
also noteworthy that for all of the methodologies utilized, the
barrier to expansion from 8 to 9 exceeds the S1-S2 energy gap
for 7. The computed energies are consistent with experimental
observations even at room temperaturesthe chemistry of 7 is
triplet dominated, with no evidence of ring-expansion products.
In a matrix, we would anticipate that the triplet nitrene 7T would
be the primary photoproduct and that not even sustained
photolysis of 7T would yield 9 (cf. phenylnitrene). Secondary
photoproducts would either arise from triplet chemistry (e.g.,
hydrogen atom abstraction) or N-oxide photochemistry.18
When considering the possible fate of 3-nitrenopyridine
1-oxide (12), it is necessary to consider two possible cyclization/
ring expansion pathways; one beginning with N-cyclization
On the other hand, Karney and Borden17 have demonstrated
that the CASSCF approach tends to overestimate the energy of
the transition state for ring opening from benzazirine to
ketenimine for aryl nitrenes. The authors noted in their original
study that dynamic electron correlation plays an important role
in the transition states of pericyclic reactions such as these and
employed Møller–Plesset perturbation corrections to account for
this effect in the form of CASPT2 energies. In this study, we
have utilized the CASSCF MP2 methodology included in the
GAUSSIAN suite to achieve these ends. We would expect this
type of calculation and DFT (which includes dynamic correlation
in the formulation of its functionals) to provide more insight
regarding the ring expansion step than CASSCF calculations
alone. We have found with phenylnitrene (see the Supporting
Information) that MP2 corrections to CASSCF wave functions
provide a partial treatment of dynamic correlation, but not to
the extent of CASPT2 models, and certainly not to the extent
of DFT models such as B3LYP. Thus, it can be argued that
B3LYP/6-31G* calculations provide a superior description of
this part of the reaction profile diagram, and these calculations
are therefore included.
With the above provisos in mind, we may consider the
reaction pathways in Figures 1 and 2. Figure 1, which includes
previously published DFT data, shows a number of consistencies
for all data sets. The first is that EST for nitrene 7 is small (5–10
(18) (a) Spence, G. G.; Taylor, E. C.; Buchardt, O. Chem. ReV. 1969, 69,
231. (b) Albini, A.; Alpegiani, M. Chem. ReV. 1984, 84, 43. (c) Shi, X.; Poole,
J. S.; Emenike, I.; Burdzinski, G.; Platz, M. S. J. Phys. Chem. A 2005, 109,
1491.
3444 J. Org. Chem. Vol. 73, No. 9, 2008

Photochemistry of Azidopyridine 1-Oxides
SCHEME 3. Potential Photoproducts of 3-Azidopyridine
1-Oxide (11)
generate 14a and/or 13b as secondary photoproducts. As with
other aryl nitrenes, photolysis of 12T will allow reaccess to the
singlet surface via 12S and may also result in the formation of
14a and/or 13b.
The thermochemical preference for 14a and 13b over their
respective isomeric forms is worthy of comment, particularly
with respect to the diazacycloheptatetraene N-oxides 14a and
14b. Some insight may be offered by considering the structures
of the isomers, and their potential for conjugative interactions
(Figure 3). All of the species shown in Figure 3 contain
potentially conjugated π-systems as substructures, each con-
strained in terms of bond lengths by the fact that they reside
within a six- or seven-membered ring. Two structural motifs
areapparent:(i)anR,ꢀ-unsaturatediminesubstructure(CdC-CdN)
observed in 13b and 14a and (ii)an N-vinylimine substructure
(CdC-NdC) observed in 8, 9, 13a, and 14b.
In cases with the R,ꢀ-unsaturated imine substructure, the
constraints of the ring geometry can also accommodate a
significant degree of conjugation. The lengths for the CdC,
C-C, and CdN bonds are 1.37, 1.43–1.44, and 1.35 Å,
respectively, in 13b and 14a. Such bond lengths are consistent
with the bond lengths observed in a conjugated diene such as
1,3-butadiene, allowing for the fact that C-N bond lengths are
generally shorter than their C-C analogues.
On the other hand, species containing the N-vinylimine
substructure have bond lengths that are not as accommodating
toward conjugative overlap. In such species, the C-N bond
lengths in these substructures vary between 1.44 and 1.45 Å. It
is worth remembering that C-N bond lengths in simple
alkylamines are of the order of 1.47 Åsit would therefore
appear that the bond order for these C-N bonds is close to 1,
and there is evidence of only a limited amount of the bond
compression that one would associate with conjugation. Simi-
larly, the bond lengths of the CdC and CdN fragments of the
substructures are much closer to isolated double bond lengths
than those found for 13b and 14a. The lower degree of
conjugation in systems such as 13a and 14b is a significant
contributor to the relative instabilities of these compounds
relative to the conjugated isomeric forms 13b and 14a. The fact
that neither 8 nor 9 apparently display significant conjugative
stabilization, coupled with the high and selective stabilization
(see above) of 7S, indicates that ring expansion would not be
favorable in the 4-nitreno system.
Electron Paramagnetic Resonance. EPR spectroscopy is the
method where any “super-stabilizing” effect of the pyridine
N-oxide moiety would manifest itself clearly in the zero field
splittings (zfs) D/hc of 7T and 12T. A triplet nitrene with more
delocalized π-spin density would have a smaller zfs interaction
between its π-spin and localized σ-spin. Based on connectivity,
a π-spin delocalized 7T should have a smaller zfs interaction
than 12T, and the experimental data bear out this expectation
(Table 3).19
toward the N-oxide moiety (12S f 13b f 14b) and the other
involving cyclization away from N-oxide (12S f 13a f 14a,
see Scheme 3). The computational results are shown in Figure
2 and present some intriguing possibilities.
The first notable feature of this system is that the EST for 12
is estimated between 15 and 17 kcal/mol, favoring 12T, a value
quite similar to that of phenylnitrene. It is also worth noting
that the calculations also indicate that the ability to delocalize
spin density is a stabilizing effect: At the CASSCF (8,8) MP2/
6-31G* level of theory, triplet 4-nitrenopyridine-1-oxide is some
9.5 kcal/mol more stable than the 3-nitreno isomer. The effect
is even more pronounced in the open shell singlet state: the
4-nitrene is some 17 kcal/mol more stable than the 3-nitrene.
Based on the EST for 12, we anticipate that at room
temperature singlet nitrene chemistry will dominate, and we will
only observe 15 at low temperatures, if at all. An interesting
question regards what form the singlet nitrene chemistry will
take. If we consider the pathway leading to 14a, we see that it
is similar to most reaction pathways of this type for simple aryl
nitrenes: the nitrene 12S overcomes a small barrier to generate
4,7-diazabicyclo[4.1.0]hepta-2,4,6-triene 4-oxide, 13a, which is
approximately isoenergetic (in aryl nitrene systems, the benza-
zirine intermediate is usually energetically less stable than the
nitrene), and undergoes a rapid reaction to yield the energetically
stable 1,4-diazacyclohepta-2,3,5,7-tetraene 1-oxide (14a).
However, if we consider the alternative pathway, we find that
1,3-diazacyclohepta-1,3,4,6-tetraene 1-oxide (14b) is approxi-
mately isoenergetic with 12S and that the minimum energy
structure for this reaction pathway is actually 2,7-
diazabicyclo[4.1.0]hepta-2,4,6-triene 4-oxide (13b). This finding
represents an unusual case for simple aryl nitrenes and implies
that in a low temperature matrix, photolysis of 11 will yield
12S, which may undergo ISC to yield 12T, or potentially
The results of natural population analysis calculations for 7T
and 12T at the B3LYP/6-31G* level of theory are shown in
Figure 4. The results for 7T indicate that there is a significant
degree of spin density associated with the N-oxide moiety in
this species (and hence delocalization of spin density for this
species as a whole). This characteristic was not observed in 12T,
and these observations are consistent with our expectations for
these species.
(19) For example, see: Dougherty, D. A. In Kinetics and Spectroscopy of
Carbenes and Biradicals Platz, M. S., Eds.; Plenum Press: New York, 1990.
J. Org. Chem. Vol. 73, No. 9, 2008 3445

Crabtree et al.
FIGURE 3. Optimized geometries for diazabicyclo[4.1.0]hepta-2,4,6-triene N-oxide and diazacycloheptatetraene N-oxide products of 3- and
4-nitrenopyridine 1-oxide, calculated at the B3LYP/6-31G* level of theory. All bond lengths in angstroms.
FIGURE 4. NPA spin and charge densities for 7T and 12T, calculated at the B3LYP/6-31G* level of theory. Spin densities are listed first, charge
densities second.
TABLE 3. Summary of EPR Data for Triplet Nitrenes 7T and 12T
glass
4-nitrenopyridine 1-oxide (7T)
D/hc (cm-1 E/hc (cm-1
3-nitrenopyridine 1-oxide (12T)
D/hc (cm-1 E/hc (cm-1
)
)
)
)
95% ethanol
2-methyltetrahydrofuran
toluene
0.71 (0.03a
<0.003
<0.007
0.006
1.159
1.076
1.060
1.054c
<0.004
<0.003
0.003
0.746
0.700
Ar matrix
0.621b,c
0.003
0.001
a The nitrene signal was distorted by overlap with a secondary signal of unknown origin. See the Supporting Information. b Broad band irradiation
295–320 nm. c Irradiation at 308 nm (Xe-Cl laser).
UV–vis Spectroscopy. The spectra obtained following pho-
tolysis of 6 and 11 in 3-methylpentane glasses are shown in
Figure 5. The primary photoproduct observed on photolysis of
6 is the triplet nitrene 7T, which exhibits a structured band at
approximately 470–520 nm. A similar band has been observed
at room temperature for this species in laser flash photolysis
studies and is consistent with TD-DFT calculations, which
predict a strongly absorbing band at 464 nm (in the gas phase).13
Sustained photolysis of this species leads to a secondary
photoproduct with a broad, unstructured band at approximately
340 nm. Minor shifts in the absorbance bands around 500 nm
suggest that the secondary photoproduct may absorb in this
region of the spectrum as well.
A scale-up experiment involving the photolysis of 6 in 200
mL of vitrified 3-methylpentane solution, followed by extraction
with D2O, gave a 1H NMR spectrum consisting of three
3446 J. Org. Chem. Vol. 73, No. 9, 2008

Photochemistry of Azidopyridine 1-Oxides
Photolysis of argon matrix-isolated 6 at 450 nm yields
qualitatively similar UV–vis spectra to the solution results,
although the system of bands around 450–550 nm is somewhat
more structured than those obtained in organic glasses (see the
Supporting Information) and does not diminish over prolonged
irradiation, presumably due to a lack of abstractable hydrogen
in the argon matrix.
Photolysis of 11 in both organic glasses and argon matrix
lead to broad, poorly structured spectra with peaks that are
difficult to characterize and in all likelihood consist of spectra
of more than one species (see discussion below). TD-DFT
calculations for 12T indicate that there is an allowed absorption
at approximately 450–500 nm, but that this is significantly less
intense than that of 7T and is not observed experimentally. 12T
was calculated to be weakly absorbing, with maxima at
approximately 300 and 260 nm. The broad unstructured bands
observed at 340 and 380 nm are consistent with ketenimine
species such as 14a or 14b (TD-DFT calculated absorbances
around 280, 383 and 290, 335 nm, respectively). Species such
as 13a and 13b were also calculated to have significant
absorbances at 320 and 350 nm, respectively (see the Supporting
Information. Matrix infrared experiments (see below) indicate
the presence of a mixture of products following photolysis of
11–12T, 13b, and 14a. The observed UV–vis spectra are
consistent with such a mixture.
Matrix Infrared Spectroscopy. The difference spectrum
obtained following photolysis of 6 in an argon matrix below
10 K is shown in Figure 6. A number of infrared absorbances
of 6 exhibit multiple signals due to matrix site effects. Photolysis
of the matrix at 308 nm generates a violet-colored species which
may be identified as the triplet species 7T by its observed color
and by absorbances at 1583, 1395, 1150, 816, and 795 cm-1
,
which are consistent with the calculated spectrum for this species
(calculated at B3LYP/6-31G* level of theory, and scaled by a
factor of 0.9614). Thus, the observation that 7T is the dominant
photoproduct in the matrix is consistent with observations in
organic glasses (and for that matter, in solution at 298 K). There
is no spectroscopic evidence to suggest the formation of either
8 or 9 in the matrix.
The matrix-isolated infrared spectra obtained after photolysis
of 11 are a somewhat more complex matter, and prolonged
irradiation or subsequent irradiation at alternate wavelengths is
requiredtofullyassignthespectralfeaturesofthephotoproductssin
a number of cases, there is significant spectral overlap between
species that can only be resolved by changes in photolysis
conditions.
FIGURE 5. UV–vis spectra obtained during low temperature photolysis
of 6 and 11 in 3-methylpentane at 77 K. Spectra were obtained at 30 s
(red-light blue) and then 60 s (blue-violet) intervals for 6 and 15 s
(red-light blue) and 60 s (blue-violet) intervals for 11.
significant components: unreacted 6, the azo-dimer 10, and a
third species which corresponded to 4-aminopyridine 1-oxide
(16). The latter compound was isolated by preparative HPLC
and characterized by 1H and 13C NMR: its structure was
confirmed by comparison with an authentic sample.
The specific mechanism of formation of 16 is uncertain, but
there are two plausible possibilities. The first involves the
abstraction of hydrogen from solvent by the iminyl moiety,
followed by disproportionation of the formed radical pair. A
second possibility is similar but involves hydrogen abstraction
from the aminoxyl moiety as an alternative step. Studies of
persistent aminoxyl radicals20 have found that the excited states
of such species are highly adept at hydrogen abstraction, and
so two separate hydrogen abstraction steps at the iminyl and
aminoxyl sites of the triplet species, with rapid tautomerization
once the glass melts (or during extraction into D2O), is at least
possible. Thus, in the absence of diazacycloheptatetraene
N-oxide species (see below), the peaks observed at 340 and
500 nm in these glass experiments are due to a mixture of triplet
nitrene and presumably a free radical intermediate formed as
the result of hydrogen atom abstraction from the solvent by
triplet nitrene.
Initial photolysis of 11 in an argon matrix with 295–320 nm
band radiation shows facile decomposition of the parent azide
to yield a mixture of three products: 12T, 14a, and 13b,
indicated by characteristic absorbances at 1543, 1888, and 1713
cm-1, respectively (see Figure 7). Further photolysis under these
conditions leads to a decrease in 12T and possibly in 14a, with
an increase in 13b. On this basis, it is possible to partially assign
bands in the infrared spectrum (see both Figure 7). However,
there remain a number of bands that overlap, and so it is
necessary to perform wavelength selective photolysis to assign
the remaining bands.
Selective irradiation of the mixture of Figure 6 at 530–680
nm should lead to triplet photochemistry, since 12T is the only
species expected to absorb in this range (based on TD-DFT
calculations). Indeed, photolysis in this wavelength range led
to diminution of the bands assigned to triplet 12T, with an
(20) Bottle, S. E.; Chand, U.; Micallef, A. S. Chem. Lett. 1997, 857.
J. Org. Chem. Vol. 73, No. 9, 2008 3447

Crabtree et al.
FIGURE 6. Differential IR spectrum following photolysis of 6 at 308 nm (red) in comparison with simulated spectra for 6 (brown) and 7T (blue),
calculated at the B3LYP/6-31G* level of theory. Peaks at 1608 and 1624 cm-1 correspond to matrix isolated H2O codeposited with 6 (violet).
Experimental vibrational frequencies for 7T are shown.
increase those for 13b and 14a, thus allowing us to unambigu-
ously assign the bands corresponding to 12T (see Figure 8).
Further irradiation at 395–450 nm leads to a decrease in bands
for 14a and an increase in those for 12T and possibly 13b (based
on a small increase in absorbance at 1715 cm-1). Again, TD-
DFT calculations indicate that 14a will have appreciable
absorbance in this wavelength range, but 12T will absorb weakly
in this range and 13b will not absorb at all. These observations
allow us to partially assign the remaining bands (Figures 7 and
8). The assignments for 12T and 14a are relatively unambigu-
ous, but the assignment of the peaks for 13b is less so, due to
the high degree of spectral overlap.
The initial irradiation at 295–320 nm is nonselective: not only
does the azide 11 absorb in this region of the spectrum, but so
do the intermediates 12T, 13b, and 14a. It appears from
subsequent photolysis experiments that 12T and 14a may
photochemically interconvert and that 14a can be converted to
13b. It has not been established whether 13b will convert to
12T or 14a. It seems likely that the singlet nitrene 12S represents
a mechanistic branching pointsit is difficult to visualize a simple
mechanism for the conversion of 14a to 13b that does not
proceed via a nitrene intermediate. In addition, it appears that
12T acts as a photochemical “reservoir” for 12S in these
experiments.
product distribution. However, where cyclization of 12S occurs,
the more stable isomers 13b and 14a are formed, but 14b and
13a are not. This suggests that 12S is formed vibrationally “hot”,
and thermochemical equilibria of 13b/14b and 13a/14a may
be established prior to relaxation/dissipation of vibrational
energy into the matrix. Under such circumstances, we would
observe the thermochemically stable species 13b and 14a.
Conclusions
It is clear that our previous description of 4-nitrenopyridine
1-oxide as an iminyl-aminoxyl biradical system is justified by
the degree of spin delocalization deduced from the EPR
spectrum of this species, relative to a “typical” aryl nitrene
system. The chemistry of this species is dominated by triplet
chemistry at low temperature and room temperatureswe have
been unable to observe any product that might arise from the
singlet nitrene, and such behavior is borne out by calculations.
The biradical nature of the intermediate makes photochemical
hydrogen abstraction in organic glasses relatively facile.
In contrast, the radical “super-stabilizing” properties of the
N-oxide group are not available to 3-nitrenopyridine 1-oxide,
and so it behaves more like a typical aryl nitrene: the triplet
state is obtained initially during low temperature photolysis, but
the singlet state can be accessed upon prolonged photolysis,
yielding products consistent with cyclization and ring expansion.
This system is unusual, however, in that both of the two possible
modes of cyclization are observed at low temperature; in one
The observed product distribution of 12T/13b/14a in all
likelihood arises out of a series of linked photostationary
equilibria; and this tends to be confirmed by the fact that
selective irradiation of certain isomers leads to a shift in the
3448 J. Org. Chem. Vol. 73, No. 9, 2008

Photochemistry of Azidopyridine 1-Oxides
FIGURE 7. Differential IR spectra following Ar matrix photolysis of 11 at 295–320 nm (red and orange) in comparison with simulated spectra for
12T (blue) 13b (violet),and 11 (green), calculated at the B3LYP/6-31G* level of theory.
mode, the product is the expected diazacycloheptatetraene
N-oxide; whereas in the other mode, the diazabicyclo[4.1.0]hepta-
2,4,6-triene N-oxide intermediate is the favored species.
How do these studies relate to the solution studies performed
by Abramowitz et al.,12 who found no evidence of ring-
expansion products when 11 was thermolyzed or photolyzed
in the presence of nucleophiles? If we assume that the azide
acts as a “normal” aryl azide, we would expect the formation
of aminoazepine products in the presence of amines.3 Our initial
LFP experiments with 11 at room temperature indicate that
photolysis of 11 in the absence of amine trap does yield
polymeric material, and that the absorbance of the formed
polymer can be quenched by the addition of diethylamine or
dibutylamine as a trap. However, the trapped nitrene product
(nominally the aminoazepine) itself is highly photolabile, and
even exposure to moderate amounts of light leads to the
formation of highly colored oligomeric materials. We note that
previous workers did not obtain a great deal of characterizable
material in their studies.12 Further study is underway to further
elucidate the room temperature chemistry of 11 with nucleo-
philes to determine the products generated and the photochem-
istry they undergo.
Computational Methodology
Density functional theory (DFT) calculations were performed
using the GAUSSIAN 03 program suite.21 Geometry optimizations
and energies were performed at the B3LYP/6-31G* level of theory
for all species,22 and vibrational frequencies were calculated at the
same level of theory, corrected by factors of 0.9614 (frequencies),
0.9806 (zero point energies), and 0.9989 (enthalpic corrections to
298 K) as recommended by Scott and Radom.23 Transition states
for nitrene and azide rearrangements were found to have a single
imaginary frequency, corresponding to the appropriate reaction
coordinate. The energetics of the open-shell singlet states of the
nitrenes listed above were estimated according to the method of
Johnson et al.,16 whereby a UDFT optimization based on the RDFT
nitrene wave function with promotion of a single electron into the
(21) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.;
Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci,
B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada,
M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.;
Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian,
H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.;
Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala,
P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski,
V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.;
Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui,Q.; Baboul,
A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
Piskorz, P.; Komaromi,I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.;
Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, ReVision
C.02,Gaussian, Inc.: Wallingford, CT, 2004.
(22) (a) Becke, A. D. Phys. ReV. A 1988, 38, 3098. (b) Becke, A. D. J. Chem.
Phys. 1993, 98, 5648. (c) Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B 1988, 37,
785.
(23) Scott, A. P.; Radom, L. J. Phys. Chem. 1996, 100, 16502.
J. Org. Chem. Vol. 73, No. 9, 2008 3449

Crabtree et al.
FIGURE 8. Differential IR spectra obtained following Ar matrix photolysis of a mixture of 12T, 13b, and 14a (see Figure 7) at 530–680 nm (red),
followed by photolysis at 395–450 nm (orange). Simulated spectra for 12T (blue), 13b (violet), and 14a (green) are calculated at the B3LYP/6-
31G* level of theory.
LUMO yielded a mixed singlet state with an S2 expectation value
of approximately 1, corresponding to a 50:50 mixture of open shell
singlet and triplet states, as is typical for this methodology. The
energy of the open shell singlet state was then estimated by the
sum method (eq 1).16
are the same types as those used by previous workers17 and are
described in more detail in the Supporting Information. Single-
point energies were calculated at the CASSCF(10,9)/6-31G*//
CASSCF(8,8)/6-31G* level of theory to determine the effect of
inclusion of the N-O π-orbital in the active space. Electron
correlation effects were investigated by including an MP2 correction
calculated at the CASSCF(8,8) MP2/6-31G* level of theory based
on the CASSCF(8,8)/6-31G* geometry. Calculations were also
performed on phenylnitrene as a comparator system where higher-
level benchmark calculation data are available17 (see the Supporting
Information).
E(OSS))2E(50:50mix)-E(T)
(1)
Natural population analysis (NPA)24 was performed on critical
intermediates.
UV–vis spectra for critical intermediates were simulated by
calculating the vertical transition energies using time-dependent
density functional theory.25 In each case, the first 15 spin-allowed
transitions were calculated at the TDB3LYP/6-31+G**//B3LYP/
6-31G* level of theory, and the calculated transition energies and
oscillator strengths are tabulated in the Supporting Information.
Experimental Methods
Compound 6 was prepared from the corresponding hydrazine,
using the method of Itai and Kamiya,10a and recrystallized from
acetone (see the Supporting Information). Compound 11 was
prepared by oxidation of 3-azidopyridine.10c,26 All solvents used
in this study were obtained in spectroscopic purity from commercial
sources, and were used without additional purification. The instru-
ments used for characterization of organic compounds are described
in the Supporting Information.
CASSCF calculations were also performed using GAUSSIAN
03 up to the CASSCF(10,9) level of theory. Geometry optimizations
and frequencies were performed at the CASSCF(8,8)/6-31G* level
of theorysvibrational frequencies and zero-point energies were
unscaled. The orbitals used for the active space for each calculation
Glassy UV–vis Spectroscopy. Solutions of the azide in deoxy-
genated solvent (deoxygenation was achieved by bubbling argon
(24) (a) Reed, A. E.; Weinstock, R. B.; Weinhold, F. J. Chem. Phys. 1985,
83, 735. (b) Reed, A. E.; Weinhold, F.; Curtiss, J. A. Chem. ReV. 1988, 88, 899.
(25) (a) For examples, see: Bauernschmitt, R.; Ahlrichs, R. Chem. Phys. Lett.
1996, 256, 454. (b) Stratmann, E. R.; Scuseria, G. E.; Frisch, M. J. J. Chem.
Phys. 1998, 109, 8218.
(26) Sawanishi, H.; Tajima, K.; Tsuchiya, T. Chem. Pharm. Bull. 1987, 35,
4101.
3450 J. Org. Chem. Vol. 73, No. 9, 2008

Photochemistry of Azidopyridine 1-Oxides
through the samples) in a 10 mm path length quartz cell were
rapidly cooled to 77 K with liquid nitrogen in a quartz-Pyrex
dewar. Solutions with a room temperature peak absorbance between
2.0 and 2.5 au were used. UV–vis spectra were obtained with a
photodiode array spectrometer following irradiation with a broad
spectrum medium pressure Hg vapor lampsno wavelength filters
were used in these experiments. Subsequent to photolysis, the glass
was allowed to anneal, was revitrified, and a final spectrum was
obtained.
temperatures by deposition of the argon matrices of the azides on
an oxygen-free high-conductivity copper rod (75 mm length, 3 mm
diameter) cooled by a closed-cycle 4.2 K cryostat. Photolysis of
the samples was achieved using one of two methods:
(a) A high pressure mercury arc lamp, in combination with quartz
optics and appropriate cutoff filters. KG1 filters were also used to
absorb IR radiation from the lamps. This method provides
broadband irradiation within the following bands, depending on
the choice of filter: 295–320 nm, 395–450 nm, 530–680 nm.
Glassy Matrix EPR Spectroscopy. Solutions of azide were
degassed (3-fold freeze–pump–thaw cycles) and sealed inside
standard 4.0 mm o.d. quartz EPR sample tubes, which were sealed
under vacuum. Samples were then frozen in liquid nitrogen in a
quartz EPR X-band cavity finger Dewar and irradiated at 350 nm
for 2–7 min using a carousel photoreactor. The dewar was placed
into the EPR cavity and the spectrum obtained over a field range
of 500–9500 gauss (modulation frequency 100 MHz, modulation
amplitude 5–10 gauss, microwave power 6.8–19.3 mW, depending
on the sample).
Argon Matrix Isolation Spectroscopy. The instrumental sys-
tems used in this study have been described previously.27 To
summarize, infrared and UV–vis spectra were obtained from argon
matrices of the azides deposited on CsI plates cooled to 3–10 K
using closed-cycle helium cryostats. IR spectra were collected
through CsI windows, and UV–vis spectra were collected through
sapphire windows. X-band EPR spectra were recorded at cryogenic
(b) Monochromatic irradiation at 308 nm using an Xe-Cl
excimer laser.
Acknowledgment. J.S.P. thanks the Lilly Endowment and
the Research Corporation Cottrell College Science Award (CC-
6456) for support of this project. W.S. thanks the Deutsche
Forschungsgemeinschaft and the Fonds der Chemischen Indus-
trie for financial support. T.E.M. thanks the Alexander von
Humboldt Foundation. P.M.L. acknowledges NSF support for
the UMass-Amherst EPR Facility (CHE 0443180).
Supporting Information Available: Synthetic methodologies
for the starting material, additional spectroscopic data obtained
in this study, and computational output in the form of optimized
geometries, energies, and frequencies for species relevant to this
study. This material is available free of charge via the Internet
at http://pubs.acs.org.
(27) (a) Sander, W.; Winkler, M.; Cakir, B.; Grote, D.; Bettinger, H. J. Org.
Chem. 2007, 72, 715. (b) Dunkin, I. R. Matrix Isolation Techniques; Oxford
University Press: Oxford, UK, 1998.
JO8001936
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