Orbital-overlap control in the solid-state reactivity of β-azido-propiophenones: Selective formation of cis-azo-dimers

Article abstract of DOI:10.1021/ol703098q

Solid-state photolysis of 1 a,b yields selectively cis-3a,b. X-ray analysis of 1 a,b reveals the molecules adopt an extended structure and as such the crystal packing arrangement consists of planar, π-stacked molecules. The shortest intermolecular distance between adjacent N-atoms is ～3.76 A and would lead to formation of trans-3a,b, whereas cis-3a,b is formed by dimerization between N-atoms that are ～3.9 A apart. We propose that the molecular orbital alignment of the adjacent nitrenes controls the solid-state reactivity.

Full text of DOI:10.1021/ol703098q

ORGANIC
LETTERS
2008
Vol. 10, No. 5
937-940
Orbital-Overlap Control in the
Solid-State Reactivity of
â
-Azido-Propiophenones: Selective
Formation of cis-Azo-Dimers
Jagadis Sankaranarayanan, Lauren N. Bort, Sarah M. Mandel, Ping Chen,
Jeanette A. Krause, Elwood E. Brooks, Pearl Tsang, and
Anna D. Gudmundsdottir*
Department of Chemistry, UniVersity of Cincinnati, Cincinnati, Ohio 45221-0172
anna.gudmundsdottir@uc.edu
Received December 24, 2007
ABSTRACT
Solid-state photolysis of 1a,b yields selectively cis-3a,b. X-ray analysis of 1a,b reveals the molecules adopt an extended structure and as such
the crystal packing arrangement consists of planar, -stacked molecules. The shortest intermolecular distance between adjacent N-atoms is
3.76 Å and would lead to formation of trans-3a,b, whereas cis-3a,b is formed by dimerization between N-atoms that are 3.9 Å apart. We
propose that the molecular orbital alignment of the adjacent nitrenes controls the solid-state reactivity.
π
∼
∼
Photoreactions in the solid-state have been shown to be
generally more regio- and stereoselective than their solution
counterparts.1 Thus, crystals have been used ingeniously to
synthesize natural products from radical intermediates in high
chemical as well as enantiomeric yield.2 Investigations of
the solid-state reactivity of radicals such as carbenes, nitrenes,
and biradicals make it possible to establish structure-
reactivity relationships. More specifically, the overlap and
orientation between the orbitals on the radical centers that
form new bonds in the products can be correlated with their
solid-state selectivity.3 In theory, the same orbital alignment
is necessary for selective bond formation between radical
centers in solution. However, it is experimentally difficult
to assess orbital alignments in solution. Thus, solid-state
studies offer a unique opportunity to investigate the influence
of orbital alignment upon radical reactivity. Furthermore,
unstable products formed during photoreactions are more
readily studied in the solid state due to the rigidity and lack
of diffusion inherent to crystals.4
(1) (a) Campos, L. M.; Garcia-Garibay, M. A. Reactive Intermediates
in Crystals: Form and Function. In ReViews of ReactiVe Intermediate
Chemistry; Platz, M. S., Moss, R. A., Jones, M., Eds.; John Wiley & Sons:
New York, 2007; p 271. (b) Scheffer, J. R.; Xia, W. Top. Curr. Chem.
2005, 254, 233. (c) Garcia-Garibay, M. A. Acc. Chem. Res. 2003, 36, 491.
(d) Garcia-Garibay, M. A.; Campos, L. M. In CRC Handbook of Organic
Photochemisty & Photobiology, 2nd ed.; Horsepool, W. M., Ed.; CRC
Press: Boca Raton, FL, 2003; Chapter 48. (e) Sakamoto, M. Chem. Eur. J.
1997, 3, 684. (f) Hollingsworth, M. D.; McBride, J. M. AdV. Photochem.
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M. A. Org. Lett. 2004, 6, 645. (c) Ellison, M.; Ng, D.; Dang, H.; Garcia-
Garibay, M. A. Org. Lett. 2003, 5, 2531. (d) Resendiz, M. J. E.; Garcia-
Garibay, M. A. Org. Lett. 2005, 7, 371. (e). Garcia-Garibay, M. A.; Mortko,
C. J. J. Am. Chem. Soc. 2005, 127, 7994.
We have recently shown that solution photolysis of â-azido
propiophenone derivatives 1 results in formation of alkyl
nitrene 2, which are long-lived intermediates because they
decay by dimerization to form 3, rather than reacting with
(3) (a) Yang, C.; Xia, W.; Scheffer, J. R.; Botoshansky, M.; Kaftory,
M. Angew. Chem., Int. Ed. 2005, 44, 5087. (b) Braga, D.; Chen, S.; Filson,
H.; Maini, L.; Netherton, M. R.; Patrick, B. O.; Scheffer, J. R.; Scott, C.;
Xia, W. J. Am. Chem. Soc. 2004, 126, 3511. (c) Shin, S. H.; Cizmeciyan,
D.; Keating, A. E.; Khan, S. I.; Garcia-Garibay, M. A. J. Am. Chem. Soc.
1997, 119, 1859. (d) Shin, S. H.; Constable, A. E.; Garcia-Garibay, M. A.
J. Am. Chem. Soc. 1996, 118, 7626. (e) Doetschman, D. C.; Hutchison, C.
A. J. Chem. Phys. 1972, 56, 3964.
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10.1021/ol703098q CCC: $40.75
© 2008 American Chemical Society
Published on Web 02/07/2008

the solvent or its precursor (Scheme 1).5 However, we were
not able to isolate and characterize 3, since it forms 4 in
Scheme 1
Figure 1. (A) IR spectra of azide 1b before (red line) and after
irradiation (blue line). (B) Raman spectra of azide 1b before (red
line) and after irradiation (blue line).
solution. Dimer 3 is presumably in equilibrium with its
tautomer 5, which undergoes an intramolecular reaction
followed by hydrolysis to form 4. Furthermore, the cis
isomers of alkyl diazenes which lack tertiary carbon atoms
next to the azo moiety are generally unstable and decompose
unless the solution is kept at cryogenic temperature,6 thus
complicating their preparation and characterization.
In this letter we describe how solid-state photolysis of 1a,b
selectively yields cis-3a,b. We used IR, Raman, and 13C
NMR spectroscopy along with molecular modeling to assign
the stereochemistry of 3a,b. Furthermore, X-ray structure
analysis of 1a,b made it possible to determine that the nitrene
dimerization did not take place between the N-atom on
adjacent molecules having the shortest intermolecular dis-
tance but rather involved molecules having a more favorable
orbital alignment for azo dimer formation.
at 2015 cm-1 and formation of a new band at 1633 cm-1,
whereas Raman spectroscopy (Figure 1b) revealed formation
of a very low-intensity band at 1633 cm-1 and more intense
bands at 754 cm-1 and a decrease of the bands at 2051, 948,
and 789 cm-1. We assign the band at 1633 cm-1 to the Nd
N stretch in cis-3, which is expected to be both IR and Raman
active. This is similar to what was observed for cis-
dimethyldiazene, which has a Raman and IR stretch at 1556
cm-1 for the NdN band.6b In comparison the NdN band in
trans-dimethyldiazene is at 1583 cm-1 and is only Raman
active because symmetrical stretching vibrations are inactive
in the infrared.6f
Finally, we monitored the solid-state reactivity of 1b via
solid-state 13C NMR spectroscopy. Figure 2 shows the solid-
To investigate which dimers form upon photolysis of the
monomers, 1a,b, the solid-state reaction of 1a,b in KBr
pellets were monitored by IR (Figure 1a). The crystals
turned yellow upon photolysis and dissolving these irra-
diated crystals released gas, presumably N2 molecules that
were trapped within the crystal lattice. To determine the
solid-state products, irradiated crystals were dissolved and
HPLC and solution NMR techniques were used to show that
4 is obtained, along with some remaining starting material.
Hence, 4 must be formed very efficiently from 3 in solution.
In the solid-state, irradiation of 1a,b in KBr pellets led to
new IR and Raman bands, mostly occurring very near those
of the parent azide, which is expected since the propiophe-
none moiety is not significantly affected by dimerization of
nitrenes 2a,b. The most noteworthy changes observed in the
IR spectra upon irradiation are depletion of the azide band
Figure 2. Solid-State 13C-CPMAS NMR spectra of 1b before (red
line) and after different extents of photolysis: ∼30% (black line)
and ∼70% (blue line) conversions, respectively.
state 13C NMR spectra of 1b before and after ∼30% and
∼70% conversions. As irradiation increases, the 47.7 ppm
peak intensity decreases while the intensity of a new peak
at 46.2 ppm increases. On the basis of the literature, the CH3
group in cis- and trans-dimethyldiazene resonates at δ 46.9
and 55.1 ppm, respectively.6a The CH group next to the Nd
N moiety in an isopropyl diazene derivative resonates at 69
ppm.7 Thus, the new 46.2 ppm peak is assigned to the CH2
(5) (a) Singh, P. N. D.; Mandel, S. M.; Sankaranarayanan, J.; Muth-
ukrishnan, S.; Chang, M.; Robinson, R. M.; Lahti, P. M.; Ault, B. S.;
Gudmundsdottir, A. D. J. Am. Chem. Soc. 2007, 129, 16263. (b) Sankara-
narayanan, J.; Mandel, S. M.; Krause, J. A.; Gudmundsdottir, A. D. Acta
Crystallogr., Sect. E 2007, E63, o721.
(6) (a) Simeonov, A. M.; McKenna, C. E. J. Org. Chem. 1995, 60, 1897.
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R. A.; Young, W. G. J. Am. Chem. Soc. 1977, 99, 1662. (c) Engel, P. S. J.
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Soc. 1975, 97, 6762.
938
Org. Lett., Vol. 10, No. 5, 2008

group in 3b since it is within the range of chemical shift
values reported for similar carbon atoms. The NMR spec-
troscopy also supports formation of a dimer such as 3b since
no other changes except for the 47.7-46.2 ppm aliphatic
carbon resonance shift were observed upon irradiation.
Formation of 4b or 5b would have yielded other resonances
corresponding to either a heterocyclic aromatic or imine
carbon resonances, respectively.
reactivity we optimized the structures of 1a,b, nitrenes 2a,b,
and cis- and trans-3a,b using the B3LYP level of theory
and 6-31G+(d) basis set as implemented in Gaussian03.8,9
For 3b we calculated the lowest energy conformers, A, and
also conformers, B, which are higher in energy but more
similar to the conformers we would expect for trans- and
cis-3b to be formed in, within the crystal lattice (Figure 4).
X-ray structural analysis of 1a,b revealed that both
compounds crystallize as the extended conformer (Figure 3).
Figure 3. Crystal packing arrangement for (A) 1a and (B) 1b.
The intermolecular N-N distances are in Å (see Table 1).
Figure 4. Molecular orbital alignment of the half full px and py
orbitals on the N atom in nitrene 2b in the crystal lattice to form
(i) trans-3a and (ii) cis-3b.
Azides 1a,1b are planar since their â-chain torsion angles
range from 178.5° to 179.7°. The crystal lattice consists of
layers of molecules with overlapping phenyl rings and azido
groups which allow for π-stacking interactions. As expected,
the chloro/bromo halide substitution in the para position does
not affect the crystal packing arrangement significantly.
For 1a,b the shortest intermolecular distance between
adjacent N1 atoms is 3.757(3) and 3.767(5) Å, respectively
(Table 1, Figure 3). Dimerization between two of these
The calculated IR and Raman spectra of cis-3bA,B have a
vibration band at 1659 and 1672 cm-1 due to the stretching
of the NdN bond, respectively. The calculated oscillation
strengths of these IR and Raman bands are similar (Table
2). In comparison, the calculated NdN stretches for trans-
3bA,B are predicted at 1671 and 1680 cm-1, respectively.
The oscillation strengths of these NdN trans-3bA,B stretches
Table 1. Specific Intermolecular Distances in Crystals of
Azides 1a,b
(8) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (b) Lee, C.; Yang,
W.; Parr, R. G. Phys. ReV. B 1988, 37, 785.
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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.; Bakken, V.; 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,
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Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian
03, Revisions A.1 and C.02; Gaussian, Inc.: Wallingford, CT, 2004.
azide
N1‚‚‚N1 (Å)
N1‚‚‚N3 (Å)
1a
1b
3.757(3), 3.898(1)
3.767(5), 3.952(1)
3.698(3)
3.694(5)
nitrogen atoms would lead to formation of trans-3a,b,
respectively, but this is not observed. The second shortest
intermolecular distance between adjacent N1 atoms is 3.898-
(1) and 3.952(1) Å for 1a,b, respectively. Dimerization
between these two nitrogen atoms yields cis-2.
To further support the characterization of the solid-state
products, 3a,b, and to better understand the solid-state
Org. Lett., Vol. 10, No. 5, 2008
939

of 2a,b takes place between two nitrene molecules in the
solid-state as it does in solution. To explain why nitrenes
2a,b prefer to dimerize with a nitrene molecule located ∼3.9
Å away rather than with one at ∼3.76 Å, we looked at the
alignment of the two half-full p-orbitals on the N-atom, px
and py, that will form the NdN bonds. In order for trans-3
to form, the two px-orbitals (Figure 4), which are located on
top of each other in the crystal lattice, would have to rotate
for good overlap. In comparison, the py- and px-nitogren
orbitals are lined up perfectly in the crystal, side to side, for
dimerization and formation of cis-3a,b. Thus, the molecular
orbital alignment must control the reactivity of the nitrenes
2a,b in the solid-state.
Lahti et al. and Sugawara et al. used ESR spectroscopy to
demonstrate that aryl nitrenes are long-lived in the solid-
state.12,13 Aryl nitrenes also decay mainly by dimerization
in the solid-state, although the stereochemistry of the azo-
products was not determined. It can be theorized that alkyl
nitrenes 2a,b are long-lived in crystals as well, and that the
restriction of the crystal lattice forces them to form cis-2a,b,
stereoselectively.
Table 2. Calculated NdN Band Intensities for 3
NdN (cm-1
)
IR (km/mol)
Raman (km/mol)
cis-3aA
trans-3aA
cis-3bA
cis-3bB
trans-3bA
trans-3bB
1659
1671
1659
1672
1671
1681
7
0
7
23
0
0
6
170
7
12
177
10
are 177 and 12 km/mol, respectively, for the Raman bands,
but zero in the IR bands as expected. Calculations show that
while all of the conformers of cis-3b have similar NdN
stretching frequencies, their calculated intensities varied
significantly. The same trends were observed in the calcula-
tions for the conformers of trans-3b. Thus, the calculations
support that cis-3 is formed in the solid-state, since we
observe NdN bands that are both IR and Raman active.
Furthermore, scaling the 1672 cm-1 band for cis-3bA by
0.9734 places the calculated band at 1627 cm-1,10 which
corresponds well with the observed band at 1633 cm-1.
Furthermore, we assign the Raman band at 754 cm-1 (Figure
1) to the symmetrical stretch of the -CH2-NdN-CH2-
moeity in cis-3b based on its calculated frequency of 787
cm-1. Finally, the Raman bands at 948 and 789 cm-1 in 1b,
which decreased upon irradiation, were assigned to coupled
NNN and CH bends, which are calculated to be 964 and
803 cm-1, respectively.
Solid-state photolysis of azides 1a,b selectively results in
cis-3a,b via dimerization between two nitrene molecules.
Crystal packing of azides 1a,b indicate that dimerization does
not take place between nearest neigboring N-atoms on
nitrenes 2a,b, but rather between N-atoms that are further
apart and have better molecular orbital alignment.
Acknowledgment. This work was supported by the
National Science Foundation (CHE-0093622 and 0703920)
and the Ohio Supercomputer Center. L.N.B. is grateful to
the UC WISE program for support. X-ray data for 1a were
collected on a Bruker SMART6000 for which NSF-MRI
funding (CHE-0215950) is gratefully acknowledged. X-ray
data for 1b were collected on a Bruker SMART1K via The
Ohio Crystallographic Consortium, funded by the Ohio Board
of Regents. We thank Dr. P. Boolchand at the University of
Cincinnati for allowing us to use his Raman spectrometer
(funded by NSF DMR-0456472).
Finally, calculations also rule out the possibility that the
primary photoproduct in crystals is 5 for which H-N (∼3400
cm-1) and imine bands (∼1710 cm-1) would have been
observed; these would be major Raman bands (due to their
calculated oscillation strength of ∼300 km/mol).
The calculations reveal that the calculated structures of
1a,b are similar to their X-ray structures, i.e., the molecules
crystallize in an extended, planar conformer, similar to the
calculated mininal energy conformer. Thus, it is reasonable
to assume that nitrenes 2a,b adopt conformations in the solid-
state similar to their calculated minmal energy conformers.
As we have shown before, triplet alkyl nitrenes decay by
dimerization with another nitrene molecule rather than
reacting with an azido precursor.5a Schuster et al. reported
similar findings for the dimerization of phenyl nitrenes.11
Thus, it seems reasonable to assume that the dimerization
Supporting Information Available: Experimental pro-
cedures and details (NMR, X-ray (CIF), and calculations).
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL703098Q
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