Conformational control and photoenolization of pyridine-3-carboxaldehydes in the solid state: Stabilization of photoenols via hydrogen bonding and electronic control

Article abstract of DOI:10.1021/jo026621n

We have investigated the solid-state photobehavior of a broad set of pyridine-3-carboxaldehydes 1-5. The introduction of a heteroatom into mesitaldehydes as in aldehydes 1 raises the question of conformational preference in the solid state. The preferred conformations have been unequivocally established from X-ray crystal structure analyses of two of the aldehydes, 1c and 2c; it is shown that intramolecular hydrogen bonding could be utilized to achieve conformational control. In contrast to mesitaldehydes, which undergo efficient photocyclization to benzocyclobutenols in the solid state, the heteroatom analogues 1b and 1c exhibit a perceptible color change (from colorless to pale yellow for 1b and yellow-orange for 1c) upon UV irradiation; the color attributed to (E)-enols is persistent for several hours. Continued irradiation leads to an intractable polymeric material. The AM1 calculations, which have been reliably applied to the thermal cyclization of xylylenols to benzocyclobutenols, reveal that the (E)-enols of 1 are more stable than those of the mesitaldehydes relative to their corresponding benzocyclobutenols. The stabilization is interpreted as arising from the possibility of engaging the heteroatom in resonance delocalization. That the contribution from such a role of the nitrogen atom is so pronounced is elegantly demonstrated by forming the fluoroborate salts; 1a-HBF₄ and 1b-HBF₄ readily exhibit highly red-shifted absorption upon exposure to UV radiation as a result of stabilization of the photoenols. Notably, such a remarkable stabilization via electronic control of the photoenols is unprecedented. All of the 2-methoxy- and 2-chloro-substituted aldehydes 2-5 exhibit photochromism. Ab initio calculations show that the methoxy group in aldehydes 2 and 3 stabilizes the (E)-enols via O-H...O hydrogen bonding as compared to those of 1 by 5-6 kcal/mol relative to their corresponding benzocyclobutenols. Thus, the presence of methoxy and halo groups at position 2 serves not only to direct the formyl oxygen toward the methyl group for H-abstraction but also to stabilize the (E)-enols.

Full text of DOI:10.1021/jo026621n

Con for m a tion a l Con tr ol a n d P h otoen oliza tion of
P yr id in e-3-ca r boxa ld eh yd es in th e Solid Sta te: Sta biliza tion of
P h otoen ols via Hyd r ogen Bon d in g a n d Electr on ic Con tr ol
Prasenjit Mal,† U. Lourderaj,† Parveen,‡ P. Venugopalan,*,‡ J . Narasimha Moorthy,*,† and
N. Sathyamurthy*,†,§
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India, Department of
Chemistry, Panjab University, Chandigarh 160 014, India, and J awaharlal Nehru Centre for Advanced
Scientific Research, J akkur, Bangalore 560 064, India
moorthy@iitk.ac.in
Received October 28, 2002
We have investigated the solid-state photobehavior of a broad set of pyridine-3-carboxaldehydes
1-5. The introduction of a heteroatom into mesitaldehydes as in aldehydes 1 raises the question
of conformational preference in the solid state. The preferred conformations have been unequivocally
established from X-ray crystal structure analyses of two of the aldehydes, 1c and 2c; it is shown
that intramolecular hydrogen bonding could be utilized to achieve conformational control. In contrast
to mesitaldehydes, which undergo efficient photocyclization to benzocyclobutenols in the solid state,
the heteroatom analogues 1b and 1c exhibit a perceptible color change (from colorless to pale yellow
for 1b and yellow-orange for 1c) upon UV irradiation; the color attributed to (E)-enols is persistent
for several hours. Continued irradiation leads to an intractable polymeric material. The AM1
calculations, which have been reliably applied to the thermal cyclization of xylylenols to
benzocyclobutenols, reveal that the (E)-enols of 1 are more stable than those of the mesitaldehydes
relative to their corresponding benzocyclobutenols. The stabilization is interpreted as arising from
the possibility of engaging the heteroatom in resonance delocalization. That the contribution from
such a role of the nitrogen atom is so pronounced is elegantly demonstrated by forming the
fluoroborate salts; 1a -HBF 4 and 1b-HBF 4 readily exhibit highly red-shifted absorption upon
exposure to UV radiation as a result of stabilization of the photoenols. Notably, such a remarkable
stabilization via electronic control of the photoenols is unprecedented. All of the 2-methoxy- and
2-chloro-substituted aldehydes 2-5 exhibit photochromism. Ab initio calculations show that the
methoxy group in aldehydes 2 and 3 stabilizes the (E)-enols via O-H‚‚‚O hydrogen bonding as
compared to those of 1 by 5-6 kcal/mol relative to their corresponding benzocyclobutenols. Thus,
the presence of methoxy and halo groups at position 2 serves not only to direct the formyl oxygen
toward the methyl group for H-abstraction but also to stabilize the (E)-enols.
In tr od u ction
aldehydes is marked by the formation of several photo-
products. For example, the simple o-methylbenzaldehyde,
a representative case, has been found to afford as many
as seven photoproducts depending on the conditions of
irradiation.7,8 The solid-state photochemistry, on the
other hand, has been explored very little.9,10 Our recent
systematic investigations on crystalline mesitaldehydes
have shown that photochemical formation of benzocy-
clobutenols from o-alkyl aromatic aldehydes proceeds via
thermal conrotatory closure of the intermediate o-xylyle-
nols/photoenols (Scheme 1).11 Accordingly, the colored
o-xylylenols from o-anisaldehydes, capable of intramo-
The solution- and solid-state photochemistry of o-alkyl
aromatic ketones has been thoroughly examined;1-6 the
synthetically useful benzocyclobutenols are invariably
isolated as photoproducts from both media. In contrast,
the solution-state photochemistry of o-alkyl aromatic
* Corresponding author. Phone: +91-512-2597438. Fax: +91-512-
2597436.
† Indian Institute of Technology.
‡ Panjab University.
§ N. Sathyamurthy is an Honorary Professor at J awaharlal Nehru
Centre for Advanced Scientific Research.
(1) Ito, Y.; Giri, B. P.; Nakasuji, M.; Hagiwara, T.; Matsuura, T. J .
Am. Chem. Soc. 1983, 105, 1117.
(7) Findlay, D. M.; Tchir, M. F. J . Chem. Soc., Chem. Commun. 1974,
514.
(8) Arnold, B. J .; Mellows, S. M.; Sammes, P. G.; Wallace, T. W. J .
Chem. Soc., Perkin. Trans. 1 1974, 401.
(9) Gore, P. H.; Hoskins, J . A.; Lott, K. A. K.; Waters, D. N.
Photochem. Photobiol. 1970, 11, 551.
(10) Kumar, V. A.; Venkatesan, K. J . Chem. Soc., Perkin Trans. 2
1991, 829.
(2) Ito, Y.; Nishimura, H.; Umehara, Y.; Yamada, Y.; Tone, M.;
Matsuura, T. J . Am. Chem. Soc. 1983, 105, 1590.
(3) Wagner, P. J .; Subrahmanyam, D.; Park, B.-S. J . Am. Chem.
Soc. 1991, 113, 709.
(4) Sobczak, M.; Wagner, P. J . Tetrahedron Lett. 1998, 39, 2523.
(5) Ito, Y.; Matsuura, T.; Fukuyama, K. Tetrahedron Lett. 1988, 29,
3087.
(6) Ito, Y.; Yasui, S.; Yamauchi, J .; Ohba, S.; Kano, G. J . Phys. Chem.
A 1998, 102, 5415.
(11) Moorthy, J . N.; Mal, P.; Natarajan, R.; Venugopalan, P. J . Org.
Chem. 2001, 66, 7013.
10.1021/jo026621n CCC: $25.00 © 2003 American Chemical Society
Published on Web 04/05/2003
3446
J . Org. Chem. 2003, 68, 3446-3453

Solid-State Photoenolization of Pyridine-3-carboxaldehydes
SCHEME 1
CHART 1
lecular stabilization via hydrogen bonding, lend them-
selves to the observation of photochromism (eq 1).12
photochromism (photoenolization, eq 3).19 This contrast-
ing photobehavior observed with the heteroatom ana-
logue prompted us to undertake the present investiga-
tions. Thus, we designed pyridine-3-carboxaldehydes 1-4
as substrates that may readily undergo photochemical
γ-hydrogen abstraction to (i) understand the influence
of ring heteroatom on the overall photochemical outcome,
(ii) unequivocally establish the solid-state conformational
control via intramolecular C-H‚‚‚O and C-H‚‚‚X inter-
actions, and (iii) examine the role of substituents on the
absorption properties of the photoenols. Herein, we report
a comprehensive account of our results that demonstrates
the phenomenon of photochromism based on stabilization
of the photodienols (formed after γ-H abstraction) via
hydrogen bonding and electronic factors; incidentally, the
photochromism20 based on γ-H abstraction of ketones was
pursued vigorously three decades ago and met with
limited success.21,22
On the other hand, the photoenols formed from halogen-
substituted mesitaldehydes,11 lacking any stabilizing
influences, undergo efficient cyclization to synthetically
useful benzocyclobutenols13-18 (eq 2).
Resu lts
Syn t h eses of P yr id in e-3-ca r b oxa ld eh yd es 1-5.
3-Bromo- and 3,5-dibromo-2,4,6-trimethylpyridine were
synthesized by bromination of collidine with NBS in a
CF3COOH-H2SO4 mixture using a recently reported
procedure23 (Scheme 2). These were readily converted
into 3-cyano-2,4,6-trimethylpyridine, 5-bromo-3-cyano-
2,4,6-trimethylpyridine, and 3,5-dicyano-2,4,6-trimeth-
ylpyridine using CuCN in DMF.24 Reduction of these
cyanopyridines with DIBAL led to isolation of the alde-
Intriguingly, the heteroaromatic analogue, namely,
pyridine-3-carboxaldehyde 5 (Chart 1), is found to exhibit
(12) Moorthy, J . N.; Mal, P.; Natarajan, R.; Venugopalan, P. Org.
Lett. 2001, 3, 1579.
(13) Choy, W.; Yang, H. J . Org. Chem. 1988, 53, 5796.
(14) Macdonald, D. I.; Durst, T. J . Org. Chem. 1988, 53, 3663.
(15) Zhang, X.; Foote, C. S. J . Org. Chem. 1994, 59, 5235.
(16) Fitzgerald, J . J .; Pagano, A. R.; Sakoda, V. M.; Olofson, R. A.
J . Org. Chem. 1994, 59, 4117.
(17) Fitzgerald, J . J .; Michael, F. E.; Olofson, R. A. Tetrahedron Lett.
1994, 35, 9191.
(18) Henteman, M. F.; Allen, J . G.; Danishefsky, S. J . Angew. Chem.,
Int. Ed. 2000, 39, 1937.
(19) Sarkar, T. K.; Ghosh, S. K.; Moorthy, J . N.; Fang, J .-M.; Nandi,
S. K.; Sathyamurthy, N.; Chakraborty, D. Tetrahedron Lett. 2000, 41,
6909.
(20) For a recent special issue on “Photochromism: Memories and
Switches”, see: Chem. Rev. 2000, 100 (5).
(21) Huffman, K. R.; Loy, M.; Ullman, E. F. J . Am. Chem. Soc. 1965,
87, 6417.
(22) Sammes, P. G. Tetrahedron 1976, 32, 405.
(23) Duan, J .; Zhang, L. H.; Dolbier, W. J ., J r. Synlett 1999, 1245.
(24) Friedman, L.; Shechter, H. J . Org. Chem. 1961, 26, 2522.
J . Org. Chem, Vol. 68, No. 9, 2003 3447

Mal et al.
SCHEME 2
F IGURE 1. Molecular structures of aldehydes 1c (left) and
2c (right) from X-ray crystal structure analysis.
on o-anisaldehydes have offered evidence for intramo-
lecular C-H‚‚‚O hydrogen bonding between the formyl
hydrogen and the methoxy oxygen such that the formyl
oxygen is oriented away from the o-methoxy group.12
Thus, in all of the o-methoxy-substituted aldehydes 2 and
3, the formyl oxygen would be expected to orient itself
away from the methoxy group.
However, for aldehydes 1, lacking any of the afore-
mentioned conformation-orienting interactions, the pref-
erences cannot be predicted. To unequivocally establish
the orientational preferences of the carbonyl group, X-ray
crystallographic analyses were carried out for aldehydes
1c and 2c as representative cases. In Figure 1 are shown
the perspective views of their molecular structures. In
both aldehydes 1c and 2c, the formyl oxygen orients itself
toward the methyl group at position 4. Evidently, the
orientation of the formyl oxygen in 2c is influenced by
the C-H‚‚‚O hydrogen bond involving the methoxy
oxygen and the formyl hydrogen atom (Figure 1);28 the
distance and angular parameters, viz., dH‚‚‚O and θC-H‚‚‚O
,
for this interaction are 2.35 Å and 102.4°, respectively.
While similar considerations must apply for all aldehydes
2 and 3, we presume that the orientational preference
found in 1c will prevail for 1b, 1a -HBF 4, and 1b-HBF 4.
Th eor etica l Stu d ies of (Z)- a n d (E)-En ols. For a
comparison of the relative stabilities of (Z)- and (E)-
enols29 and also to assess the contribution of intramo-
lecular O-H‚‚‚O hydrogen bonding to the stabilization
of the latter, ab initio calculations were carried out at
the Hatree-Fock (HF) level using the 6-31G** basis set.30
The geometry in all cases was fully optimized, with no
symmetry restrictions. Frequency calculations were also
carried out to ensure the energy minimum in each case.
The differences in the energies of (Z)- and (E)-enols are
given in Table 1. As can be seen, the (Z)-enols are more
stable than the (E)-isomers for all aldehydes 1. In
contrast, the (E)-enols are more stable than the (Z)-
isomers for all of the methoxy-substituted aldehydes 2
and 3. This difference in behavior can be attributed to
hydes 1a , 1b, and 1c, respectively (Scheme 2). Pyri-
dinium salts 1a -HBF 4 and 1b-HBF 4 were prepared by
treating CH2Cl2 solutions of 1a and 1b with appropriate
amounts of fluoroboric acid and isolated by treating the
resulting material with a large excess of diethyl ether.
Aldehydes 2 were synthesized starting from 2-methoxy-
3-cyano-4,6-dimethylpyridine in an analogous manner.
Aldehydes 3 and 4 were prepared by DIBAL reduction
of the commercially available 2,6-dimethoxy-3-cyano-4-
methylpyridine and 2-chloro-3-cyano-4,6-dimethylpyri-
dine, respectively. The synthesis and photochemistry of
the aldehyde 5 have been reported previously.19
Con for m a tion a l P r efer en ces of Ald eh yd es 1-5 in
th e Solid Sta te. The formyl group of aldehydes 1-5
may, in principle, orient itself in either of the two possible
ways, i.e., the formyl oxygen oriented toward or away
from the ring heteroatom. The crystal structure database
analyses25 of o-halo-substituted aldehydes have shown
that the formyl hydrogens can participate in intramo-
lecular C-H‚‚‚X interaction such that the formyl oxygen
is oriented away from the halogen atom.26,27 Thus, in the
case of aldehydes 4 and 5, the conformational preferences
are a priori predictable. Indeed, such a preference due
to the intramolecular C-H‚‚‚X interaction was suggested
from ab initio calculations and confirmed unequivocally
from X-ray crystal structure analysis of one of the
aldehydes, i.e., 5.19 Similarly, our photochemical results
(28) Sum of the van der Waals radii of H and O is 2.7 Å. The dipole-
dipole and steric repulsions in the alternative conformation may also
be responsible for the observed conformational preference.
(29) Strictly speaking, the ring heteroatom as well as the methoxy
or chloro substituents in the dienols call for a reversal of the E and Z
designations that are applicable to the photoenols arising from simple
o-methyl benzaldehydes. However, for the sake of uniformity, we have
ignored the priority for the heteroatom and opted to designate all the
dienols in conformity with the designations used for photoenols of
benzaldehyde.
(30) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
J ohnson, B. G.; Robb, M. A.; Cheeseman, J . R.; Keith, T.; Petersson,
G. A.; Montgomery, J . A.; Raghavachari, K.; Al-Laham, M. A.;
Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B.; Cioslowski, J .;
Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala,
P. Y.; Chen, W.; Wong, M. W.; Andres, J . L.; Replogle, E. S.; Gomperts,
R.; Martin, R. L.; Fox, D. J .; Binkley, J . S.; Defrees, D. J .; Baker, J .;
Stewart, J . P.; Head-Gordon, M.; Gonzalez, C.; Pople, J . A. Gaussian
94, revision C.2; Gaussian, Inc.: Pittsburgh, PA, 1995.
(25) Koppenhoefer, B.; Bats, J . W. Acta Crystallogr. 1986, C42, 1612.
(26) For a recent database analysis of a C-H‚‚‚X hydrogen bond,
see: Thallapally, P. K.; Nangia, A. CrystEngComm 2001, 27. Brammer,
L.; Bruton, E. A.; Sherwood, P. Cryst. Growth Des. 2001, 1, 277.
(27) For our recent contribution on the influence of C-H‚‚‚X
interaction in the self-assembly of benzoic acids, see: Moorthy, J . N.;
Natarajan, R.; Mal, P.; Venugopalan, P. J . Am. Chem. Soc. 2002, 124,
6530.
3448 J . Org. Chem., Vol. 68, No. 9, 2003

Solid-State Photoenolization of Pyridine-3-carboxaldehydes
F IGURE 2. Absorption spectra of 1b (a), 2b (b), 1a -HBF 4 (c), and 1b-HBF 4 (d) before (solid line) and after (dotted line) exposure
to UV radiation.
TABLE 1. Resu lts of a b In itio a n d Sem iem p ir ica l
AM1 results in Table 1 reveals that the (E)-enols are
more stable than the cyclobutenols in all cases. The
calculations also show that the difference in the energies
is ca. 1-2 kcal/mol for all aldehydes 1, while it is ca. 7-17
kcal/mol in the case of aldehydes 2 and 3. This difference
in the enthalpies of reaction in going from aldehydes 1
to 2 and 3 simply reflects the stabilization of the (E)-
enols via intramolecular O-H‚‚‚O hydrogen bonding.
Ca lcu la tion s for Ald eh yd es 1-3
∆H (Eenol - CB)a (kcal/mol)
b
entry aldehyde ∆Eenols (kcal/mol)
AM1
ab initio
1
2
3
4
5
6
7
8
1a
1b
1c
2a
2b
2c
2d
3
-1.37
-0.71
-1.45
3.85
4.24
3.48
-01.82
-01.92
-01.04
-07.83
-11.31
-07.17
-13.26
-16.59
11.83
13.39
11.31
1.57
2.91
0.85
4.70
3.82
4.52
6.90
a
AM1-calculated heats of reaction for the conversion of (E)-enol
b
to the corresponding cyclobutenol. Difference in the energies of
For comparison, we also performed ab initio calcula-
tions for aldehydes 1 and 2. As can be seen from the
values in Table 1, the (E)-enols are predicted to be less
stable than the cyclobutenols. This is not surprising, as
the AM1 calculations depend on parameters chosen
judiciously from thermodynamic and spectroscopic data.
It turns out that the AM1 method does give qualitatively
correct results for the reaction under consideration.32
Nonetheless, it is gratifying to note that the ab initio
calculations do show that the energies of reaction in the
case of aldehydes 2 and 3 are far less positive than those
for aldehydes 1.
(Z)- and (E)-enols (EZ - EE), as obtained from ab initio calculations.
the stabilization through O-H‚‚‚O hydrogen bonding in
the (E)-enols of 2 and 3 and its absence in the (E)-enols
of 1 (vide infra). Thus, with the assumption that (Z)-enols
of 1 and 2 are energetically similar (since they lack
stabilization through intramolecular hydrogen bonding),
one may conclude readily that the (E)-enols of 2 are more
stable than those of 1 by ca. 5 kcal/mol, i.e., ∆EZ - E(2) -
∆EZ - E(1) ≈ 5 kcal/mol.
Solid -Sta te P h otobeh a vior a n d UV-Visible Ab-
sor p tion Sp ectr a of th e P h otoen ols. With the excep-
tion of aldehydes 1a and 2a , which are liquids, all other
aldehydes 1-5 exhibit a striking color change upon
exposure to UV-vis radiation. The aldehyde 1b changes
from colorless to a pale yellow color, while 1c turns
yellow-orange. All aldehydes 2 and 3 turn bright orange-
red, while 4 and 5 exhibit a brick-red color. In all cases,
the attendant color changes are persistent for several
hours. Particularly noteworthy is the change in the
absorption properties on varying the substitutents. Fig-
ure 2 shows the changes in UV-vis absorption, on
E n t h a lp ies of R ea ct ion for (E)-E n ol t o Cyclo-
bu ten ol Con ver sion . To assess the relative stabilities
of the cyclobutenols and the (E)-enols, we computed the
enthalpies of reaction (eq 4) for aldehydes 1-3 using the
semiempirical AM1 method (QCMP 137, MOPAC6/PC),31
and the results are included in Table 1. A perusal of the
(31) Dewar, M. J . S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J . J . P.
J . Am. Chem. Soc. 1985, 107, 3902.
(32) Coll, G.; Costa, A.; Deya, P. M.; Flexas, F.; Rotger, C.; Saa, J .
M. J . Org. Chem. 1992, 57, 6222.
J . Org. Chem, Vol. 68, No. 9, 2003 3449

Mal et al.
SCHEME 3
exposure to UV radiation, of aldehydes 1b and 2b
(spectra a and b, respectively) as representative cases.
The observed color changes are readily attributed to (E)-
enols12,33,34 formed by hydrogen abstraction from the
o-methyl group by the formyl oxygen. The intermediate
(E)-enols responsible for the observed color revert to the
starting aldehydes on heating (ca. 60-70 °C) or on
standing at room temperature for several hours (ca. 1-2
days).35
The advantage of the heteroatom in the ring is il-
lustrated by the fact that the liquid aldehyde 1a could
be converted into a crystalline salt (1a -HBF 4) by treat-
ment with fluoroboric acid. The crystalline 1a -HBF 4 and
1b-HBF 4 also exhibited remarkable photochromism in
that the salts turned brick-red upon exposure to UV
radiation (spectra c and d, respectively, in Figure 2).
While the color persisted for several minutes under N2,
the reversion was expedited by absorption of trace
amounts of moisture by the hygroscopic salts. It is worth
noting that the salt formation brings about a dramatic
bathochromic shift in the absorption (compare spectra a
and d for the photoenols from 1b and 1b-HBF 4, respec-
tively).
Discu ssion
The presence of a nitrogen atom in pyridine-3-carbox-
aldehydes 1 raises the question of conformational prefer-
ence of the formyl oxygen in the solid state. The photoir-
radiation of 1 is expected to lead regiospecifically to two
of the four possible photoenols (Scheme 3), as the reac-
tions in the crystalline medium proceed with a minimum
displacement of atomic positions;36,37 of course, the con-
formation in which the aldehydes crystallize will deter-
mine which of the two regioisomeric photoenols will be
formed. The X-ray crystal structure analysis of one of the
aldehydes, i.e., 1c (Figure 1), reveals that the carbonyl
group orients itself toward the methyl group at position
4. We assume that similar considerations apply to 1b,
1a -HBF 4, and 1b-HBF 4 as well. In the case of aldehydes
2 and 3, the orientation of the carbonyl group toward the
methyl group is preferred due to an intramolecular C-H‚
‚‚O hydrogen bond involving the methoxy oxygen and the
formyl hydrogen. As mentioned earlier, a similar prefer-
ence in o-anisaldehydes was suggested from our photo-
chemical results on o-anisaldehydes.12 In the present
instance, we have confirmed such a preference from X-ray
crystal structure analysis of one of the aldehydes, 2c
(Figure 1). Insofar as aldehydes 4 and 5 are concerned,
a scenario analogous to that for aldehydes 2 and 3 has
been shown to operate.19 The X-ray analyses of o-halo
aromatic aldehydes have shown that the C-H‚‚‚X inter-
action between the halogen and formyl hydrogen leads
to the carbonyl group being directed away from the
halogen atom.25 X-ray crystal structure analysis of 5 has
confirmed this preference.19
We have subjected aldehydes 1b and 1c, as represen-
tative cases, to photolysis in a Luzchem photoreactor
1
fitted with 350 nm lamps for 10-15 h. The H NMR (400
MHz) analyses of the solid irradiated mixtures indicated
no evidence for the formation of cyclobutenols. The TLC
analysis indicated a complex pattern, in addition to a
highly polar material that eluted only in a highly polar
solvent. An intractable polymeric material was obtained
in both cases. A thorough analysis of the photoproducts
has been carried out for aldehyde 5;19 in a preparative
photolysis, the cyclobutenol was isolated in 10% yield,
and other bimolecular and oxidation products were
obtained in 42% yield, with the remainder being an
intractable polymeric material (eq 5). The solid-state
reactions, in general, proceed with minimum displace-
ment of atomic positions.36 Strict control of the lattice
on the reaction coordinate is expected to lead specifically
to one of several photoproducts. The bimolecular product
in eq 5 suggests that the formation of persistent photo-
enols leads to creation of defects/disruptions in the crystal
lattice. Presumably, the disruptions arising from the
buildup of (E)-enols on continued irradiation increase the
proximity between the neighboring molecules in the
crystal lattice to permit bi- and/or polymolecular reac-
tions that are typical of olefins to take place. The
formation of intractable polymeric material should be
explicable by these considerations.
With this knowledge on the orientation of the formyl
oxygen in the solid state of aldehydes 1-5, we shall now
consider the observed results of photoexcitation. The
primary event of photochemical excitation of aldehydes
1-5 is the methyl hydrogen abstraction by the n,π*-
triplet excited carbonyl group. From their extensive
studies on photochemical γ-hydrogen abstraction of ke-
tones in the solid state, Scheffer and co-workers have set
forth certain geometrical parameters, viz., d, ∆o, τo and
(33) Yang, N. C.; Rivas, C. J . Am. Chem. Soc. 1961, 83, 2213.
(34) Zwicker, E. F.; Grossweiner, L. I.; Yang, N. C. J . Am. Chem.
Soc. 1963, 85, 2671.
(35) We have carried out the photoinduced-coloration and bleaching
cycles 5-10 times and observed no significant decomposition of the
aldehydes, as monitored by 1H NMR spectroscopy. The long lifetimes
of the colored photoenols precluded fatigue resistance to be established
for
a larger number of cycles. Given the fact that the continued
irradiation leads to an intractable polymeric material, the aldehdyes
are unlikely to sustain a large number of coloration-bleaching cycles.
(36) Cohen, M. D. Angew. Chem., Int. Ed. Engl. 1975, 14, 386.
(37) Ramamurthy, V.; Weiss, R. G.; Hammond, G. S. Adv. Photo-
chem. 1993, 18, 67.
3450 J . Org. Chem., Vol. 68, No. 9, 2003

Solid-State Photoenolization of Pyridine-3-carboxaldehydes
stand this shift in reactivity of the intermediate (E)-enols
in going from mesitaldehydes to their heteroatom ana-
logues, we performed semiempirical AM1 calculations to
determine the heats of conversion for thermal cyclization
of (E)-enols to benzocyclobutenols.32 A comparison of the
AM1 results for mesitaldehydes and the heteroaromatic
pyridine-3-carboxaldehydes 1 reveals the effect of intro-
ducing a heteroatom into the ring (Scheme 4); the (E)-
enols of pyridine-3-carboxaldehydes 1 are found to be
more stable than those of the mesitaldehydes relative to
the corresponding cyclobutenols. Whether or not these
gas-phase results apply to the condensed-phase results
described herein is debatable. The fact that the (E)-enols
are readily observed in 1 and not in mesitaldehydes
suggests that the energy differences similar to those
predicted from theoretical calculations must apply in the
solid state also. What is it that causes the (E)-enols of
pyridine carboxaldehydes 1 to be comparatively more
stable than those of the mesitaldehydes relative to their
corresponding cyclobutenols? Quite conceivably, the het-
eroatom contributes to additional stabilization of the (E)-
enols through resonance delocalization as shown in eq
6. Such a resonance contribution suggests that any factor
that stabilizes the excess charge on nitrogen may be
expected not only to enhance the stability of the inter-
mediate dienol but also to shift its absorption bathochro-
mically. The fact that such an expectation is nicely met
is elegantly demonstrated by the photobehavior of HBF4
salts of 1a and 1b. While 1b exhibits a pale yellow color,
its tetrafluoroborate salt turns a brick-red color with a
highly red-shifted absorption, thereby attesting to the
fact that the resonance delocalization of the kind shown
in eqs 6 and 7 contributes to the stability of the photo-
enols relative to their corresponding cyclobutenols.
F IGURE 3. Scheffer’s geometrical parameters that describe
the feasibility of γ-hydrogen abstraction.
θ, which quantitatively describe the feasibility of H-
abstraction (Figure 3).38 The abstraction is said to be at
its best when the distance parameter d e 2.7 Å (sum of
van der Waals radii of H and O) and the angular
parameters θ, ∆o, and τo are 180, 90-120, and 0°, respec-
tively; experimentally, the latter are seldom realized. The
most crucial distance parameter d is less than 2.7 Å for
both aldehydes 1c and 2c (Figure 3). Further, the angular
parameters for both 1c and 2c compare well with (and,
in fact, are better than) the experimentally observed
averages (d ) 2.63 ( 0.06 Å, θ ) 114 ( 1°, ∆o ) 81 ( 4°,
and τo ) 58 ( 3°) determined for a broad set of phenyl
alkyl ketones that undergo γ-hydrogen abstraction.38
Thus, γ-hydrogen abstraction by the triplet excited
carbonyl can occur in both cases in a topochemical fashion
to form triplet biradicals that collapse to the colored
photoenols (Scheme 1).
Theoretical studies have shown that the triplet excited
biradical formed after hydrogen abstraction is twisted39
and hence may form either the (Z)- or the (E)-enol. It is
now generally accepted that the (Z)-enols are very short-
lived and easily revert to the precursor aldehydes.40 Thus,
the possibility of (Z)-enols being responsible for the
observed color change in all of the aldehydes 1-5 may
be ruled out. On the other hand, the (E)-enols would be
longer-lived, as the reverse hydrogen transfer would be
difficult. Ab initio calculations suggest that the (E)-enols
of 2 and 3 are more stable than the (Z)-isomers by ca.
3-5 kcal/mol, while the opposite is revealed for aldehydes
1.41 Clearly, intramolecular O-H‚‚‚O hydrogen bonding
plays a significant role in stabilizing the (E)-enols. The
color due to (E)-enols is quite persistent for all of the
crystalline aldehydes 1-5, and this permitted their
characterization through UV-vis absorption spectros-
copy. It is worth reiterating that aldehyde 1b turns pale
yellow and 2b bright red.
A striking contrast between the pyridine-3-carboxal-
dehydes and the mesitaldehydes11 is that the (E)-enols
of the latter convert to the benzocyclobutenols, while the
pyridine analogues live sufficiently long to permit reac-
tions typical of olefins resulting in highly intractable
polymeric material on continued irradiation. To under-
The results given in Table 1 show that the (E)-enols
are more stable than their corresponding benzocy-
clobutenols. The energy difference is as much as 7-17
kcal/mol for the (E)-enols of aldehydes 2 and 3, which
underscores the importance of O-H‚‚‚O hydrogen bond-
ing in addition to the electronic effect of nitrogen in the
ring discussed above in preventing cyclization. An analo-
gous scenario involving C-H‚‚‚X interactions must pre-
vail in the case of the (E)-enols of aldehydes 4 and 5;
otherwise, the photochromism would not be observed.
All of the crystalline aldehydes 1-5 exhibit photo-
chromism and yield intractable material on continued
irradiation. In contrast, 2-methoxy-3-acetylpyridines are
reported to undergo photocyclization to the cyclobutenols
(38) Ihmels, H.; Scheffer, J . R. Tetrahedron 1999, 55, 885.
(39) Wagner, P. J .; Sobczak, M.; Park, B.-S. J . Am. Chem. Soc. 1998,
120, 2488.
(40) Haag, R.; Wirz, J .; Wagner, P. J . Helv. Chim. Acta 1977, 60,
2595.
(41) Although the (Z)-enols of aldehydes 1 are more stable than those
of 2 and 3, their existence is limited by a competitive and facile 1,5-
reverse hydrogen transfer that regenerates the precursor aldehydes.
This process is difficult for (E)-enols and thus increases their lifetime
despite the higher energy. Therefore, the observed color on exposure
of aldehydes 1 to UV irradiation should be attributed to (E)-enols.
J . Org. Chem, Vol. 68, No. 9, 2003 3451

Mal et al.
SCHEME 4
introduction of a heteroatom into mesitaldehydes as in
aldehydes 1 raises the question of conformational prefer-
ence in the solid state. The preferred conformations have
been unequivocally established from X-ray crystal struc-
ture analyses of two of the aldehydes; it is shown that
intramolecular hydrogen bonding could be utilized to
achieve conformational control. In contrast to mesital-
dehydes, which undergo efficient photocyclization to
benzocyclobutenols in the solid state, heteroatom ana-
logues 1b and 1c exhibit a perceptible color change (to
pale yellow for 1b and yellow-orange for 1c) upon UV
irradiation; the color attributed to (E)-enols is persistent
for several hours. Continued irradiation leads to a highly
polymeric material. The AM1 calculations, which have
been reliably applied to the thermal cyclization of xy-
lylenols to benzocyclobutenols, reveal that the (E)-enols
of 1 are more stable than those of the mesitaldehydes
relative to their corresponding benzocyclobutenols. The
stabilization is interpreted as arising from the possibility
of engaging the heteroatom in resonance delocalization.
That the contribution from such a role of the nitrogen is
so pronounced is elegantly demonstrated by forming the
fluoroborate salts; 1a -HBF 4 and 1b-HBF 4 readily exhibit
highly red-shifted absorption upon exposure to UV radia-
tion as a result of stabilization of the photoenols. Such a
remarkable stabilization via electronic control of the
photoenols is unprecedented. All the 2-methoxy- and
2-chloro-substituted aldehydes 2-5 exhibit photo-
chromism. Ab initio calculations show that the methoxy
group in aldehydes 2 and 3 stabilizes the (E)-enols via
O-H‚‚‚O hydrogen bonding as compared to those of 1 by
5-6 kcal/mol relative to their corresponding benzocy-
clobutenols. Thus, the presence of methoxy and halo
groups at position 2 serves not only to direct the formyl
oxygen toward the methyl group for H-abstraction but
also to stabilize the (E)-enols.
(eq 8).42 The photoenols in this case would be analogous
to the ones formed from aldehydes 2 and 3 and thus could
be expected to be stabilized by intramolecular hydrogen
bonding. The observed efficient cyclization suggests that
severe steric encumbrance between the methyl and the
hydrogens of the dienolic moiety should be sufficiently
high to cause cyclization to thermodynamically more
stable cyclobutenols. This appears to be one of the
reasons as to why photochromism is observed more often
in aldehydes than in ketones in the solid state;43 invari-
ably, cyclobutenols are the products of photolysis of
ketones.
Exp er im en ta l Section
The phenomenon of photochromism via γ-hydrogen
abstraction in o-alkyl aromatic carbonyl compounds was
extensively explored by Ullman and co-workers three
decades ago with the objective of ultimately developing
photochromic materials.21,22 Employing an approach that
involved stabilization of photoenols through intramolecu-
lar hydrogen bonding, they demonstrated photochromism
of certain chromone derivatives in benzene solutions at
25 °C. However, a systematic study of possible photo-
chromic materials based on γ-hydrogen abstraction has
since been lacking, except for three reports on fortuitous
observation of photochromism in the solid state. Our
recent11,12,19 and present investigations demonstrate how
hydrogen bonding and electronic stabilization offered by
the nitrogen atom may be exploited to observe photo-
chromism more easily in o-alkyl aromatic aldehydes than
with ketones.
Solid -Sta te P h otolysis a n d UV-Vis Absor p tion Sp ec-
tr a . The UV-vis absorption spectra for all the aldehydes were
recorded by forming a fine layer in a 1.00 mm quartz cuvette
by slow evaporation of the solution of aldehydes in an ap-
propriate solvent. The spectra were recorded before and after
a brief exposure (ca. 1 min) to UV-vis radiation from a high-
pressure mercury lamp.
For examining the photochemistry in the solid state, the
gently powdered crystals of 1b and 1c were dispersed in a test
tube and purged thoroughly with N2 gas. The samples were
irradiated in a photoreactor fitted with 350 nm lamps. The
samples were shaken from time to time to ensure uniform
exposure to the radiation. After 10-15 h, the samples were
analyzed by 1H NMR spectroscopy (400 MHz), which revealed
no evidence for cyclobutenols and other readily discernible
photoproducts.11 In a preparative photolysis employing 100 mg
of the compound, only polymeric material could be isolated
with no indication whatsoever of the formation of cyclobutenols.
The TLC analysis indicated a complex pattern.
X-r a y Cr ysta llogr a p h ic Deta ils of Ald eh yd es 1c a n d
2c. The protocol adopted for the X-ray crystal structure
determination of aldehydes 1c and 2c is described below. The
individual parameters and refinement conditions pertaining
to each compound are recorded in the table entitled Crystal
Data and Structure Refinement (Supporting Information).
Crystals suitable for single-crystal diffraction studies of both
compounds were grown from ethyl acetate-hexane mixtures
by the slow evaporation method. A good single crystal was
Su m m a r y a n d Con clu sion s
We have investigated the solid-state photobehavior of
a broad set of pyridine-3-carboxaldehydes 1-5. The
(42) Sakamoto, M.; Fujihira, M.; Takahashi, M.; Enomoto, K.;
Nishimiya, N.; Fujita, T.; Watanabe, S. J . Chem. Soc., Chem. Com-
mmun. 1993, 1023.
(43) To the best of our knowledge, only one example of a ketone
exhibiting solid-state photochromism is known: see ref 9.
3452 J . Org. Chem., Vol. 68, No. 9, 2003

Solid-State Photoenolization of Pyridine-3-carboxaldehydes
mounted along its largest dimension and used for data
collection. The intensity data were collected on a single-crystal
diffractometer equipped with a molybdenum-sealed tube (λ )
0.71073 Å) and highly oriented graphite monochromator. The
lattice parameters and standard deviations were obtained by
a least-squares fit to 40 reflections (10.23° < 2θ < 29.98°). Data
were collected by 2θ-θ scan mode with a variable scan speed
ranging from 2.0°/min to a maximum of 60.0°/min. Three
reflections were used to monitor the stability and orientation
of the crystal and were remeasured after every 97 reflections.
Their intensities did not change significantly during the entire
data collection period. All other relevant information about the
data collection is presented in the tables for each of the two
compounds.
The structure was solved in both cases by direct methods
using the SHELX-9744 package and also refined using the same
program. All the non-hydrogen atoms were refined anisotro-
pically. The hydrogen atoms were included in the ideal
positions with fixed isotropic U values and were riding with
their respective non-hydrogen atoms. A weighting scheme of
the form w ) 1/[σ2(Fo2) + (aP)2 + bP] was used. The difference
Fourier map, after the refinement, was essentially featureless
in all cases. Final atomic coordinates, bond lengths, bond
angles, anisotropic displacement parameters, hydrogen atom
coordinates, and torsion angles have been recorded in the
tables for both aldehydes.
Sem iem p ir ica l AM1 Ca lcu la tion s. All calculations were
run using the MOPAC 6/PC version 6.12. The ground-state
energies were computed using the key words “AM1” and
“Precise”. When Herbert’s test was not satisfied, the initial
geometries were changed and the energies recomputed until
Peter’s and Herbert’s tests were satisfied.
Ab In itio Ca lcu la tion s. All ab initio calculations were
carried out at the HF/6-31G** level using the GAUSSIAN9430
suite of programs. The geometries were optimized without any
symmetry restrictions.
Ack n ow led gm en t. We thank the Department of
Science and Technology (DST), India, for financial
support. P.M. is grateful to Council of Scientific and
Industrial Research (CSIR), India, for a senior research
fellowship. We thank Dr. D. Chakraborty for some of
the preliminary ab initio calculations. We thank one of
the referees for critical comments and highly pertinent
suggestions.
Su p p or tin g In for m a tion Ava ila ble: Syntheses and char-
acterization data for all aldehydes 1-4, 1H and 13C NMR
spectra of 1a -HBF 4 and 1b-HBF 4, crystallographic data for
1c and 2c, summary output files of AM1 calculations and ab
initio calculations for 2a -d as representative examples, and
UV-vis absorption spectra for aldehydes 1c, 2c, 2d , 3, and 4
before and after irradiation. This material is available free of
charge via the Internet at http://pubs.acs.org.
(44) Sheldrick, G. M. SHELX-97, Program for the solution and
refinement of crystal structures; University of Go¨ttingen: Go¨ttingen,
Germany, 1997.
J O026621N
J . Org. Chem, Vol. 68, No. 9, 2003 3453