Synthesis, structure, and two polymorphs of 4-((1,3-Dioxoisoindolin-2-yl) methyl)-1-methoxypyridinium tetrafluoroborate

Article abstract of DOI:10.1007/s10870-010-9835-2

4-((1,3-Dioxoisoindolin-2-yl)methyl)-1-methoxypyridinium tetrafluoroborate, C₁₅H₁₃BF₄N₂O₃, 1, was obtained by alkylation of the corresponding N-oxide and has been characterized by ¹H and

Full text of DOI:10.1007/s10870-010-9835-2

J Chem Crystallogr (2011) 41:48–52
DOI 10.1007/s10870-010-9835-2
ORIGINAL PAPER
Synthesis, Structure, and Two Polymorphs of 4-((1,3-
Dioxoisoindolin-2-yl)methyl)-1-methoxypyridinium
tetrafluoroborate
Edward J. Valente
James P. McVaugh
•
Emily H. Stewart
Wolfgang H. Kramer
•
•
Received: 28 April 2009 / Accepted: 19 June 2010 / Published online: 3 July 2010
Ó Springer Science+Business Media, LLC 2010
Abstract 4-((1,3-Dioxoisoindolin-2-yl)methyl)-1-meth-
oxypyridinium tetrafluoroborate, C H BF N O , 1, was
obtained by alkylation of the corresponding N-oxide and
homolytic CH-activation chemistry competes with photo-
induced electron transfer in the presence of electron donor
groups. As part of our study of nitrogen onium salts as
irreversible photooxidants we linked a N-methoxypyridi-
nium moiety with a methylene spacer to phthalimide. Het-
eroaromatic nitrogen onium salts contain a fragmentable
nitrogen–oxygen bond that can be cleaved homolytically by
irradiation with the appropriate wavelength of light [9],
yielding methanol and the unsubstituted heterocycle in
steady-state photolysis experiments. Time-resolved studies
with N-methoxy quinolinium, isoquinolinium, and phe-
nanthridinium revealed the formation of a heteroaromatic
radical cation and a methoxy radical as transient species
[10, 11].
1
5
13
4 2 3
1
13
has been characterized by H and C NMR, IR, UV
spectroscopy and by X-ray crystallography. The crystal
undergoes a reversible phase transition between 173 and
2
93 K. At room temperature, crystals are orthorhombic,
˚
space group Pna21 with a = 7.2487(3) A, b = 17.8359
3
˚ ˚ ˚
8) A, c = 12.4077(6) A, V = 1604.16(12) A , and Z = 4.
At 173 K, cations adopt four conformations in monoclinic
(
˚
space group Cc with a = 24.7076(29) A, b = 14.4145(9)
˚
˚
A, c = 21.8765(25) A, b = 126.249(17)°, V = 6283.3(7)
3
˚
A , and Z = 16. The compound is photostable in the
crystal and does not undergo homolytic N–O bond cleav-
age as observed in solution.
We herein report the synthesis, spectroscopic properties
and crystal structure of the title compound 1, C H BF
4
1
5
13
Keywords Phthalimide Á Crystal structure Á
Phase transition Á N-methoxypyridinium Á N-oxide Á
Photochemistry
N O , which undergoes a phase transition between 293 and
2 3
173 K in the crystal.
Experimental
Introduction
1
13
H NMR and C NMR spectra were obtained at 400 MHz
The photochemistry of phthalimides has been extensively
studied [1–8]. Due to its high oxidizing power in the first
excited singlet and first and second excited triplet states,
on a JEOL Eclipse FT-NMR spectrometer with d -DMSO
6
as solvent at room temperature. Selected NMR data is
given in Table 2. Chemical shifts were reported in d (ppm),
relative to TMS, and J values in Hz. IR spectra were
recorded on a Perkin Elmer Spectrum 100 FT-IR Spec-
trometer. UV spectra were recorded on a Shimadzu
UV-2450 UV–Visible Spectrophotometer. Phthalic anhy-
dride, 3-(aminomethyl)pyridine and trimethyloxonium tet-
rafluoroborate were purchased from Aldrich and hydrogen
peroxide (35 wt%) solution in water was purchased from
ACROS and used as received. Solvents were purchased
from typical sources and used directly.
E. H. Stewart Á J. P. McVaugh Á W. H. Kramer (&)
Department of Chemistry and Biochemistry, Millsaps College,
1701 N. State St., Jackson, MS 39210, USA
e-mail: kramewh@millsaps.edu
E. J. Valente
Department of Chemistry, University of Portland,
5000 N. Willamette Blvd., Portland, OR 97203, USA
e-mail: valentee@up.edu
1
23

J Chem Crystallogr (2011) 41:48–52
49
2
-Pyridin-3-ylmethyl-isoindole-1,3-dione, 2
123.9 (d, 2 C, CHpht), 129.4 (d, 1 C, CHpyr), 132.5 (s, 2 C,
Cqpht), 135.1 (d, 2 C, CHpht), 139.8 (d, 1 C, CHpyr), 140.1
(s, 1 C, Cqpyr), 140.4 (d, 1 C, CHpyr), 144.4 (d, 1 C, CHpyr),
168.2 (s, 2 C, C=O). UV/Vis maxima: 264 nm (3780),
293 nm (1320). IR 3107.25, 1772.89, 1710.59, 1496.28,
1461.41, 1395.03, 1353.57, 1048.40 (br), 988.13, 951.85,
917.41, 749.55, 722.47, 710.01.
To 34.0 g (229 mmol) phthalic anhydride, 24.8 g
229 mmol) 3-(aminomethyl)pyridine was added and sus-
(
pended in 90 mL DMF; the mixture was heated to 150 °C
for 3 h. The product precipitated on slow addition of water.
The colorless precipitate was recrystallized from DMF/
1
water and air dried. Yield: 48.1 g (202 mmol, 88%). H
NMR: 4.81 (s, 2 H, CH ), 7.35 (dd, J = 4.8, 8.0 Hz, 1 H,
2
X-Ray Crystallography
Hpyr), 7.71 (dt, J = 2.0, 8.0 Hz, 1 H, Hpyr), 7.83 (dd,
J = 2.4, 5.6 Hz, 2 H, Hpht), 7.87 (dd, J = 2.4, 5.6 Hz, 2 H,
Hpht), 8.48 (dd, J = 1.2, 4.8 Hz, 1 H, NCHpyr), 8.58 (d,
Single crystals suitable for X-ray diffraction were obtained
by recrystallization of 1 from acetone. Data were obtained
on an Oxford Diffraction Gemini diffractometer with
1
3
J = 2.0 Hz, 1H, NCHpyr). C NMR: 39.1 (t, 1 C, CH2),
23.8 (d, 2 C, CHpht), 124.2 (d, 1 C, CHpyr), 132.1 (s, 2 C,
Cqpht), 132.9 (s, 1 C, Cqpyr), 135.1 (d, 2 C, CHpht), 136.0
d, 1 C, CHpyr), 149.3 (d, 1 C, NCHpyr), 149.5 (d, 1 C,
NCHpyr), 168.2 (s, 2 C, C=O). UV/Vis maxima: 260 nm
2730), 293 nm (1650). IR 3025.56, 1763.44, 1702.56,
˚
1
MoKa radiation (k = 0.71073 A) and a 1.0 mm collima-
tor. The room temperature data set [293(2) K] was col-
lected first, and then the same specimen was cooled to
173(2) K for collection of the second data set. The crystal
does not undergo any visual change on cooling, or on
warming back to room temperature. The structures were
solved with SHELXS-97 and refined with SHELXL-97
(
(
1
7
428.64, 1395.64, 1310.41, 1081.51, 1072.03, 933.94,
22.54.
[
12]. For each structure, the non-H atoms were found in
2
-(1-Oxy-pyridin-3-ylmethyl)-isoindole-1,3-dione, 3
initial E-maps. After refining positions and anisotropic
displacement parameters, H-atoms were observed in the
difference maps, but placed in calculated positions, riding
To 8.00 g (33.5 mmol) 2 dissolved in 70 mL of glacial
acetic acid, 7 mL of hydrogen peroxide (35 wt%) was
added and the solution was kept at 80 °C for 24 h. The
product precipitated on slow addition of water. The col-
orless precipitate was recrystallized from DMF/water and
on their attached atoms, with U ’s equivalent to 120% of
iso
the U ’s of the attached atoms. Relevant details of the
eq
crystallographic experiments are given in Table 1. No
restraints were imposed except those to fix the origins in
1
air dried. Yield: 7.80 g (30.6 mmol, 92%). H NMR: 4.76
(
s, 2 H, CH ), 7.27 (d, J = 8.4 Hz, 1 H, Hpyr), 7.36 (dd,
2
J = 6.4, 8.4 Hz, 1 H, Hpyr), 7.85 (dd, J = 2.8, 5.6 Hz, 2 H,
Hpht), 7.90 (dd, J = 2.8, 5.6 Hz, 2 H, Hpht), 8.13 (d,
Table 1 Crystallographic data for 4-((1,3-dioxoisoindolin-2-yl)
methyl)-1-methoxypyridinium tetrafluoroborate 1
1
3
J = 6.4 Hz, 1 H, Hpyr), 8.26 (s, 1 H, Hpyr). C NMR: 38.5
t, 1 C, CH ), 123.8 (d, 2 C, CHpht), 124.9 (d, 1 C, CHpyr),
CCDC deposit number 724898
724899
173(2)
(
Temperature(K)
293(2)
Pna21
2
1
27.0 (d, 1 C, CHpyr), 132.3 (s, 2 C, Cqpht), 136.1 (d, 2 C,
CHpht), 136.8 (s, 1 C, Cqpyr), 138.3 (d, 1 C, CHpyr), 138.4
d, 1 C, CHpyr), 168.2 (s, 2 C, C=O). UV/Vis maximum:
Space group
Cc
a ( A˚ )
7.2487(3)
17.8359(8)
12.4077(6)
90
24.7076(29)
14.4145(9)
21.8765(25)
126.249(17)
6283.3(7)
16
(
˚
b (A)
2
1
77 nm (12970). IR 3025.04, 1771.29, 1698.37, 1606.75,
407.11, 1361.39, 1269.40, 1154.15, 939.53, 726.64.
˚
c (A)
b (degrees)
3
V (A )
˚
1604.16(12)
4
4
-((1,3-Dioxoisoindolin-2-yl)methyl)-1-
Z
methoxypyridinium tetrafluoroborate, 1
F(000)
3
Size (mm )
728
2912
0.86 9 0.18 9 0.10 0.86 9 0.18 9 0.10
To 0.80 g (3.15 mmol) 3, 0.56 g (3.62 mmol) trim-
ethyloxonium tetrafluoroborate (95%) was added and the
mixture was stirred for 24 h in 20 mL of DCM. The
product precipitated, was filtered and washed with cold
Reflections/Rint
Completeness
Data/restraints
Parameters
9976 (0.0256)
98.9
24360 (0.0502)
98.3
3918/1
226
13983/2
902
1
DCM, and air dried. Yield: 0.87 g (2.44 mmol, 77%). H
wR
2
(all data)
0.167
0.194
NMR: 4.42 (s, 3 H, OCH ), 5.05 (s, 2 H, CH ), 7.89 (dd,
3
2
R
1
(I [ 2r
I
)
0.067
0.086
J = 2.8, 5.6 Hz, 2 H, Hpht), 7.94 (dd, J = 2.8, 5.6 Hz, 2 H,
Hpht), 8.23 (dd, J = 6.8, 8.2 H, 1 H, Hpyr), 8.65 (d,
J = 8.2 Hz, 1 H, Hpyr), 9.40 (m, 1 H, Hpyr), 9.55 (m, 1 H,
Goodness-of-fit
Flack parameter
1.01
1.02
-0.3(17)
?0.32, -0.25
-1.0(11)
?0.45, -0.33
3
˚
Dqmax,min (e/A )
1
3
Hpyr). C NMR: 38.5 (t, 1 C, CH ), 70.3 (q, 1 C, CH ),
2
3
123

5
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J Chem Crystallogr (2011) 41:48–52
1
Table 2 H-NMR shifts of selected hydrogens in 1–3
these non-centrosymmetric space groups; a small extinc-
tion factor [0.00043(16)] was indicated for the low tem-
perature determination.
a
e
Pht
N
c
d
Results and Discussion
b
Synthesis of Title Compound
Proton position
2 (pyridine)
3 (N-oxide)
1 (N–OMe)
The title compound was prepared in three steps from
a
b
c
d
e
4.81
7.35
7.71
8.48
8.58
4.76
7.27
7.36
8.13
8.26
5.05
8.23
8.65
9.40
9.55
3
-(methylamino)pyridine (see Fig. 1). Condensation with
phthalic anhydride yielded 2-pyridin-3-ylmethyl-isoindole-
1
2
,3-dione, 2. Oxidation of the pyridine nitrogen of 2 gave
-(1-oxy-pyridin-3-ylmethyl)-isoindole-1,3-dione, 3. The
title compound 1 4-((1,3-Dioxoisoindolin-2-yl)methyl)-1-
methoxypyridinium tetrafluoroborate was obtained by alkyl-
ation of 3 with trimethyloxonium tetrafluoroborate.
Spectral Data
1
The H-NMR shift of the methylene spacer between
phthalimide and pyridine can serve as a good indicator for
the electron density of the pyridine ring (Table 2). Oxi-
dation of the pyridine nitrogen to the N-oxide increases the
electron density of the ring [13] as consistent with a
1
decrease in the chemical shift in the H-NMR spectrum
(
4.76 vs. 4.81 ppm). Alkylation of the N-oxide oxygen
localizes the positive charge on the nitrogen and the pyri-
dine becomes electron deficient, as evidenced by the
increase in the proton chemical shift (5.05 ppm). The
proton NMR signals of the pyridine hydrogens exhibit a
similar behavior.
Fig. 2 Ultraviolet–visible absorbance spectra of 1, 2, and 3
The absorption spectra of the compounds show a clear
separation of the chromophors (phthalimide and pyridine/
pyridinium) for the unsubstituted pyridine 2 as well as
the N-methoxy compound 1 (Fig. 2). The absorption of the
pyridine N-oxide in 3 is much stronger and buries the
phthalimide absorption near 280 nm.
Photochemistry of the Title Compound
N-methoxyheteroaromatic compounds react upon irradia-
tion in solution with a homolytic N–O bond cleavage [9].
The transient species (heteroaromatic radical cation and
Fig. 1 (a) Phthalic anhydride,
O
O
DMF, 150 °C, (b) H
acetic acid, 80 °C,
2
O
2
, glacial
O
N
NH2
N
N
a
b
N
N
(
3 4
c) Me OBF , DCM
O
O
2
3
c
O
+
O
N
N
-
O
BF
4
1
1
23

J Chem Crystallogr (2011) 41:48–52
51
Fig. 3 Unit cells of the
monoclinic phase (top, 173 K)
˚
viewed down b (14.4 A);
orthorhombic phase (bottom,
2
˚
93 K) viewed down a (7.2 A)
3
Molecular (ion pair) volume decreases from 401.0 A in
˚
methoxy radical) decay rapidly producing methanol and
the N-unsubstituted heterocycle. The quantum yield of ion
formation is about 0.6 (measured for N-methoxyquinolin-
ium BF , N-methoxyisoquinolinium BF , N-methoxyphe-
3
the orthorhombic cell to 392.7 A in the monoclinic cell or
˚
2.1%, consistent with the lower vibrational motions. Cat-
ions and anions remain in approximately the same relative
lattice positions. The unique monoclinic axis (b) coincides
with the orthorhombic a axis and its dimension is roughly
doubled. The remaining monoclinic axes with similar
4
4
nathridinium BF ) [Kramer WH, Gould IR, unpublished
4
results]. The major deactivation pathway proposed is the
reformation of the N–O bond in the geminate ion pair.
Irradiation of the title compound 1 in the crystal
˚
lengths (a, c: 24.7, 21.9 A, respectively) correspond to the
(
kex = 254 nm) did not lead to changes in the structure; the
[011] and [01-1] directions of the orthorhombic cell. The
single conformation of the cations in the monoclinic cell is
resolved into four distinct cation conformations in the
orthorhombic lattice (Fig. 3).
compound is photostable. The restricted movement in the
crystal might lead to a direct reformation of the N–O bond
after photochemical activation and bond fragmentation.
N-methoxy groups are oriented well out of the pyridine
ring planes (C3 –N–O–CH torsion 111.0°), and disposed
Crystal Structures
ar
3
‘
‘exo’’ to the phthalimide ring in the orthorhombic cell.
˚
The pyridinium nitrogen (cation) is 3.940(3) A from the
Crystals occur as colorless rods. At room temperature
(
293 K), they are in the orthorhombic system and polar
tetrafluoroborate boron (anion). The symmetry is reduced
on cooling such that each cation/anion pair becomes
resolved into four nearly equivalent conformers. Three of
these conformers have ‘‘exo’’ N-methoxy groups (tor-
sions of 111.2(2)°, 105.0(2)°, 98.4(2)°), a fourth is in the
space group Pna2 (#33) with Z = 4. On cooling to 173 K,
1
the crystals become monoclinic, space group Cc (#9) with
Z = 16. The crystals show no obvious, visual changes on
cooling or warming between these two temperatures.
123

5
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J Chem Crystallogr (2011) 41:48–52
Centre (CCDC 724898, 724899, respectively). Copies of
the data can be obtained, free of charge, on application to
the Director, CCDC, 12 Union Road, Cambridge CB2 1EZ,
United Kingdom (fax: 44-1223-336033; e-mail: deposit@
ccdc.cam.ac.uk).
Acknowledgments This project was financially supported by the
MS-INBRE NIH NCRR award P20 RR016476 and Millsaps College.
EJV acknowledges the support of NSF grant MRI 0618148 for
crystallographic resources. EHS acknowledges support by the Mills-
aps College Wiener Fellowship.
Fig. 4 Thermal ellipsoid plot of one of the cation/anion pairs of 1 (at
73 K) showing the cation methoxy group in the endo conformation
50% probability enclosures)
References
1
(
1
2
. Kanaoka Y (1975) J Soc Org Synth Chem Tokyo 33:949
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‘
‘endo’’ conformation, with an C3 –N–O–CH torsion of
ar
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3
-
92.2(2)°. The orientations of the four tetrafluoroborate
4
. Mazzocchi PH (1981) In: Padwa A (ed) Organic photochemistry,
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5
. Griesbeck AG, Mauder H (1995) In: Horspool WM, Song PS
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3
.836(3) A, 3.996(3) A, and 3.937(3) A for the three
˚
‘‘exo’’ conformers, and 3.765(3) A for the ‘‘endo’’ con-
6
7
. Oelgem o¨ ller M, Griesbeck AG (2002) J Photochem Photobiol C
former (Fig. 4).
3
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Conclusion
8
9
6
5:2221
This work reports the synthesis, spectroscopic character-
ization, and crystal structure of a bifunctional cationic
compound, methylene-linked phthalimide and N-meth-
oxypyridinium. The crystal structure undergoes a phase
transition between 298 and 173 K and the compound is
photostable in the crystal. In solution, the major deactiva-
tion pathway decreasing the photochemical ion yield is
discussed to be the reformation of the N–O bond in the
geminate ion pair. The photostability of the compound in
the crystal lattice supports this argument.
. Mee JA, Heseltine DW, Taylor EC (1970) J Am Chem Soc
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1
0. Lorance ED, Kramer WH, Gould IR (2004) J Am Chem Soc
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(
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1
Supplemental material
Crystallographic data for 1 at 293 and 173 K have been
deposited with the Cambridge Crystallographic Data
1
23