Synthesis of 1,3-diazepines and ring contraction to cyanopyrroles

Article abstract of DOI:10.1039/b311247k

Several tetrazolo[1,5-a]pyridines/2-azidopyridines undergo photochemical nitrogen elimination and ring expansion to 1,3-diazacyclohepta-1,2,4, 6-tetraenes (7,10,13,16,19,22) as well as ring cleavage to cyanovinylketenimines (8,17,20b) in low temperature Ar matrices. 6,8-Dichlorotetrazolo[1,5-a]pyridine/2-azido-3,5-dichloropridine 6 undergoes ready exchange of the chlorine in position 8 (3) with ROH/RONa. 8-Chloro-6-trifluoromethylletrazolo[1,5-a]pyridine 15 undergoes solvolysis of the CF₃ group to afford 8-chloro-6-methoxycarbonyltetrazolo[1,5-a]pyridine 18. Several tetrazolopyridines/2-azidopyridines afford 1H- or 5H-1,3-diazepines in good yields on photolysis in the presence of alcohols or amines (11,14,23,25). 5-Chlorotetrazolo[1,5-a]pyridines/2-azido-6-chloropyridines 21 and 38 undergo a rearrangement to 1H-and 3H-3-cyanopyrroles 27 and 45, respectively. The mechanism of this rearrangement was investigated by ¹⁵N-labelling and takes place via transient 1,3-diazepines. The structures of 6,8-dichloro-tetrazolo[1,5-a]pyridine 6T, 6-chloro-8-ethoxytetrazoIo[1,5-a]pyridine 9Tb, dipyrrolylmethane 28, and 2-isopropoxy-4-dimethylamino-5H-1,3-diazepine 25b were determined by X-ray crystallography. In the latter case, this represents the first reported X-ray crystal structure of a 5H-1,3-diazepine.

Full text of DOI:10.1039/b311247k

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Synthesis of 1,3-diazepines and ring contraction to cyanopyrroles†‡
Ales Reisinger, Paul V. Bernhardt and Curt Wentrup*
Department of Chemistry, School of Molecular and Microbial Sciences,
The University of Queensland, Brisbane, Qld 4072, Australia. E-mail: wentrup@uq.edu.au
Received 16th September 2003, Accepted 14th November 2003
First published as an Advance Article on the web 10th December 2003
Several tetrazolo[1,5-a]pyridines/2-azidopyridines undergo photochemical nitrogen elimination and ring
expansion to 1,3-diazacyclohepta-1,2,4,6-tetraenes (7,10,13,16,19,22) as well as ring cleavage to
cyanovinylketenimines (8,17,20b) in low temperature Ar matrices. 6,8-Dichlorotetrazolo[1,5-a]pyridine/
2-azido-3,5-dichloropridine 6 undergoes ready exchange of the chlorine in position 8 (3) with ROH/RONa.
8-Chloro-6-trifluoromethyltetrazolo[1,5-a]pyridine 15 undergoes solvolysis of the CF3 group to afford
8-chloro-6-methoxycarbonyltetrazolo[1,5-a]pyridine 18. Several tetrazolopyridines/2-azidopyridines afford
1H- or 5H-1,3-diazepines in good yields on photolysis in the presence of alcohols or amines (11,14,23,25).
5-Chlorotetrazolo[1,5-a]pyridines/2-azido-6-chloropyridines 21 and 38 undergo a rearrangement to 1H-
and 3H-3-cyanopyrroles 27 and 45, respectively. The mechanism of this rearrangement was investigated by
15N-labelling and takes place via transient 1,3-diazepines. The structures of 6,8-dichloro-tetrazolo[1,5-a]pyridine
6T, 6-chloro-8-ethoxytetrazolo[1,5-a]pyridine 9Tb, dipyrrolylmethane 28, and 2-isopropoxy-4-dimethylamino-
5H-1,3-diazepine 25b were determined by X-ray crystallography. In the latter case, this represents the first
reported X-ray crystal structure of a 5H-1,3-diazepine.
hydrazine followed by diazotization, or in the the case of
Introduction
6,8-dichlorotetrazolo[1,5-a]pyridine 6T by direct nucleophilic
substitution with azide ion. In most cases examined here, the
compounds can exist as a tetrazole (T) or an azide (A). The
tetrazole form is usually favoured in the solid state, but equi-
libria exist in solution (see Experimental section for details).
Sublimation of 6T at 67 ЊC with matrix deposition of the
material in Ar at 12 K affords the azide 6A (Scheme 2), charac-
terized by a strong absorption at 2141 cmϪ1. Photolysis of this
matrix for 1 min resulted in rapid bleaching of the azide and the
appearance of a new, strong absorption at 1984 cmϪ1, a value
typical of seven-membered ring carbodiimides.3 Accordingly,
this spectrum is assigned to the carbodiimide 7. Further photo-
lysis for 1 h caused slower formation of an additional com-
pound absorbing at 3300, strongly at 2029, and weakly at 2220
cmϪ1, suggesting that ring opening to the ketenimine 8 took
place. We have examined such ring opening reactions in several
other cases, including cyanopyridylnitrenes,5 1-isoquinolyl-
nitrene,6 and the unsubstituted 2-pyridylnitrene.7 The details
of the ring opening reactions of 6, and those of 15 and 18
mentioned below, are the subjects of ongoing research.8 It is
noteworthy that 2-pyridylnitrenes carrying electronegative
atoms or groups in positions 3 and 5 appear to be particularly
prone to ring opening to ketenimines.
The photolysis of variously substituted tetrazolo[1,5-a]pyr-
idines/2-azidopyridines 1 is a convenient method of synthesis
of 1,3-diazepines.1,2 The reaction proceeds via ring expansion
of the first-formed 2-pyridylnitrenes 2 to 1,3-diazacyclohepta-
1,2,4,6-tetraenes 3 (Scheme 1), which in several cases have been
characterized by matrix-isolation IR spectroscopy.3,4 In the
presence of a nucleophile, 3 affords the 1H- or 5H-diazepines
4 and 5 depending on substituents. For Nu = OR the 1H-
diazepines 4 are invariably formed, and they are calculated to
be the most stable, but for Nu = NR2, the 5H-tautomers 5 are
more stable.1 Here we report synthetically useful variants based
on chlorotetrazolopyridines as well as the unexpected ring
contraction of 1,3-diazepines to pyrroles.
Compound 6 allows the synthesis of several trisubstituted
diazepines 11 (75–90 % yield) because the chlorine atom in pos-
ition 8 in 6 is readily replaced by alkoxy groups in a quantitative
dark reaction with sodium alkoxide in alcohol, yielding the new
tetrazoles 9. The photolysis of 9T (the azide 9A was not
observed) in an Ar matrix at ca. 10 K gave rise to a strong
absorption at 1995 cmϪ1, ascribed to the carbodiimide 10.
The X-ray crystal structures of the new tetrazoles 6T and
9Tb are shown in Figs. S3 and S5.§ In the dichloro compound
6T, a single molecule on a general site constitutes the asym-
metric unit. The aromatic rings are staggered (Fig. S4). The
chlorine atom in position 8 is situated above the centre of the
five-membered ring of an adjacent, centrosymmetrically related
Scheme 1
Results and discussion
Tetrazolo[1,5-a]pyridines/2-azidopyridines were prepared from
the 2-chloropyridines by exchange of the chlorine with
† Diazepines. Part 2. For Part 1 see ref. 1.
‡ Electronic supplementary information (ESI) available: drawings of
the crystal structures of compounds 6T and 9Tb (ORTEP); bond
lengths and angles for compounds 6T, 9Tb, 25h and 28, and 15N NMR
spectra of 21, 30, 27 and 37. See http://www.rsc.org/suppdata/ob/b3/
b311247k/
§ CCDC reference numbers 6T (222023); 9Tb, 25b and 28: 218060–
218062. See http://www.rsc.org/suppdata/ob/b3/b311247k/ for crystallo-
graphic data in.cif or other electronic format.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 2 4 6 – 2 5 6
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4
246

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The 6-trifluoromethyl-8-chloro analog 15T analogously
afforded the azide 15A (2145, 2149 cmϪ1; Ar, 7 K), and photo-
lysis of this azide gave rise to a medium-strength absorption at
1992 cmϪ1, ascribed to carbodiimide 16. In addition, a relatively
strong absorption appeared at 2060 cmϪ1. This is probably due
to ring opening of the pyridylnitrene to ketenimine 17.9 Weak
peaks assignable to cyano groups were present at 2220 cmϪ1, as
well as a medium band assigned to NH at 3343 cmϪ1. Surpris-
ingly, however, compound 15T did not exchange the chlorine
atom on reaction with NaOMe/MeOH in the dark at room
temperature. Instead, the trifluoromethyl group solvolysed, pre-
sumably via the orthoester, to the 6-methoxycarbonyl derivative
18. Matrix deposition of 18 afforded the azide 18A, and photo-
lysis afforded the carbodiimide 19 (1988, 1729 cmϪ1) as well as
the ring-opened ketenimine 20 (3355, 2052, 1737 cmϪ1).9 Com-
pound 15 did not give tractable diazepines on photolysis in
alcohols in the absence of alkali alkoxides. Neither 12 nor 15
gave tractable diazepines on photolysis in the presence of
amines.
The 6-chloro derivative 21 exists as the tetrazole 21T in the
solid state, but a mixture of azide and tetrazole exists in chloro-
form solution. Heating a KBr pellet containing 21T to 60–70 ЊC
for 1 min caused complete conversion to the azide 21A.
Deposition of 21 in an Ar matrix also gave rise to 21A, which
photolyzed to a cyclic carbodiimide 22 (1989 cmϪ1; Ar, 7 K)
(Scheme 4). The chlorine atom in position 5 of compound 21
is readily replaced in photolysis reactions in solution. Thus,
photolysis in excess pyrrolidine afforded the disubstituted
diazepine 23 as the only isolated product in 33% yield. Photo-
lysis of 21 in the presence of ethanol or methanol followed by
addition of a secondary amine after the light source had been
switched off afforded the 2-alkoxy-4-amino-1,3-diazepines 25
in 52–92% yield, thereby revealing that the chlorine atom must
be substituted in the dark at the level of the 2-alkoxy-4-chloro-
1,3-diazepine 24 in one of its tautomeric forms. A possible path
involving the 4H-tautomer 24Ј, which is related to 24 by a 1,5-
sigmatropic shift, is shown in Scheme 5, but other tautomers of
24 could also be involved.
The structure of 25h was established by X-ray crystallo-
graphy (Fig. 1).§ The ring has a slightly twisted boat structure.
Double bond character is clearly defined for C2–N1 (1.289(2)
Å), C4–N3 (1.308(2) Å) and C6–C7 (1.325(3) Å), whereas
bonds C2–N3 (1.361(2) Å), C2–O8 (1.359(2) Å) and C4–N12
(1.340(2) Å) fall between typical single and double bonds.
There have been no previously published structures of 5H-1,3-
diazepines. The closest analogue is a tricyclic 3,4-dihydro-1,3-
diazepine derivative.10 Structures of a few 1H-1,3-diazepines
have been published.2,11
Scheme 2
molecule. Compound 9Tb crystallizes as a π-stacked pair of
crystallographically unique molecules (Fig. S6), with some of
the intermolecular distances being N1 ؒ ؒ ؒ O1Ј (3.301(4) Å),
N2 ؒ ؒ ؒ C8Ј (3.307(5) Å), N3 ؒ ؒ ؒ C8aЈ (3.266(5) Å) and
N4 ؒ ؒ ؒ N1Ј (3.280(4) Å). The corresponding bond lengths and
angles in the two independent molecules of 9Tb are similar, so
for brevity only bond lengths involving unprimed atoms are
mentioned in comparison with 6T. In the crystal structures of
6T and 9Tb the corresponding N–N bond lengths are: N2–N3
(1.295(3) Å for 6T and 1.309(4) Å for 9Tb) by comparison with
N1–N2 (1.357(3) Å for 6T and 1.342(4) Å for 9Tb) and N3–N4
(1.374(3) Å for 6T and 1.364(4) Å for 9Tb). Similarly, an
unsymmetrical bonding pattern is seen in the six-membered
ring, with C5–C6 (1.346(3) Å for 6T and 1.347(5) Å for 9Tb)
and C7–C8 (1.349(3) Å for 6T and 1.359(4) Å for 9Tb) being
significantly shorter than C6–C7 (1.426(3) Å for 6T and
1.406(5) Å for 9Tb) and C8–C8a (1.408(3) Å for 6T and
1.416(5) Å for 9Tb). The two C–N bond lengths within the six-
membered ring are essentially the same: N4–C8a (1.357(3) Å
for 6T and 1.351(4) Å for 9Tb) and N4–C5 (1.365(3) Å for 6T
and 1.374(4) Å for 9Tb). Evidently substitution of chloro by an
ethoxy group in the 8 position has no significant influence on
the bond lengths within the bicyclic ring system The only
related published structure is that of 5,7-diphenyl-8-cyano-
tetrazolo[1,5-a]pyridine,9 where a similar bonding pattern was
seen.
Compared to the chlorine atom in position 8 in tetrazole/
azide 6, the chlorine atom in position 6 is far less reactive. In
agreement with this, the 6-chloro-8-trifluoromethyl analog 12
did not undergo an exchange reaction of the chlorine with
NaOMe/MeOH, but on photolysis in alcohols it afforded the
diazepine 14, which can exist in two tautomeric forms, 14 and
Fig. 1 ORTEP drawing of 5H-diazepine 25h.
1
14Ј (Scheme 3). The H and 13C NMR spectra demonstrated
The photolysis of 21 in the presence of diisopropylamine did
not afford the expected diazepine 26 (Scheme 6). Instead, a
that the equilibrium lies predominantly on the side of 14. The
deposition of 12T in an Ar matrix afforded the azide 12A (2146
cmϪ1; Ar, 7 K). Photolysis of this material at 7 K afforded the
1
white crystalline material was obtained, the H and 13C NMR
data of which indicated that it was either 3-cyano-2-(diiso-
propylamino)pyrrole 27 or the 2,5-isomer. Derivatization by
carbodiimide 13, absorbing strongly at 1991 cmϪ1
.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 2 4 6 – 2 5 6
247

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Scheme 3
Scheme 5
Scheme 6
Scheme 4
and only one of the many possible conformers is shown. The
bond lengths and angles are as expected for a pyrrole derivative.
The most closely related structure in the literature is that of the
corresponding acetone derivative of ethyl 3,4-dimethylpyrrole-
2-carboxylate.12
rapid reaction with acetone afforded the condensation product
28, whose structure was determined by X-ray crystallography,
thereby proving that 27 was the 2,3-disubstituted pyrrole.
The structure of the dipyrrylmethane 28 is shown in Fig. 2.§
Disorder was resolved in three of the four isopropyl groups,
The mechanism of formation of 27 was established in a
15N-labelling experiment. The doubly labelled hydrazine 29 was
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 2 4 6 – 2 5 6
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Fig. 2 ORTEP drawing of bispyrrolylmethane 28.
prepared from 2,6-dichloropyridine and 15N2-hydrazinium
sulfate (96.2% 15N2, diluted with unlabelled material to afford
48.1% 15N2). Diazotization afforded the crystalline 15N115N2-
tetrazole 30T. In chloroform solution this compound exists
largely in the azide form 30A. In the 15N NMR spectrum of this
compound in CDCl3 solution, the two labelled nitrogen atoms
appeared at Ϫ260 and Ϫ125 ppm referenced to nitromethane.
The other two N atoms, N3 and N4 were not labelled; they
appear at Ϫ127 and Ϫ85 ppm, respectively, in the natural
abundance 15N NMR spectrum of 21A. Photolysis of 30T/30A
in excess diisopropylamine afforded the labelled 3-cyano-2-
(diisopropylamino)pyrrole 37, which was labelled on the pyrrole-
nitrogen only (Ϫ198 ppm). This signal remained positive in the
DEPT90 spectrum, thereby identifying it as the NH signal. In
the natural abundance 15N NMR spectrum of the unlabelled
pyrrole 27, the pyrrole N appears at Ϫ198 ppm, the cyano
group at Ϫ105 ppm, and the tertiary amine-N at Ϫ295 ppm.
Following our experience with other 2-amino-1,3-diaze-
pines,1 reaction of the diazacycloheptatetraene 31 should afford
the 1H-diazepine 32 initially, but, given time, it would be
expected to tautomerize to the more stable 5H-isomer 33 and
to exchange the Cl for N(iPr)2. The labelling results require that
either 32 or 33 undergoes a rearrangement to 37. This can
take place as indicated in Scheme 7: a 4π electrocyclization
(disrotatory photochemically) affords transient diazabicyclo-
[2,3,0]heptadienes 34 or 35, which can undergo dehydro-
halogenation (X = Cl) or dehydroamination (X = N(iPr)2) with
ring opening to 36 and 37. A photochemical cyclization of
1-substituted 1H-azepines to 2-azabicyclo[2,3,0]heptadienes
has been reported.13
Scheme 7
carbons carrying the CF3 groups show long range couplings to
19F, causing narrow quartets at 153 (C5) and 57 (C3) ppm. The
imine carbon C2 appears at 163, the vinylic CH(4) at 104, and
the CN group at 110 ppm. The assignments are supported by a
DEPT90 spectrum.
We have recorded hindered rotations of dialkylamino groups
of the type described above in several 1,3-diazepine derivatives,
e.g. in 25a–k, where the free energies of rotation about the C–N
The bis(trifluoromethyl)-6-chloro derivative 38 exists as the
azide 38A at room temperature (2153 cmϪ1; neat film). The
compound behaves similarly to 21. Photolysis in ethanol fol-
lowed by addition of diisopropylamine in the dark afforded the
diazepine 40, presumably via the unobserved intermediate 39
(Scheme 8). Photolysis of 38A in diisopropylamine afforded the
3H-pyrrole 45. In analogy with the mechanism presented in
Scheme 7, it is suggested that the initial product is a habitual
1H-diazepine 41, which may tautomerise to a 5H-diazepine 42.
Both of these diazepines can undergo a photochemical (or
thermal) 4π electrocyclization to 43 or 44, which by elimination
of HX (X = Cl or N(iPr)2) will give rise to the isolated product
45. The structure of 45 is supported by the mass spectrum, the
IR spectrum (weak band at 2250 cmϪ1 for an unconjugated
bonds were measured by NMR methods as 15–16 kcal molϪ1 14
.
The free energies of activation for ring inversion of the
diazepines (9.5–12 kcal molϪ1) and for the exchange of H
between N1 and N3 in diazepines (15.8–16.5 kcal molϪ1) have
also been measured14 and will be the subjects of forthcoming
publications.
Conclusion
Tetrazolo[1,5-a]pyridines/2-azidopyridines undergo photo-
chemical nitrogen elimination and ring expansion to 1,3-diaza-
cyclohepta-1,2,4,6-tetraenes as well as ring cleavage to cyano-
vinylketenimines, both of which are characterized by their
Ar matrix IR spectra. The 1,3-diazacyclohepta-1,2,4,6-tetraenes
are in many cases trapped by nucleophiles in solution photolysis
to afford 1H- or 5H-1,3-diazepines in good yields (11,14,23,25).
5-Chlorotetrazolo[1,5-a]pyridines/2-azido-6-chloropyridines 21
and 38 undergo a rearrangement to 1H- and 3H-3-cyanopyrroles
27 and 45, respectively. The mechanism of this rearrange-
ment was investigated by 15N-labelling and takes place via a
photochemical electrocyclic ring closure in transient 1,3-
diazepines.
1
nitrile), and in particular by the H and 13C NMR spectra,
which show hindered rotation of the congested diisopropyl
group, so that the four CH3 groups and the two CH groups
appear as individual signals in the 13C NMR spectrum at 19–21
and 50–54 ppm, respectively. The two methine CH groups also
appear as individual, broad peaks with unresolved couplings at
3.7 and 4.4 in the 1H NMR spectrum. The two CF3 groups are
characterized by the 19F-couplings, giving rise to quartets
around 120 ppm in the 13C NMR spectrum. The quaternary
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 2 4 6 – 2 5 6
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Compound 9Tb: C7H13ClN4O, M = 198.62, triclinic, space
¯
group P1, a = 7.792(1), b = 10.213(2), c = 11.8009(3) Å, α =
105.66(2), β = 94.91(3), γ = 102.04(2)Њ, U = 874.9(3) Å3, Z = 4, Dc
= 1.508 g cmϪ3, µ = 3.99 cmϪ1, 3313 reflections measured, 3068
unique (Rint = 0.0380), R1 = 0.0438 (for 1429 observed data,
I > 2σ), wR2 = 0.1235 (all data).
Compound 25h: C10H17N3O, M = 195.27, monoclinic, space
group P 21/a, a = 11.185(2), b = 8.1266(4), c = 12.711(3) Å, β
= 107.343(9), U = 1102.9(3) Å3, Z = 4, Dc = 1.176 g cmϪ3
,
µ = 0.79 cmϪ1, 2052 reflections measured, 1939 unique
(Rint = 0.0114), R1 = 0.0394 (for 1433 observed data, I > 2σ),
wR2 = 0.1190 (all data).
Compound 28: C25H38N6, M = 422.61, triclinic, space group
¯
P 1, a = 10.9884(9), b = 11.953(1), c = 12.2879(8) Å, α =
65.573(6), β = 79.700(6), γ = 63.521(6)Њ, U = 1315.2(2) Å3, Z = 2,
Dc = 1.067 g cmϪ3, µ = 0.65 cmϪ1, 4922 reflections measured,
4622 unique (Rint = 0.0442), R1 = 0.0577 (for 2840 observed
data, I > 2σ), wR2 = 0.1826 (all data).
General procedure for the synthesis of 2-hydrazinopyridines
The appropriate 2-chloropyridine (ca. 0.04–0.08 moles) was
added to a large excess of hydrazine hydrate (30–50 ml), and
20–40 ml of ethanol was then added to make the solution
homogeneous. The resulting solution was refluxed (oil bath,
80–90 ЊC) until TLC analysis (silica gel/dichloromethane)
showed no starting 2-chloropyridine remained. The heat
was then removed and the volume of the solution was reduced
under vacuum. If no crystals appeared during refluxing or
cooling, the resultant slurry was extracted with ether (3 ×
100 ml), and the combined ether extracts were dried (MgSO4)
and evaporated to give the appropriate 2-hydrazinopyridine.
The crude 2-hydrazinopyridines were purified by gentle
sublimation (30–50 ЊC, 0.5–0.1 mbar) or recrystallized from
chloroform. The hydrazinopyridines are numbered as the
azides/tetrazoles. Thus, for example tetrazole 12T is made from
hydrazine 12H.
Scheme 8
Experimental section
General methods for matrix isolation and photolysis have been
reported previously.6,15 Ar matrix isolation experiments were
carried out at 7–10 K. The unfiltered light from a 1000 W high
pressure Hg/Xe lamp was used for the irradiations. IR spectra
were recorded with 1 cmϪ1 resolution. 15N NMR spectra were
recorded at 40.56 MHz with 30 s delay between scans to minim-
ize NOE; a 30Њ flip angle was used. The 15N NMR spectra of 21
and 30 were recorded in CDCl3 (azide forms dominating), and
those of 27 and 37 in benzene-d6; 10 M HNO3 was used as an
external reference, and the chemical shifts were recalculated
relative to nitromethane. Melting points are uncorrected.
3,5-Bis(trifluoromethyl)-2,6-dichloropyridine was too reac-
tive towards hydrazine hydrate for the above procedure. See the
modified procedure under the preparation of 2-hydrazino-
pyridine 38H.
General procedure for synthesis of 2-azidopyridines/tetra-
zolo[1,5-a]pyridines from 2-hydrazinopyridines
The appropriate 2-hydrazinopyridine (ca. 0.04 moles) was
added to 20 ml of ice-cold water, and enough concentrated
hydrochloric acid was added to obtain a solution with a pH = 1.
Usually, a clear solution was obtained at this acidity. A pre-
cooled solution of sodium nitrite (1.2 molar excess) in ca. 10 ml
of water was added dropwise with stirring. Mild frothing
usually occurred on addition of each drop. The pH of the solu-
tion was monitored during the reaction, and a few drops
of concentrated HCl was added if the acidity significantly
decreased. After addition of the sodium nitrite solution, the
reaction mixture was extracted with dichloromethane (3 ×
30 ml), the combined extracts were dried (MgSO4) and evapor-
ated to give the appropriate 2-azido/tetrazolo[1,5-a]pyridine.
The 2-azidopyridines/tetrazolo[1,5-a]pyridines were further
purified by distillation and/or sublimation (50–100 ЊC, 0.1–
0.5 mbar).
Crystallography
Cell constants were determined by least-squares fits to the
setting parameters of 25 independent reflections measured on
an Enraf-Nonius CAD4 four-circle diffractometer employing
graphite-monochromated Mo Kα radiation (0.71073 Å) and
operating in the ω-2θ scan mode. Data reduction was per-
formed with the WinGX package.16 Structures were solved by
direct methods with SHELXS and refined by full-matrix least-
squares analysis with SHELXL-97.17 All non-H atoms were
refined with anisotropic thermal parameters. H-atoms were
included in estimated positions using a riding model. Drawings
were produced with ORTEP.18
3,5-Dichloro-2-hydrazinopyridine 6H
Crystal data
Obtained from 2,3,5-trichloropyridine as white crystals, mp
179 ЊC from chloroform; yield 94.5%; 1H NMR (400 MHz,
CDCl3) δ 8.06 (d, J 1.8 Hz, 1H, 6-H), 7.49 (d, J 1.8 Hz, 1H,
4-H), 6.23 (br s, 1H, NH), 3.95 (br s, 2H, NH); 13C NMR (100
MHz, CDCl3) δ 154.1, 144.1, 135.9, 120.4, 114.9. Anal. calcd.
for C5H5N3Cl2 C, 33.73; H, 2.83; N, 23.60%. Found C, 33.50; H,
2.78; N, 23.70%.
Compound 6T: C5H2Cl2N4, M = 189.01, monoclinic, space
group P21/a, a = 7.178(1), b = 13.107(2), c = 8.274(2) Å, β =
114.13(8)Њ, U = 710.4(2) Å3, Z = 4, Dc = 1.767 g cmϪ3, µ = 8.41
cmϪ1, 1352 reflections measured, 1247 unique (Rint = 0.0287),
R1 = 0.0296 (for 1065 observed data, I > 2σ), wR2 = 0.0962 (all
data).
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 2 4 6 – 2 5 6
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6,8-Dichlorotetrazolo[1,5-a]pyridine 6T
Anal. calcd. for C7H7ClN4O: C, 42.33; H, 3.55; N, 28.21%.
Found: C, 42.10; H, 3.45; N, 28.42%.
Method 1. The hydrazine 6H was diazotised as described above
to give 6T as slightly off-white white plates, mp 78–79 ЊC from
70% ethanol; yield 87%; 1H NMR (400 MHz, CDCl3) tetrazole
isomer 6T δ 8.80 (d, J 1.5, 1H), 7.69 (d, J 1.5, 1H); azide isomer
6A δ 8.17 (d, J 2.2, 1 H), 7.64 (d, J 2.2, 1H); ratio tetrazole :
azide (20 ЊC) 4 : 1; 13C NMR (100 MHz, CDCl3) tetrazole
isomer 6A δ 145.3, 132.3, 124.8, 123.1, 121.0; azide isomer 6A
δ 149.9, 146.7, 138.0, 127.4, 122.2. In CCl4 the tetrazole : azide
ratio was 1 : 3.7 (20 ЊC), in pyridine-d5 the tetrazole : azide ratio
was 18 : 1 (20 ЊC), and in DMSO-d6 the tetrazole : azide ratio
was 98 : 1 (20ЊC) as determined from the 1H NMR spectra. IR
(KBr; only tetrazole 6T present) ν 3105m, 1537m, 1477vs,
1324m, 1148s, 1070s, 798vs cmϪ1. Anal. calcd. For C5H2N4Cl2
C, 31.77, H, 1.07, N, 29.64%. Found C, 31.71; H, 1.01; N,
28.78%.
5-Chloro-2-hydrazino-3-trifluoromethylpyridine 12H
Pale yellow solid; mp 79–80 ЊC; yield 80%. 1H NMR (400 MHz,
DMSO-d6) δ 8.32 (d, 1 H, 6-H, J4,6 = 1.8 Hz), 7.90 (br s, 1 H,
N-H ), 7.82 (d, 1 H, 4-H, J4,6 = 1.8 Hz), 4.37 (br s, 2 H, NH2);
13C NMR (100 MHz, DMSO-d6) δ 154.3 (q, 2-C, JC,F = 1.4 Hz),
149.8 (6-C), 134.6 (q, 4-C, JC,F = 5.5 Hz), 123.0 (q, CF3, JC,F
=
272.6 Hz), 116.8 (5-C), 107.2 (q, 3-C, JC,F = 32.6 Hz); IR (KBr)
3320.4 and 3281.0 br (NH ), 1606.2 vs, 1572.8 vs, 1486.4 s,
1458.8 s, 1403.6 m, 1384.6 m, 1347.6 w, 1299.1 vs, 1258.3 w,
1233.4 m, 1156.5 vs, 1138.8 vs, 1121.6 vs, 1050.9 s, 980.0 w,
915.0 m, 883.6 w, 777.0 w, 723.2 w, 662.5 w cmϪ1; Anal. calcd.
for C6H5ClF3N3: C, 34.06; H, 2.38; N, 19.86%. Found: C, 33.91;
H, 2.15; N, 19.90%.
Method 2. 2,3,5-Trichloropyridine (5.1 g; 0.020 mol) was dis-
solved in 20 ml of DMF and excess NaN3 was added. The
mixture was stirred at 65 ЊC for 70 h, cooled, and then slowly
added to 100 ml of ice-cold water with stirring. The resulting
precipitate was filtered, washed thoroughly with water, dried,
and sublimed. Recrystallization from 70% ethanol afforded 6T
in 46% yield.
6-Chloro-8-trifluoromethyltetrazolo[1,5-a]pyridine 12T
1
White solid; mp 80–81 ЊC; yield 71%. H NMR (400 MHz,
CDCl3) tetrazole isomer δ 9.06 (m, 1 H, 6-H), 7.97 (m, 1 H,
4-H); azide isomer 12A δ 8.38 (d, 1 H, 6-H, J4,6 = 4.9 Hz), 7.83
(d, 1 H, 4-H, J4,6 = 4.9 Hz); 13C NMR (100 MHz, CDCl3) tetra-
zole isomer 12T δ 143.9 (2-C), 132.4 (q, 4-C, JC,F = 5.0 Hz),
126.7 (6-C), 124.3 (5-C), 121.0 (q, CF3, JC,F = 272.0 Hz), 119.2
(q, 3-C, JC,F = 38.0 Hz); azide isomer 12A δ 150.6 (2-C), 150.4
(6-C), 136.0 (q, 4-C, JC,F = 5.0 Hz), 127.0 (5-C), 121.5 (q, CF3,
JC,F = 271.0 Hz), 116.5 (q, 3-C, JC,F = 34.0 Hz), IR (KBr) tetra-
zole isomer 12T 3100.1 w, 1641.0 m, 1604.0 s, 1583.4 s, 1490.9 s,
1414.4 w, 1384.5 w, 1364.3 vs, 1341.9 w, 1303.1 s, 1243.0 m,
1227.1 m, 1175.4 vs, 1153.2 vs, 1150.0 vs, 1104.4 w, 1076.4 w,
973.2 m, 919.2 m, 889.7 w, 868.7 w, 803.1 m, 774.9 m, 723.2 m,
667.5 w cmϪ1; azide isomer 12A (KBr, after heating the KBr
pellet to 60–70 ЊC for 5 min) 2145.1 (vazide) s, 1591.0 s, 1575.7 vs,
1520.9 w, 1486.9 w, 1433.2 vs, 1381.9 w, 1357.4 w, 1317.3 w,
1296.3 vs, 1234.8 vs, 1202 m, 1164 w, 1143.9 w, 1132.1 w, 1083.8
w, 1049.3 m, 968.4 w, 908.7 m, 886.6 w, 845.0 m, 809.1 m,
782.3 w, 729.2 w, 720 m, 762.3 w cmϪ1; MS (EI) m/z 222 (Mϩ, 62
%), 194 (98), 175 (10), 167 (100), 159 (9), 147 (8), 139 (2),
132 (11), 98 (50), 82 (8), 75 (6), 64 (5), 53 (3). HRMS, calcd.
for 12C6H2ClF3N4: 221.9920; found: 221.9920. Anal. calcd. for
C6H2ClF3N4: C, 32.38; H, 0.91; N, 25.17%. Found: C, 32.61; H,
1.02; N, 24.72%.
6-Chloro-8-methoxytetrazolo[1,5-a]pyridine 9Ta
A 1 g (0.0053 mol) portion of 3,5-dichlorotetrazolo[1,5-a]-
pyridine 6T was added to a solution of methanol (30 ml) and
2 M NaOMe/methanol (10 ml), and stirred overnight. When no
starting material was detected on a TLC plate (silica gel/chloro-
form, ca. 12 h), concentrated hydrochloric acid was slowly
added to neutralize the solution to pH = 7. After filtration, the
volume was reduced under vacuum, and the residue was
extracted with CH2Cl2 (3 × 30 ml) to obtain crude 9Ta, which
was further purified by sublimation (100 ЊC/0.1–0.5 mbar) to
give 9Ta as a white solid; mp 126 ЊC; yield: 92%; 1H NMR (400
MHz, CDCl3) δ 8.43 (d, 1 H, 6-H, J4,6 = 2.9 Hz), 6.82 (d, 1 H,
4-H, J4,6 = 2.9 Hz), 4.06 (s, 3 H, OCH3); 13C NMR (100 MHz,
CDCl3) δ 148.0 (2-C), 131.1 (3-C), 126.2 (5-C), 115.9 (6-C),
109.8 (4-C), 57.2 (OCH3). The substitution of the chlorine
atom on 3-C by the methoxy group was confirmed by an NOE
experiment, which showed a 16% enhancement of 4-H on
irradiation of the methoxy group at 4.06 ppm. No enhancement
was observed for the proton at 6-C. IR (KBr) 3059 w, 2984 m,
1562 vs, 1488 vs, 1474 w, 1456 w, 1436 w, 1415 m, 1401 w, 1357
w, 1333 s, 1289 s, 1210 s, 1196 s, 1123 s, 1102 m, 1077 w, 1004 s,
970 m, 909 m, 878 m, 817 s, 808 m, 765 w cmϪ1. MS (EI) m/z
184 (Mϩ, 55%), 155 (51), 141 (42), 129 (61), 114 (100), 101 (56),
86 (25), 77 (10), 64 (12), 53 (28). HRMS, calcd. for 12C6H5-
ClN4O: 184. 0135; found: 184.0156. Anal. calcd. for C6H5-
ClN4O: C, 39.04; H, 2.73; N, 30.35%. Found: C, 39.07; H, 2.65;
N, 30.61%.
3-Chloro-2-hydrazino-5-trifluoromethylpyridine 15H
1
White solid; mp 85–86 ЊC; yield 47%. H NMR (200 MHz,
CDCl3) δ 8.30 (m, 1 H, 6-H, J4,6 = 2.1 Hz, JH,F = 0.9 Hz), 7.61
(dd, 1 H, 4-H, J4,6 = 2.1 Hz, JH,F = 0.4 Hz), 6.79 (br s, 1 H,
N-H ), 4.09 (br s, 2 H, NH2); 13C NMR (50 MHz, CDCl3)
δ 157.0 (2-C), 143.5 (q, 6-C, JC,F = 4.5 Hz), 133.0 (q, 4-C,
JC,F = 3.2 Hz), 123.0 (q, CF3, JC,F = 269.0 Hz), 116.7 (q, 5-C,
JC,F = 33.4 Hz), 114.2 (3-C); MS (EI) m/z 211 (Mϩ, 100%), 192
(21), 183 (16), 182 (14), 181 (54), 147 (9), 146 (39), 141 (8), 127
(5), 126 (13), 85 (8), 83 (6), 76 (11), 75 (15), 69 (18), 52 (6),
28 (15). HRMS, calcd. for 12C6H5ClF3N3: 211.0124; found:
211.0128. Anal. calcd. for C6H5ClF3N3: C, 34.06; H, 2.38; N,
19.86%. Found: C, 34.05; H, 2.46; N, 19.98%.
6-Chloro-8-ethoxytetrazolo[1,5-a]pyridine 9Tb
Using sodium ethoxide instead of the methoxide, compound
9Tb was prepared in the same way as described for 9Ta. White
solid; mp 146 ЊC; yield: 90%. 1H NMR (200 MHz, CDCl3)
δ 8.44 (d, 1 H, 6-H, J4,6 = 1.4 Hz), 6.80 (d, 1 H, 4-H, J4,6 = 1.4
Hz), 4.33 (q, 2 H, OCH2CH3, JCH2,CH3 = 7.0 Hz); 1.54 (t, 3 H,
OCH2CH3, JCH2,CH3 = 7.0 Hz); 13C NMR (50 MHz, CDCl3)
δ 146.9 (2-C), 143.2 (3-C), 125.8 (5-C), 115.5 (6-C), 110.4 (4-C),
66.6 (OCH2CH3), 14.2 (OCH2CH3); IR (KBr) 3110.5 w, 3061.2
w, 2982.6 w, 2943.3 w, 1560.3 vs, 1490.3 m, 1484.5 m, 1468.8 w,
1447.3 w, 1413.5 w, 1396.3 m, 1367.9 w, 1357.0 w, 1328.6 m,
1290.8 m, 1210.4 s, 1118.9 m, 1098.3 w, 1072.0 w, 1025.4 m,
1003.8 m, 926.5 m, 868.9 m, 828.0 w, 819.3 m, 762 w cmϪ1; MS
(EI) m/z 198 (Mϩ, 65%), 169 (75), 155 (75), 141 (13), 129 (47),
114 (35), 101 (44), 87 (100), 79 (74), 60 (22), 53 (35), 38 9 (21).
HRMS, calcd. for 12C7H7ClN4O: 198.0312; found: 198. 0308.
8-Chloro-6-trifluoromethyltetrazolo[1,5-a]pyridine 15T
1
White solid; mp 41–42 ЊC; yield 71%. H NMR (400 MHz,
CDCl3) tetrazole isomer 15T δ 9.17 (m, 1 H, 6-H), 7.88 (m, 1 H,
4-H); azide isomer 15A δ 8.50 (m, 1 H, 6-H), 7.89 (m, 1 H, 4-H);
13C NMR (100 MHz, CDCl3) tetrazole isomer 15T δ 143.7
(2-C), 127.2 (q, 6-C, JC,F = 2.0 Hz), 124.5 (3-C), 123.1 (q, 4-C,
JC,F = 5.4 Hz), 121.8 (q, CF3, JC,F = 272.9 Hz), 121.7 (q, 5-C,
JC,F = 36.3 Hz); azide isomer 15A δ 154.9 (2-C), 148.1 (6-C),
135.6 (q, 4-C, JC,F = 3.4 Hz), 123.9 (q, 5-C, JC,F = 34.3 Hz), 122.8
(q, CF3, JC,F = 272.2 Hz), 120.8 (3-C); IR (KBr) 3105.1 w,
2144.7 (vazide) w, 1648.3 m, 1610.4 br s, 1414.4 m, 1384.5 w,
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 2 4 6 – 2 5 6
251

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1369.4 m, 1335.2 vs, 1245.4 m, 1190.6 m, 1150.7 s, 1128.3 s,
1100.7 w, 1072.0 w, 974.2 w, 893.0 w, 762.6 w, 697.1 m, 661.2 w
cmϪ1; MS (EI) m/z 222 (Mϩ, 45%), 194 (100), 175 (24), 167 (25),
163 (10), 159 (24), 151 (11), 143 (10), 132 (12), 113 (10), 98 (27),
82 (10), 75 (10), 63 (5), 53 (12). HRMS, calcd. for 12C6H2-
ClF3N4: 221.9923; found: 221.9919. Anal. calcd. for C6H2-
ClF3N4: C, 32.38; H, 0.91; N, 25.17%. Found: C, 32.47; H, 0.88;
N, 24.96%.
Anal. calcd. for C5H3ClN4: C, 38.86; H, 1.96; N, 36.25%.
Found: C, 38.71; H, 1.91; N, 36.48%.
6-Chloro-2-[15N2]-hydrazinopyridine 29
1.7 g of [15N2]-hydrazine sulfate (H2N–NH2ؒH2SO4, 96.2 atom-
%
15N2) was mixed with an equal amount of unlabelled product
to obtain 0.026 moles of 48.1% 15N2 hydrazine sulfate to which
2.9 g (0.027 moles) of solid Na2CO3 was added. The two com-
pounds were mixed and ground, and 15 drops of H2O were
added to initiate liberation of hydrazine hydrate. When the
violent bubbling and frothing ceased, the resulting mixture
of hydrazine hydrate and sodium sulfate was diluted with 12 ml
of ethanol, and 0.5 g of 2,6-dichloropyridine was added. The
mixture was then refluxed for 60 h. Although TLC (silica gel,
dichloromethane) showed that starting material was still
present, the reaction was stopped due to the appearance of the
unwanted by-product 2-chloro-6-hydroxypyridine according to
GCMS analysis. Evaporation of the solvent under vacuum
left a yellow–brown solid, which was extracted with dichloro-
methane and washed with a saturated solution of Na2CO3 and
brine. Evaporation of the extract furnished a yellow solid
(0.34 g); this was a mixture of starting material and 2-chloro-6-
[15N2]-hydrazinopyridine (48.1 atom-% 15N2), which was used
for the next step without further purification.
8-Chloro-6-methoxycarbonyltetrazolo[1,5-a]pyridine 18T
A 0.5 g (0.0024 mol) portion of 3-chloro-5-trifluoromethyl-
tetrazolo[1,5-a]pyridine 15T was dissolved in 20 ml of meth-
anol and 5 ml of 3 M NaOMe in methanol (large excess) was
added. The mixture was then stirred overnight at room temper-
ature. After approximately 12 h no 15T was detected on the
TLC plate (silica gel/chloroform). Concentrated hydrochloric
acid was slowly added to neutralize the solution to pH = 7.
After filtration, the volume was reduced under vacuum, and the
residue was extracted with CH2Cl2 (3 × 30 ml) to obtain crude
18T, which was further purified by sublimation (100 ЊC/0.1–0.5
mbar) to give 18T as a white solid; mp 135–136 ЊC; yield: 71%.
1H NMR (400 MHz, DMSO-d6) δ 9.91 (d, 1 H, 6-H, J4,6
1.1 Hz), 8.29 (d, 1 H, 4-H, J4,6 = 1.1 Hz), 3.94 (s, 3 H, OMe); 13
=
C
NMR (100 MHz, DMSO-d6) δ 162.9 (C=O), 148.2 (2-C), 130.9
(6-C), 129.0 (4-C), 120.7 (5 or 3-C), 120.4 (3 or 5-C) 53.2 (CH3);
IR (KBr) 3066.4 m, 3010.7 w, 1725 vs (vC=O), 1621.9 m, 1590.1
br m, 1494.7 w, 1436.9 s, 1402.4 w, 1384.6 w, 1369.0 m, 1330.3
m, 1315.3 s, 1241.9 s, 1190.3 w, 1149.6 w, 1109.3 w, 1080.8 m,
995.3 w, 962.5 m, 890.4 w, 765.6 m, 736.7 w cmϪ1; MS (EI) m/z
212 (Mϩ, 36%), 184 (100), 153 (64), 141 (19), 127 (30), 121 (47),
114 (41), 98 (62), 73 (75), 63 (66), 59 (81), 53 (43), 47 (32),
37 (47). Anal. calcd. for C7H5ClN4O2: C, 39.55; H, 2.37; N,
26.35%. Found: C, 39.55; H, 2.40; N, 26.36%.
During optimization of the reaction using commercially
available hydrazine sulfate, it was found that adding small
amount of H2O into the mixture of solid Na2CO3 and hydra-
zine sulfate, as well as carrying out the reaction in a relatively
large volume of ethanol (12 ml) improved yields and minimized
formation of the unwanted by-product 2-chloro-6-hydroxy-
pyridine. Increasing the amount of 2,6-dichloropyridine above
0.5 g did not improve the yield.
The method for a preparation of hydrazine hydrate from
hydrazine sulfate reported by Nenitzescu et al.,19 which uses a
boiling solution of sodium acetate and H2O, was examined and
found to be unsuitable for this experiment.
6-Chloro-2-hydrazinopyridine 21H
1
White crystalline solid; yield 78%; mp. 126–127 ЊC. H NMR
1,2-[15N2]-5-Chlorotetrazolo[1,5-a]pyridine 30T
(200 MHz, DMSO-d6) δ 7.84 (br s, 1 H, N–H), 7.43 (apparent t,
1 H, 4-H, J = 8–8.5 Hz), 6.63 (d, 1 H, 5-H, J4,5 = 8.2 Hz), 6.50 (d,
1 H, 3-H, J3,4 = 7.2 Hz), 4.18 (br s, 2 H, NH2); 13C NMR
(50 MHz, DMSO-d6) δ 162.3 (2-C), 148.2 (6-C), 139.8 (4-C),
110.6 (5-C), 104.3 (3-C); Anal. calcd. for C5H6ClN3: C, 41.83;
H, 4.21; N, 29.27%. Found: C, 41.74; H, 4.17; N, 29.43%.
A 0.34 g portion of the crude 2-chloro-6-[15N2]-hydrazino-
pyridine 29 containing ca. 0.15 g of 2,6-dichloropyridine was
added to 3 ml of water and diazotized as described above to
give 0.22 g of crude 30T.
3,5-Bis(trifluoromethyl)-6-chloro-2-hydrazinopyridine 38H
6-Chlorotetrazolo[1,5-a]pyridine 21T
The precursor, 3,5-bis(trifluoromethyl)-2,6-dichloropyridine,
was found to be very reactive towards hydrazine hydrate. There-
fore, the general method was modified. Thus, 5 g (0.018 moles)
of 3,5-bis(trifluoromethyl)-2,6-dichloropyridine was dissolved
in 30 ml of ethanol and cooled to ca. 10 ЊC in an water bath. On
addition of ca. 1.5 molar excess of hydrazine (2–3 min), the
solution turned yellow, and a large amount of a precipitate was
formed. The volume was then reduced under vacuum, and the
resultant slurry was extracted with ether (3 × 30 ml). The com-
bined ether extracts were dried (MgSO4), evaporated, and the
crude residue was purified by gentle sublimation (50–60 ЊC, 0.1–
0.5 mm Hg) to afford the hydrazone 38H as a pale yellow crys-
1
White crystalline solid; yield 69.8%; mp 78–79 ЊC. H NMR
(400 MHz, CDCl3) azide isomer (21A) δ 7.55 (apparent triplet,
1 H, 4-H, J = 7–8 Hz), 7.03 (dd, 1 H, 5-H, J4,5 = 7.9 Hz, J3,5
=
0.6 Hz), 6.69 (dd, 1 H, 3-H, J3,4 = 7.9 Hz, J3,5 = 0.5 Hz); 13C
NMR (100 MHz, CDCl3) δ 154.5 (2-C), 150.1 (6-C), 140.8
1
(4-C), 120.1 (3-C), 112.2 (5-C); H NMR (400 MHz, CDCl3)
tetrazole isomer (21T) δ 8.00 (d, 1 H, 3-H, J3,4 = 8.3 Hz), 7.67
(apparent triplet, 1 H, 4-H, J = 7–8 Hz), 7.27 (d, 1 H, 5-H, J4,5
=
8.3 Hz); 13C NMR (100 MHz, CDCl3) δ 149.7 (2-C), 132.4
(4-C), 119.8 (6-C), 116.4 (3-C), 114.2 (5-C); 15N NMR (CDCl3,
referenced to external nitromethane) δ Ϫ260, Ϫ125, Ϫ127,
Ϫ85; IR (KBr): in the solid state at room temperature the
tetrazole form predominates; warming the KBr pellet to
ca. 60–70 ЊC for 1 min caused complete conversion of 21T to
the azido-form 21A, which did not equilibrate back to 21T after
15 min at room temperature, possibly due to the KBr matrix;
tetrazole isomer (21T) 3099.1 w, 3070.7 w, 1618.3 s, 1537.5 m,
1489.3 vs, 1353.7 w, 1326.4 s, 1242.4 m, 1230.8 m, 1126.2 w,
1122.4s, 1100.3 vs, 1010.2 m, 989.9 s, 838.4 w, 805.5 vs, 748.8 m
cmϪ1; azide isomer 21A (60–70 ЊC) 2127 vs (vazide), 1538.8 vs,
1564.4 m, 1498.8 w, 1425.9 vs, 1292.8 s, 1164.1 m, 987.9 w, 900.7
m, 787.6 m, 721.5 w, 658.1 w cmϪ1; MS (EI) m/z 154 (Mϩ, 78 %),
126 (100), 113 (5), 99 (72), 91 (28), 73 (13), 64 (46), 53 (7).
HRMS, calcd for 12C5H3ClN4: 154.0046; found: 154.0046.
1
talline solid; yield 98%; mp. 96–97 ЊC. H NMR (200 MHz,
CDCl3) δ 7.92 (s, 1 H, 4-H), 7.03 (br s, 1 H, N–H), 4.16 (br s,
2 H, NH2); 13C NMR (50 MHz, CDCl3) δ 156.6 (2-C), 151.7
(6-C), 135.8 (m, 4-C), 122.5 (q, CF3, JC,F = 269.5 Hz), 122.0
(q, CF3, JC,F = 269.0 Hz), 113.3 (q, 5-C, JC,F = 34.1 Hz), 105.8
(q, 3-C, JC,F = 33.5 Hz); Anal. calcd. for C7H4ClF6N3: C, 30.07;
H, 1.44; N, 15.03%. Found: C, 30.28; H, 1.43; N, 15.26%.
2-Azido-3,5-bis(trifluoromethyl)-6-chloropyridine 38A
Clear oil; purified by distillation (Kugelrohr apparatus, 25 ЊC,
1
0.1–0.5 mbar); yield 60%. H NMR (200 MHz, CDCl3) δ 8.17
(m, 1 H, 4-H, JH,F = 0.4 Hz); 13C NMR (50 MHz, CDCl3)
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 2 4 6 – 2 5 6
252

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δ 154.9 (2-C), 151. 5 (6-C), 137.0 (m, 4-C, JC,F = 5 Hz), 121.5
(q, CF3, JC,F = 270.5 Hz), 121.3 (q, CF3, JC,F = 271.5 Hz), 121.0
(q, 5-C, JC,F = 34.5 Hz), 114.2 (q, 3-C, JC,F = 34.9 Hz); IR (neat
film) 2153 vs (vazide), 1609 vs, 1561 vs, 1508 w, 1438 m, 1413 m,
C7H6N2ClF3O: C, 37.11; H, 2.67; N, 12.36%. Found: C, 37.06;
H, 2.68; N, 12.48%.
6-Chloro-2-ethoxy-4-trifluoromethyl-1H-1,3-diazepine 14b
1310 vs, 1279 vs, 1266 vs, 1147 vs, 1055 vs, 947 m, 774 w cmϪ1
;
Purified by double Kugelrohr distillation (0.1–0.5 mm Hg, 40–
60 ЊC) to afford yellow–orange crystalline solid, mp 75–76 ЊC;
MS (EI) m/z 290 (Mϩ, 25 %), 262 (100), 243 (15), 227 (14), 212
(9), 172 (21), 167 (15), 156 (13), 150 (7), 141 (14), 132 (8), 127
(7), 120 (10), 112 (8), 98 (10), 89 (7), 86 (6) 82 (6), 75 (9).
HRMS, calcd. for 12C7H1ClF6N4: 289.9797; found: 289. 9793.
Anal. calcd. for C7H1ClF6N4: C, 28.94; H, 0.35; N, 19.28%.
Found: C, 28.84; H, 0.37; N, 19.62%.
1
yield: 57%. H NMR (400 MHz, CDCl3) δ 5.88 (s, 1 H, 5-H),
5.68 (d, 1 H, 7-H, J1,7 = 7.0 Hz), 4.92 (br, 1 H, N-H ), 4.20 (q, 2
H, OCH2CH3, JCH2 CH3
JCH2 CH3
= 6.9 Hz); 13C NMR (100 MHz, CDCl3) δ 158.5 (2-C),
139.6 (q, 4-C, JC,F = 31.6 Hz), 128.9 (7-C), 121.0 (q, CF3, JC,F
,
= 6.9 Hz), 1.26 (t, 3 H, OCH2CH3,
,
=
273.6 Hz), 117.7 (q, 5-C, JC,F = 4.7 Hz), 116.6 (6-C), 65.8
(OCH2CH3), 13.8 (OCH2CH3); MS (EI) m/z 240 (Mϩ, 38%),
212 (66), 197 (11), 177 (26), 176 (34), 169 (36), 157 (17), 149
(49), 143 (30), 122 (15), 115 (100), 114 (26), 87 (13), 79 (17), 69
(26), 52 (26). HRMS, calcd. for 12C8H8N2ClF3O: 240. 0277;
found: 240.0274. Anal. calcd. for C8H8N2ClF3O: C, 39.94; H,
3.35; N, 11.64%. Found: C, 39.78; H, 3.34; N, 11.57%.
General procedures for the synthesis of 1,3-diazepines
The azides/tetrazoles (100–150 mg) were photolysed in N2-
purged dioxane solutions using a quartz vessel. Alcohols
were dried using magnesium metal, amines were refluxed
over and distilled from potassium hydroxide, and dioxane was
distilled from Na metal immediately prior to use. Products
were purified by column chromatography and/or Kugelrohr
distillation.
4-Chloro-2-diethylamino-4-methoxy-5H-1,3-diazepine 11a
For the synthesis of 2-alkoxy-4-dialkylamino-5H-1,3-diaze-
pines the starting azido/tetrazolo[1,5-a]pyridine (ca. 1 mmol)
was dissolved in a mixture of absolute dioxane (120 ml) and the
appropriate alcohol (20–30 ml) in a quartz vessel. The mixture
was purged with high purity dry nitrogen for about 1 h. The
degassed solution was irradiated with the high pressure Hg/Xe
lamp while stirring the mixture in an ice bath. Reaction times
were usually 1–2 h. The resulting crude reaction mixture was
removed from the UV source, divided into two equal portions,
and an appropriate amine was added into each half with
stirring. When dimethylamine was needed, the gas was passed
directly into the reaction mixture, or a saturated solution of
dimethylamine (large excess) in dioxane was used. While stir-
ring, the solution was then allowed to warm to room temper-
ature (30 min). The volume was reduced under vacuum, and the
resulting oily residue was purified by chromatography on
deactivated aluminium oxide (90, neutral). The aluminium
oxide was deactivated by aqueous methanol (20%) and then
dried in the air overnight at room temperature. The low volatil-
ity of these compounds does not usually permit purification by
distillation even under very low pressure (10Ϫ4–10Ϫ5 bar), and
mainly decomposition-polymerization occurs at temperatures
as low as 80–100 ЊC.
The crude residue was chromatographed on deactivated silica
gel 100 using CH2Cl2/MeOH (20 : 1) as an eluent to give 11a
1
as a red oil; yield: 87%. H NMR (200 MHz, CDCl3) δ 6.69
(s, 1H, 7-H), 3.74 (s, 3H, OCH3), 3.37 (q, 4H, N(CH2CH3)2,
J = 7.0 Hz), 2.99 (s, 2H, 5-H), 1.08 (t, 6H, N(CH2CH3)2,
J = 7.0 Hz); 13C NMR (50 MHz, CDCl3) δ 158.5 (4-C), 153.3
(2-C), 135.9 (7-C), 102.8 (6-C), 55.1 (OCH3), 41.7 N(CH2CH3)2,
39.5 (5-C), 13.3 N(CH2CH3)2; IR (neat film) 2975 m, 2958 m,
1650 vs, 1637 m, 1548 vs, 1523 m, 1407 m, 1391 m, 1379 m, 1369
m, 1324 vs, 1319 s, 1282 s, 1257 s, 1194 m, 1181 m, 1084 w, 1039
m, 909 w, 904 w, 853 w, 801 w, 752 w. MS (EI) m/z 229 (Mϩ,
100%), 214 (44), 202 (29), 200 (91), 194 (48), 188 (9), 186 (25),
166 (20), 159 (28), 157 (35), 149 (12), 141 (18), 143 (46), 132
(27), 123 (16), 115 (30), 88 (14), 72 (96), 56 (32), 53 (14). HRMS,
12
calcd. for C10H16N3ClO: 229.0986; found: 229. 0983. Anal.
calcd. for C10H16N3ClO: C, 52.29; H, 7.02; N, 18.29%. Found:
C, 52.34; H, 7.25; N, 18.18%.
4-Chloro-2-diisopropylamino-4-methoxy-5H-1,3-diazepine 11b
The crude residue was chromatographed on deactivated silica
gel 100 using hexane/ethyl acetate (10 : 90) or CH2Cl2/MeOH
1
(100 : 1) as an eluent to give 11b as a red oil; yield: 78%. H
2-Dialkylamino-5H-diazepines were prepared by photolysis
of the corresponding tetrazolo[1,5-a]-pyridines in the presence
of the appropriate secondary amine. All products were unstable
and slowly decomposed when neat and exposed to air at room
temperature, but were more stable in the fridge and/or in
solution.
NMR (200 MHz, CDCl3) δ 6.59 (s, 1H, 7-H), 4.10 (br, 2H, iPr,
J = 6.9 Hz), 3.68 (s, 3H, OCH3), 2.88 (s, 2H, 5-H), 1.14 (d, 12H,
iPr, J = 6.9 Hz); 13C NMR (50 MHz, CDCl3) δ 156.8 (4-C),
153.4 (2-C), 136.0 (7-C), 101.5 (6-C), 55.0 (OCH3), 45.2 (iPr),
39.4 (5-C), 20.8 (iPr); IR (neat film) 2989 m, 2972 m, 1643 vs,
1625 m, 1545 vs, 1511 m, 1442 m, 1409 m, 1389 m, 1372 m, 1363
m, 1360 m, 1319 s, 1282 s, 1252 s, 1192 m, 1187 m, 1154 w, 1070
w, 107 m, 905 w, 890 w, 872 w, 834 w, 754 w. MS (EI) m/z 257
(Mϩ, 30%), 214 (100), 200 (30), 178 (15), 166 (18), 159 (20), 157
(61), 145 (24), 136 (22), 132 (28), 117 (11), 115 (22), 100 (9), 97
(10), 88 (16), 80 (19), 69 (42). HRMS, calcd. for 12C12H20N3OCl:
257. 1295; found: 257.1298. Anal. calcd. for : C12H20N3OCl: C,
55.92; H, 7.82; N, 16.30%. Found: C, 55.81; H, 7.67; N, 16.72%.
6-Chloro-2-methoxy-4-trifluoromethyl-1H-1,3-diazepine 14a
Purified by Kugelrohr distillation (40–60 ЊC, 0.1–0.5 mm Hg)
followed by recrystallization from petroleum ether. Yellow–
orange needles; mp 75–76 ЊC; yield: 49%. 1H NMR (400 MHz,
CDCl3) δ 5.89 (br s, 1 H, 5-H), 5.67 (br s, 1 H, 7-H), 4.76 (br s,
1 H, N-H ), 3.77 (OCH3); 13C NMR (100 MHz, CDCl3) δ 158.9
(2-C), 139.5 (q, 4-C, JC,F 31.6 Hz), 128.6 (7-C), 120.7 (q, CF3,
JC,F = 273.6 Hz), 117.9 (q, 5-C, JC,F = 4.7 Hz), 116.8 (6-C); IR
(KBr) 3264 br (NH ), 3086.0 m, 3018.7 w, 3000.5 w, 2951.6 m,
1669.2 s, 1652.0 s, 1629.4 s, 1486.4 m, 1459.6 m, 1384.6 m,
1336.2 m, 1291.9 vs, 1278.1 vs, 1206.5 w, 1181.1 m, 1168.4 s,
1156.8 s, 1124.2 vs, 1082.6 m, 1057.7 w, 1009.3 s, 987.6 w,
901.1 m, 845.8 w, 831.3 m, 802.6 m, 767.9 w, 733.1 m, 710.7 m,
684.1 m, 626.8 w cmϪ1; MS (EI) m/z 226 (Mϩ, 100%), 207 (5),
199 (5), 191 (5), 184 (19), 183 (5), 176 (36), 171 (20), 169 (64),
167 (5), 156 (6), 155 (5), 151 (6), 150 (10), 149 (17), 148 (20), 144
(13), 142 (32), 134 (9), 129 (8), 118 (11), 116 (7), 114 (26), 91 (7),
69 (12), 58 (41), 57 (6), 52 ( 6), 43 (17). HRMS, calcd. for
12C7H6N2ClF3O: 226. 01207; found: 226.01233. Anal. calcd. for
4-Chloro-2-diethylamino-4-ethoxy-5H-1,3-diazepine 11c
The crude residue was chromatographed on deactivated silica
gel 100 using CH2Cl2/MeOH (20 : 1) as an eluent to give 11c as
a red oil; yield: 89%. 1H NMR (200 MHz, CDCl3) δ 6.74 (s, 1H,
7-H), 4.19 (q, 2H, (OCH2CH3), J = 7.0 Hz), 3.42 (q, 4H,
N(CH2CH3)2, J = 7.0 Hz), 3.01 (s, 2H, 5-H), 1.30 (t, 3H,
OCH2CH3), 1.11 (t, 6H, N(CH2CH3)2, J = 7.0 Hz); 13C NMR
(50 MHz, CDCl3) δ 158.5 (4-C), 153.9 (2-C), 135.6 (7-C), 102.6
(6-C), 64.0 (OCH2CH3), 41.8 N(CH2CH3)2, 39.9 (5-C), 13.9
(OCH2CH3), 13.3 N(CH2CH3)2; IR (neat film) 2975 m, 2963 m,
1640 vs, 1625 w, 1529 vs, 1429 m, 1405 m, 1373 m, 1370 m, 1318
s, 1284 s, 1251 s, 1194 m, 1189 m, 1080 w, 1039 m, 904 w, 901 w,
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 2 4 6 – 2 5 6
253

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857 w, 760 w. MS (EI) m/z 243 (Mϩ, 79%), 216 (33), 214 (100),
203 (30), 200 (16), 186 (23), 180 (25), 172 (21), 157 (11), 150
(10), 145 (20), 144 (26), 143 (45), 100 (10), 97 (12), 82 (16),
4-Diethylamino-2-methoxy-5H-1,3-diazepine 25b
Purified by column chromatography (Al2O3 90/neutral-deactiv-
ated) eluting with diethyl ether : hexane (10 : 1). Pale pink oil;
12
75 (11), 72 (62), 56 (9). HRMS, calcd. for: C11H18N3OCl:
1
yield: 84%. H NMR (acetone-d6, 301 K, 400 MHz) δ 6.52 (d,
243.1136; found: 243. 1145. Anal. calcd. for C11H18N3OCl:
C, 54.21; H, 7.44; N, 17.24%. Found: C, 53.91; H, 7.65; N,
16.88%.
1 H, 7-H, J6,7 = 6.52 Hz), 4.78 (q, 1 H, 6-H, J6,7 = 6.52, J5,6
=
6.80 Hz), 3.59 (s, 3 H, OCH3), 3.42 (q, 4 H, NCH2CH3 3J = 7.12
Hz), 2.75 (d, 2 H, 5-H, J5,6 = 6.80 Hz), 1.18 and 1.05 (t, 6 H,
3
NCH2CH3, J = 7.12 Hz); 13C NMR (acetone-d6, 100 MHz)
4-Chloro-2-diisopropylamino-4-ethoxy-5H-1,3-diazepine 11d
δ 160.6 (2-C), 155.1 (4-C), 139.8 (7-C), 102.9 (6-C), 53.0
(OCH3),43.8and44.0(NCH2CH3),29.9(C-5),14.3and12.4(NCH2-
CH3); IR (neat) 2976 m, 2938 w, 1603.9 vs, 1575.3 vs, 1520.4 vs,
1475.7 m, 1429.6 m, 1381.4 w, 1362.2 w, 1312.6 vs, 1275.9 s,
1248.8 vs, 1213.0 vs, 1148.1 m, 1117.1 w, 1080.1 w, 1053.3 m,
1021.3 w, 882.1 m, 805.0 w, 778.0 w, 701.8 m cmϪ1; MS (EI)
m/z 195 (Mϩ, 100%), 180 (88), 166 (21), 152 (11), 124 (21), 113
The crude residue was chromatographed on deactivated silica
gel 100 using CH2Cl2/MeOH (95 : 5) as an eluent to give 11d
1
as a red oil; yield: 75%. H NMR (200 MHz, CDCl3) δ 6.68
(s, 1H, 7-H), 4.16 (q, 2H, OCH2CH3, J = 7.0 Hz), 4.15 (br,
2H, iPr, J = 6.8 Hz), 2.93 (s, 2H, 5-H), 1.27 (t, 3H, OCH2CH3,
J = 7.0 Hz), 1.20 (d, 12H, iPr, J = 6.8 Hz); 13C NMR (50 MHz,
CDCl3) δ 156.5 (4-C), 153.6 (2-C), 135.5 (7-C), 102.2 (6-C), 64.0
(OCH2CH3), 45.6 (iPr), 39.9 (5-C), 20.7 (iPr), 14.0 (OCH2-
CH3). IR (neat film) 2977 m, 2959 m, 1651 vs, 1632 m, 1548 vs,
1528 m, 1433 m, 1408 m, 1354 m, 1373 m, 1369 m, 1319 s, 1284
s, 1253 s, 1234 m, 1192 m, 1187 m, 1073 w, 1041 m, 906 w, 901 w,
853 w, 766 w. MS (EI) m/z 271 (Mϩ, 29%), 242 (12), 230 (33),
228 (100), 200 (22), 172 (13), 165 (12), 158 (20), 143 (18),
118 (24), 115 (27), 111 (13), 100 (9), 90 (19), 83 (47), 69 (41), 58
(25), 53 (23), 43 (53), 41 (56). HRMS calcd. for: 12C13H22N3OCl:
271.1450; found: 271.1456. Anal. calcd. for: C13H22N3OCl:
C, 57.45; H, 8.16; N, 15.46%. Found: C, 57.34, H, 8.51; N,
15.29%.
12
(13), 81 (12), 72 (12), 54 (22). HRMS, calcd. for C10H17N3O:
195.1373; found: 195.1372. Anal. calcd. for C10H17N3O: C,
61.51; H, 8.78; N, 21.52%. Found: C, 61.59; H, 8.88; N,
21.39%.
4-Diisopropylamino-2-methoxy-5H-1,3-diazepine 25c
Purified by column chromatography (Al2O3 90/neutral-deactiv-
ated) eluting with diethyl ether. Pale yellow solid; mp 46–47 ЊC;
1
yield: 92%. H NMR (acetone-d6, 297 K, 500 MHz) δ 6.54 (d,
7 H, 1-H, J6,7 = 6.50 Hz), 4.71 (q, 6 H, 1-H, J6,7 = 6.50 Hz), 4.09
br (2 H, NiPr), 3.59 (s, 3 H, OCH3), 2.78 br (2 H, 5-H), 1.23 and
1.12 br (12 H, NiPr); 13C NMR (acetone-d6, 297 K, 125 MHz)
δ 159.6 (2-C), 153.5 br (4-C), 139.6 (7-C), 103.0 (6-C), 53.0
(OCH3), 48.1 br (2 × CH, NiPr), 32.6 (5-C), 21.5 and 20.2 br
(4 × CH3, NiPr); IR (KBr) 2980 m, 2963 m, 1605.0 vs, 1561.4 vs,
1510.7 vs, 1482.6 s, 1459.7 m, 1424.9 m, 1385.4 m, 1371.0 s,
1290.4 s, 1247.9 s, 1209.6 s, 1191.8 m, 1180.5 m, 1147.1 s, 1111.9
w, 1059.6 w, 1026.9 w, 1008.6 w, 876.0 w, 777.2 w, 759.8 w, 754.4
w, 702.2 m, 621 w cmϪ1; MS (EI) m/z 223 (Mϩ, 73%), 208 (10),
180 (100), 166 (15), 143 (14), 138 (39), 124 (13), 123 (24), 108
(8), 98 (9), 81 (16), 70 (9), 57 (23), 54 (15), 43 (23), 41 (16).
2,4-Dipyrrolidino-5H-1,3-diazepine 23
Purified by column chromatography (Al2O3, dichloromethane/
methanol, 3%) and decolourized by charcoal to obtain 23
1
as a yellow oil; yield 33%. H NMR (400 MHz, acetone-d6)
δ 6.55 (d, 1 H, 7-H, J6,7 = 7.6 Hz), 5.27 (q, 1 H, 6-H, J6,7
=
7.6 Hz, J5,6 = 7.0 H), 3.75 (t, 4 H, pyrrolidine, J = 6.7 Hz), 3.56
(t, 4 H, pyrrolidine, J = 7.0 Hz), 3.18 (d, 2 H, 5-H, J5,6 = 7.0 Hz),
2.02 (quint, 4 H, pyrrolidine, J = 6.7 Hz), 1.94 (quint, 4 H,
J = 7.0 Hz); 13C NMR (100 MHz, acetone-d6) δ 157.4 (2-C),
152.6 (4-C), 129.5 (7-C), 104.3 (6-C), 49.4 and 48.9 (pyrrol-
idine), 31.6 (5-C), 26.1 and 15.1 (pyrrolidine); IR (neat film)
2974.3m, 2878.5 m, 1661.9 m, 1615.8 vs, 1579.0 vs, 1575.4 vs,
1516.4 w, 1447.1 vs, 1435 vs, 1374.3 w, 1338.3 m, 1260.2 w,
1244.2 w, 1188.2 w, 1123.1 w, 1019.4 w, 974.8 w, 873.7 w, 695.0
cmϪ1. MS (EI) m/z 232 (Mϩ, 100%), 217 (77), 203 (52), 189 (28),
177 (24), 176 (23), 163 (30), 162 (39), 148 (10), 135 (38),
120 (17), 108 (21), 93 (14), 81 (23), 72 (28), 69 (19), 55 (22),
12
HRMS, calcd. for C12H21N3O: 223.1687; found: 223.1678.
Anal. calcd. for C12H21N3O: C, 64.54; H, 9.48; N, 18.82%.
Found: C, 64.37; H, 9.66; N, 18.64%.
2-Methoxy-4-pyrrolidino-5H-1,3-diazepine 25d
Purified by column chromatography (Al2O3 90/neutral-deactiv-
ated) eluting with ethyl actate. Yellow oil; yield: 74%. 1H NMR
(acetone-d6, 301 K, 400 MHz) δ 6.50 (d, 1 H, 7-H, J6,7 = 6.52
Hz), 4.82 (q, 1 H, 6-H, J6,7 = 6.52, J5,6 = 6.92 Hz), 3.60 (s, 3 H,
12
3
41 (32), 39 (28). HRMS, calcd. for C13H20N4 : 232.1688;
OCH3), 3.50 and 3.35 (t, 4 H, pyrrolidine ring, J = 6.88 Hz),
found: 232.1690. Anal. calcd. for: C13H20N4: C, 67.21; H, 8.68;
N, 24.12%. Found: C, 67.28; H, 8.41; N, 23.89%.
2.71 (d, 2 H, 5-H, J5,6 = 6.92 Hz), 1.94 and 1.84 (qnt, 4 H,
3
pyrrolidine ring, J = 6.88 Hz); 13C NMR (acetone-d6, 301 K,
100 MHz) δ 160.4 (2-C), 154.5 (4-C), 139.7 (7-C), 101.6 (6-C),
53.0 (OCH3), 48.4 and 47.9 (pyrrolidine ring), 31.6 (C-5), 26.3
and 25.2 (pyrrolidine ring); IR (neat film) 2971 m, 2962 m,
1615.0 vs, 1567.4 vs, 1511.0 vs, 1483.1 s, 1479.8 m, 1434.1 m,
1382.2 m, 1374.7 s, 1294.4 s, 1249.1 s, 1181.7 m, 1170.1 m,
1156.4 m, 1146.7 s, 1112.3 w, 1061.5 w, 1023.9 w, 1008.6 w,
4-Dimethylamino-2-methoxy-5H-1,3-diazepine 25a
Purified by column chromatography (Al2O3 90/neutral-deactiv-
ated) eluting with diethyl ether, followed by diethyl ether/ethyl
acetate (50 : 50) mixture to remove minor impurities. The
product, pale yellow oil, was then eluted using ethyl acetate
987.2 w, 787.8 w, 769.1 w, 751.2 w, 734.1 m, 702.9 m, cmϪ1
;
1
only; yield: 62.5%. H NMR (acetone-d6, 301 K, 400 MHz)
12
HRMS, calcd. for C10H15N3O: 193.1215; found: 193.1217.
Anal. calcd. for C10H15N3O: C, 62.15; H, 7.82; N, 21.74%.
Found: C, 62.41; H, 8.19; N, 21.51%.
δ 6.51 (d, 1 H, 7-H, J6,7 = 6.52 Hz), 4.82 (q, 1 H, 6-H, J6,7 = 6.52,
J5,6 = 7.00 Hz), 3.60 (s, 3 H, OCH3), 3.07 (s, 3 H, NCH3), 2.94
(s, 3 H, NCH3), 2.73 (d, 2 H, 5-H, J5,6 = 7.00 Hz); 13C NMR
(acetone-d6, 301 K, 100 MHz) δ 160.3 (2-C), 156.5 (4-C), 139.7
(7-C), 101.9 (6-C), 53.1 (OCH3), 38.4 (br, N(CH3)2), 30.0 (5-C);
IR (neat) 1605.4 vs, 1583.6 vs, 1524.6 vs, 1438.7 m, 1415.6 m,
1308.1 s, 1281.4 m, 1249.0 s, 1209.4 w, 1154.5 w, 1116.9 w,
1051.3 m, 1003 w, 887.1 w, 778.3 w, 706.2 m, 618.5 w cmϪ1; MS
(EI) m/z 167 (Mϩ, 100%), 152 (47), 137 (13), 125 (18), 109 (9),
85 (15), 82 (77), 70 (8), 66 (5), 54 (12). HRMS, calcd. for
12C8H13N3O: 167.1059; found: 167.1054. Anal. calcd. for C8H13-
N3O: C, 57.46; H, 7.84; N, 25.13%. Found: C, 57.41; H, 7.53; N,
24.88%.
4-Dimethylamino-2-ethoxy-5H-1,3-diazepine 25e
Purified by column chromatography (Al2O3 90/neutral-deactiv-
ated) eluting with diethyl ether/hexane (1 : 1) followed by ether
to obtain pale red oil; yield: 52%. 1H NMR (acetone-d6, 301 K,
400 MHz) δ 6.50 (d, 1 H, 7-H, J6,7 = 6.52 Hz), 4.81 (q, 1 H, 6-H,
J6,7 = 6.52, J5,6 = 6.90 Hz), 4.05 (q, 2 H, OCH2CH3, J = 7.08 Hz),
3.06 and 2.93 (s, 6 H, NCH3), 2.73 (d, 2 H, 5-H, J5,6 = 6.90 Hz),
1.20 (t, 3 H, OCH2CH3, J = 7.08 Hz); 13C NMR (acetone-d6,
301 K, 100 MHz) δ 159.8 (2-C), 156.4 (4-C), 139.9 (7-C), 101.6
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 2 4 6 – 2 5 6
254

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(6-C), 61.4 (OCH2CH3), 38.4 (br, N(CH3)2), 29.8 (5-C), 14.9
(OCH2CH3); IR (neat) 2977.3 w, 1604.6 vs, 1583.2 vs, 1520.3 vs,
1444.6 m, 1418.9 m, 1361.8 m, 1301.1 s, 1243.2 s, 1207.9 m,
1154.8 w, 1107.5 w, 1052.3 m, 1005.2 w, 883.9 w, 787.3 w, 704.2
m cmϪ1; MS m/z 181 (Mϩ, 100%), 152 (47), 137 (13), 125 (18),
109 (9), 85 (15), 82 (77), 70 (8), 66 (5), 54 (12). HRMS, calcd. for
12C9H15N3O: 167.1059; found: 167.1054. Anal. calcd. for C9H15-
N3O: C, 59.64; H, 8.34; N, 23.18%. Found: C, 59.63; H, 8.35; N,
23.18%.
195.1372. Anal. calcd. for C10H17N3O: C, 61.51; H, 8.78; N,
21.52%. Found: C, 61.30; H, 8.99; N, 21.58%.
4-Diethylamino-2-isopropoxy-5H-1,3-diazepine 25i
Purified by column chromatography (Al2O3 90/neutral-deactiv-
ated) eluting with diethyl ether. Pale yellow oil; yield: 72%.
1H NMR (acetone-d6, 301 K, 500 MHz) δ 6.49 (d, 1 H, 7-H,
J6,7 = 6.50 Hz), 4.96 (sep, 1 H, OCH(CH3)2, J = 6.00 Hz), 4.76
(q, 1 H, 6-H, J6,7 = 6.50, J5,6 = 7.00 Hz), 3.41 (q, 4 H,
N(CH2CH3)2, J = 7.00 Hz), 2.74 (d, 2 H, 5-H, J5,6 = 7.00 Hz),
1.18 (d, 6 H, OCH(CH3)2, J = 6.00 Hz), 1.05 (br t, 6 H,
NCH2CH3, J = 7.00 Hz); 13C NMR (acetone-d6, 301 K, 125
MHz) δ 159.1 (2-C), 154.7 (4-C), 139.6 (7-C), 102.2 (6-C), 67.0
(OCH(CH3)2), 43.7 (N(CH2CH3)2), 29.7 (C-5), 22.1 (OCH-
(CH3)2), 14.0 and 12.2 (NCH2CH3); IR (neat film) 2975.7 m,
2934.6 w, 1602.6 vs, 1575.3 vs, 1520.0 vs, 1471.5 m, 1432.6 m,
1381.3 w, 1368.3 w, 1350.6 m, 1329.3 m, 1305.3 m, 1270.2 vs,
1251.6 vs, 1212.7 vs, 1195.9 w, 1141.0 w, 1111.9 m, 1079.9 m,
1030.6 w, 986.8 w, 936.5 w, 881.8 m, 801.4 w, 783.0 w, 699.6 m
cmϪ1; MS m/z 223 (Mϩ, 83%), 181 (45), 166 (47), 165 (100), 150
(42), 136 (47), 110 (35), 99 (62), 82 (59), 72 (38), 56 (39), 43 (38).
4-Diethylamino-2-ethoxy-5H-1,3-diazepine 25f
Purified by column chromatography (Al2O3 90/neutral-deactiv-
1
ated) eluting with diethyl ether. Pale red oil; Yield: 79%. H
NMR (acetone-d6, 301 K, 400 MHz) δ 6.50 (d, 1 H, 7-H, J6,7
=
6.64 Hz), 4.77 (q, 1 H, 6-H, J6,7 = 6.64, J5,6 = 7.08 Hz), 4.05
(q, 2 H, OCH2CH3, J = 7.08 Hz), 3.42 (q, 4 H, NCH2CH3,
J = 7.06 Hz), 2.75 (d, 2 H, 5-H, J5,6 = 7.08 Hz), 1.20 (t,
3 H, OCH2CH3, J = 7.08 Hz), 1.06 br (t, 6 H, NCH2CH3,
J = 7.06 Hz); 13C NMR (acetone-d6, 100 MHz) δ 160.0 (2-C),
155.1 (4-C), 139.9 (7-C), 102.8 (6-C), 61.4 (OCH2CH3), 44.0
and 43.8 (NCH2CH3), 30.1 (C-5), 14.9, 14.9 (OCH2CH3), 14.3
and 12.5 (NCH2CH3); IR (neat film) 2976.8 m, 2934.5 w, 1603.8
s, 1575.4 vs, 1520.2 vs, 1472.3 m, 1381.4 w, 1359.3 m, 1309.4 s,
1271.2 s, 1248.9 vs, 1212.0 vs, 1148.9 m, 1117.3 w, 1080.0 w,
1053.9 m, 881.2 w, 803.5 w, 787.6.0 w, 700.7 m cmϪ1; MS (EI)
m/z 209 (Mϩ, 100%), 194 (33), 181 (18), 165 (41), 150 (23), 136
(25), 127 (9), 109 (21), 99 (21), 82 (100), 72 (18), 56 (25), 43 (23).
12
HRMS, calcd. for C12H21N3O: 223.1688; found: 223.1687.
Anal. calcd. for C12H21N3O: C, 64.54; H, 9.48; N, 18.82%.
Found: C, 64.97; H, 9.61; N, 18.60%.
4-Diisopropylamino-2-isopropoxy-5H-1,3-diazepine 25j
12
Purified by column chromatography (Al2O3 90/neutral-deactiv-
ated) eluting with diethyl ether. Pale yellow oil; yield: 65%.
1H NMR (acetone-d6, 301 K, 400 MHz) δ 6.53 (d, 7 H, 1-H,
J6,7 = 6.48 Hz), 4.96 (sep, 1 H, OiPr, J = 6.16 Hz), 4.68 (q, 6 H,
1-H, J6,7 = 6.48, J6,5 = 6.48 Hz), 4.12 br (2 H, N(iPr)2), 2.79 br
(2 H, 5-H), 1.25 br (12 H, N(iPr)2), 1.20 (d, 6 H, OiPr,
J = 6.16 Hz); 13C NMR (acetone-d6, 301 K, 100 MHz) δ 158.6
(2-C), 153.4 br (4-C), 139.6 (7-C), 102.6 (6-C), 67.3 (OiPr), 48.0
br (2 × CH, NiPr), 32.8 (5-C), 22.4 (2 × CH3, OiPr), 21.6 and
20.1 br (4 × CH3, NiPr); IR (KBr) 2974.6 m, 2934.0 m, 1600.7
m, 1557.8 vs, 1505.6 vs, 1463.3 s, 1372.4 s, 1284.5 s, 1251.2 s,
1203.5 m, 1154.8 m, 1108.2 s, 1040.4 w, 936.6 w, 781.5 w, 698.0
w cmϪ1; MS (EI) m/z 251 (Mϩ, 40%), 209 (19), 208 (16), 193
(38), 178 (28), 166 (53), 152 (11), 150 (38), 123 (40), 120 (32),
118 (90), 116 (100), 111 (15), 108 (89), 85 (35), 84 (27), 83 (44),
82 (47), 81 (52), 59 (48), 58 (45), 43 (59), 28 (42). HRMS, calcd.
HRMS, calcd. for C11H19N3O: 209.1525; found: 209.1527.
Anal. calcd. for C11H19N3O: C, 63.13; H, 9.15; N, 20.08%.
Found: C, 62.98; H, 9.19; N, 19.85%.
4-Diisopropylamino-2-ethoxy-5H-1,3-diazepine 25g
Purified by column chromatography (Al2O3, 90/ neutral,
deactivated) eluting with ether/hexane (3 : 1) mixture. Yield:
87.7%. 1H NMR (acetone-d6, 301 K, 400 MHz) δ 6.53 (d, 1 H,
7-H, J6,7 = 6.48 Hz), 4.65 (q, 1 H, 6-H, J6,7 = 6.48, J5,6 = 6.52 Hz),
4.11 (app. sep, br, 2 H, N(CH(CH3)2)2), 4.06 (q, 2 H, OCH2CH3,
J = 7.08 Hz), 2.76 (br, 2 H, 5-H), 1.25 (d, br, 12 H, N(CH-
(CH3)2)2, J = 6.76 Hz), 1.12 (t, 3 H, OCH2CH3, J = 7.08 Hz); 13
C
NMR (acetone-d6, 301 K, 100 MHz) δ 159.3 (2-C), 153.5 (4-C),
139.8 (7-C), 102,8 (6-C), 61.3 (OCH2CH3), 48.1 (N(CH-
(CH3)2)2), 21.6 and 20.2 (br, N(CH(CH3)2)2), 15.0 (OCH2CH3);
IR (neat film) 2974.2 m, 2934.5 w, 1601.4 s, 1558.9 vs, 1515.8 vs,
1462.4 m, 1370.9 m, 1348.4 m, 1285.3 vs, 1248.5 s, 1202.3 m,
1153.3 m, 1135.2 m, 1107.1 w, 1058.7 m, 1036.4 w, 1006.0 w,
873.6 w, 785.6 w, 766.1 w, 697.0 m, 623 w cmϪ1; MS m/z 237
(Mϩ, 100%), 222 (9), 208 (6), 194 (99), 180 (9), 166 (14), 152
(19), 138 (7), 123 (33), 108 (41), 82 (δ), 71 (33), 58 (20), 56 (21),
12
for C14H25N3O: 251.199838; found: 251.199213. Anal. calcd.
for C14H25N3O: C, 66.89; H, 10.02; N, 16.72%. Found: C, 66.71;
H, 9.97; N, 16.97%.
2-Isopropoxy-4-pyrrolidino-5H-1,3-diazepine 25k
12
Purified by column chromatography (Al2O3 90/neutral-deactiv-
54 (24). HRMS, calcd. for C13H23N3O: 237.1849; found:
ated) eluting with diethyl ether/methylene chloride (10 : 2)
237.1841. Anal. calcd. for C13H23N3O: C, 65.88; H, 9.77; N,
17.70%. Found: C, 65.71; H, 9.90; N, 17.41%.
1
solvent mixture. Yellow oil; yield: 65%. H NMR (acetone-d6,
301 K, 500 MHz) δ 6.47 (d, 1 H, 7-H, J6,7 = 6.50 Hz), 4.96 (sep,
1 H, OiPr, J = 6.50 Hz), 4.80 (q, 1 H, 6-H, J6,7 = 6.50, J5,6
=
4-Dimethylamino-2-isopropoxy-5H-1,3-diazepine 25h
7.00 Hz), 3.49 and 3.34 (t, 4 H, pyrrolidine ring, J = 7.00 Hz),
2.70 (d, 2 H, 5-H, J5,6 = 7.00 Hz), 1.94 and 1.84 (qnt, 4 H,
pyrrolidine ring, J = 7.00 Hz), 1.18 (d, 6 H, OiPr, J = 6.50 Hz);
13C NMR (acetone-d6, 301 K, 125 MHz) δ 159.4 (2-C), 154.4
(4-C), 139.8 (7-C), 101.2 (6-C), 67.3 (OiPr), 48.3 and 47.9
(pyrrolidine ring), 31.6 (C-5), 26.3 and 25.2 (pyrrolidine ring),
22.3 (OiPr); IR (neat film) 2974.2 m, 2873.6 w, 1601.9 s, 1575.4
vs, 1520.0 vs, 1483.1 s, 1460.2 m, 1380.8 w, 1368.7 w, 1350.8 m,
1326.8 w, 1280.2 vs, 1248.4 vs, 1189.3 w, 1125.4 w, 1109.9 m,
Purified by column chromatography (Al2O3 90/neutral-deactiv-
ated) eluting with diethyl ether. Pale pink solid, mp 64–65 ЊC;
1
yield: 63%. H NMR (acetone-d6, 301 K, 500 MHz) δ 6.50 (d,
1 H, 7-H, J6,7 = 6.50 Hz), 4.99 (sep, 1 H, OCH(CH3)2, J = 6.50
Hz), 4.78 (q, 1 H, 6-H, J6,7 = 6.50, J5,6 = 7.00 Hz), 2.99 (br s, 6 H,
N(CH3)2), 2.72 (d, 2 H, 5-H, J5,6 = 7.00 Hz), 1.20 (d, 6 H,
OCH(CH3)2, J = 6.50 Hz); 13C NMR (acetone-d6, 301 K, 125
MHz) δ 159.2 (2-C), 156.3 (4-C), 139.9 (7-C), 101.4 (6-C), 67.3
(OCH(CH3)2), 38.4 (br, N(CH3)2), 29.8 (5-C), 22.3 (OCH-
(CH3)2); IR (KBr) 3023.2 w, 2971.1 w, 1605.0 vs, 1589.2 s,
1522.9 vs, 1438.0 w, 1416.2 w, 1369.3 w, 1328.2 m, 1294.0 m,
1280.1 s, 1250.9 s, 1206.3 m, 1172.4 w, 1143.3 w, 1108.6 s, 1008.7
m, 929.7 w, 885.1 m, 782.7 w, 701.5 m cmϪ1; MS (EI) m/z 195
(Mϩ, 60%), 153 (39), 138 (60), 137 (91), 136 (34), 109 (48), 71
(79), 43 (33). HRMS, calcd. for 12C10H17N3O: 195.1374; found:
1020.3 m, 968.4 w, 935.5 w, 884.2 m, 783.4 w, 696.7 m cmϪ1
;
MS (EI) m/z 221 (Mϩ, 92%), 179 (55), 164 (64), 163 (99),
162 (53), 131 (78), 119 (100), 110 (23), 109 (32), 100 (32),
97 (40), 82 (45), 70 (85), 55 (56), 43 (40), 41 (39). HRMS, calcd.
12
for C12H19N3O: 221.1527; found: 221.1528. Anal. calcd. for:
C, 65.13; H, 8.65; N, 18.99%. Found: C, 65.32, H, 8.77, N,
18.64%.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 2 4 6 – 2 5 6
255

View Article Online
5,7-Bis(trifluoromethyl)-4-diethylamino-2-ethoxy-5H-1,3-
diazepine 40
192 (14), 191 (100), 190 (6), 188 (16), 180 (5), 176 (12), 174 (9),
149 (6), 148 (9), 134 (14), 107 (4), 106 (7), 43 (19), 41 (7).
12
HRMS, calcd. for C25H38N6: 422.3158; found: 422. 3157.
Purified by column chromatography (deactivated silica gel
100, hexane/CH2Cl2, 90 : 10). White solid; mp 72–73 ЊC;
yield 81%. 1H NMR (400 MHz, acetone-d6) δ 5.40 (d, 1 H, 6-H,
J5,6 = 9.9 Hz), 5.07 (m, 1 H, 5-H), 4.10 (q, 2 H, OCH2CH3,
3J = 7.2 Hz), 3.58 (m, 4 H, NCH2CH3, 3J = 6.8 Hz), 1.23 (t, 3 H,
OCH2CH3, 3J = 7.2 Hz), 1.20 (t, 6 H, NCH2CH3, 3J = 6.8 Hz);
13C NMR (100 MHz, acetone-d6) δ 160.1 (C-2), 149.3 (C-4),
143.8 (q, C-7, JC,F = 31 Hz), 125.0 (q, CF3, JC,F = 273 Hz), 122.5
(q, CF3, JC,F = 272 Hz), 96.3 (C-6), 62.8 (OCH2CH3), 45.4, 45.1
(NCH2CH3), 43.4 (q, C-5, JC,F = 31 Hz), 14.6 (OCH2CH3), 13.7,
12.1 (NCH2CH3). IR (KBr) 3081.0 w, 2991.4 w, 2943.2 w,
2909.6 w, 2882.1 w, 1634.4 m, 1583.0 vs, 1523.8 vs, 1510.1 s,
1477.8 s, 1456.6 m, 1387.2 m, 1360.6 m, 1330.9 m, 1311.8 s,
1279.7 m, 1255.7 vs, 1213.8 m, 1180.8 vs, 1169.7 vs, 1152.7 vs,
1127.3 vs, 1117.0 s, 1097.8 m, 1074.9 m, 1061.9 m, 1029.2 m,
1016.4 m, 983.5 w, 954.8 m, 933.5 w, 898.4 m, 885.0 w, 835.2 m,
806.0 w, 784.4 w, 752.9 w, 744.8 w, 732.1 w, 704.9 w, 685.8 w. MS
(EI) m/z (Mϩ, 100%), 326 (10), 301 (51), 286 (21), 276 (26), 274
(25), 245 (34), 217 (23), 166 (12), 151 (17), 99 (46), 72 (87), 70
Anal. calcd. for C25H38N6: C, 70.09; H, 9.06; N, 19.89%. Found:
C, 70.33; H, 9.11; N, 19.58%.
2-Diisopropylamino-3,5-bis(trifluoromethyl)-3H-pyrrole-3-
carbonitrile 45
This compound was obtained from 38T under the general con-
ditions for preparation of diazepines in the presence diiso-
1
propylamine; white solid; mp 59–60 ЊC; 50% yield. H NMR
(400 MHz, CDCl3) δ 5.80 (s, 1H), 4.33 and 3.69 (two broadened
singlets due to slow isopropyl rotation, 1H each), 1.5–1.2
(broadened multiplet, 12H); 13C NMR (100 MHz, CDCl3) δ 163
(s, C=N), 153.5 (q, C–CF3), 121.5 (q, CF3), 119.2 (q, CF3), 110.4
(s, CN), 104.10 (s, CH), 104.06 (s, CH), 57.0 (C(q)-CF3), 53.7
(broadened s, CH), 49.7 (broadened s, CH), 20.9, 19.9, 19.2,
18.6 (four broadened isopropyl CH3 groups); IR (KBr) ν 2260w
cmϪ1; MS m/z 327. Anal Calcd for C13H15N3F6 C, 47.71; H,
4.62; N, 12.84%. Found C, 47.84; H, 4.58; N, 12.32%.
12
(63), 58 (90), 43 (95). HRMS, calcd. for C13H17N3OF6:
345.1276; found: 345.1277. Anal. calcd. for C13H17N3OF6: C,
45.22; H, 4.96; N, 12.17%. Found: 44.99; H, 5.12; N, 11.89%.
Acknowledgements
This work was supported by the Australian Research Council.
We thank Mr Riko Burgard for the matrix photolysis of 18A.
3-Cyano-2-diisopropylaminopyrrole 27
This compound was obtained from 21T using the general
method for preparation of azepines in the presence of diiso-
propylamine and purified by distillation/sublimation (∼50 ЊC,
1 × 10Ϫ2 mm Hg); white waxy solid; mp 39–40 ЊC; yield 52%; 1H
NMR (400 MHz, acetone-d6) δ 10.3 (br, 1 H, N–H), 6.57 (dd,
References
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2 A. Reisinger and C. Wentrup, Chem. Commun., 1996, 813.
3 R. A. Evans, M. W. Wong and C. Wentrup, J. Am. Chem. Soc., 1996,
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4 O. L. Chapman, Pure Appl. Chem., 1979, 51, 331.
5 C. Addicott, PhD thesis, The University of Queensland, 2002.
6 C. Addicott, A. Reisinger and C. Wentrup, J. Org. Chem., 2003, 68,
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7 P. Bednarek and C. Wentrup, unpublished results, The University of
Queensland, 2003.
1 H, 5-H, J1,5 = 2.7 Hz, J4,5 = 3.3 Hz), 6.25 (dd, 1 H, 4-H, J1,4
=
2.6 Hz, J4,5 = 3.3 Hz), 3.54 (sept, 2 H, iPr, 3J = 6.5 Hz), 1.02 (d,
12 H, iPr, 3J = 6.5 Hz); 13C NMR (100 MHz, acetone-d6) δ 143.1
(C-5), 118.4 (CN), 115.5 (C-2), 110.2 (C-3), 89.7 (C-4), 50.4
(iPr), 21.9 (iPr); 15N NMR (CDCl3 referenced to external
nitromethane) δ Ϫ198 (pyrrole-N), Ϫ105 (CN), Ϫ295 (amino
group); IR (KBr) 3324 br, 2970 s, 2959 m, 2915 w, 2219 vs, 2187
vs, 1618 m, 1605 m, 1564 vs, 1533 m, 1445 s, 1429 s, 1381 s, 1355
m, 1346 s, 1323 m, 1284 m, 1251 m, 1203 w, 1189 m, 1143 m,
1122 m, 1081 m, 961 w, 884 w. MS (EI) m/z (Mϩ, 51%), 176 (18),
148 (10), 134 (100), 118 (8), 107 (69), 92 (6). 191.1423. Anal.
calcd. for C11H17N3: C, 69.07; H, 8.96; N, 21.97%. Found: C,
69.29; H, 9.23; N, 21.88%.
8 F. Borget, R. Burgard, F. Duvernai and C. Wentrup, unpublished
results, The University of Queensland, 2003.
9 U. H. Patel, C. G. Dave, M. M. Jotani and H. C. Shah, Acta
Crystallogr., Sect. E: Struct. Rep. Online, 2002, 58, o431.
10 D. Donati, S. Fusi and F. Ponticelli, J. Chem. Res., Synop., 1997, 170.
11 P. Molina, A. Arques, A. Alias, M. C. Foces-Foces and A. L.
Llamas-Saiz, J. Chem. Soc., Chem. Commun., 1992, 424; J. C.
Teulade, A. Gueiffier, J. P. Chapat, G. Grassy, A. Carpy, A. H’Naifi,
B. Perly and J. Couquelet, Chem. Pharm. Bull., 1989, 37, 2293.
12 D. A. Lightner, A. K. Tipton and D. A. Lightner, Monatsh. Chem.,
2000, 131, 451.
13 T. Mukai, T. Kumagai and Y. Yamashita, Heterocycles, 1981, 15,
1569.
14 A. Reisinger, PhD Thesis, The University of Queensland, 2001.
15 A. Kuhn, C. Plüg and C. Wentrup, J. Am. Chem. Soc., 2000, 122,
1945.
16 L. J. Farrugia, J. Appl. Crystallogr., 1999, 32, 837.
17 G. M. Sheldrick, SHELX97 – Programs for Crystal Structure
Analysis (Release 97–2), Institut für Anorganische Chemie der
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496.
3,3Ј-Dicyano-2,2Ј-diisopropyldimethyldipyrrolylmethane 28
Obtained from 27 by recrystallization from hot acetone; white
solid, mp 269–270 ЊC, yield 98%. 1H NMR (400 MHz, acetone-
d6) δ 10.2 (br, 2 H, N–H), 5.99 (s, 2 H, 3-H), 3.52 (sept, 4 H, iPr,
3J = 6.4 Hz), 1.60 (s, 6 H, CH3), 0.97 (d, 24 H, iPr, 3J = 6.4 Hz);
13C NMR (100 MHz, DMSO-d6) δ 142.1 (C-5), 135.4 (C-2),
118.2 (CN), 104.9 (C-3), 87.6 (C-4), 48.9 (iPr), 34.4 (C-CH3),
27.8 (br, CH3), 21.3 (iPr). IR (KBr) 3251.6 br, 2975.0 m, 2935.6
w, 29873 w, 2222.4 vs, 1589.9 s, 1580.1 s, 1517.3 w, 1437.1 m,
1384.0 m, 1365.2 w, 1330.6 w, 1298.4 w, 1255.8 w, 1188.5 m,
1126.7 w, 1106.9 w, 1056 w, 1018.3 w, 924.3 w, 807.0 w, 796.3 m.
MS (EI) m/z 422 (Mϩ, 7%), 407 (3), 238 (18), 232 (28), 194 (10),
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 2 4 6 – 2 5 6
256