Synthesis and some reactions of bicyclo[2.21]hept-2-ene-endo,endo-5,6- dicarboximidoacetic acid azide

Full text of DOI:10.1023/B:RUJO.0000013149.46416.76

Russian Journal of Organic Chemistry, Vol. 39, No. 11, 2003, pp. 1676 1678. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 11, 2003,
pp. 1745 1746.
Original Russian Text Copyright
,
2003 Tarabara, Yarovoi, Kas yan.
SHORT
COMMUNICATIONS
Synthesis and Some Reactions
of Bicyclo[2.2.1]hept-2-ene-endo,endo-5,6-dicarboximidoacetic
Acid Azide
I. N. Tarabara, M. Yu. Yarovoi, and L. I. Kas,yan
Dnepropetrovsk National University, Dnepropetrovsk, 49050 Ukraine
Received May 10, 2003
The preparation of polyfunctional compounds
containing groups capable of different transformations
is an urgent task of the modern chemistry. Bicyclo-
[2.2.1]hept-2-ene-endo,endo-5,6-dicarboximidoacetic
acid (I) may serve as an example of such compound.
endo,endo-5,6-dicarboximidoacetic acid azide. To
prepare azide IV a method was used involving con-
version of acid I into its methyl ester, then into
hydrazide with subsequent diazotization of the latter.
Ester II was obtained by esterification of acid I in
anhydrous alcohol in the presence of the catalytic
amount of phosphorus oxychloride [2] with 86%
yield of the target product.
The goal of this study was the synthesis and
investigation of reactions of bicyclo[2.2.1]hept-2-ene-
The maximum yield and purity of hydrazide III
were achieved by carrying out the reaction at 0 C and
equimolar reagents ratio. At excess hydrazine hydrate
or at higher temperature apparently occurred a con-
current transhydrazination reaction in the imide ring
of ester II, and the yield of hydrazide was considerab-
ly reduced.
tions of two types of NH bonds in agreement with the
known published data [3]. The transformation of the
ester group is obvious from the lack in the IR spec-
1
trum of hydrazide III of the strong band at 1220 cm
corresponding to the stretching vibrations of the
fragment C O C in the ester group [4] and observed
in the spectrum of ester II.
Further hydrazide III was converted into azide IV
by treatment with the nitrous acid obtained in situ
from sodium nitrite and hydrochloric acid. Azide IV
by heating with equimolar quantity of appropriate
amines in anhydrous benzene was transformed into
substituted carbamides V, VI.
The structure of compounds II and III was
confirmed by the IR spectra. In the IR spectrum of
compound III the hydrazine moiety appeared as a set
of three absorption bands in the regions 3570, 3500,
1
and 3330 cm corresponding to the stretching vibra-
1070-4280/03/3911-1676$25.00 2003 MAIK Nauka/Interperiodica

SYNTHESIS AND SOME REACTIONS
1677
Taking into consideration the low stability of
carbonylazides and also to avoid the side process of
azide group cycloaddition to the multiple bond of the
bicyclic skeleton the azide synthesis was carried out
in water medium at 15 C.
1680, 1620, 1490, 1418, 1325, 1175. Found, %:
N 17.76. C11H13N3O3. Calculated, %: N 17.87.
Bicyclo[2.2.1]hept-2-ene-endo,endo-5,6-dicarb-
oximidoacetic acid azide (IV). Into a flask cooled
in a bath of ice-salt mixture was charged 5.2 g
(0.022 mol) of hydrazide III, 3 ml of water, 4.2 ml
(0.046 mol) of 34% water solution of hydrochloric
acid, and at stirring was quickly added from a
dropping funnel a solution of 1.52 g (0.022 mol) of
sodium nitrite in 3 ml of water. In 5 min the separat-
ed precipitate was filtered off, thoroughly washed on
the filter with water till neutral washings, and dried
in air for 2 days. Yield of azide IV 4.5 g (83%), mp
83 84 C (decomp.).
The most convincing proofs of the structure of
compounds V, VI were obtained by analysis of the
1H NMR spectra where alongside the peaks belonging
to the bicyclic skeleton and substituents appeared a
triplet and a singlet from protons of two nonequival-
ent NH groups at 6.99 and 8.51 ppm for compound V
and at 7.30 and 11.22 ppm for compound VI.
Relative simplicity of the preparation and the high
reactivity of azide IV permit recommending it as a
new accessible reagent for the synthesis of biological-
ly active compounds belonging to various classes.
N-(Bicyclo[2.2.1]hept-2-ene-endo,endo-5,6-di-
carboximido-methyl)-N-(p-bromophenyl)carb-
amide (V) was obtained by heating at reflux for 2 h
of a mixture of 0.2 g (0.081 mmol) of azide IV and
0.18 g (0.081 mmol) of p-bromoaniline in 5 ml of
anhydrous benzene. The separated precipitate was
filtered off, washed on the filter with benzene, dried,
and recrystallized from 2-propanol. Yield of com-
pound V 0.25 g (71%), mp 264 265 C. IR spectrum,
Bicyclo[2.2.1]hept-2-ene-endo,endo-5,6-dicarb-
oximidoacetic acid (I) was synthesized by procedure
from [1].
Methyl bicyclo[2.2.1]hept-2-ene-endo,endo-5,6-
dicarboximidoacetate (II). To a stirred dispersion
of 15.7 g (0.071 mol) of acid (I) in 20 ml of an-
hydrous methanol was added at room temperature
0.60 ml (0.0071mol) of POCl3, and the stirring was
continued at the same temperature till the completion
of reaction (TLC monitoring). Within first 1 2 h the
acid dissolved, and to the end of the process gradually
separated a precipitate. The excess solvent was
removed in a vacuum, the crystals of the product
were filtered off and carefully washed on the filter
with water and with a solution of sodium hydrogen
carbonate. Then the product was dried in air and
recrystallized from hexane to obtain 14.4 (86%) of
ester II, mp 89 90 C. (publ.: mp 80 82 C [5]). IR
1
cm : 3375, 1755, 1700, 1680, 1590, 1545, 1340,
1
1235. H NMR spectrum, , ppm: 8.51 s (1H, NH),
7.29 m (4H, H arom), 6.69 t (1H, NH), 6.00 m (2H,
H2, H3), 4.65 d (2H, CH2), 3.30 m (4H, H1, H4, H5,
H6), 1.64 d (1H, H7s), 1.57 d (1H, H7a). Found, %:
N 10.71. C17H16BrN3O3. Calculated, %: N 10.77.
N-(Bicyclo[2.2.1]hept-2-ene-endo,endo-5,6-di-
carboximidomethyl)-N -2-(5-trifluoromethyl-1,3,4-
thiadiazolyl)carbamide (VI) was prepared by a
similar procedure from 0.6 g (2.44 mmol) of azide IV
and 0.41 g (2.44 mmol) of 5-trifluoromethyl-1,3,4-
thiadiazol-2-ylamine. Yield 0.80 g (85%), mp 226
1
1
spectrum, cm : 3065, 2880, 1745, 1700, 1415,
227 C. IR spectrum, cm : 3420, 3220, 1770, 1710,
1
1325, 1220, 1180. Found, %: N 5.98. C12H13NO4.
Calculated, %: N 5.96.
1680, 1555, 1335, 1220. H NMR spectrum, , ppm:
11.23 s (1H, NH), 7.30 t (1H, NH), 5.99 m (2H, H2,
H3), 4.72 d (2H, CH2), 3.30 m (4H, H1, H4, H5, H6),
1.63 d (1H, H7s), 1.57 d (1H, H7a). Found, %:
N17.93. C14H12F3N5O3S. Calculated, %: N 18.09.
Bicyclo[2.2.1]hept-2-ene-endo,endo-5,6-dicarb-
oximidoacetic acid hydrazide (III). To a stirred
dispersion of 5.4 g (0.023 mol) of ester II in 15 ml
of 2-propanol was added dropwise at 0 C within
30 min a solution of 1.4 ml (0.023 mol) of 80%
aqueous hydrazine hydrate in 3 ml of 2-propanol. The
crystalline ester within 2 3 h dissolved, and the stir-
ring was continued till the completion of reaction
(TLC monitoring). The excess alcohol was evaporat-
ed in a vacuum till the volume of the reaction mixture
was 7 8 ml, the precipitate formed was filtered off,
dried, and recrystallized from a small portion of
2-propanol. Yield 4.8 g (89%), mp 163 164 C. IR
IR spectra were recorded on spectrophotometer
1
UR-20 from samples pelletized with KBr. H NMR
spectra were registered on spectrometer Bruker
DAX-500 (operating frequency 500 MHz) from solu-
tions of compounds in DMSO-d6. HMDS was used
as internal reference. The reaction progress was
monitored and the homogeneity of compounds syn-
thesized was checked by TLC on Silufol UV-254
plates, eluent ether, development in iodine vapor.
Elemental analyses were carried out on Karlo Erba
analyzer.
1
spectrum, cm : 3570, 3500, 3330, 3070, 1755,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003

1678
TARABARA et al.
3. Grekov, Organicheskaya khimiya gidrazina (Organic
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003