Synthesis of 3-diazopyrrolidin-2-ones

Full text of DOI:10.1134/S1070428012060231

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 6, pp. 872–874. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © Yu.R. Galina, A.N. Lobov, R.M. Sultanova, V.A. Dokichev, Yu.V. Tomilov, 2012, published in Zhurnal Organicheskoi Khimii, 2012,
Vol. 48, No. 6, pp. 874–876.
SHORT
COMMUNICATIONS
Synthesis of 3-Diazopyrrolidin-2-ones
a
a
a
a
b
Yu. R. Galina , A. N. Lobov , R. M. Sultanova , V. A. Dokichev , and Yu. V. Tomilov
a
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: dokichev@anrb.ru
b
Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
Received October 29, 2011
DOI: 10.1134/S1070428012060231
Aliphatic diazo compounds are reactive and un-
stable substances that are widely used in organic syn-
thesis [1, 2]. At present much attention is given to
preparation of four-, five-, six-, and seven-membered
cyclic α-diazo amides, taking into account that nitro-
gen-containing heteroring is a pharmacophoric frag-
ment responsible for a broad spectrum of physiologi-
cal activity of many synthetic and natural compounds
and that a diazo group provides the possibility for
purposeful modification of the heterocyclic fragment
one (II). Stable 3-diazodihydropyrroles or 3-diazopyr-
rolidinediones have been reported [6–8], but attempts
to obtain 3-diazopyrrolidin-2-one or its alkyl-substitut-
ed derivatives were unsuccessful [14]. In particular,
diazotization of 5-amino-3-exo-azatricyclo[5.2.1.0 ]-
decan-4-one led to a mixture of isomeric 3-acetoxy-
pyrrolidinones [14].
2
,6
We have found that heating of a solution of
3
-aminopyrrolidin-2-one (I) or 5-amino-3-exo-azatri-
2,6
cyclo[5.2.1.0 ]decan-4-one (II) with isopentyl nitrite
[3–11]. For example, α-diazo lactams are intermediate
in chloroform in the presence of ~15 mol % of glacial
products in the synthesis of practically important
derivatives of α-oxo lactams (β-lactamase inhibitors)
acetic acid gives 3-diazopyrrolidin-2-one (III) and
2,6
5
-diazo-3-exo-azatricyclo[5.2.1.0 ]decan-4-one (IV)
[
[
4] and indolocarbazoles (protein kinase inhibitors)
8]. 3-Diazopyrrolidin-2-ones attract interest as struc-
in 36 and 65% yield, respectively. We failed to isolate
diazo lactam III as individual substance; it decom-
posed in diethyl ether even at room temperature to
produce a mixture of compounds which were difficult
to identify. Therefore, the formation of III was proved
by trapping it with triphenylphosphine. The latter
reacted with 3-diazopyrrolidin-2-one (III) to give
stable crystalline phosphazene V. In the synthesis of
diazo lactam III, acetic acid was neutralized with solid
NaHCO , for a saturated aqueous solution of NaHCO
tural fragments for the synthesis of γ-aminobutyric
acid (the main neurotransmitter inhibitor in central
nervous system of mammalians) analogs exhibiting
nootropic and antiarrhythmic activity [12, 13].
In the present work we succeeded in developing
a procedure for the synthesis of previously unknown
3
-diazopyrrolidin-2-ones from 3-aminopyrrolidin-2-one
2
,6
(I) and 5-amino-3-exo-azatricyclo[5.2.1.0 ]decan-4-
3
3
PPh3
NH2
N2
N
N
Me CHCH CH ONO
PPh3
2
2
2
O
O
O
N
N
N
H
H
H
I
III
V
NH2
N2
Me CHCH CH ONO
2
2
2
O
O
N
N
H
H
II
IV
8
72

SYNTHESIS OF 3-DIAZOPYRROLIDIN-2-ONES
873
induced vigorous decomposition of the diazo com-
pound.
85 ml of chloroform, 6.0 g (51 mmol) of isopentyl
nitrite and 0.36 g (6.0 mmol) of glacial acetic acid
were added in succession under stirring over a period
of 10 min. The mixture was heated for 15 min under
reflux, cooled to 10°C, washed with 25 ml of a satu-
The structure of compounds IV and V was deter-
1
13
15
31
mined on the basis of their H, C, N, and P NMR
1
5
and IR spectra. The N NMR spectrum of IV in
rated solution of NaHCO , and evaporated under
3
CDCl contained signals from the diazo fragment at
3
reduced pressure. Diethyl ether, 300 ml, was added to
the residue, the precipitate was filtered off, the filtrate
was evaporated under reduced pressure, and the resi-
due was washed with hexane and dried under reduced
pressure. Yield 4.6 g (65%), orange crystals, decom-
δN –102.29 and 36.27 ppm and a signal at
δN –256.94 ppm which was assigned to the amide
nitrogen atom, taking into account the presence in the
1
15
H– N HSQC spectrum of a cross peak with the NH
proton (δ 6.95 ppm).
–
1
position point 126°C. IR spectrum, ν, cm : 3221,
To conclude, we have proposed a convenient proce-
dure for the synthesis of 3-diazopyrrolidinones.
3
1
6
072, 2069 (C=N ), 1678, 1647, 1417, 1394, 1377,
2
313, 1290, 1269, 1248, 1080, 939, 867, 817, 738,
1
48. H NMR spectrum (CDCl ), δ, ppm: 1.17 d.d.d.d
3
-Aminopyrrolidin-2-one (I) and 5-amino-3-exo-
3
2
3
2
,6
(
1H, endo-9-H, J = 16.1, J
= 12.4,
= 2.2 Hz), 1.23 d.d.d.d
azatricyclo[5.2.1.0 ]decan-4-one (II) were synthe-
endo-9, endo-8
3
4
Jendo-9,exo-8 = 3.5, J
sized according to the procedures described in [15, 16].
endo-9,syn-10
2
3
5
(1H, endo-8-H, J = 15.9, Jendo-8, endo-9 = 12.4,
3
-[(Triphenyl-λ -phosphanylidene)hydrazinyli-
3
4
Jendo-8,exo-9 = 3.2, J
= 2.2 Hz), 1.26 d.t.t (1H,
endo-8,syn-10
dene]-pyrrolidin-2-one (V). Compound I, 1.0 g
2
3
3
anti-10-H, J = 10.7, J
= 4.7, J
= 4.7,
anti-10,1
anti-10,7
(
(
10 mmol), was dissolved in 35 ml of chloroform, 1.5 g
13 mmol) of isopentyl nitrite and 0.09 g (1.5 mmol) of
4
4
Janti-10,2 = 1.8, J
= 1.8 Hz), 1.60 d.d.d.d (1H,
anti-10,6
3
2
3
exo-8-H, J = 15.9, J
= 10.4, J
= 3.5,
exo-8,exo-9
exo-8,endo-9
glacial acetic acid were added in succession under
stirring over a period of 10 min, and the mixture was
heated for 15 min under reflux, cooled to 10°C, treated
3
2
Jexo-8,7 = 4.7 Hz), 1.57 d.d.d.d (1H, exo-9-H, J = 16.1,
3
3
3
Jexo-9,exo-8 = 10.4, J
= 3.2, J
= 4.7 Hz),
= 3.9,
exo-9,endo-8
exo-9,1
2
3
1
.78 d.t.t (1H, syn-10-H, J = 10.7, J
syn-10,1
with solid NaHCO , and evaporated under reduced
3
4
4
3
Jsyn-10,7 = 3.9, J
= 2.2, J
= 2.2 Hz),
= 4.7,
syn-10,endo-8
syn-10,endo-9
pressure. Cold (0°C) diethyl ether, 150 ml, was added
to the residue, a solution of 2.6 g (10 mmol) of tri-
phenylphosphine in 20 ml of diethyl ether was then
added, and the mixture was left to stand for 20 h in the
dark. The precipitate was filtered off and washed with
diethyl ether. Yield 1.3 g (36%), light yellow crystals,
3
3
2
.21 t.d (1H, 1-H, J
= 4.7, J
1
,exo-9
1,anti-10
3
3
J1,syn-10 = 3.9 Hz), 2.26 t.d (1H, 7-H, J
= 4.7,
7,exo-8
3
3
3
3
J7,anti-10 = 4.7, J
J6,2 = 7.5, J
J2,6 = 7.5, J = 1.2, J
= 3.9 Hz), 3.30 d.d (1H, 6-H,
= 1.8 Hz), 3.56 d.d.d (1H, 2-H,
7,syn-10
4
6,anti-10
3
4
= 1.8 Hz), 6.95 br.s (1H,
2,3
2,anti-10
13
NH). C NMR spectrum (CDCl ), δ , ppm: 25.15
3
C
7
–
1
mp 208–209°C (decomp.). IR spectrum, ν, cm : 3176,
9
8
10
1
(
C ), 27.26 (C ), 31.54 (C ), 39.67 (C ), 42.30 (C ),
3
1
4
4
7
074, 1691, 1591, 1456, 1437, 1379, 1307, 1115,
6
5
2
4
3.40 (C ), 54.88 (C ), 59.91 (C ), 172.06 (CO).
1
5
059, 1000, 906, 816, 743, 719, 698, 602, 540, 527,
N NMR spectrum (CDCl ), δ , ppm: –256.94 (NH),
3
N
1
96. H NMR spectrum (CDCl ), δ, ppm: 3.06 t (2H,
3
–
102.29 (C=N=N), 36.27 (C=N=N). Mass spectrum,
3
3
+
-H, J = 7.1 Hz), 3.46 t (2H, 5-H, J = 7.1 Hz),
m/z (I , %): 177.1 (100) [M] , 165.0 (9), 149.1 (40)
[M – N ] , 120.0 (50), 108 (100). Found: m/z 178.0975
rel
3
4
+
.43 t.d (6H, m-H, J = 7.7, J = 2.9 Hz), 7.52 t.d
HP
2
3
4
+
+
(
3H, p-H, J = 7.7, J = 1.5 Hz), 7.69 d.d.d (6H, o-H,
[M + H] . C H N O. Calculated: 178.0975 [M + H] .
9
11
13
3
3
3
4
J = 7.7, J = 11.3, J = 1.5 Hz), 8.26 br.s (1H, NH).
1
15
31
HP
The H, C, N, and P NMR spectra were
recorded on a Bruker Avance III spectrometer at 500,
26, 51, and 202 MHz, respectively; the chemical
1
3
4
C NMR spectrum (CDCl ), δ , ppm: 24.19 (C ),
3
C
5
m
3
i
3
8.63 (C ), 128.62 (C , J = 11.4 Hz), 128.76 (C ,
CP
4
1
1
p
o
JCP = 93.5 Hz), 132.09 (C , J = 2.1 Hz), 133.35 (C ,
JCP = 8.0 Hz), 149.05 (C=N, J = 42.5 Hz), 170.19
1
CP
3
shifts were determined relative to tetramethylsilane ( H
and C, internal reference), MeNO ( N, external),
and H PO ( P, external). The IR spectra were meas-
2
CP
13
15
1
5
2
(C=O). N NMR spectrum (CDCl ), δ , ppm: –257.19
31
3
N
1
3
4
(
NH), –204.32 (N=P, J = 60.3 Hz), 5.64 (N=C,
JNP = 17.1 Hz). P NMR spectrum (CDCl ):
NP
ured on a Shimadzu IR Prestige-21 instrument from
samples dispersed in mineral oil. The mass spectra
2
31
3
δP 19.36 ppm. Found, %: C 70.19; H 5.32; N 10.99.
(
electron impact, 70 eV) were obtained on a Thermo
C H N OP. Calculated, %: C 70.77; H 5.40; N 11.25.
2
2
20
3
Finnigan MAT 95 XP high-resolution mass spectrom-
eter (ion source temperature 250°C, direct inlet probe
temperature 50–270°C, heating rate 10 deg/min). The
2
,6
5
-Diazo-3-exo-azatricyclo[5.2.1.0 ]decan-4-one
(IV). Compound II, 6.6 g (40 mmol), was dissolved in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 6 2012

8
74
GALINA et al.
melting points were measured on a Boetius melting
point apparatus. The elemental compositions were
determined on a EURO EA-3000 C,H,N,S-analyzer.
8. Wood, J.L., Petsch, D.T., Stoltz, B.M., Hawkins, E.M.,
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hedron, 2002, vol. 58, p. 3137.
This study was performed under financial support
by the Chemistry and Materials Science Department,
Russian Academy of Sciences (basic research program
1
0. Albrecht, D., Vogt, F., and Bach, T., Chem. Eur. J.,
2
010, vol. 16, p. 4284.
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1. Flynn, G.A., Beight, D.W., Huber, E.W., and Bey, P.,
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