Fused Imidazoles: I. Synthesis of 6,7-Dihydro-5H-pyrrolo[1,2-a]imidazole Derivatives

Article abstract of DOI:10.1134/S107042801806012X

Dehydration of substituted 2-(2-oxopyrrolidin-1-yl)acetamides with phosphoryl chloride provides a convenient method of synthesis of 2-chloro-6,7-dihydro-5H-pyrrolo[1,2-a]imidazoles. The latter can be readily converted to various derivatives via introduction and modification of a substituent in the 3-position. The chlorine atom in the 2-position can be removed by hydrogenation over Raney nickel.

Full text of DOI:10.1134/S107042801806012X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2018, Vol. 54, No. 6, pp. 901–911. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © M.A. Kavina, V.V. Sizov, I.P. Yakovlev, 2018, published in Zhurnal Organicheskoi Khimii, 2018, Vol. 54, No. 6, pp. 898–908.
Fused Imidazoles: I. Synthesis
of 6,7-Dihydro-5H-pyrrolo[1,2-a]imidazole Derivatives
M. A. Kavinaa, b, V. V. Sizova,* and I. P. Yakovlevb
a Scientific and Production Company “CHEM” Ltd.,
ul. Zavodskaya 3, bld. 142, Kuzmolovskii, Leningrad oblast, 188663 Russia
*e-mail: vvsizov@list.ru
b St. Petersburg State Chemical Pharmaceutical Academy,
ul. Professora Popova 14, St. Petersburg, 197376 Russia
Received October 4, 2017
Abstract—Dehydration of substituted 2-(2-oxopyrrolidin-1-yl)acetamides with phosphoryl chloride provides
a convenient method of synthesis of 2-chloro-6,7-dihydro-5H-pyrrolo[1,2-a]imidazoles. The latter can be
readily converted to various derivatives via introduction and modification of a substituent in the 3-position. The
chlorine atom in the 2-position can be removed by hydrogenation over Raney nickel.
DOI: 10.1134/S107042801806012X
We previously described a new general synthesis of
4-substituted 2-(2-oxopyrrolidin-1-yl)acetamides [1].
In the present article we report the use of these com-
pounds as a starting material in the synthesis of fused
heterocyclic systems, 6,7-dihydro-5H-pyrrolo[1,2-a]-
imidazole derivatives, and some of their chemical
properties.
pyrroles [21, 22]. A particular case is the recyclization
of 5-(morpholin-4-yl)-2-(3-phthalimidopropyl)-1,3-ox-
azole-4-carbonitrile by the action of hydrazine [23].
The only example of the synthesis of 6,7-dihydro-
5H-pyrrolo[1,2-a]imidazoles from 2-(2-oxopyrrolidin-
1-yl)acetamide was described in [24]. However, the
authors did not continue study in this line, and the
absence of any other data does not allow us to
unambiguously determine the scope of the described
reaction.
With the goal of developing a new general method
for the synthesis of 2-chloro-6,7-dihydro-5H-pyrrolo-
[1,2-a]imidazoles 3 we studied dehydration of previ-
ously prepared 2-(4-R1,R2-2-oxopyrrolidin-1-yl)acet-
amides 1 with phosphoryl chloride. The reactions were
carried using a slight excess of POCl3, and the reaction
mixtures were heated at 60–90°C for 2–3 h (until hy-
drogen chloride no longer evolved). We thus obtained
a series of 2-chloro-6,7-dihydro-5H-pyrrolo[1,2-a]-
imidazoles 3a–3g in 70–90% yields. The reaction of
1b with POCl3 at room temperature gave nitrile 2b as
the only product (Scheme 1).
The chemical properties of pyrroloimidazoles 3
largely resemble those intrinsic to imidazoles. Com-
pounds 3 undergo electrophilic substitution of hydro-
gen in the 3-position; for example, their bromination
and Vilsmeier–Haack formylation afforded the corre-
sponding derivatives 4 and 5. Modification of the
carbonyl group makes it possible to obtain a series of
The known methods for the preparation of substi-
tuted 6,7-dihydro-5H-pyrrolo[1,2-a]imidazoles can be
classified with respect to the structure of initial com-
pounds. The first group of methods is based on the use
of substituted imidazoles. It includes cyclization of
N-allylimidazoles [2, 3], alkylation of imidazoles with
2-bromobenzyl bromide with subsequent cyclization
[4], reactions of 2-haloimidazoles with cyclopropanes
containing ester groups [5], condensations of imidaz-
ole [6–8], reaction of imidazole-2-carbaldehyde with
benzylhydroxylamine, followed by reduction [9, 10],
and cyclization of 2-(4-chlorobutyl)imidazole [11].
The second group of methods utilizes derivatives of
dihydropyrrol-2-amine, 2-alkoxydihydropyrrole, and
pyrrolidin-2-one. Examples are condensations of dihy-
dropyrrol-2-amine with haloacetophenones [12–14],
2-bromo-1-(pyridin-2-yl)ethanone [15], ethyl bromo-
acetate [16], 4-chlorobutanenitrile [17], and 2-amino-
2-cyanoacetamide [18], as well as the syntheses of
6,7-dihydro-5H-pyrrolo[1,2-a]imidazoles from pyrroli-
din-2-ones in the presence of trimethyloxonium tetra-
fluoroborate [19, 20] and from 2-alkoxydihydro-
901

KAVINA et al.
902
Scheme 1.
R2
R1
Cl
O
Ph
20°C
H2O
N
N
–HOPOCl2
–2HCl
CN
CN
Cl–
2b
R2
R1
R2
R1
O
Cl
2POCl3
–HCl
60–90°C
NH2
O
NH
Cl
N
N
–OPOCl2
Cl
N
R2
R1
R2
R1
1a–1g
60–90°C
N
–HOPOCl2
–HCl
N
N
Cl
Cl
3a–3g
R1 = H, R2 = H (a), Ph (b), 4-ClC6H4 (c), 4-MeO C6H4 (d), 2,4-Cl2C6H3 (e), 3-O2NC6H4 (f); R1R2 = (CH2)5 (g).
Scheme 2.
R2
R1
R2
R1
R2
R1
N
N
N
KMnO4
N
N
N
Cl
Cl
Cl
Br
CH2OH
6a, 6b, 6g
COOH
4a, 4b, 4g
7a, 7b, 7g
NaBH4
Br2
R2
R1
R2
R1
R2
R1
N
N
N
DMF/POCl3
PhNHNH2
N
N
N
Cl
Cl
Cl
H
CHO
N
N
Ph
3a, 3b, 3g
5a, 5b, 5g
NH2OH
8a, 8b
R2
R1
R2
R1
N
N
NHNH2
N
N
Cl
Cl
NH2
OH
N
N
10a, 10b, 10g
9a, 9b, 9g
R1 = H, R2 = H (a), Ph (b); R1R2 = (CH2)5 (g).
other derivatives such as alcohols 6, carboxylic acids
7, phenylhydrazones 8, hydrazones 9, and oximes 10
(Scheme 2).
in 75% yield (with no account taken of the loss of acid
7a during the isolation procedure due to its good solu-
bility in water). Water-insoluble acid 7b was isolated
in 60–65% yield. In the oxidation of aldehyde 5g with
a stoichiometric amount of potassium permanganate,
acid 7g (which is also poorly soluble in water) was
formed in as low as 30% yield, and 65% of the initial
aldehyde remained unchanged. Therefore, ~70% of
The presence of a substituent in position 6 signif-
icantly reduces the stability of 2-chloro-6,7-dihydro-
5H-pyrrolo[1,2-a]imidazoles to oxidation. The oxida-
tion of aldehyde 5a with potassium permanganate in
aqueous acetone at room temperature gave acid 7a
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 6 2018

FUSED IMIDAZOLES: I.
903
Scheme 3.
R1
Cl
N
R2
DMSO, 180°C
N
N
9a, 9b
N
N
R2
N
R1
Cl
11a, 11b
R1 = H, R2 = H (a), Ph (b).
Scheme 4.
N
N
N
N
DMSO, 180°C
DMSO, 180°C
N
N
O
N
N
Cl
Cl
Cl
Cl
OH
OH
CN
N
NH2
N
10a
12
10g
13g
Ph
Ph
Ph
N
N
N
DMSO, 180°C
N
N
N
Cl
OH
Cl
Cl
+
CN
N
O
NH2
10b
14
13b
potassium permanganate is consumed for oxidative
decomposition of 5% of the initial compounds.
sure); 6,7-dihydro-5H-pyrrolo[1,2-a]imidazoles 15a,
15b, 15d, and 15g were obtained in nearly quantitative
yield (Scheme 6). Herein, hydrazine was used as
a source of hydrogen. The reduction of compounds 3c
and 3e under analogous conditions resulted in removal
of chlorine from both imidazole fragment and phenyl
substituent, while the reaction with nitrophenyl deriva-
tive 3f was accompanied by reduction of the nitro
group to amino with the formation of 3-(6,7-dihy-
dro-5H-pyrrolo[1,2-a]imidazol-6-yl)aniline (16)
The chlorine atom in position 2 of compounds 3 is
weakly reactive even when an electron-withdrawing
substituent is present in the neighboring position. For
example, phenylhydrazones 8, hydrazones 9, and
oximes 10 failed to cyclize to the corresponding pyra-
zoles or oxazoles. Phenylhydrazones 8a and 8b
remained intact on heating in high-boiling solvents
(DMSO, DMF, anisole), whereas hydrazones 9a and
9b in DMSO at <180°C were converted to 1,2-bis[(2-
chloro-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-
methylidene]hydrazine (11a) and 1,2-bis [(2-chloro-6-
phenyl-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-
methylidene]hydrazine (11b), respectively (Scheme 3).
Scheme 5.
R2
R1
R2
R1
N
N
POCl3
N
N
Cl
Cl
Depending on their structure, oximes 10a, 10b, and
10g in DMF at 120°C in the presence of anhydrous
potassium carbonate were converted to the correspond-
ing nitrile, amide, or both (Scheme 4). Nitriles 13a,
13b, and 13g were synthesized by treatment of 10a,
10b, and 10g with phosphoryl chloride (Scheme 5).
Amide 14 was also prepared according to the classical
scheme, through the corresponding acid chloride
which was treated with ammonia.
OH
CN
13a, 13b, 13g
N
10a, 10b, 10g
R1 = H, R2 = H (a), Ph (b); R1R2 = (CH2)5 (g).
Scheme 6.
R2
R1
R2
R1
H2/Raney Ni
NaOH, EtOH
N
N
N
N
Cl
Compounds 3a, 3b, 3d, and 3g were subjected to
reductive dehalogenation by hydrogenation over
Raney nickel in ethanol at 100–110°C (under pres-
3a, 3b, 3d, 3g
15a, 15b, 15d, 15g
R1 = H, R2 = H (a), Ph (b); R1R2 = (CH2)5 (g).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 6 2018

KAVINA et al.
904
Scheme 7.
Cl
H2/Raney Ni
2NaOH, EtOH
H2/Raney Ni
3NaOH, EtOH
N
N
N
Ph
Cl
Cl
Cl
Cl
N
N
N
3c
15b
3e
O2N
H2N
H2/Raney Ni
NaOH, EtOH
N
N
Cl
N
N
3f
16
(Scheme 7). The reductive dehalogetation of 3-substi-
tuted 2-chloro-6,7-dihydro-5H-pyrrolo[1,2-a]imidaz-
oles 6 and 7 afforded the corresponding derivatives un-
substituted at the 2-position (Scheme 8).
Quantum Access MAX instrument. The elemental
analyses were obtained with a Thermo Scientific
FLASH 2000 CHNS analyzer. The melting points were
measured in the range 20–360°C on a PTP melting
point apparatus with an electric heater.
Scheme 8.
2-(2-Oxo-4-phenylpyrrolidin-1-yl)acetonitrile
(2b). A mixture of 2 g (10 mmol) of compound 1b and
13 g (85 mmol) of phosphoryl chloride was kept for
1 h at room temperature until it became homogeneous.
The resulting solution was poured onto ice under vig-
orous stirring and extracted with methylene chloride.
The extract was filtered and evaporated to dryness
under reduced pressure. Yield 86%, brown oily mate-
R2
R1
R2
R1
H2/Raney Ni
NaOH, EtOH
N
N
N
N
Cl
CH2OH
6a, 6b, 6g
CH2OH
17a, 17b, 17g
R2
R1
R2
R1
H2/Raney Ni
NaOH, EtOH
1
N
N
rial. H NMR spectrum, δ, ppm: 2.40–2.46 m (1H,
N
N
Heq in CH2), 2.70–2.77 m (1H, Hax in CH2), 3.39–
3.43 m (1H, Heq in CH2), 3.63 quint (1H, CH, J =
8.0 Hz), 3.80–3.85 m (1H, Hax in CH2), 4.39 s (2H,
1-CH2), 7.22–7.34 m (5H, Ph). Found, %: C 71.72;
H 6.18; N 13.92. C12H12N2O. Calculated, %: C 71.98;
H 6.04; N 13.99.
Cl
COOH
7a, 7b, 7g
COOH
18a, 18b, 18g
The structure of the newly synthesized compounds
1
was confirmed by H NMR spectra and elemental
Compounds 3a–3g (general procedure). A suspen-
sion of 10 mmol of 2-(4-R1,R2-2-oxopyrrolidin-1-yl)-
acetamide 1a–1g in 30 mmol of phosphoryl chloride
was heated to 60–90°C and stirred at that temperature
for 2–3 h (until hydrogen chloride no longer evolved).
The mixture was cooled to room temperature and
poured into cold water. The solution was acidified to
pH 2.0, treated with charcoal, and filtered. The filtrate
was neutralized to pH 8.0–8.5. After cooling to room
temperature, the precipitate was filtered off, washed
with water, and dried at 55–60°C. The crude product
was dissolved in toluene, the solution was filtered to
remove insoluble impurities and evaporated to dryness,
and the residue was dried at a temperature not
exceeding 65°C.
analyses.
Thus, the dehydration of 2-(2-oxopyrrolidin-1-yl)-
acetamides with phosphoryl chloride provides a gen-
eral method of synthesis of substituted 2-chloro-6,7-
dihydro-5H-pyrrolo[1,2-a]imidazoles. The chemical
properties of the latter make it possible to use them as
starting materials for the synthesis of difficultly acces-
sible heterocyclic compounds containing an imidazole
ring. The chlorine atom on C2 can be regarded as
a specific protecting group (which can be readily re-
moved by hydrogenation) in the synthesis of 3-substi-
tuted 6,7-dihydro-5H-pyrrolo[1,2-a]imidazoles.
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker
2-Chloro-6,7-dihydro-5H-pyrrolo[1,2-a]imidaz-
ole (3a). The aqueous solution neutralized to pH 8.0–
8.5 was concentrated under reduced pressure until
a suspension was formed. The suspension was cooled
Avance III UltraShield Plus spectrometer at 400 MHz
using DMSO-d6 as solvent. HPLC/MS analysis was
performed using a Thermo Scientific Fisher TSQ
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 6 2018

FUSED IMIDAZOLES: I.
905
to room temperature, and the precipitate was filtered
off and dried in air. The product was then treated
according to the general procedure. Yield 82%, light
brown prisms, mp 79–81°C (from PhMe); published
data [24]: mp 73.0–76.0°C. H NMR spectrum, δ,
ppm: 2.45–2.55 m (2H, CH2), 2.74 t (2H, CH2, J =
8.0 Hz), 3.96 t (2H, CH2, J = 8.0 Hz), 7.08 s (1H, CH).
2-Chloro-6-(3-nitrophenyl)-6,7-dihydro-5H-pyr-
rolo[1,2-a]imidazole (3f). Yield 82%, yellow prisms,
mp 138–139°C (from PhH). H NMR spectrum, δ,
1
ppm: 2.88–2.94 m (1H, Heq in CH2), 3.26–3.30 m (1H,
Hax in CH2), 4.01–4.05 m (1H, Heq in CH2), 4.35 quint
(1H, CH, J = 8.0 Hz), 4.43–4.48 m (1H, Hax in CH2),
7.24 s (1H, CH), 7.67 t (1H, Harom, J = 8.0 Hz), 7.85 d
(1H, Harom, J = 4.0 Hz), 8.15 d (1H, Harom, J = 4.0 Hz),
8.24 br.s (1H, Harom). Found, %: C 54.62; H 3.92;
N 15.90. C12H10ClN3O2. Calculated, %: C 54.66;
H 3.88; N 15.94.
1
2-Chloro-6-phenyl-6,7-dihydro-5H-pyrrolo-
[1,2-a]imidazole (3b). Yield 88%, light brown prisms,
1
mp 132–134°C (from PhMe). H NMR spectrum, δ,
ppm: 2.80–2.86 m (1H, Heq in CH2), 3.20–3.26 m (1H,
Hax in CH2), 3.92–3.96 m (1H, Heq in CH2), 4.15 quint
(1H, CH, J = 8.0 Hz), 4.38–4.43 m (1H, Hax in CH2),
7.21 s (1H, CH), 7.25–7.38 m (5H, Ph). Found, %:
C 64.83; H 5.27; N 12.77. C12H11ClN2. Calculated, %:
C 64.91; H 5.11; N 12.81.
2′-Chloro-5′,7′-dihydrospiro[cyclohexane-1,6′-
pyrrolo[1,2-a]imidazole] (3g). Yield 85%, brown
1
prisms, mp 69–71°C (from petroleum ether). H NMR
spectrum, δ, ppm: 1.39–1.63 m (10H, C5H10), 2.61 s
(2H, CH2), 3.75 s (2H, CH2), 7.02 s (1H, CH). Found,
%: C 62.65; H 7.33; N 13.25. C11H15ClN2. Calculated,
%: C 62.70; H 7.18; N 13.30.
2-Chloro-6-(4-chlorophenyl)-6,7-dihydro-5H-
pyrrolo[1,2-a]imidazole (3c). Yield 82%, light brown
1
prisms, mp 111–113°C (from PhH). H NMR spec-
Compounds 4a, 4b, and 4g (general procedure).
Bromine, 1.05 mmol, was added to a solution of
1 mmol of compound 3a, 3b, or 3g in 10 mL of
aqueous ethanol at room temperature. The mixture was
stirred for 30 min, and the crystalline solid was filtered
off, washed on a filter with water, 3% aqueous
sodium carbonate, water again, and propan-2-ol, and
dried at 60°C.
trum, δ, ppm: 2.79–2.85 m (1H, Heq in CH2), 3.19–
3.25 m (1H, Hax in CH2), 3.90–3.95 m (1H, Heq in
CH2), 4.16 quint (1H, CH, J = 8.0 Hz), 4.38–4.42 m
(1H, Hax in CH2), 7.21 s (1H, CH), 7.39 d.d (4H, C6H4,
J = 4.0, 12.0 Hz). Found, %: C 56.89; H 4.21; N 11.02.
C12H10Cl2N2. Calculated, %: C 56.94; H 4.13; N 11.07.
2-Chloro-6-(4-methoxyphenyl)-6,7-dihydro-5H-
pyrrolo[1,2-a]imidazole (3d). Yield 78%, brown
3-Bromo-2-chloro-6,7-dihydro-5H-pyrrolo-
[1,2-a]imidazole (4a). Yield 75%, light brown prisms,
mp 124–126°C (from petroleum ether). 1H NMR spec-
trum, δ, ppm: 2.45–2.55 m (2H, CH2), 2.82 t (2H, CH2,
J = 8.0 Hz), 3.93 t (2H, CH2, J = 8.0 Hz). Found, %:
C 32.48; H 2.83; N 12.59. C6H6BrClN2. Calculated, %:
C 32.54; H 2.79; N 12.65.
1
prisms, mp 82–84°C (from PhH). H NMR spectrum,
δ, ppm: 2.76–2.82 m (1H, Heq in CH2), 3.15–3.21 m
(1H, Hax in CH2), 3.74 s (3H, CH3), 3.86–3.91 m (1H,
Heq in CH2), 4.09 quint (1H, CH, J = 8.0 Hz), 4.34–
4.38 m (1H, Hax in CH2), 6.91 d (2H, Harom, J = 4.0 Hz),
7.19 s (1H, CH), 7.26 d (2H, Harom, J = 4.0 Hz). Found,
%: C 62.74; H 5.27; N 11.22. C13H13ClN2O. Calcu-
lated, %: C 62.78; H 5.33; N 11.26.
3-Bromo-2-chloro-6-phenyl-6,7-dihydro-5H-pyr-
rolo[1,2-a]imidazole (4b). Yield 84%, light brown
prisms, mp 129–131°C (from petroleum ether).
1H NMR spectrum, δ, ppm: 2.91–2.97 m (1H, Heq in
CH2), 3.29–3.35 m (1H, Hax in CH2), 3.92–3.96 m (1H,
Heq in CH2), 4.20 quint (1H, CH, J = 8.0 Hz), 4.38–
4.42 m (1H, Hax in CH2), 7.23–7.38 m (5H, Ph).
Found, %: C 48.39; H 3.49; N 9.37. C12H10BrClN2.
Calculated, %: C 48.43; H 3.44; N 9.41.
2-Chloro-6-(2,4-dichlorophenyl)-6,7-dihydro-
5H-pyrrolo[1,2-a]imidazole (3e). A colorless oily
material precipitated from the aqueous solution
neutralized to pH 8.0–8.5. It was separated and
extracted with three portions of hot petroleum ether.
The extract was cooled to 0–5°C, and the precipitate
was filtered off and dried in air. Yield 76%, colorless
1
prisms, mp 84–85°C (from petroleum ether). H NMR
3′-Bromo-2′-chloro-5′,7′-dihydrospiro[cyclohex-
ane-1,6′-pyrrolo[1,2-a]imidazole] (4g). Yield 88%,
white prisms, mp 156–158°C (from i-PrOH). 1H NMR
spectrum, δ, ppm: 1.37–1.59 m (10H, C5H10), 2.71 s
(2H, CH2), 3.74 s (2H, CH2). Found, %: C 45.57;
H 4.97; N 9.62. C11H14BrClN2. Calculated, %:
C 45.62; H 4.92; N 9.67.
spectrum, δ, ppm: 2.83–2.89 m (1H, Heq in CH2),
3.23–3.29 m (1H, Hax in CH2), 3.98–4.02 m (1H, Heq
in CH2), 4.38–4.51 m (1H, Hax in CH2, 6-H), 7.21 s
(1H, CH), 7.41–7.46 m (2H, 2H, Harom), 7.66 s (1H,
Harom). Found, %: C 50.06; H 3.25; N 9.68.
C12H9Cl3N2. Calculated, %: C 50.12; H 3.19; N 9.74.
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KAVINA et al.
906
2-Chloro-6,7-dihydro-5H-pyrrolo[1,2-a]imidaz-
dryness. Yield 74%, light brown prisms, mp 78–80°C
(from PhMe). 1H NMR spectrum, δ, ppm: 1.35–1.58 m
(10H, C5H10), 2.74 s (2H, CH2), 3.98 s (2H, CH2),
9.63 s (1H, CHO). Found, %: C 60.33; H 6.38;
N 11.69. C12H15ClN2O. Calculated, %: C 60.38;
H 6.33; N 11.74.
ole-3-carbaldehyde (5a). Compound 2a, 5 g
(29.3 mmol), was dissolved in 12 mL of DMF at room
temperature, and 9 g (59 mmol) of phosphoryl chloride
was added dropwise on cooling with water. The
mixture was stirred for 16 h at 60°C, cooled to room
temperature, and poured into 100 mL of an ice–water
mixture. The aqueous solution was treated with char-
coal and filtered, the filtrate was neutralized to pH 8.0–
8.5 and evaporated under reduced pressure, and the
residue was dispersed in boiling propan-2-ol. The
suspension was filtered to remove inorganic salts, and
the filtrate was evaporated to dryness under reduced
pressure. The oily residue was extracted with boiling
toluene, the extract was filtered, and the solvent was
distilled off under reduced pressure. Yield 75%, light
Compounds 6a, 6b, and 6g (general procedure).
Aldehyde 5a, 5b, or 5g, 10 mmol, was dissolved at
25°C in 20–30 mL of methanol or ethanol, 10 mmol of
sodium tetrahydridoborate was added, and the mixture
was stirred for 2 h at room temperature. When the
reaction was complete (TLC, eluent petroleum ether–
benzene–ethanol, 1:2.5:2.5), the mixture was diluted
with water, and the precipitate was filtered off, washed
with water and diethyl ether, and dried in air.
1
(2-Chloro-6,7-dihydro-5H-pyrrolo[1,2-a]imidaz-
ol-3-yl)methanol (6a). The reaction was carried out in
methanol. Yield 73%, colorless prisms, mp 175–176°C
brown prisms, mp 57–59°C (from hexane). H NMR
spectrum, δ, ppm: 2.50–2.57 m (2H, CH2), 2.85 t (2H,
CH2, J = 8.0 Hz), 4.18 t (2H, CH2, J = 8.0 Hz), 9.64 s
(1H, CHO). Found, %: C 49.22; H 4.22; N 16.36.
C7H7ClN2O. Calculated, %: C 49.28; H 4.18; N 16.42.
1
(from aq. EtOH). H NMR spectrum, δ, ppm: 2.44–
2.55 m (2H, CH2), 2.73 t (2H, CH2, J = 8.0 Hz), 3.96 t
(2H, CH2, J = 8.0 Hz), 4.36 s (2H, CH2), 5.13 br.s
(1H, OH). Found, %: C 48.65; H 5.30; N 16.17.
C7H9ClN2O. Calculated, %: C 48.71; H 5.26; N 16.23.
2-Chloro-6-phenyl-6,7-dihydro-5H-pyrrolo-
[1,2-a]imidazole-3-carbaldehyde (5b). Compound
2b, 5 g (20.3 mmol), was dissolved in 15 mL of DMF
at room temperature, and 6 g (39.5 mmol) of phos-
phoryl chloride was added dropwise with vigorous
stirring and cooling with cold water. The mixture was
heated to 60°C, stirred for 16 h at that temperature,
cooled to room temperature, and poured onto ice. The
precipitate was filtered off, washed with water,
squeezed, and dried at 60°C. Yield 83%, light brown
(2-Chloro-6-phenyl-6,7-dihydro-5H-pyrrolo-
[1,2-a]imidazol-3-yl)methanol (6b). The reaction was
carried out in ethanol. Yield 80%, colorless prisms,
1
mp 167–169°C (from aq. i-PrOH). H NMR spectrum,
δ, ppm: 2.81–2.87 m (1H, Heq in CH2), 3.21–3.28 m
(1H, Hax in CH2), 3.92–3.97 m (1H, Heq in CH2),
4.17 quint (1H, CH, J = 8.0 Hz), 4.39 d (2H, CH2, J =
2.0 Hz), 4.42–4.46 m (1H, Hax in CH2), 5.16 t (1H,
OH, J = 8.0 Hz), 7.26–7.38 m (5H, Ph). Found, %:
C 62.72; H 5.31; N 11.18. C13H13ClN2O. Calculated,
%: C 62.78; H 5.27; N 11.26.
1
prisms, mp 64–66°C (from petroleum ether). H NMR
spectrum, δ, ppm: 2.93–2.99 m (1H, Heq in CH2),
3.33–3.39 m (1H, Hax in CH2), 4.09–4.14 m (1H, Heq
in CH2), 4.25 quint (1H, CH, J = 8.0 Hz), 4.66–4.71 m
(1H, Hax in CH2), 7.26–7.39 m (5H, Ph), 9.68 s
(1H, CHO). Found, %: C 63.24; H 4.53; N 11.30.
C13H11ClN2O. Calculated, %: C 63.29; H 4.49; N 11.36.
(2′-Chloro-5′,7′-dihydrospiro[cyclohexane-1,6′-
pyrrolo[1,2-a]imidazol-3-yl])methanol (6g). The re-
action was carried out in ethanol. Yield 76%, colorless
2′-Chloro-5′,7′-dihydrospiro[cyclohexane-1,6′-
pyrrolo[1,2-a]imidazole]-3′-carbaldehyde (5g).
Compound 2g, 5 g (21 mmol), was dissolved in 10 mL
of DMF at room temperature, and 7 g (46 mmol) of
phosphoryl chloride was added dropwise with vigorous
stirring and cooling with cold water. The mixture was
heated to 60°C, stirred for 16 h at that temperature,
cooled to room temperature, and poured into 160 mL
of water containing ice. The mixture was stirred for
2 h, and the precipitate was filtered off, washed with
water, squeezed, and dried at 60°C. The crude product
was dissolved in toluene, the undissolved impurities
were filtered off, and the filtrate was evaporated to
1
prisms, mp 131–133°C (from aq. i-PrOH). H NMR
spectrum, δ, ppm: 1.36–1.78 m (10H, C5H10), 2.62 s
(2H, CH2), 3.78 s (2H, CH2), 4.35 d (2H, CH2, J =
4.0 Hz), 5.10 t (1H, OH, J = 8.0 Hz). Found, %:
C 59.81; H 7.22; N 11.58. C12H17ClN2O. Calculated,
%: C 59.87; H 7.16; N 11.64.
Compounds 7a and 7b (general procedure). Alde-
hyde 5a or 5b, 30 mmol, was dispersed in 30 mL of
50% aqueous acetone, 20 mmol of potassium perman-
ganate was added, and the mixture was stirred for 1 h
at 25–30°C until KMnO4 was consumed completely.
The precipitate of manganese dioxide was filtered off,
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FUSED IMIDAZOLES: I.
907
1
and the filtrate was treated with charcoal, filtered,
diluted with 30 mL of water, and acidified to pH 5.5–
6.0. The precipitate was filtered off, washed with water
and propan-2-ol, and dried at 65°C.
from i-PrOH). H NMR spectrum, δ, ppm: 2.50–
2.58 m (2H, CH2), 2.79 t (2H, CH2, J = 8.0 Hz), 4.24 t
(2H, CH2, J = 8.0 Hz), 6.74 t (1H, Harom, J = 8.0 Hz),
6.97 d (2H, Harom, J = 4.0 Hz), 7.21 t (2H, Harom, J =
8.0 Hz), 7.77 s (1H, CH), 10.31 s (1H, NH). Found, %:
C 59.82; H 5.16; N 21.42. C13H13ClN4. Calculated, %:
C 59.89; H 5.03; N 21.49.
2-Chloro-6,7-dihydro-5H-pyrrolo[1,2-a]imidaz-
ole-3-carboxylic acid (7a). Yield 75%, white prisms,
1
mp 236–237°C (decomp.; from H2O). H NMR spec-
trum, δ, ppm: 2.45–2.55 m (2H, CH2), 2.81 t (2H, CH2,
J = 8.0 Hz), 4.15 t (2H, CH2, J = 8.0 Hz), 13.06 br.s
(1H, COOH). Found, %: C 45.00; H 3.82; N 14.96.
C7H7ClN2O2. Calculated, %: C 45.06; H 3.78; N 15.01.
2-Chloro-6-phenyl-3-[(phenylhydrazinylidene)-
methyl]-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole
(8b). Yield 96%, light brown prisms, mp 185–187°C
1
(decomp.; from i-PrOH). H NMR spectrum, δ, ppm:
2.87–2.93 m (1H, Heq in CH2), 3.27–3.33 m (1H, Hax
in CH2), 4.15–4.28 m (1H, Heq in CH2, 6-H), 6.68 t
(1H, Harom, J = 8.0 Hz), 6.90 d (2H, Harom, J = 4.0 Hz),
7.14 t (2H, Harom, J = 8.0 Hz), 7.24–7.40 m (5H, Ph),
7.78 s (1H, CH), 10.22 s (1H, NH). Found, %:
C 67.69; H 5.13; N 16.57. C19H17ClN4. Calculated, %:
C 67.75; H 5.09; N 16.63.
2-Chloro-6-phenyl-6,7-dihydro-5H-pyrrolo-
[1,2-a]imidazole-3-carboxylic acid (7b). Yield 65%,
white prisms, mp 246–247°C (decomp.; from DMF–
i-PrOH). 1H NMR spectrum, δ, ppm: 2.90–2.96 m (1H,
Heq in CH2), 3.28–3.35 m (1H, Hax in CH2), 4.07–
4.12 m (1H, Heq in CH2), 4.20 quint (1H, CH, J =
8.0 Hz), 4.63–4.68 m (1H, Hax in CH2), 7.26–7.40 m
(5H, Ph), 13.14 br.s (1H, COOH). Found, %: C 59.38;
H 4.26; N 10.60. C13H11ClN2O2. Calculated, %:
C 59.44; H 4.22; N 10.66.
2-Chloro-3-(hydrazinylidenemethyl)-6,7-dihy-
dro-5H-pyrrolo[1,2-a]imidazole (9a). Aldehyde 5a,
2.86 g (20 mmol), was dissolved in water, 3.90 g
(50 mmol) of hydrazine hydrate was added, and the
mixture was stirred for several hours at room tem-
perature. The precipitate was filtered off, washed with
propan-2-ol, and dried in air. Yield 87%, light yellow
prisms, mp 175–177°C (decomp.; from aq. i-PrOH).
1H NMR spectrum, δ, ppm: 2.42–2.50 m (2H, CH2),
2.73 t (2H, CH2, J = 8.0 Hz), 4.03 t (2H, CH2, J =
8.0 Hz), 6.77 s (2H, NH2), 7.62 s (1H, CH). Found, %:
C 45.50; H 4.97; N 30.31. C7H9ClN4. Calculated, %:
C 45.54; H 4.91; N 30.35.
2′-Chloro-5′,7′-dihydrospiro[cyclohexane-1,6′-
pyrrolo[1,2-a]imidazole]-3′-carboxylic acid (7g).
A solution of 20 mmol of potassium permanganate in
water was slowly added dropwise to a solution of
30 mmol of aldehyde 5g in acetone heated to 40°C.
The mixture was stirred until the color disappeared,
and the precipitate of manganese dioxide was filtered
off and washed with acetone on a filter. Acetone was
distilled off from the filtrate under reduced pressure,
the precipitate of unreacted initial compound 5g was
filtered off, and the aqueous solution was acidified to
pH 5.5–6.0. The white solid was filtered off and
washed with water and diethyl ether. Yield 30%, color-
less prisms, mp 242–243°C (decomp.; from aqueous
2-Chloro-3-(hydrazinylidenemethyl)-6-phenyl-
6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (9b). Alde-
hyde 5b, 4.94 g (20 mmol), was dissolved in aqueous
ethanol, 3.90 g (50 mmol) of hydrazine hydrate was
added, and the mixture was stirred for 12 h at room
temperature. The precipitate was filtered off, washed
with propan-2-ol, and dried in air. Yield 90%, light
brown prisms, mp 188–190°C (decomp.; from PhMe).
1H NMR spectrum, δ, ppm: 2.83–2.89 m (1H, Heq in
CH2), 3.21–3.27 m (1H, Hax in CH2), 3.98–4.03 m (1H,
Heq in CH2), 4.16 quint (1H, CH, J = 8.0 Hz), 4.53–
4.58 m (1H, Hax in CH2), 6.60 s (2H, NH2), 7.23–
7.37 m (5H, Ph), 7.62 (1H, CH). Found, %: C 59.83;
H 5.07; N 21.43. C13H13ClN4. Calculated, %: C 59.89;
H 5.03; N 21.49.
1
i-PrOH). H NMR spectrum, δ, ppm: 1.31–1.58 m
(10H, C5H10), 2.71 s (2H, CH2), 3.96 s (2H, CH2),
13.07 br.s (1H, COOH). Found, %: C 56.52; H 5.98;
N 10.94. C12H15ClN2O2. Calculated, %: C 56.58;
H 5.94; N 11.00.
Compounds 8a and 8b (general procedure).
Aldehyde 5a or 5b, 20 mmol, was dissolved in propan-
2-ol, 22 mmol of phenylhydrazine was added, and the
mixture was heated to the boiling point and refluxed
for 30 min with stirring. After cooling to room tem-
perature, the precipitate was filtered off, washed with
propan-2-ol, and dried in air.
2′-Chloro-3′-(hydrazinylidenemethyl)-5′,7′-dihy-
drospiro[cyclohexane-1,6′-pyrrolo[1,2-a]imidazole]
(9g). Aldehyde 5g, 4.77 g (20 mmol), was dissolved
in aqueous ethanol, 3.90 g (50 mmol) of hydrazine
2-Chloro-3-[(phenylhydrazinylidene)methyl]-
6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (8a). Yield
93%, light brown prisms, mp 209–210°C (decomp.;
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KAVINA et al.
908
hydrate was added, and the mixture was stirred for
12 h at room temperature. The precipitate was filtered
off, washed with propan-2-ol, and dried in air. Yield
90%, orange prisms, mp 152–154°C (from PhMe).
1H NMR spectrum, δ, ppm: 1.34–1.66 m (10H, C5H10),
2.62 s (2H, CH2), 3.84 s (2H, CH2), 6.76 s (2H, NH2),
7.61 (1H, CH). Found, %: C 57.07; H 6.91; N 22.10.
C12H17ClN4. Calculated, %: C 57.03; H 6.78; N 22.17.
4.25 t (2H, CH2, J = 8.0 Hz), 8.42 s (1H, CH=N).
Found, %: C 49.91; H 4.22; N 24.85. C14H14Cl2N6.
Calculated, %: C 49.87; H 4.18; N 24.92.
1,2-Bis[(2-chloro-6-phenyl-6,7-dihydro-5H-pyr-
rolo[1,2-a]imidazol-3-yl)methylidene]hydrazine
(11b). A mixture of 1 g (2 mmol) of hydrazone 9b and
5 mL of DMSO was heated to 180°C and stirred for
2 h at that temperature. The mixture was cooled, and
the precipitate was filtered off and washed with DMSO
and acetone. Yield 80%, light brown needles, mp 277–
Compounds 10a, 10b, and 10g (general proce-
dure). Aldehyde 5a, 5b, or 5g, 20 mmol, was dispersed
in water (5a) or aqueous ethanol (5b, 5g), 26 mmol of
hydroxylamine hydrochloride was added, and the mix-
ture was heated until it became homogeneous. After
cooling, the precipitate was filtered off, washed with
water, and dried at a temperature not exceeding 60°C.
1
279°C (decomp., from DMSO). H NMR spectrum, δ,
ppm: 2.96–3.02 m (1H, Heq in CH2), 3.32–3.38 m (1H,
Hax in CH2), 4.16–4.29 m (1H, Heq in CH2, 6-H), 4.76–
4.81 m (1H, CH), 7.28–7.38 m (5H, Ph), 8.41 s (1H,
CH=N). Found, %: C 63.74; H 4.46; N 17.10.
C26H22Cl2N6. Calculated, %: C 63.81; H 4.53; N 17.17.
2-Chloro-6,7-dihydro-5H-pyrrolo[1,2-a]imidaz-
ole-3-carbaldehyde oxime (10a). Yield 79%, colorless
Compounds 12, 13b, 13g, and 14 (general proce-
dure). Oxime 10a, 10b, or 10g, 36 mmol, was dis-
solved in 20 mL of DMF, 56 mmol of freshly calcined
potassium carbonate was added, and the mixture was
heated to 120°C and stirred for 48 h at that tempera-
ture. The mixture was cooled to room temperature and
diluted with water, and the precipitate was filtered off,
washed with water, and dried.
1
prisms, mp 218–219°C (from i-PrOH). H NMR spec-
trum, δ, ppm: 2.46–2.55 m (2H, CH2), 2.78 t (2H, CH2,
J = 8.0 Hz), 4.07 t (2H, CH2, J = 8.0 Hz), 7.93 s
(1H, CH), 11.31 s (1H, OH). Found, %: C 45.33;
H 4.36; N 22.58. C7H8ClN3O. Calculated, %: C 45.30;
H 4.34; N 22.64.
2-Chloro-6-phenyl-6,7-dihydro-5H-pyrrolo-
[1,2-a]imidazole-3-carbaldehyde oxime (10b). Yield
83%, white prisms, mp 206–208°C (from i-PrOH).
1H NMR spectrum, δ, ppm: 2.88–2.94 m (1H, Heq in
CH2), 3.26–3.32 m (1H, Hax in CH2), 4.01–4.06 m (1H,
Heq in CH2), 4.21 quint (1H, CH, J = 8.0 Hz), 4.54–
4.59 m (1H, Hax in CH2), 7.26–7.38 m (5H, Ph), 7.96 s
(1H, CH), 11.34 s (1H, OH). Found, %: C 59.68;
H 4.56; N 15.98. C13H12ClN3O. Calculated, %:
C 59.66; H 4.62; N 16.06.
2-Chloro-6,7-dihydro-5H-pyrrolo[1,2-a]imidaz-
ole-3-carboxamide (12). Yield 66%, brown prisms,
1
mp 206–208°C (from H2O). H NMR spectrum, δ,
ppm: 2.43–2.50 m (2H, CH2), 2.77 t (2H, CH2, J =
8.0 Hz), 4.15 t (2H, CH2, J = 8.0 Hz), 6.90 s (1H,
NH2), 7.61 s (1H, NH2). Found, %: C 45.34; H 4.38;
N 22.58. C7H8ClN3O. Calculated, %: C 45.30; H 4.34;
N 22.64.
2′-Chloro-5′,7′-dihydrospiro[cyclohexane-1,6′-
pyrrolo[1,2-a]imidazole]-3′-carbonitrile (13g). Yield
71%, brown needles, mp 150–152°C (from i-PrOH).
1H NMR spectrum, δ, ppm: 1.35–1.65 m (10H, C5H10),
2.76 s (2H, CH2), 3.96 s (2H, CH2). Found, %:
C 61.10; H 5.94; N 17.79. C12H14ClN3. Calculated, %:
C 61.15; H 5.99; N 17.83.
2′-Chloro-5′,7′-dihydrospiro[cyclohexane-1,6′-
pyrrolo[1,2-a]imidazole]-3′-carbaldehyde oxime
(10g). Yield 85%, light brown prisms, mp 158–160°C
(from PhMe). 1H NMR spectrum, δ, ppm: 1.43–1.59 m
(10H, C5H10), 2.68 s (2H, CH2), 3.88 s (2H, CH2),
7.91 s (1H, CH), 11.28 s (1H, OH). Found, %:
C 56.72; H 6.28; N 16.49. C12H16ClN3O. Calculated,
%: C 56.80; H 6.36; N 16.56.
2-Chloro-6-phenyl-6,7-dihydro-5H-pyrrolo-
[1,2-a]imidazole-3-carboxamide (14) and 2-chloro-
6-phenyl-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole-
3-carbonitrile (13b). Yield of product mixture 77%,
light brown powder. The mixture consisted of 44% of
14 and 56% of 13b.
1,2-Bis[(2-chloro-6,7-dihydro-5H-pyrrolo[1,2-a]-
imidazol-3-yl)methylidene]hydrazine (11a). A mix-
ture of 1 g (3 mmol) of hydrazone 9a and 5 mL of
DMSO was heated to 180°C and stirred for 2 h at that
temperature. The mixture was cooled, and the precip-
itate was filtered off and washed with DMSO and
acetone. Yield 80%, light yellow needles, mp 312–
2-Chloro-6-phenyl-6,7-dihydro-5H-pyrrolo-
[1,2-a]imidazole-3-carboxamide (14). A mixture of
5 g (19 mmol) of acid 7b and 13.1 g (0.11 mol) of
thionyl chloride was stirred at 60°C until hydrogen
1
314°C (from DMSO). H NMR spectrum, δ, ppm:
2.52–2.57 m (2H, CH2), 2.85 t (2H, CH2, J = 8.0 Hz),
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FUSED IMIDAZOLES: I.
909
chloride no longer evolved. The mixture was cooled,
excess thionyl chloride was removed under reduced
pressure, and the residue was dissolved in methylene
chloride. The solution was added on cooling to 25 mL
of 25% aqueous ammonia, and the mixture was stirred
for 15 min at room temperature. Methylene chloride
was distilled off, and the precipitate was filtered off.
Yield 81%, light brown prisms, mp 142–143°C (from
hydrate (hydrogen source), and 0.5 g of freshly pre-
pared Raney nickel were added. The mixture was
heated to 100–110°C in a high-pressure reactor and
was stirred for 16–18 h at that temperature. The mix-
ture was then cooled, the catalyst was filtered off, and
the solvent was distilled off under reduced pressure.
The residue was extracted with toluene, the extract was
filtered to remove undissolved impurities, and the
filtrate was evaporated to dryness.
1
PhMe–petroleum ether). H NMR spectrum, δ, ppm:
2.86–2.92 m (1H, Heq in CH2), 3.24–3.30 m (1H, Hax
in CH2), 4.06–4.10 m (1H, Heq in CH2), 4.17 quint
(1H, CH, J = 8.0 Hz), 4.63–4.68 m (1H, Hax in CH2),
7.26–7.40 m (5H, Ph), 6.98 br.s and 7.69 br.s (1H each,
NH2). Found, %: C 59.70; H 4.66; N 16.00.
C13H12ClN3O. Calculated, %: C 59.66; H 4.62; N 16.06.
6,7-Dihydro-5H-pyrrolo[1,2-a]imidazole (15a).
Yield 97%, light brown prisms rapidly flowing on
1
exposure to air, mp 72–74°C (from octane). H NMR
spectrum, δ, ppm: 2.48–2.56 m (2H, CH2), 2.71 t (2H,
CH2, J = 8.0 Hz), 3.93 t (2H, CH2, J = 8.0 Hz), 8.84 s
(1H, CH), 7.00 s (1H, CH). Found, %: C 66.59;
H 7.49; N 25.85. C6H8N2. Calculated, %: C 66.64;
H 7.46; N 25.90.
Compounds 13a, 13b, and 13g (general proce-
dure). Oxime 10a, 10b, or 10g, 10 mmol, was added
with stirring to 85 mmol of phosphoryl chloride, and
the mixture was heated to the boiling point and
refluxed with stirring until hydrogen chloride no
longer evolved (0.5–1 h). The mixture was cooled,
poured into water containing ice, and stirred for
30 min, and the precipitate was filtered off, washed
with water, and dried.
6-Phenyl-6,7-dihydro-5H-pyrrolo[1,2-a]imidaz-
ole (15b). Yield 98%, colorless prisms, mp 104–105°C
1
(from octane). H NMR spectrum, δ, ppm: 2.78–
2.84 m (1H, Heq in CH2), 3.17–3.23 m (1H, Hax in
CH2), 3.90–3.94 m (1H, Heq in CH2), 4.18 quint (1H,
CH, J = 8.0 Hz), 4.37–4.42 m (1H, Hax in CH2), 6.90 s
(1H, CH), 7.08 s (1H, CH), 7.25–7.39 m (5H, Ph).
Found, %: C 78.17; H 6.51; N 15.15. C12H12N2. Cal-
culated, %: C 78.23; H 6.57; N 15.21.
2-Chloro-6,7-dihydro-5H-pyrrolo[1,2-a]imidaz-
ole-3-carbonitrile (13a). Yield 84%, white prisms,
1
mp 80–82°C (from i-PrOH). H NMR spectrum, δ,
6-(4-Methoxyphenyl)-6,7-dihydro-5H-pyrrolo-
[1,2-a]imidazole (15d). After removal of the solvent,
the residue was extracted with methylene chloride, the
extract was filtered and evaporated, and the liquid resi-
due was left to stand on exposure to air; after several
hours, it crystallized. Yield 96%, light brown prisms,
ppm: 2.49–2.57 m (2H, CH2), 2.87 t (2H, CH2, J =
8.0 Hz), 4.14 t (2H, CH2, J = 8.0 Hz). Found, %:
C 50.11; H 3.65; N 25.01. C7H6ClN3. Calculated, %:
C 50.17; H 3.61; N 25.07.
2-Chloro-6-phenyl-6,7-dihydro-5H-pyrrolo-
[1,2-a]imidazole-3-carbonitrile (13b). Yield 91%,
light brown prosms, mp 150–151°C (from i-PrOH).
1H NMR spectrum, δ, ppm: 2.94–3.01 m (1H, Heq in
CH2), 3.35–3.42 m (1H, Hax in CH2), 4.13–4.18 m (1H,
Heq in CH2), 4.26 quint (1H, CH, J = 8.0 Hz), 4.60–
4.64 m (1H, Hax in CH2), 7.26–7.43 m (5H, Ph).
Found, %: C 64.02; H 4.19; N 17.19. C13H10ClN3.
Calculated, %: C 64.07; H 4.14; N 17.24.
1
mp 70–73°C (from octane). H NMR spectrum, δ,
ppm: 2.30–2.36 m (1H, Heq in CH2), 2.68–3.73 m (1H,
Hax in CH2), 3.30 s (3H, CH3), 3.34–3.44 m (1H, Heq in
CH2), 3.66 quint (1H, CH, J = 8.0 Hz), 3.87–3.92 m
(1H, Hax in CH2), 6.47 d (2H, Harom, J = 4.0 Hz),
6.50 br.s (1H, CH), 6.65 br.s (1H, CH), 6.82 d (2H,
H
arom, J = 4.0 Hz).
5′,7′-Dihydrospiro[cyclohexane-1,6′-pyrrolo-
2′-Chloro-5′,7′-dihydrospiro[cyclohexane-1,6′-
pyrrolo[1,2-a]imidazole)-3′-carbonitrile (13g). Yield
90%, colorless needles, mp 151–152°C (from i-PrOH).
[1,2-a]imidazole] (15g). Yield 98%, light brown
prisms rapidly flowing on exposure to air, mp 47–49°C
1
(from octane). H NMR spectrum, δ, ppm: 1.41–
1.54 m (10H, C5H10), 2.58 s (2H, CH2), 3.73 s (2H,
CH2), 6.84 s (1H, CH), 6.99 s (1H, CH). Found, %:
C 74.91; H 9.22; N 15.84. C11H16N2. Calculated, %:
C 74.96; H 9.15; N 15.89.
Reductive hydrodehalogenation (general proce-
dure). Initial 2-chloro-6,7-dihydro-5H-pyrrolo[1,2-a]-
imidazole derivative, 10 mmol, was dissolved in 25–
30 mL of water (3a, 7a, 7b, 7g) or ethanol (all other
substrates), and 10 mmol (per chlorine atom) of
aqueous sodium hydroxide, 2–3 equiv of hydrazine
3-(6,7-Dihydro-5H-pyrrolo[1,2-a]imidazol-6-yl)-
aniline (16). When the reaction was complete, the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 6 2018

KAVINA et al.
910
mixture was cooled, the catalyst was filtered off, the
filtrate was diluted with water, the solvent and residual
hydrazine were distilled off, and the residue was crys-
tallized from aqueous ethanol. Yield 91%, gray prisms,
solution was acidified to pH 6.0 with acetic acid. After
3 h, the precipitate was filtered off, washed with water,
and dried. Yield 75%, colorless prisms, mp 262–263°C
1
(from H2O). H NMR spectrum, δ, ppm: 2.50–2.58 m
1
(2H, CH2), 2.79 t (2H, CH2, J = 8.0 Hz), 4.11 t (2H,
CH2, J = 8.0 Hz), 7.49 s (1H, CH). Found, %: C 55.18;
H 5.32; N 18.33. C7H8N2O2. Calculated, %: C 55.26;
H 5.30; N 18.41.
mp 177–178°C (from aq. EtOH). H NMR spectrum,
δ, ppm: 2.70–2.76 m (1H, Heq in CH2), 3.11–3.17 m
(1H, Hax in CH2), 3.81–3.85 m (1H, Heq in CH2),
4.00 quint (1H, CH, J = 8.0 Hz), 4.31–4.35 m (1H, Hax
in CH2), 5.05 br.s (2H, NH2), 6.43–6.49 m (3H, Harom),
6.91 s (1H, CH), 6.97 t (1H, Harom, J = 8.0 Hz), 7.08 s
(1H, Harom). Found, %: C 72.36; H 6.72; N 21.03.
C12H13N3. Calculated, %: C 72.33; H 6.58; N 21.09.
6-Phenyl-6,7-dihydro-5H-pyrrolo[1,2-a]imidaz-
ole-3-carboxylic acid (18b). The reduction was
carried out using 2 equiv of sodium hydroxide. When
the reaction was complete, the mixture was cooled, the
catalyst was filtered off, and the filtrate was acidified
to pH 6.0 with acetic acid. The precipitate was filtered
off, washed with water, and dried at 90°C. Yield 88%,
white prisms, mp 230–231°C (decomp.; from i-PrOH).
1H NMR spectrum, δ, ppm: 2.88–2.94 m (1H, Heq in
CH2), 3.26–3.32 m (1H, Hax in CH2), 4.03–4.08 m (1H,
Heq in CH2), 4.25 quint (1H, CH, J = 8.0 Hz), 4.59–
4.64 m (1H, Hax in CH2), 7.26–7.37 m (5H, Ph), 7.57 s
(1H, CH), 12.72 br.s (1H, COOH). Found, %: C 68.36;
H 5.34; N 12.22. C13H12N2O2. Calculated, %: C 68.41;
H 5.30; N 12.27.
(6,7-Dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-
methanol (17a). After removal of the solvent, the
residue was recrystallized from propan-2-ol. Yield
86%, white prisms, mp 175–176°C (from i-PrOH).
1H NMR spectrum, δ, ppm: 2.47–2.57 m (2H, CH2),
2.69 t (2H, CH2, J = 8.0 Hz), 3.90 t (2H, CH2, J =
8.0 Hz), 4.36 s (2H, CH2), 5.01 br.s (1H, OH), 6.70 s
(1H, CH). Found, %: C 60.88; H 7.36; N 20.24.
C7H10N2O. Calculated, %: C 60.85; H 7.30; N 20.28.
(6-Phenyl-6,7-dihydro-5H-pyrrolo[1,2-a]imidaz-
ol-3-yl)methanol (17b). When the reaction was com-
plete, the mixture was cooled, the catalyst was filtered
off, the filtrate was diluted with water, and most part of
ethanol was distilled off under reduced pressure. The
residue was filtered off and washed with water and
propan-2-ol. Yield 93%, white prisms, mp 115–117°C
5′,7′-Dihydrospiro[cyclohexane-1,6′-pyrrolo-
[1,2-a]imidazole]-3′-carboxylic acid (18g). The
reduction was carried out using 2 equiv of sodium
hydroxide. After removal of the solvent and unreacted
hydrazine, the residue was dissolved in water again,
and the solution was acidified to pH 6.0 with acetic
acid. The precipitate was filtered off, washed with
water, and dried. Yield 87%, colorless prisms, mp 217–
1
(from i-PrOH). H NMR spectrum, δ, ppm: 2.77–
2.83 m (1H, Heq in CH2), 3.17–3.23 m (1H, Hax in
CH2), 3.86–3.91 m (1H, Heq in CH2), 4.19 quint (1H,
CH, J = 8.0 Hz), 4.36–4.41 m (1H, Hax in CH2,
CH2OH), 5.05 br.s (1H, OH), 6.77 s (1H, CH), 7.28–
7.34 m (5H, Ph). Found, %: C 72.91; H 6.63; N 13.01.
C13H14N2O. Calculated, %: C 72.87; H 6.59; N 13.07.
1
218°C (decomp.; from i-PrOH). H NMR spectrum, δ,
ppm: 1.42–1.58 m (10H, C5H10), 2.70 s (2H, CH2),
3.95 s (2H, CH2), 7.03 s (1H, CH), 13.01 br.s (1H,
COOH). Found, %: C 65.37; H 7.26; N 12.66.
C12H16N2O2. Calculated, %: C 65.43; H 7.32; N 12.72.
(5′,7′-Dihydrospiro[cyclohexane-1,6′-pyrrolo-
[1,2-a]imidazol]-3-yl)methanol (17g). After removal
of toluene, the liquid residue was dissolved in methy-
lene chloride, the solution was filtered and evaporated
to dryness, and the residue was kept for 12 h at 70°C
under reduced pressure to remove residual solvent.
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