1,2-Deoxygenation of vic-dihydroxyindenoimidazoles: Optimization of a novel deoxygenation reagent

Article abstract of DOI:10.1515/znb-2004-1011

Treatment of vic-dihydroxyindeno[1,2-d]imidazoles with N,N,N′, N′-tetraalkyl sulfurous diamides yields indeno[1,2-d]imidazoles by deoxygenation. Isochromeno[3,4-d]imidazoles are formed as byproducts. An X-ray crystal structure analysis confirmed the struc

Full text of DOI:10.1515/znb-2004-1011

1,2-Deoxygenation of vic-Dihydroxyindenoimidazoles:
Optimization of a Novel Deoxygenation Reagent
Hans-Jo¨rg Hemmerlinga, Angelika Merschenz-Quackb,∗, and Hartmut Wunderlichb
a Institut fu¨r Pharmazeutische Chemie
b Institut fu¨r Anorganische Chemie und Strukturchemie, Heinrich-Heine-Universita¨t Du¨sseldorf,
Universita¨tsstr.1, D-40225 Du¨sseldorf
∗ Present address: FH Ju¨lich, Dep. Ju¨lich, Ginsterweg 1, D-52428 Ju¨lich
Reprint requests to Dr. H.-J. Hemmerling. E-mail: H-J.Hemmerling@uni-duesseldorf.de
Z. Naturforsch. 59b, 1143 – 1152 (2004); received March 11, 2004
Dedicated to Prof. Dr. Hans-Dieter Ho¨ltje on the occasion of his 65th birthday
Treatment of vic-dihydroxyindeno[1,2-d]imidazoles with N,N,N’,N’-tetraalkyl sulfurous diamides
yields indeno[1,2-d]imidazoles by deoxygenation. Isochromeno[3,4-d]imidazoles are formed as
byproducts. An X-ray crystal structure analysis confirmed the structure of deoxygenated products.
The ratio of products depending on the reaction conditions was analyzed. A mechanism of the reac-
tion is discussed.
Key words: Indeno[1,2-d]imidazoles, Isochromeno[3,4-d]imidazoles, N,N,N’,N’-Tetraalkylsulfur-
ous Diamides, 1,2-Bis-deoxygenation, Crystal Structure
Introduction
Ninhydrin (1), the hydrate of indan-1,2,3-trione, is
well known as an analytical reagent for the detection
of α-amino acids and its forensic application in finger-
print development. In synthetic applications of 1 with
suitable 1,3-dinucleophiles, the carbonyl functionali-
ties are involved in a (2+3)-cyclization to form indene-
annulated heterocycles [1]. Thus the addition of urea
or thiourea to 1 gives imidazole derivatives 2a [2a].
The reaction of β-aminocrotonic acid derivatives and
1 yields indenopyrroles 2b [2b]. The addition of ac-
etamides to 1 gives rise to the formation of indenopyr-
role derivatives 2c [2c].
Scheme 1.
indan-1-one with thiocyanates (Scheme 1: 1A) or 2-
bromoindan-1-one with amidines (Scheme 1: 1B) [4].
But these synthetic routes suffer from unefficiency and
no general applicability. We therefore realized that the
direct transformation of 4 and 5 to the fully unsatu-
rated indenoimidazoles 6 and 8 would represent a par-
We recently reported on the addition of N-sub- ticularly useful tool. As one way to reach this goal
stituted amidines 3a – g to 1 which afforded mixt- we considered the 1,2-bis-deoxygenation of 4 and 5.
ures of regioisomeric indenoimidazoles 4 and 5 Though 1,2-bis-deoxygenations of vic-diols to gener-
(Scheme 1) [3]. Because indenoimidazoles show ate an olefinic bond are well known in the literature [5],
some biological and pharmaceutical effects, syntheses compounds such as 2 or 4, 5, respectively, have not
have been developed using the reaction of 2-amino- been subject to this type of reaction till now. We there-
c
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H.-J. Hemmerling et al. · 1,2-Deoxygenation of vic-Dihydroxyindenoimidazoles
fore decided to study the reaction of 4, 5 with elec-
trophilic reagents used in the syntheses of olefins from
vic-diols.
In the present work we report on the results of
our studies of developing a novel 1,2-deoxygenation
reagent and its use for the olefination of the vic-diols 4
and 5.
Results
We recently published the synthesis of mixtures of
regioisomeric indenoimidazoles 4 and 5 by addition of
N-substituted amidines 3a – g to 1 [3]. The major prod-
ucts were identified as compounds 4a – g. Due to equi-
libria in solutions, attempts to isolate the pure regioi-
somers 5 were not successful. Therefore the following
experiments refer to purified mixtures of 4 and 5 even
if not explicitly mentioned.
Fig. 1. Molecular structure of 6g×HClO4 in the solid state
with displacement parameters of 25% probability [10].
Preliminary experiments to deoxygenate 4g were
made using procedures which have proven to be ef-
ficient in olefin synthesis by deoxygenation of vic-
diols. The Corey-Winter elimination proved unsuited
because the cyclic precursors, needed in this reaction,
could not be obtained when 4g was allowed to re-
act with thioxocarbonyldiimidazole [6]. In another ap-
proach attempts to get the cyclic precursor of the East-
wood fragmentation by reacting 4g with dimethylfor-
mamide dimethyl acetal gave small amounts of 7g as
the only product [7].
Scheme 2. R1, R2 refer to Scheme 1.
groups in full agreement with the result of X-ray analy-
sis. In the 1H NMR spectra the expected aromatic and
aliphatic protons could be detected but no exchange-
able proton was found; likewise the 13C NMR spectra
include no signals corresponding to hydroxy substi-
tuted aliphatic bridgehead carbons of the educts. The
carbonyl resonance appears at δ = 180 ppm indicating
the incorporation in an unsaturated cyclus.
Reaction of vic-Dihydroxyindenoimidazoles with
Sulfurous Acid Derivatives
The olefin forming radical 1,2-elimination of 2,1,3-
thiadioxolane-2,2-dioxides has been published re-
cently [8, 9]. The substrates of this reaction usually are
synthesized by reacting vic-diols and thionyl chloride
to yield 2,1,3-thiadioxolane-2-oxides, which after ox-
idation gave the heterocyclic precursors of the olefi-
nation. The approach to synthesize 2,1,3-thiadioxolan-
2-oxides via the reaction of 4g and thionyl chloride /
pyridine (10) resulted in the formation of largely in-
tractable polymers from which two compounds could
be isolated. Besides isochromene 7g deoxygenation
product 6g was found in small amounts.
Mass spectrum and elemental analysis of isochrom-
enoimidazole 7g confirm the loss of water. 1H and
13C NMR spectra are consistent with the proposed
1
structure. In the H NMR spectrum the anisotropy of
the carbonyl group causes a significant downfield shift
of aromatic ortho-proton 4-H to δ = 8.3 ppm. The
13C NMR spectrum shows a carbonyl resonance at
δ = 160.9 ppm indicating a lactone carbonyl [11]. No
resonances of hydroxysubstituted aliphatic bridgehead
carbons were detected.
Because 6g represented just the type of product we
were searching for we were prompted to study this re-
action in detail.
The structure of 6g was confirmed by X-ray diffrac-
tion analysis of the HClO4 adduct (Fig. 1) [10] which
was validated by spectral and analytical data. The mass
spectrum of 6g with a molecular ion of 238 amu and
When 4 suspended in trichloromethane was allowed
the elemental analysis confirm the loss of two OH to react with thionyl chloride, only small amounts of
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H.-J. Hemmerling et al. · 1,2-Deoxygenation of vic-Dihydroxyindenoimidazoles
1145
Table 1. Yields of deoxygenation products 6 (+8) and trans-
formation products 7 (+9)a.
served when 4d/5d was used with the same reagent
in dichloromethane. The addition of 20% acetic acid
to the solution of 4/5 in dimethyl formamide caused
a significant improvement in the formation of deoxy-
genation products. The yields of 6a/8a raised to 46%,
for 6b from 11% to 80 % and for 6g/8g from 25% to
52%. In all cases only small amounts of 7/9 could be
detected.
Reagent
10
10a
10b
10b
(SOCl2/pyridine)
Yield [%]
(acetic acid)
Yield [%] Yield [%] Yield [%]
Starting
compoundsb
4a (+5a)
4b (+5b)
4c
4d (+5d)
4f (+5f)
4g (+5g)
a
6
21c
7
7
6
7
6
–
7
–
9
2
0
6
7
56
49
64
69
37
65
45c 11
46c < 1
10 24 11
35 44 21
52 28 64
80
–
16
–
13
20
4
65
–
0
–
No deoxygenatedcompoundcould be obtained from
the reaction of the highly sensitive diol 4e with 10b, but
10c gave the deoxygenation product 6e with a yield
–
–
25 < 1
23c
23c 12 25c < 1 52c
7
The ratio of products were analyzed by means of 1H NMR spec-
troscopic analysis and by HPLC of the crude reaction products;b the of 35%. No reaction at all could be observed in the
experiments were performed with purified mixtures of regioisomers
reaction of 10d with 4/5.
as indicated; c yields refer to mixtures of 6 and 8.
From DMF destillates of the reaction mixtures a
crystalline solid deposited, which produced a mass
spectrometric molecular ion of 125 amu or 153 amu,
respectively, depending on whether 10b or 10c had
been used for deoxygenation. However, analytically
7 were found besides recovered educts. When this re-
action was executed in the presence of pyridine, the
compounds dissolved and the colour of the solution
quickly changed from light yellow to deep orange. Af-
pure samples of the corresponding sulfonic acids
ter several hours at ambient temperature, work-up re-
R2NSO3H (R = CH3; R = C2H5) could not be obtained.
sulted in the isolation of deoxygenation product 6 in
poor yields besides a 3 – 8 fold excess of transforma-
tion product 7. Column chromatographic separation on
silica yielded mixtures of 6 and 7 which were analyzed
by integration of the downfield aromatic multiplets in
the 1H NMR spectra and by HPLC and UV detection.
Neither a cyclic nor acylic sulfurous acid ester could
be isolated. Changing the reaction conditions by mod-
ifying solvent and temperature gave only very limited
Fig. 2. Intramolecular NOE-enhancement of regioisomers 6a
and 8a.
improvements (Table 1).
The deoxygenation of the mixtures of 4a/5a and
In order to enhance the yields of the deoxygena-
tion products 6 and to avoid the formation of the
transformation products 7, the sulfurous acid diamides
SO(NR2)2 10a– d (a: R = 1-imidazolyl, b: R = CH3,
c: R = C2H5, d: R = iso-C3H7) were synthesized and
allowed to react with 4 and 5.
4g/5g respectively gave mixtures of the regioisomers
6a/8a and 6g/8g. Distinction of the regioisomers 6a
and 8a was established by 1H NMR spectroscopy.
After assignment of protons had been accomplished
by H,H correlation, the structures of 6a and 8a were
confirmed by measuring homonuclear NOE difference
spectra (Fig. 2). Upon irradiation of the methyl-H res-
onance of 8a a marked enhancement of the 4-H multi-
plet and of the ortho-protons of the phenyl substituent
in 2-position was observed. Irradiation of the methyl-H
resonance of 6a only caused enhancement of the latter
protons but not of the 4-H multiplet.
Treatment of mixtures of 4/5 with 10a in DMF re-
sulted in a rapid coloring of the solution with for-
mation of 6/8 in higher yields besides still consider-
able amounts of 7/9 and with decreased overall yields
(Table 1). Using 10b, no significant change of the
rate of formation of deoxgenation products 6/8 was
observed monitoring by tlc. The mixture of products
Additionally, reduction experiments were done
contained only small amounts of 7/9 but the overall with compounds 6a,g and 8a,g for further charac-
yields decreased. This may be caused by decompo- terisation of the regioisomers. The reduction with
sition of educts, due to the prolonged reaction times sodium borohydride afforded the hydroxy compounds
necessary. Only small yields of 6b and 7b/9b could be 11a,g and14a,g, respectively. Catalytic hydrogenation
detected when 4b/5b was treated with 10b, whereas yielded 12a,g or 15a,g which were subsequently quat-
4d/5d gave pure deoxygenation product 6d in 64% ernized by methylation with dimethyl sulfate. The
yield under the same conditions. No reaction was ob- treatment of the sulfates with 70% perchloric acid gave
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H.-J. Hemmerling et al. · 1,2-Deoxygenation of vic-Dihydroxyindenoimidazoles
Scheme 4. Proposed mechanism of deoxygenation products
formation 6, 8 and transformation products formation 7, 9.
Scheme 3. Reduction experiments of regioisomers 6a, 8a and
6g, 8g.
can be explained by dissociation of the gem-hydroxy
group and formation of iminium compound 4B with α-
hydroxy ketone functionalities. Intermediate 4B under-
goes a rearrangement to form isochromeno-imidazoles
7. Similar transformations of α-hydroxy-indanones
have been published [16].
In conclusion, we found a facile and effi-
cient method for the synthesis of indeno[1,2-d]imi-
dazoles and indeno[2,1-d]imidazoles via 1,2-bis-de-
oxygenation of the respective vic-diols 4 and 5. The ap-
plicability of this previously unreported reaction to fur-
ther vic-diols with hemi-N,O-ketal functionalities will
be studied.
the quaternary perchlorates 13g and 16g, respectively
(Scheme 3).
Discussion
The formation of regioisomeric indenoimidazoles
6 and 8 from the diols 4 and 5 requires the 1,2-
elimination of hydroxy groups which then results in
an olefinic bond. Examples of this type of deoxygena-
tion have been published but to the best of our knowl-
edge never by reaction of vic-diols with sulfurous di-
amides. In the formation of 6 we assume that a cycliza-
tion to β-sultins could be accomplished by alcoholysis
of N,N,N’,N’-tetraalkylsulfurous diamides and the in-
tramolecular nucleophilic addition of sulfur to the in-
termediate iminium compound 4A (Scheme 4) gener-
ated by dissociation of the second gem-hydroxyamine
functionality [12]. The fragmentation of the tricyclic
intermediate results in the formation of 6. The addition
of acetic acid to the reaction may increase the forma-
tion of 4A and probably enhances the reactivity by in-
termediate formation of a mixed amidosulfurous acid
anhydride [13].
The process and our results may have some similari-
ties to the olefin forming 1,2-elimination of β-hydroxy
sulfinamides reported by Corey and Durst. They ar-
gued for a 1,2-cycloelimination pathway, which re-
quired hydroxy- and sulfinic acid amide functionalities
standing cis to one another and the intermediate forma-
tion of β-sultins which gave olefins by decomposition
[14]. The easy fragmentation of β-sultins at ambient
temperature was already reported elsewhere [15].
The formation of the isochromeno-imidazoles
Experimental Section
General Information: Melting points: Bu¨chi melting point
apparatus by Dr. Tottoli; not corrected. IR spectra: Perkin
Elmer 177 and FT-IR 1600, using KBr discs. 1H NMR spec-
tra and 13C NMR spectra: Varian FT 80 (80 MHz/20 MHz),
Bruker AC 200F (200 MHz/50 MHz) and Varian VXR 300
(300 MHz/75 MHz) in the designated solvents with TMS
as internal standard, using the δ (ppm) scale; signals la-
beled by * exchanged by addition of D2O. EI mass-spectra:
Finnigan 4200 quadrupole mass spectrometer, equipped with
a MASPEC datasystem; 70 eV ionizing potential. Micro-
analyses: Perkin Elmer Elemental Analyzer 2400. HPLC-
analyses: Hewlett-Packard 1084B, equipped with a Waters
PAD-Detector 990. Catalytic hydrogenation: Low-pressure
apparatus “Roche-Ku¨hner”. Solvents were purified by stan-
dard methods and dried over molecular sieves or sodium.
Thionyl chloride was purified by the procedure of Mar-
tin and Fieser [17]. Bis-(1-imidazolyl)sulfoxide 10a [18a],
N,N,N’,N’-tetramethylsulfurous diamide 10b, N,N,N’,N’-
which is favored in the reaction of thionyl chloride tetraethylsulfurous diamide 10c [18b] and N,N,N’,N’-
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H.-J. Hemmerling et al. · 1,2-Deoxygenation of vic-Dihydroxyindenoimidazoles
1147
tetraisopropylsulfurous diamide 10d [18c] were prepared ac-
C17H12N2O (260.30): calcd. C 78.44, H 4.65, N 10.76; found
cording to the literature.
C 78.34, H 4.80, N 10.43.
3-Methyl-2-phenyl-3H-indeno[2,1-d]imidazol-8-one (8a)
General Procedures
Following general procedure A, a mixture of 4a/5a
(2.94 g, 0.01 mol) was treated with 10. After 12 h at 20 ◦C
CHCl3 (100 ml) was added and the solution was extracted
with 5 × 20 ml portions of aequeous 5% HCl solution. The
organic layers were washed with water, dried over sodium
sulfate and the solvent removed in vacuo. The residue was
purified by flash chromatography on silica, elution with
CHCl3/MeOH (98 : 2; v/v), to yield 380 mg (14.6%) of
6a. The HCl-extracts were unified, washed with CHCl3,
and basified by adding aqueous 10% sodium carbonate. Ex-
traction of the aqueous solution with trichloromethane gave
organic extracts which were evaporated. The residue was
purified by flash chromatography on silica, elution with
CHCl3/MeOH (98 : 2; v/v) to yield 165 mg (6.5%) of 8a.
A) Reaction with thionyl chloride/pyridine (10)
vic-Dihydroxyindenoimidazoles 4/5 (0.01 mol) and dry
pyridine (0.1 mol), dissolved in 100 ml of CHCl3, were
placed in a round-bottom flask. Nitrogen was passed through
the solution. To the stirred and cooled solution thionyl chlo-
ride (0.05 mol in 20 ml of CHCl3) was added, so that the
temperature did not exceed 30 ◦C. After stirring for several
hours at 20 ◦C, water (30 ml) was added under cooling and
vigorous stirring. The organic layer was separated and the
solvent removed in vacuo. The residue was purified by col-
umn chromatography on silica (CHCl3).
B) Deoxygenation with bis(1-imidazolyl)sulfoxide 10a
◦
˜
M. p. 195 C (MeOH). – IR (KBr): ν = 1710 (C=O), 1612,
1529, 1519 cm−1. – 1H NMR (300 MHz, CDCl3): δ = 3.80
(s, 3H, CH3), 6.93 – 6.96 (m, 1H, 4-H), 7.05 – 7.10 (m, 1H,
6-H), 7.16 – 7.21 (m, 1H, 5-H), 7.28 – 7.31 (m, 1H, 7-H),
7.42 – 7.45 (m, 3H, 3’-H, 4’-H, 5’-H), 7.60 – 7.64 (m, 2H,
The diols 4/5 (0.01 mol) were dissolved in 30 ml of an
appropriate solvent (DMF or tetramethylurea) and a solu-
tion of 10a in 80 ml of THF was added by suction. Nitrogen
was passed through the solution and stirring was continued
for several hours. Then the solvent was removed in vacuo,
150 ml of water were added to the residue and the solution
was extracted with CHCl3. After removing the solvent from
organic extracts, the residue was purified by column chro-
matography on silica.
1
2’-H, 6’-H). – 13C { H} NMR (75 MHz, CDCl3): δ =
34.0 (CH3), 116.9, 123.7, 128.6, 128.8, 129.1, 129.4, 129.6,
132.8, 133.0, 137.9, 141.2, 154.4 154.5, 183.8 (C=O). – MS
(EI, 70 eV): m/z (%) = 260 (1) [M+], 149 (2), 135 (29),
134 (32), 105 (100). – C17H12N2O (260.30): calcd. C 78.44,
H 4.65, N 10.76; found C 78.16, H 4.55, N 10.78.
C) Deoxygenation with N,N,N’,N’-tetraalkylsulfurous di-
amides 10b, 10c
1-Cyclohexyl-2-phenyl-1H-indeno[1,2-d]imidazol-8-one
(6b)
The diols 4/5 (0.01 mol) were dissolved in 30 ml of DMF
or tetramethylurea and 10b or 10c (0.05 mol) in 20 ml of
the same solvent was added. After stirring at 20 ◦C for 48 h
300 ml of water were added and the solution was extracted
with CHCl3. The reaction products were separated by col-
umn chromatography on silica (CHCl3).
◦
˜
M. p. 169 – 70 C (MeOH/H2O). – IR (KBr): ν = 1697
(C=O), 1616, 1603 cm−1. – 1H NMR (80 MHz, CDCl3): δ =
1.3−2.4 (m, 10H, cyclohexyl-H), 4.1 (m, 1H, NCH(CH2)2),
6.95 – 7.7 (m, 9H, aromat. H). – 13C NMR (20 MHz,
CDCl3): δ = 24.6, 25.5, 32.4 (5 CH2), 57.0 (NCH), 118.1,
123.5, 128.4, 128.9, 129.0, 130.0, 130.4, 135.2, 137.0, 138.3,
156.3, 165.3, 179.3 (C=O). – MS (EI, 70 eV): m/z (%) =
328 (18) [M+], 246 (100), 218 (8), 190 (9), 143 (6), 130 (10),
115 (43), 114 (33), 89 (11), 88 (20), 77 (10), 41 (61). –
C22H12N2O (328.41): calcd. C 80.46, H 6.14, N 8.53; found
C 80.45, H 6.13, N 8.48.
D) Deoxygenation in DMF-acetic acid
According to general procedure C, but 5 ml of acetic acid
were added just before addition of 10b or 10c.
1-Methyl-2-phenyl-1H-indeno[1,2-d]imidazol-8-one (6a)
1-Benzyl-2-phenyl-1H-indeno[1,2-d]imidazol-8-one (6c)
◦
˜
M. p. 126 – 7 C (MeOH). – IR (KBr): ν = 1704 (C=O),
◦
1613, 1492, 1467, 1405, 1161 cm−1. – 1H NMR (300 MHz,
M. p. 135 – 6 C (MeOH). - IR (KBr): ν = 1690 (C=O),
˜
CDCl3): δ = 3.83 (s, 3H, CH3), 7.10 – 7.13 (m, 1H, 6- 1608, 1485, 1446, 1402, 1275, 1245 cm−1. – 1H NMR
H), 7.24 – 7.27 (m, 2H, 4-H, 5-H), 7.34 – 7.37 (m, 1H, 7- (80 MHz, [D6 ]-DMSO): δ = 5.31 (s, 2H, CH2), 7.0 – 7.7
H), 7.48 – 7.52 (m, 3H, 3’-H, 4’-H, 5’-H), 7.8 – 8.1 (m, (m, 14H; aromat. H). – 13C{1H} NMR (20 MHz, [D6]-
2H, 2’-H, 6’-H). – 13C{ H} NMR (75 MHz, CDCl3): δ = DMSO): δ = 21.6 (CH2), 118.4, 123.6, 127.0, 127.7, 128.3,
1
33.6 (CH3), 118.4, 123.5, 128.4, 128.7, 128.8, 128.9, 130.0, 128.5, 129.0, 129.2, 130.2, 133.3, 135.8, 136.9, 138.4, 157.1,
132.0, 133.3, 136.8, 138.5, 156.7, 163.8, 180.2 (C=O). – MS 164.4, 179.9 (C=O). – MS (EI, 70 eV): m/z (%) = 336 (10)
(EI, 70 eV): m/z (%) = 260 (17) [M+], 177 (30), 159 (100). – [M+], 245 (3), 114 (14), 91 (100), 98 (4), 88 (4), 65 (13). –
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H.-J. Hemmerling et al. · 1,2-Deoxygenation of vic-Dihydroxyindenoimidazoles
C23H16N2O (336.39): calcd. C 82.12, H 4.79, N 8.33; found 117.9, 123.5, 127.3, 128.3, 133.0, 137.5, 137.7, 164.5, 170.3,
C 82.02, H 5.01, N 8.39.
178.9. MS (EI, 70 eV): m/z (%) = 210 (100) [M+], 209 (29),
182 (14), 181 (10), 154 (11), 149 (8), 130 (13), 127 (11),
115 (11), 114 (14), 57 (11). – C13H10N2O (210.23): calcd.
C 74.27, H 4.79, N 13.32; found C 74.11, H 4.90, N 13.10.
1,2-Diphenyl-1H-indeno[1,2-d]imidazol-8-one (6d)
◦
˜
M. p. 211 – 2 C (MeOH). – IR (KBr): ν = 1704, 1700 sh
(C=O), 1614, 1595 cm−1. – 1H NMR (80 MHz, CDCl3):
6,7,8,9-Tetrahydro-indeno[1’,2’:4,5]imidazo[1,2-a]pyridin-
11-one (6f)
δ = 7.0 − 7.55 (m, 14H, aromat. H). – 13C { H} NMR
1
(20 MHz, CDCl3): δ = 118.8, 123.9, 125.7, 126.6, 128.7,
◦
˜
M. p. 124 – 5 C (MeOH). – IR (KBr): ν = 2967,
128.8, 129.0, 129.2, 129.7, 130.2, 131.4, 133.7, 135.5, 136.1,
138.1, 155.7, 164.3, 179.5 (C=O). – MS (EI, 70 eV): 1698 (C=O), 1674, 1611, 1499, 1481, 1409, 1392, 1296,
m/z (%) = 322 (54) [M+], 321 (20), 294 (6), 219 (11), 1142 cm−1. – 1H NMR (200.13 MHz, CDCl3): δ = 1.9−2.1
190 (49), 164 (12), 114 (26), 88 (36), 77 (100), 76 (11), (m; 4H; 7-H, 8-H), 2.85 – 3.05 (m, 2H; 6-H), 4.0 – 4.15
1
51 (56). – C22H14N2O×HClO4 (422.82): calcd. C 62.49, (m, 2H, 9-H), 7.0 – 7.4 (m, 4H; aromat. H). – 13C{ H}
H 3.58, N 6.63; found C 62.64, H 3.61, N 6.52.
NMR (50.32 MHz, CDCl3): δ = 20.0, 22.2, 25.2, 44.5,
118.0, 123.4, 128.3, 129.4, 133.0, 137.0, 138.5, 155.3, 164.6,
179.4. – MS (EI, 70 eV): m/z (%) = 224 (100) [M+],
196 (32), 195 (29), 169 (8), 168 (8), 130 (29), 129 (17),
115 (17), 114 (33), 102 (18), 101 (10), 88 (23). – C14H12N2O
(224.26): calcd. C 74.98, H 5.39, N 12.49; found C 74.78,
H 5.28, N 12.32.
2,3,4a,9a-Tetrahydro-4a,9a-dihydroxy-1H-indeno[1,2-d]-
pyrrolo[1’,2’-a]imidazol-9-one (4e); 2,3,4a,9b-tetrahydro-
4a,9b-dihydroxy-1H-indeno[2,1-d]pyrrolo[1’,2’-a]imid-
azol-5-one (5e)
Equimolar amounts of 1 and 2-iminopyrrolidine hy-
drochloride (3g) were suspended in methanol and stirred sev-
eral days at ambient temperature. The solid was separated
and washed with CHCl3. A mixture of regioisomeric hy-
drochlorides was obtained in 95% yield. M. p. 164 – 6 ◦C –
7,8,9,10-Tetrahydro-6H-indeno[1’,2’:4,5]imidazo[1,2-a]
azepin-12-one (6g)
From 4g/5g by proc◦edure A, work-up as described for
˜
˜
IR (KBr): ν = 3375 (OH), 3190, 3020, 1740 (C=O), 1618, 6a/8a. – M. p. 149 – 50 C (MeOH). – IR (KBr): ν = 2930,
1605, 1588, 1575, 1420, 1360, 1207, 1148 cm−1. – 1H NMR 1718 sh, 1699 (C=O), 1610, 1477, 1411, 1337, 1306 cm−1. –
(80 MHz, [D6]-DMSO): δ = 2.0−2.6 (m, 2H, CH2(CH2)2), 1H NMR (200.13 MHz, CDCl3): δ = 1.8 (m, broad, 6H,
2.6 – 3.0 (m, 2H, CCH2 CH2), 3.2 – 3.9 (m, 2H, NCH2), 7.2 – 7-H, 8-H, 9-H), 2.9 (m (broad), 2H, 6-H), 4.25 (m (broad),
1
1
8.0 (m, 4H, aromat. H), 11 – 13∗ (broad, 3H). – 13C { H} 2H, 10-H), 6.8 – 7.4 (m, 4H, aromat. H). – 13C{ H} NMR
NMR (20 MHz, [D6]-DMSO): δ = 20.2, 22.6, 22.9, 23.8, (50.32 MHz, CDCl3): δ = 25.1, 28.3, 29.9, 30.7, 46,7, 117.8,
24.3 (all CH2), 89.2, 90.7, 96.9, 98.0 (all COH), 124.3, 124,6, 123.4, 128.0, 133.0, 137.1, 138.4, 161.2, 162.9, 180.0. – MS
125.6, 131.4, 131.6, 133.1, 133.4, 137.7, 146.8, 148.7, 170.4, (EI, 70 eV): m/z (%) = 238 (100) (M+), 210 (18), 209 (39),
170.9, 171.3, 192.1, 193.7 (2 C=O). – C13H12N2O3×HCl 197 (27), 184 (5), 183 (10), 812 (7), 181 (6), 168 (6),
(280.71): calcd. C 55.62, H 4.67, N 9.98; found C 55.52, 130 (16), 115 (14), 114 (19), 102 (11), 88 (14). – C15H14N2O
H 4.62, N 9.83.
(238.29): calcd. C 75.61, H 5.92, N 11.76; found C 75.66,
H 5.93, N 11.68.
2,3-Dihydro-1H-indeno[1,2-d]pyrrolo[1’,2’-a]imidazol-9-
one (6e)
7,8,9,10-Tetraahydro-6H-indeno[2’,1’:4,5]imidazo[1,2-a]-
azepin-12-one (8g)
To a suspension of the hydrochlorides of 4e, 5e (1.40 g,
0.005 mol) in DMF (20 ml), acetic acid (5 ml) and 10c
From 4g/5g by procedure A, work-up as described for
◦
˜
(3.84 g, 0.02 mol) were added. The mixture was stirred for 6a/8a. – M. p. 165 – 6 C (MeOH). – IR (KBr): ν = 2928,
12 h at ambient temperature and then evaporated in vacuo. 1704 (C=O), 1608, 1533, 1508, 1448 cm−1. – 1H NMR
The residue was dissolved in CH2Cl2 (100 ml) and washed (80 MHz, CDCl3): δ = 1.85 (m (broad), 6H, 7-H, 8-H, 9-
with water (3 × 50 ml). The organic layers were unified, H), 2.85 (m (broad), 2H, 6-H), 4.0 (m (broad), 2H, 10-H),
dried and concentrated. The residue was subjected to column 6,7 – 7.5 (m, 4, aromat. H). – 13C{ H} NMR (20 MHz,
1
chromatography (silica, CHCl3-MeOH, 99 : 1, v/v). M. p. CDCl3): δ = 25.5, 28.7, 29.8, 30,7, 47.7, 116.4, 123.6, 128.5,
◦
˜
197 – 8 C (EtOAc) – IR (KBr): ν = 1697 (C=O), 1608, 132.4, 133.4, 138.1, 139.6, 153.4, 158.2, 183.4. – MS: m/z
1503, 1404, 1384 cm−1. – 1H NMR (200.13 MHz, CDCl3): (%) = 238 (100) [M+], 237 (51), 210 (24), 209 (39), 197 (8),
δ = 2.6 − 2.85 (m, 2H, 2-H), 2.88 – 3.0 (m (t), 2H, 3-H), 195 (10), 183 (10), 182 (29), 181 (29), 154 (12), 130 (41),
4.0 – 4.15 (m (t), 2H, 1-H), 7.0 – 7.5 (m, 4H, aromat. H). – 129 (23), 128 (13), 127 (17), 115 (23), 114 (25), 103 (20),
13C{ H} NMR (50.32 MHz, CDCl3): δ = 23.4, 25.7, 44.7, 102 (39), 101 (11), 89 (12), 88 (18). – C15H14N2O (238.29):
1
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1149
calcd. C 75.61, H 5.92, N 11.76; found C 75.44, H 5.97, 134.6 135.4, 135.6, 142.3, 144.1, 160.5. – MS (EI, 70 eV):
N 11.56.
m/z (%) = 352 (40) [M+], 261 (18), 130 (64), 102 (71),
91 (100). – C23H16N2O2 (352.38): calcd. C 78.39, H 4.58,
N 7.95; found C 78.37, H 4.54 N 7.84.
3-Methyl-2-phenyl-3H-isochromeno[4,3-d]imidazol-5-one
(7a)
2,3-Diphenyl-3H-isochromeno[4,3-d]imidazol-5-one (7d)
◦
˜
M. p. 185 – 6 C (MeOH). – IR (KBr): ν = 1746 (C=O),
1710, 1626, 1557, 1531, 1514, 1469, 1251, 1003 cm−1. –
1H NMR (200,13 MHz, CDCl3): δ = 3.79 (s, 3H, CH3),
7.3 – 7.9 (m, 7, aromat. H), 8.06 (d, J = 7.6 Hz, 1H,
◦
˜
M. p. 234 C (EtOH). – IR (KBr): ν = 1738 sh;
1728 (C=O), 1624, 1595, 1500, 992 cm−1. – 1H NMR
(80 MHz, CDCl3): δ = 7.15−7.6 (m, 11H, aromat. H), 7.81
(m, J8−H,7−H = J8−H,9−H = 8.0 Hz, J8−H,6−H = 1.1 Hz, 1H,
8-H), 8.15 (d, J = 8.3 Hz, 1H, 9-H), 8.30 (dd, J = 8.1, 1.1 Hz,
1H, 6-H). – MS (EI, 70 eV): m/z (%) = 338 (38) [M+],
207 (4), 180 (100), 130 (7), 102 (12), 77 (97). – C22H14N2O2
(338.37): calcd. C 78.09, H 4.17, N 8.28; found C 78.10,
H 4.08, N 8.26.
8-H), 8.29 (d, J = 7.9 Hz, 1H, 6-H). – 13C{ H} NMR
1
(50.32 MHz, [D6]-DMSO): δ = 30.8, 116.2, 117.6, 120.2,
126.0, 128.5, 128.8, 129.3, 129.5, 131.4, 134.7, 135.6, 142.5,
143.8, 160.8. – MS (EI, 70 eV): m/z (%) = 276 (67) [M+],
233 (30), 138 (14), 130 (10), 118 (100), 102 (17), 91 (11),
77 (65), 51 (27). – C17H12N2O2 (276.31): calcd. C 73.90,
H 4.38, N 10.14; found C 73.78, H 4.45, N 10.09.
8,9,10,11-Tetrahydroisochromeno[4’,3’:4,5]imidazo[1,2-a]-
pyridin-5-one (7f)
1-Methyl-2-phenyl-1H-isochromeno[3,4-d]imidazol-5-one
(9a)
◦
˜
Perchlorate: M. p. 254 – 5 C (EtOH). - IR (KBr): ν =
◦
˜
M. p. 233 – 4 C (MeOH). – IR (KBr): ν = 1712 (C=O),
1614, 1518, 1470, 1450, 1421, 1366, 1258 cm−1. – 1H NMR
(80 MHz, CDCl3): δ = 4.11 (s, 3H, CH3), 7.4 – 7.9 (m, 8H,
aromat. H), 8.42 (d, J = 7.8 Hz, 1H, 6-H). MS (EI, 70 eV):
m/z (%) = 276 (22) [M+], 145 (19), 130 (8), 117 (100),
102 (12). – C17H12N2O2 (276.30): calcd. C 73.90, H 4.38,
N 10.14; found C 73.95, H 4.44, N 9.91.
1
2948, 1857, 1628, 1556, 1530 cm−1. – H NMR (80 MHz,
CDCl3): δ = 1.85 − 2.2 (m, 4H, 9-H,10-H), 2.9 – 3.05 (m,
2H, 11-H), 3.95 – 4.2 (m, 2H, 8-H), 7.1 – 8.35 (m, 4H, aro-
mat. H). – C14H12N2O2×HClO4 (340,71): cald. C 49.35,
H 3.84, N 8.22; found C 49.45, H 3.78, N 8.22.
9,10,11,12-Tetrahydro-8H-isochromeno[4’,3’:4,5]imidazo-
[1,2-a]azepin-5-one (7g)
3-Cyclohexyl-2-phenyl-3H-isochromeno[4,3-d]imidazol-5-
one (7b)
◦
˜
M. p. 184 – 5 C (EtOH). – IR (KBr): ν = 1758 sh,
1748 (C=O), 1625 cm−1. – 1H NMR (80 MHz, CDCl3):
δ = 1.9 (m (broad), 6H, 9-H, 10-H, 11-H), 3.0 (m (broad),
2H, 12-H), 4.1 (m (broad), 2H; 8-H), 7.3 – 7.45 (m, 1H,
aromat. H), 7.65 – 7.8 (m, 1H, aromat. H), 7.92 (m (d),
◦
˜
M. p. 206 C. (EtOH). – IR (KBr): ν = 2934, 1737
(C=O), 1627, 1501, 1250, 1000, 990 cm−1. – 1H NMR
(200.13 MHz, CDCl3): δ = 1.1−2.5 (m, 10H, 5 cyclohexyl-
CH2), 4.19 (tt, Jax,ax = 12.2 Hz, Jax,eq = 3.7 Hz, 1H,
CH-cyclohexyl), 7.41 (m, J7−H,6−H = J7−H,8−H = 7.6 Hz,
J7−H,9−H = 1.0 Hz, 7-H), 7.45 – 7.65 (m, 5H, H-phenyl),
7.78 (m, J8−H,7−H = J8−H,9−H = 7.8 Hz, 1H, 8-H), 8.08 (d,
J = 7.7 Hz, 1H, 9-H), 8.31 (d, J = 7.7 Hz, 1H, 6-H). – MS
(EI, 70 eV): m/z (%) = 344 (17) [M+], 262 (100), 234 (5),
207 (9), 159 (6), 130 (22), 104 (26), 103 (38), 102 (14),
55 (20). – C22H20N2O2 (344.40): calcd. C 76.72, H 5.85,
N 8.14; found C 76.78, H 6.02 N 8.04.
1H, aromat. H), 8.26 (m (d), 1H, aromat. H). – 13C{ H}
1
NMR (20 MHz, CDCl3): δ = 25.9, 28.6, 30.2, 30,9, 43.6,
114.0, 117.3, 119.9, 125.5, 131.4, 135.0, 135.5, 140.9, 147.4,
160.9. – C15H14N2O2 (254.29): calcd. C 70.85, H 5.55,
N 11.01; found C 70.53, H 5.53, N 10.96.
9,10,11,12-Tetrahydro-8H-isochromeno[3’,4’:4,5]imidazo-
[1,2-a]azepin-5-one (9g)
◦
˜
M. p. 221 – 2 C (CHCl3/Et2O). – IR (KBr): ν =
2950, 1722 (C=O), 1710, 1615, 1494, 1470, 1383, 1352,
1261 cm−1. – 1H NMR (80 MHz, CDCl3): δ = 1.95 (m,
3-Benzyl-2-phenyl-3H-isochromeno[4,3-d]imidazol-5-one
(7c)
◦
˜
M. p. 164 C (EtOH). - IR (KBr): ν = 1736 (C=O), 1628, broad, 6H; 9-H, 10-H, 11-H), 2.95 (m, broad, 2H, 12-H),
1506, 998 cm−1. – 1H NMR (200.13 MHz, CDCl3): δ = 4.45 (m, broad, 2H, 8-H), 7.28 (m, 1H, aromat. H), 7.64 (m,
5.33 (s, 2H, CH2), 7.0 – 7.65 (m, 11H; aromat. H), 7.78 2H, aromat. H), 8.29 (m (t), 1, aromat. H). – 13C{ H} NMR
1
(m (t), J8−H,7−H = J8−H,9−H = 7.8 Hz, 1H, 8-H), 8.09 (d, (20 MHz, [D6]-DMSO): δ = 25.1, 28.0, 29.3, 30.4, 47.3,
J = 7.8 Hz; 1H, 9-H), 8.29 (d, J = 7.9 Hz, 1H, 6-H). – 13C 107.7, 117.6, 118.6, 125.3, 130.6, 132.4, 134.9, 149.7, 151.3,
1
{ H} NMR (50.23 MHz, CDCl3): δ = 47.3, 116.3, 117.8, 161.8. – C15H14N2O2 (254.29): calcd. C 70.85, H 5.55,
120.2, 126.1, 126.5, 128.1, 128.8, 129.0, 129.3, 129.5, 131.4, N 11.01; found C 71.03, H 5.70, N 11.01.
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1150
H.-J. Hemmerling et al. · 1,2-Deoxygenation of vic-Dihydroxyindenoimidazoles
1,8-Dihydro-8-hydroxy-1-methyl-2-phenylindeno[1,2-d]-
imidazole (11a)
124.6, 127.9, 136.7, 140.6, 148.8, 154.4. – MS (EI, 70 eV):
m/z (%) = 240 (100) [M+], 239 (35), 238 (40), 223 (23),
211 (12), 197 (14), 183 (12), 167 (11), 158 (24), 156 (11),
130 (13), 116 (15), 115 (15), 103 (11), 102 (14), 101 (11),
96 (25), 90 (11), 89 (48). – C17H14N2O (262.31): calcd.
C 77.84, H 5.38, N 10.68; found C 77.91, H 5.38, N 10.66.
6a (300 mg, 1.2 mmol), dissolved in 20 ml of methanol,
was treated with sodium borohydride (1.00 g, 26.4 mmol).
After 2 h, water (100 ml) was added and the aqueous solu-
tion was extracted with CH2Cl2. The extract was separated
by column chr◦omatography on silica. Yield: 162 mg (67%).
6,7,8,9,10,12-Hexahydro-12-hydroxyindeno[2’,1’:4,5]imid-
azo[1,2-a]azepine (14g)
˜
M. p. 219 – 20 C (EtOH). – IR (KBr): ν = 3125, 3060, 1617,
1
1604, 1495, 1470, 1288, 1278 cm−1. – H NMR (80 MHz,
8g (300 mg, 1.2 mmol) was hydrogenated as described
for the ◦syntheses of 11g. Yield: 188 mg (46%). M. p.
[D6]-DMSO): δ = 3.84 (s, 3H, CH3), 5.37, 5.47 (B-part of
AB-type subspectrum, 1H, 8-H), 5.83, 5.93 (A-part of AB-
type subspectrum, 1H∗, OH), 7.0 – 7.8 (m, 9H, aromat. H). –
MS (EI, 70 eV): m/z (%) = 262 (52) [M+], 245 (12), 159
(65), 130 (49), 118 (100). – C17H14N2O (262.31): calcd.
C 77.84, H 5.38, N 10.68; found C 77.94, H 5.58, N 10.68.
˜
203 – 4 C (toluene). – IR (KBr): ν = 3170, 2925, 1610,
1510, 1503 sh, 1462, 1435, 1405, 1052 cm−1. – 1H NMR
(80 MHz, [D6]-DMSO): δ = 1.76 (broad, 6H, 7-H, 8-H, 9-
H), 2.85 (m, broad, 2H, 6-H), 4.25 (m, broad, 2H, 10-H),
4.93, 5.02 (B-part of AB-type subspectrum, after addition of
D2O: s, 1H, 12-H), 5.44∗, 5.68∗ (A-part of AB-type sub-
spectrum, 1H, OH), 6.9 – 7.45 (m, 4H, aromat. H). – 13C
{1H} NMR (20 MHz, [D6]-DMSO): δ = 25.5, 28.5, 29.3,
30.1, 46.1, 67.2, 115.8, 124.2, 124.9, 127.8, 132.5, 134.7,
148.7, 154.5. – MS (EI, 70 eV): m/z (%) = 240 (74) [M+],
239 (20), 238 (14), 211 (28), 184 (14), 183 (32), 159 (13),
158 (38), 157 (14), 145 (17), 130 (13), 129 (10), 117 (10),
116 (16), 115 (15), 103 (14), 102 (18), 96 (100), 90 (10),
89 (29). – C15H16N2O×HClO4 (340.76): calcd. C 52.87,
H 5.03, N 8.22; found C 52.86, H 5.01, N 8.11.
6,7,8,9,10,12-Hexahydro-12-hydroxyindeno[1’,2’:4,5]imid-
azo[1,2-a]azepine (11g)
6g (1.00 g, 4.2 mmol) was treated with lithium aluminium
hydride (500 mg, 13.2 mmol) in dry THF (50 ml). After
2 h, water was added under cooling and the solution was ex-
tracted with Et2O. The solvent was removed in vacuo to yield
a white solid◦which was crystallized. Yield: 560 mg (55%).
˜
M. p. 235 – 6 C (toluene). – IR (KBr): ν = 3100, 2940, 1610,
1
1498, 1470, 1440, 1394, 1295 cm−1. – H NMR (80 MHz,
[D6]-DMSO): δ = 1.4−1.9 (m (broad), 6H, 7-H, 8-H, 9-H)
2.75 – 2.95 (m (broad), 2H, 6-H), 4.0 – 4.2 (m (broad), 2H,
10-H), 5.21, 5.30 (B-part of AB-type subspectrum, after ad-
dition of D2O: s, 12-H), 5.68∗, 5.77∗ (A-part of AB-type
subspectrum; 1H, OH), 6.9 – 7.45 (m, 4H, aromat. H). –
6,7,8,910,12-Hexahydroindeno[1’,2’:5,4]imidazo[1,2-a]-
azepine (12g)
A solution of 6g (1.00 g, 4.2 mmol) in 50 ml of ethanol
and 1 ml of conc. hydrochloric acid was hydrogenated over
Pd/carbon. The hydrogen uptake ceased after 185 ml. After
filtration of the catalyst, the solvent was removed in vacuo
to yield a white solid which was suspended in dilute hy-
drochloric acid and extracted with dichloromethane. Evapo-
ration of organic extracts gave a colourless solid, which was
crystallized. An analytically pure sample was obtained by
gene◦ration of the perchlorate. Yield: 677 mg, (72%). M. p.
1
13C{ H} NMR (20 MHz, [D6]-DMSO): δ = 25.6, 28.3,
29.2, 30.1, 45.9, 66.2, 116.1, 123.8, 124.6, 127.9, 136.7,
140.6, 148.8, 154.4. – MS (EI, 70 eV): m/z (%) = 240 (100)
[M+], 239 (35), 238 (40), 223 (23), 211 (12), 197 (14),
183 (12), 167 (11), 158 (24), 156 (11), 130 (13), 116 (15),
115 (15), 103 (11), 102 (14), 101 (11), 96 (25), 90 (11),
89 (48). – C15H16N2O (240.30): calcd. C 74.97, H 6.71,
N 11.66; found C 75.10, H 6.73, N 11.46.
˜
154 C (CHCl3/Et2O). – IR (KBr): ν = 2930, 1610, 1512,
1447, 1413, 1388 cm−1. – 1H NMR (80 MHz, CDCl3):
δ = 1.85 (broad, 6H, 7-H, 8-H, 9-H), 2.95 (m (broad), 2H,
6-H), 3.42 (s, 2H, 12-H), 3.90 (m (broad), 2H, 10-H), 7.0 –
3,8-Dihydro-8-hydroxy-3-methyl-2-phenylindeno[1,2-d]-
imidazole (14a)
1
7.6 (m, 4H, aromat. H). – 13C{ H} NMR (20 MHz, CDCl3):
8a (300 mg, 1.2 mmol) was hydrogenated as described
for t◦he syntheses of 11a. Yield: 195 mg (62%). – M. p.
δ = 26.0, 28.1, 28.9, 30.2, 31.0, 47.4, 117.3, 123.2, 125.1,
127.0, 138.1, 142.9, 144.2, 154.3. – C15H16N2O×HClO4,
M. p. 210 ◦C, calcd. (324.76): C 55.48, H 5.28, N 8.63; found
C 55.32, H 5.08, N 8.46.
˜
192 C (EtOH/Et2O). – IR (KBr): ν = 3505, 3320, 1638,
1
1595, 1575, 1483, 1440, 1178 cm−1. – H NMR (80 MHz,
[D6]-DMSO): δ = 1.4 − 1.9 (broad, 6H, 7-H, 8-H, 9-H),
2.75 – 2.95 (m (broad), 2H, 6-H), 5.21, 5.30 (B-part of AB-
type subspectrum, after addition of D2O: s, 1H, 12-H), 5.68∗,
5.77∗ (A-part of AB-type subspectrum, 1H, OH), 6.9 – 7.45
3,8-Dihydro-3-methyl-2-phenylindeno[1,2-d]imidazole
(15a)
1
(m, 4H, aromat. H). – 13C { H} NMR (20 MHz, [D6]-
10% Pd/carbon (0.30 g) was added to a solution of 8a
DMSO): δ = 25.6, 28.3, 29.2, 30.1, 45.9, 66.2, 116.1, 123.8, (200 mg, 0.77 mmol) in 100 ml of methanol. The solu-
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H.-J. Hemmerling et al. · 1,2-Deoxygenation of vic-Dihydroxyindenoimidazoles
1151
tion was hydrogenated at atmospheric pressure. The reac- 6,7,8,910,12-Hexahydro-5-methylindeno[2’,1’:4,5]imidazo-
tion finished after a hydrogen uptake of 18 ml. After re- [1,2-a]azepinium Perchlorate (16g)
moval of the catalyst, the solvent was evaporated in vacuo
Preparation from 15g (200 mg, 0.9 mmol) as described for
and the residue was crytallized. An analytical sample was ob-
tained by generation of the perchlorate. Yield: 138 mg (73%).
13g. Yield: 138 mg (46%). M. p. 239 – 40 ◦C (EtOH/Et2O). –
IR (KBr): ν = 2934, 1521, 1436, 1400 cm−1. – 1H NMR
◦
˜
˜
M. p. 194 C (CH2Cl2/Et2O). – IR (KBr): ν = 3326, 3208,
3107, 3071, 2940, 1609, 1583, 1564, 1483 cm−1. – 1H NMR
(80 MHz, CD3CN): δ = 3.98 (s, 2H, 8-H), 4.08 (s, 3H,
CH3), 7.35 – 7.9 (m, 9H, aromat. H). Perchlorate: M. p. 238 –
(80 MHz, [D6]-DMSO): δ = 0.88 (broad, 6H, 7-H, 8-H, 9-
H), 3.20 (m (broad), 2H, 10-H), 3.89 (s, 5, 12-H, CH3), 4.60
1
(broad, 2H, 6-H), 7.3 – 7.95 (m, 4H, aromat. H). – 13C{ H}
9
◦C (EtOH/Et2O). – C17H14N2×HClO4 (346.77): calcd.
NMR (20 MHz, [D6]-DMSO): δ = 23.2, 24.0, 26.5,
28.7, 29.0, 33.7, 48.7, 118.6, 126.2, 126.3, 127.2, 130.6,
C 58.88, H 4.36, N 8.08; found C 58.54, H 4.42, N 8.01.
−
134.7, 137.4, 143.0, 151.7. – C16H19N2 +ClO4 (338.79):
calcd. C 56.72, H 5.65, N 8.27; found C 56.73, H 5.49,
N 8.25.
6,7,8,9,10,12-Hexahydroindeno[2’,1’:4,5]imidazo[1,2-a]-
azepine (15g)
A solution of 8g (0.80 g, 3.4 mmol) in 80 ml of ethanol
was hydrogenated on 10% Pd/carbon (0.50 g). Hydrogen up-
take ceased after 155 ml. Filtration of the catalyst and re-
moval of the solvent yielded an oily residue which was dis-
solved in CH2Cl2. The extraction with 3% hydrochloric acid,
followed by basification of the aequeous extracts with aque-
ous ammonia gave an oil, which was separated. The purifica-
tion by flash chromatography on alumina (activation III, elu-
tion with CHCl3) gave 15g. Yield: 548 mg (72%). M. p. 157 –
Crystal Structure Analysis of 6g×HClO4 by X-Ray Diffrac-
tion
The solid-state structure of the HClO4-adduct of 6g was
established by X-ray crystal structure analysis. The molec-
ular structure is displayed in Fig. 1. Except atoms C8, C9,
˚
and C10 the cation is planar within 0.127(2) A. The ions are
linked together by a hydrogen bond N2-HN...O11 with dis-
˚
tances N...O 2.869(4), N-H 0.80(3), H...O 2.10(3) A and an
◦
angle N-H...O of 162(3)◦.
˜
8 C (cyclohexane). – IR (KBr): ν = 2910, 1607, 1513, 1450,
1445, 1434, 1402, 1358 cm−1. – 1H NMR (80 MHz, CDCl3):
δ = 1.87 (broad, 6H, 7-H, 8-H, 9-H), 2.98 (m (broad), 2H,
6-H), 3.47 (s, 2H, 12-H), 4.25 (m (broad), 2H, 10-H), 7.0 –
Crystal data: C15H15ClN2O5, molecular mass: 338.7,
monoclinic space group P21/n, a = 13.472(4), b = 6.356(2),
◦
3
˚
˚
c = 18.581(6) A, β = 106.42(2) , V = 1526.2(8) A
1
7.5 (m, 4H, aromat. H). – 13C{ H}NMR (20 MHz, CDCl3):
(by refinement of 25 reflections, 27 < 2θ < 32◦, λ(Mo-
Kα ) = 0.71073 A), Z = 4, Dc = 1.474 mg mm−3, Dm
=
,
˚
δ = 25.9, 29.0, 30.2, 30.4, 31.1, 47.1, 115.4, 123.4, 125.8,
126.4, 134.3, 135.8, 145.1, 146.8, 154.8. – MS (EI, 70 eV):
m/z (%) = 224 (100) [M+], 195 (10), 183 (10), 168 (18),
156 (6), 142 (15). – C15H16N2O (224.31): calcd. C 80.32,
H 7.19, N 12.49; found C 80.41, H 7.49, N 12.36.
1.466 mg mm−3, F(000) = 704; µ(Mo-Kα ) = 0.28 mm−1
approximate dimensions of crystal (yellow color) 0.7×0.3×
0.2 mm.
Data collection: X-ray intensities were measured with
monochromatized Mo-Kα -radiation on a Siemens/STOE
diffractometer AED2, variable ω/θ-scan, scan range 1.17◦
(plus separation) in ω, scan speed 0.6 – 3.5◦ min−1. 3098 in-
tensities measured (3 < 2θ < 50◦), indices hkl ranged from
0,0,−22 to 15, 7, 21. The final set of data contained 2428
symmetry-independent reflections (Rint = 0.016) of which
6,7,8,9,10,12-Hexahydro-11-methylindeno[1’,2’:4,5]imid-
azo[1,2-a]azepinium Perchlorate (13g)
12g (400 mg, 1.8 mmol) was dissolved in dry toluene. Af-
ter addition of dimethylsulfate (2 ml, 11.9 mmol) a white
solid was formed which was isolated after 48 h (m. p. 105 –
1808 were classified observed (F > 4σF ).
0
◦
6 C) and dissolved in acetic acid. Addition of 70% per-
Structure solution and refinement: Direct methods [19]
chloric acid gave a precipitate which was isolated by suc- revealed all non-H atoms. Full matrix least-squares refine-
tion. Yield: 255 mg (42%). M. p. 215 ◦C (EtOH). – IR (KBr): ment [20] on F2 using anisotropic displacement parame-
ν = 2940, 1748, 1510, 1436, 1402, 1090 cm−1. – 1H NMR ters (212 parameters) converged at wR2 = 0.136 for all data
˜
(80 MHz, [D6]-DMSO): δ = 1.86 (broad, 6H, 7-H, 8-H, and R1 = 0.043 for the observed data. H atoms were in-
9-H), 3.20 (m (broad), 2H, 6-H), 3.93 (s, 2H, 12-H), 4.08 cluded in a riding mode except the one at N2 which was
(s, 3H, CH3), 4.30 (broad, 2H, 10-H), 7.3 – 7.9 (m, 4H, aro- refined freely. The residual electron density ranged from
1
mat. H). – 13C{ H} NMR (20 MHz, [D6]-DMSO): δ = 23.3, −0.25 to 0.57 eA−3, with the maximum in the vicinity of
˚
23.8, 26.4, 28.8, 29.0, 33.7, 49.1, 118.4, 126.1, 127.3, 130.9, the Cl atom. However, a split model for the ClO4−-ion did
134.7, 137.7, 143.0, 151.5. – C16H19N2 ClO4 (338.79): not improve the results. Preliminary results have been re-
calcd. C 56.72, H 5.65, N 8.27; found C 56.54, H 5.71, ported [10]. Crystallographic data for the structure have been
+
−
N 8.15.
deposited with the Cambridge Crystallographic Data Centre
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1152
H.-J. Hemmerling et al. · 1,2-Deoxygenation of vic-Dihydroxyindenoimidazoles
CCDC-103288. Copies of the data can be obtained free of Cambridge CB2 1EZ (U.K.) (Fax: int.code+(1223)336-033;
charge on application to the Director, CCDC, 12 Union Road, e-mail for inquiry: fileserv@ccdc.cam.ac.uk).
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