Aminoimidazo[1,2-a]pyridines: Regioselective synthesis of substituted imidazonaphthyridines, azacarbolines and cyclazines

Article abstract of DOI:10.1016/S0040-4020(01)01141-3

In order to study the regioselectivity of thermal cyclocondensation, aminoimidazo[1,2-a]pyridines (AIP) 5a-e were prepared, further converted into iminophosphoranes 7a-e, and ultimately converted regioselectively in angular annulated imidazonaphthyridines (IN) 8a, 10a, 11a, 12a or linear annulated dipyridoimidazole (DPI) 17a. From 2-substituted derivative 23, the peri annulated product 24a was obtained. The starting amines 5a-f reacted with aldehydes to yield regioselectively IN 8a-c, 10a-c, 11a-c, 12a,b, DPI 16a-e, 17a-d and TIBO like structures (±)-13 and 24a-c, as proved by X-ray analysis. The 1,2- or 1,4-addition between amines and α,β-unsaturated aldehydes concerning the pyridine and imidazole moieties is discussed in the light of these results.

Full text of DOI:10.1016/S0040-4020(01)01141-3

TETRAHEDRON
Pergamon
Tetrahedron 58 62002) 295±307
Aminoimidazo[1,2-a]pyridines: regioselective synthesis of
substituted imidazonaphthyridines, azacarbolines and cyclazines
a
Jean M. Chezal, Emmanuel Moreau, Olivier Chavignon, Vincent Gaumet, Jacques Metin,
a
a
a
a
Â
Yves Blache,b Anna Diez,c Xavier Fradera,d Javier Luqued and Jean C. Teuladea,p
a
Â
Faculte de Pharmacie, UMR-INSERM 484, 28 Pl. H. Dunant, B.P. 38, 63001 Clermont-Ferrand cedex 1, France
b
Â
Laboratoire de Chimie Organique Pharmaceutique, EA. 2414, Faculte de Pharmacie, 15 Av. Ch. Flahault,
34060 Montpellier, France
c
 Á Á
Laboratori de Quõmica Organica, Facultat de Farmacia, Universitat de Barcelona, 08028 Barcelona, Spain
d
 Á
Departament de Fisicoquõmica, Facultat de Farmacia, Universitat de Barcelona, 08028 Barcelona, Spain
Received 23 August 2001; revised 22 October 2001; accepted 14 November 2001
AbstractÐIn order to study the regioselectivity of thermal cyclocondensation, aminoimidazo[1,2-a]pyridines 6AIP) 5a±e were prepared,
further converted into iminophosphoranes 7a±e, and ultimately converted regioselectively in angular annulated imidazonaphthyridines 6IN)
8a, 10a, 11a, 12a or linear annulated dipyridoimidazole 6DPI) 17a. From 2-substituted derivative 23, the peri annulated product 24a was
obtained. The starting amines 5a±f reacted with aldehydes to yield regioselectively IN 8a±c, 10a±c, 11a±c, 12a,b, D PI16a±e, 17a±d and
TIBO like structures 6^)-13 and 24a±c, as proved by X-ray analysis. The 1,2- or 1,4-addition between amines and a,b-unsaturated aldehydes
concerning the pyridine and imidazole moieties is discussed in the light of these results. q 2002 Published by Elsevier Science Ltd.
1. Introduction
The use of acrolein would enable us to determine whether
the reactions went to completion. If this were the case, the
results obtained by using crotonaldehyde as a reactant
would provide further insight into the reaction mechanism.
In the case of thermal annulation, we decided to extend
these studies to acetaldehyde and propanal because using
the aldol condensation products would increase the potential
for diversi®cation, giving rise to small collections of the
three families of compounds.
Tricyclic dipyridoimidazoles show considerable pharmaco-
logical potential. Dipyridoimidazoles 6GLU-P1, P2)1,2 are
azaisosteres of carbolines,3 and are thus of pharmacological
interest as potential anticancer compounds. On an other
hand, some pyrido[4,3-b]indoles 6Trp-P1 and P2) have
been reported to have genotoxic activity.4 Imidazonaph-
thyridines are analogs of methoxatin,5 and have potential
implications as inhibitors of bacterial coenzymes. Finally,
pyridoimidazodiazepines can be regarded as isosteres of
4,5,6,7-tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-261H)-
ones 6TIBO),6 and are therefore of great interest as potential
anti-HIV agents.
2. Results and discussion
Amines 5a and 5c±e were prepared as described
previously.7b,10±12 Multigram quantities of the required
amines 5b and 5f13 were obtained from esters 1b and 1f14
as shown in Scheme 1. Thus, the esters were transformed to
the corresponding carbohydrazides 2b,f, treatment of which
with NaN3 and NaNO2/HCl gave carbazides 3b,f. Heating
of compounds 3b,f in EtOH gave the corresponding
carbamates 4b,f by a Curtius rearrangement. Saponi®cation
of the carbamates led to amines 5b and 5f in 55 and 47%
overall yield, respectively.
As a continuation of our work on the synthesis and the
applications of pyridoimidazoles,7 we envisaged the
preparation of dipyridoimidazoles, imidazonaphthyridines,
and pyridoimidazodiazepines by heteroannulation of the
appropriate aminoimidazo[1,2-a]pyridines 5 6Fig. 1). To
our knowledge there are very few precedents for this kind
of heteroannulation.1,7b From among the known methods for
obtaining nitrogen heterocycles, we chose to study the
heteroannulation via the iminophosphoranes,8,9 and the
direct thermal condensation of the AIPs with aldehydes.
Two routes to synthesis of iminophosphoranes 7a±e were
developed 6Scheme 2). Diazotation of amines 5a±c with
NaNO2/HCl followed by addition of NaN3 yielded azides
6a±c as stable solids, wich were then converted to 7a±c by
the Staudinger reaction using P6C6H5)3 in CH2Cl2. However,
this method was unsatisfactory with amines 5d±f. Azide 6d
Keywords: imidazo[1,2-a]pyridine; imidazonaphthyridine; azacarboline;
cyclazine.
Corresponding author. Tel.: 133-4-73-178000; fax: 133-4-73-178012;
e-mail: J-claude.teulade@u-clermont1.fr
p
0040±4020/02/$ - see front matter q 2002 Published by Elsevier Science Ltd.
PII: S0040-4020601)01141-3

296
J. M. Chezal et al. / Tetrahedron 58 =2002) 295±307
Figure 1.
was obtained in low yields, probably because the inter-
mediate diazonium salt generated from 5d is unstable.15
Amine 5e led to a complex mixture of products from
which only 2-aminopyridine 68%) could be identi®ed,
indicating the presence of a ring opening process.16 2-AIP
5f did not react.
Iminophosphoranes 7a±e reacted with acrolein in nitro-
benzene or 1,2-dichlorobenzene to give the corresponding
imidazonaphthyridines 8a, 10a, 11a, 12a, and dipyrido-
imidazole 17a 6Scheme 3, Table 1). Attempts to improve
the cyclization by varying the temperature and the reaction
times were unsuccessful.
The second method for obtaining iminophosphoranes 7a±c
consisted of treatment of amines 5a±c with P6C6H5)3/CCl4/
NEt3 in CH3CN. This was successful in yielding 7a±e, but
once again 5f did not react.
Scheme 3. Reagents and conditions: 6i) nitrobenzene, D; 6ii) 1,2-dichloro-
benzene, D; see Schemes 4, 6 and 8 for chemical structures.
Table 1. Reactions of iminophosphoranes 7a±e and 23 with acrolein
63 equiv.)
Scheme 1. Reagents and conditions: 6i) NH2NH2, EtOH, D; 6ii) NaNO2/
HCl, NaN3; 6iii) EtOH, D; 6iv) NaOH 65N), D.
Entry
Iminophosphorane
Method C 6% yield)
1
2
3
4
5
6
7a
7b
7c
7d
7e
23
8a 617)a
10a 63)a
11a 69)a
12a 69)a
17a 616)b
24a 613)b
a
Nitrobenzene, D.
1,2-Dichlorobenzene, D.
b
Thermal condensation of amine 5a with acrolein, crotonal-
dehyde, or acetaldehyde, in re¯uxing 1,2-dichlorobenzene
6method A) led to the desired [1,7]naphthyridines 8a±b
6Scheme 4, Table 2). The regioselectivity of the condensa-
tion with unsaturated aldehydes 6or saturated aldehydes
after aldolization/crotonization) indicated that the reaction
proceeds via a conjugate 1,4-addition followed by ring
closure and ®nal aromatization 6Scheme 7, entry 1). The
Scheme 2. Reagents and conditions: 6i) NaNO2/HCl, 08C, NaN3; 6ii) PPh3,
CH2Cl2, rt; 6iii) PPh3, CCl4, NEt3, CH3CN.

J. M. Chezal et al. / Tetrahedron 58 =2002) 295±307
297
fact that compound 6^)-9, the non-aromatic intermediate,
was obtained together with naphthyridine 8c in the conden-
sation of 5a with propanal proved the proposed mechanism.
Addition of 10% Pd/C to the reaction mixture 6method B)
resulted in a considerable increase in the yields of the
naphthyridines 8a±c.
Under the conditions of method B, amines 5b and 5c yielded
the corresponding isomeric [1,6] and [1,5]naphthyridines
10a±c, 11a±c by angular annulation 6Scheme 4). The
cyclization of 6-AIP 5c on C5 rather than on C7 can be
explained by the higher electron density of C5 6Fig. 2),
and by the higher thermodynamic stability of compounds
11. Theoretical calculations showed that compound 11b is
about 9.1 kcal mol21 more stable than the linear naph-
thyridine 15. Similar calculations allowed us to explain
the preferred cyclization of compound 5b on C8 rather
than on C6, naphthyridine 10b being more stable than
compound 14 by 10.9 kcal mol21
.
In the case of compound 5d, both an angular and a peri
annulation process can take place a priori. However, only
the angular annulated compounds 12a and 12b were
obtained using an excess of acrolein, crotonaldehyde or
acetaldehyde, and the yields were extremely low. In contrast
only the peri annulated structure 6^)-13 was detected in the
reaction of 5d with an excess of propanal.
Scheme 4. Reagents and conditions: 6i) 1,2-dichlorobenzene, D 6method
A); 1,2-dichlorobenzene, 10% Pd/C, D 6method B).
We then investigated the thermal condensation of the 2-AIP
5f and 3-AIP 5e, in which the amino group is at the more
activated imidazole ring. Amine 5f reacted with acrolein,
crotonaldehyde, acetaldehyde, and propanal to yield
Table 2. Thermal condensation of amines 5a±f and 22 with aldehydes
Entry
Amine
Aldehyde
Method Aa 6% yield)
Method Bb 6% yield)
1
2
3
4
5
6
7
8
5a
5a
5a
5a
5b
5b
5b
5b
5c
5c
5c
5c
5d
5d
5d
5d
5e
5e
5e
5e
5f
Acrolein
8a 617)
8b 618)
8b 69)
6^)-9 624)±8c 617)
10a 62)
10b 612)
10b 64)
10c 620)
11a 610)
11b 64)
11b 631)
11c 625)
12a 61)
12b 61)
12b 65)
6^)-13 62)
17a 66)
17b 613)
17c 623)
17d 68)
8a 632)
8b 658)
8b 644)
8c 648)
10a 64)
10b 618)
10b 65)
10c 613)
11a 679)
11b 639)
11b 658)
11c 653)
12a 62)
Crotonaldehyde
Acetaldehyde
Propanal
Acrolein
Crotonaldehyde
Acetaldehyde
Propanal
9
Acrolein
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
Crotonaldehyde
Acetaldehyde
Propanal
Acrolein
Crotonaldehyde
Acetaldehyde
Propanal
12b 614)
12b 62)
NDc
Acrolein
17a 630)
6^)-20 623)
17c 641)
16d 648)
16a 628)
16b 627)
16c 628)
16d 617)±16e 618)
24a 627)
6^)-24b 642)
6^)-24b 611)
6^)-24c 627)
Crotonaldehyde
Acetaldehyde
Propanal
Acrolein
16a 638)
16b 617)
16c 640)
5f
5f
5f
22
22
22
22
Crotonaldehyde
Acetaldehyde
Propanal
16d 68)
Acrolein
24a 630)
6^)-24b 618)±25a 68)
6^)-24b 644)
6^)-24c 653)
Crotonaldehyde
Acetaldehyde
Propanal
a
1,2-Dichlorobenzene, D.
1,2-Dichlorobenzene, 10% Pd/C, D.
NDˆnot detected.
b
c

298
J. M. Chezal et al. / Tetrahedron 58 =2002) 295±307
Figure 2. 6a) Electron density at the bond critical point 6in e); 6b) energy differences of regioisomers.
a-azacarbolines 16a±e. Interestingly, reaction of 5f with
crotonaldehyde gave compound 16b 6Scheme 5), indicating
that the reaction is driven by a hard±hard and soft±soft
af®nity rather than by a 1,4-addition 6Scheme 7, entry 2),
which would have led to isomer 16c. However, the fact that
reaction of 5f with acetaldehyde yielded azacarboline 16c
indicates that the reaction of acetaldehyde with the amine is
faster than the aldol condensation. Accordingly, reaction of
5f with propanal 6Table 2, entry 24) provided compound
16d. In the presence of 10% Pd/C 6method B) the reaction
with propanal afforded an equimolar mixture of isomers 16d
and 16e, which indicated that the palladium can accelerate
the aldol condensation.
yielded the expected enimine 19, proving that the reaction
occurs through a 1,2-addition followed by electrophilic
aromatic substitution 6SEAr) on the p-excessive imidazole
ring 6Scheme 7, entry 2). In addition, condensation of 5e
with 1.5 equiv. of acetaldehyde at rt gave imine 18, and the
thermal condensation of 18 with more acetaldehyde yielded
the expected cyclization product 17c 6Scheme 7, entry 3).
These results and the fact that compounds 17b and 17c have
very similar stability 6DG<0.1 kcal mol21 according to
theorical calculations), con®rm that the condensation of
saturated aldehydes with the amines 5 is faster than aldol
condensation.
The role of palladium in the condensations remained to be
clari®ed. Its addition was relevant in the case of 5b and 5c,
in which the SEAr occurs on positions C8 and C5. In
contrast, it was not signi®cant for cyclizations on the C6
and C7 positions. Pertinent to this issue is the drastic effect
of adding of 10% Pd/C on the outcome of the reaction of 5e
with crotonaldehyde 6Table 2, entry 18). Thus, instead of the
linear cyclization product 17c, diazepine 6^)-20 was
obtained in 23% yield. However, this was not observed
using acetaldehyde or acrolein. This could be explained
by considering that the Pd usually complexes the inter-
mediate enimine on the exocyclic conjugated p-system,
which then is ®xed in its cisoid conformation, and cyclizes
on the less hindered C2 position; however, in the presence
of crotonaldehyde, the Pd complex seems to involve the
heterocycle and renders position C5 more nucleophilic
than C2.
Scheme 5. Reagents and conditions: 6i) 1,2-dicholoro benzene, D 6method
A); 1,2-dichlorobenzene, 10% Pd/C, D 6method B).
The results of the thermal condensation of 3-AIP 5e and the
chosen aldehydes 6Scheme 6) led to the expected azacarbo-
lines 17a±d, as a result of linear or peri annulation. The
regioselectivity of these reactions was consistent with the
above reasoning.
In the light of the results that showed the nucleophilicity of
position C5, which is consistent with the nucleophilicity of
C5 that we had already observed in the 4-azaindole series,7a
Condensation of 5e with crotonaldehyde in toluene at 708C

J. M. Chezal et al. / Tetrahedron 58 =2002) 295±307
299
Scheme 6. Reagents and conditions: 6i) Method A or B 6except for crotonaldehyde) 6cf Table 2); 6ii) crotonaldehyde, method B; 6iii) ethanal 61.5 equiv.),
CH2Cl2, rt, 36 h; 6iv) ethanal 61.1 equiv.) 1,2-dichlorobenzene, 10% Pd/C, D, 2.5 h; 6v) crotonaldehyde, toluene, 708C, 10 h; 6vi) 1,2-dichlorobenzene,
crotonaldehyde, 10% Pd/C, D.
we focused our attention on the synthesis of cyclazines 24.
Cyclazines 24 are unprecedented isosteres of TIBO,6 and
therefore constitute a new class of potential non-competitive
inhibitors of HIV-1 reverse transcriptase.
among other signals a doublet at 129.5 ppm with a coupling
1
constant of JP±Cˆ100 Hz, characteristic of the methine
carbon bonded to phosphor.
Condensation of iminophosphorane 23 with acrolein
yielded the expected diazepine 24a in 13% yield 6Table 1).
On the other hand, thermal condensation of amine 22 with
the selection of aldehydes 6Table 2) in 1,2-dichlorobenzene
at 1808C, yielded the expected [1,3]diazepines 24a±c.
When using crotonaldehyde in the absence of 10% Pd/C,
diazepine 6^)-24b was produced together with the inter-
mediate enimine 25a 68%). In agreement with our previous
The suitable starting substrate, 2-substituted 6and thus C2
blocked) 3-AIP 22, was obtained by reduction16 of the
nitroso compound 2117 6Scheme 8). Since we wanted to
assay both heteroannulation methods, amine 22 was treated
with triphenylphosphine to yield iminophosphorane 23,
using the same procedure as for preparation of imino-
phosphoranes 7. The 13C NMR spectrum of 23 displayed
Scheme 7.

300
J. M. Chezal et al. / Tetrahedron 58 =2002) 295±307
Scheme 8. Reagents and conditions: 6i) HBr, Sn, 08C; 6ii) PPh3, CCl4, NEt3; 6iii) 1,2-dichlorobenzene, D 6method A) or 1,2-dichlorobenzene, 10% Pd/C, D
6method B).
observations 6^)-24b was obtained in higher yield 642%)
and as the only product in the presence of 10% Pd/C. Use of
propanal resulted in isolation of the intermediate enimine
25b which cyclized suitably when reaction times were
extended.
4. Experimental
4.1. General procedures
Melting points were determined on an Electrothermal
IA9300 6capillary) and are not corrected. NMR 6proton
400 MHz or carbon 100 MHz) were recorded on a Bruker
AC 400 spectrophotometer using CDCl3, CD3ODor
DMSO-d6 as solvent. Infrared spectra were recorded on a
Beckman Acculab 2 spectrophotometer and on a FTIR
Nicolet Impact 410. Mass spectral analyses were performed
on a Hewlett±Packard 5985B or 5989A instrument.
Toluene, 1,2-dichlorobenzene and nitrobenzene were dried
over Na. Other solvents were stored over molecular sieves.
Enimines 25a,b were isolated by column chromatography
and identi®ed by their spectral data 6see Section 4). The
structure of azepines 24 was also determined from their
1H and 13C NMR data, and con®rmed by an X-ray crystal
structure determination on 6^)-24b 6Fig. 3).
4.2. Single crystal X-ray diffraction analysis of 1^)-24b
C17H14N3Br
Intensities were collected on an Enraf-Nonius CAD-4
diffractometer19 using the v22u scan technique.
C17H14N3Br crystallized in space group P21/n with
Ê
aˆ7.75566), bˆ12.49063), cˆ15.30464) A and bˆ
96.0564)8. Of the 4293 unique re¯ections measured
6Mo Ka radiation), 1262 were considered observed
6I$2s6I)). The ®nal re®nement residuals were Rˆ0.066
6on F) and wR2ˆ0.146 6on F2). The data reduction was
processed using the XCAD4 program20 and corrected for
Lorentz and polarization effects. The structure was solved
by direct methods21 and all non-hydrogen atoms were
re®ned anisotropically. All hydrogen atoms were treated
as riding with Uiso6H)ˆ1.5Ueq6C) for methyl H atoms and
1.2Ueq6C) for others. All programs used for this study were
performed using the WinGX package.22
Figure 3. ORTEP18 diagram of compound 6^)-24b showing 50% prob-
ability displacements ellipsoids for non-H atoms. H-atoms are included
with small arbitrary radii.
3. Conclusion
Aminoimidazopyridines have proved to be suitable building
blocks for the preparation of imidazonaphthyridines,
dipyridoimidazoles, and pyridoimidazodiazepines. Both
the heteroannulation methods explored were successful for
our purposes. However, the thermal condensation of the
starting amines with aldehydes in the presence of 10% Pd/
C was generally superior to their condensation with imino-
phosphoranes: the Staudinger step is unnecessary, the yields
are often better, and the possibility of using saturated
aldehydes offers a larger scope for diversi®cation. In the
reaction of 3-AIP with crotonaldehyde regioselectivity of
the thermal cyclization was observed.
4.3. Method for the theoretical calculations
Calculations have been performed at the Density Functional
level of theory using the B3LYP23 method and the
6-31G6d)24 basis set. All the structures have been subjected
to geometry optimization. The minimum-energy nature of
the stationary points has been veri®ed from inspection of the
vibrational frequencies. These values were used to compute
zero-point energy, thermal and entropy corrections to the
free energy 6at 298 K and 1 atm) using the standard
procedure implemented in Gaussian 98.25
We have thus prepared a small collection of compounds
within the three structural families considered, and we
have applied the method to obtain compounds 24, three
new isosteres of TIBO.
4.3.1. Ethyl 1imidazo[1,2-a]pyridin-7-yl)carboxylate
11b). To a solution of 2-aminoisonicotinic acid ethyl
ester27 65.81 g, 35 mmol) and NaHCO3 65.00 g, 59.5
mmol) in 250 mL of EtOH, chloroacetaldehyde 650% in

J. M. Chezal et al. / Tetrahedron 58 =2002) 295±307
301
H2O) 628.8 g, 158 mmol) was added. The mixture was
re¯uxed for 9 h and the solvent was evaporated. 200 mL
of H2O were added and the residue was basi®ed with
Na2CO3 and extracted with CH2Cl2. The organic layers
were dried over Na2SO4, ®ltered and evaporated under
reduced pressure. Chromatography 6neutral Al2O3,
CH2Cl2) yield 1b 65.38 g, 81%); mp 73±758C; IR 6KBr)
1740, 1350, 1250 cm21; MS m/z 190 6M1, 91), 162 658),
4.3.5. 2-Carbazidoimidazo[1,2-a]pyridine 13f). This was
prepared according to the procedure used for the
synthesis of compound 3b. From 2f 6reaction time 4 h) to
yield 3f 619.6 g, 76%); mp 138±1408C; 6note: explosion
hazards!);26 IR 6KBr) 2148, 1682 cm21; MS m/z 187 6M1,
23), 159 684), 145 621), 104 6100), 90 622), 77 648), 63 624),
1
51 662); H NMR 6CDCl3) d 6.94 6t, 1H, Jˆ6.5 Hz), 7.31
6m, 1H), 7.69 6d, 1H, Jˆ9 Hz), 8.18 6d, 1H, Jˆ6.5 Hz), 8.26
6s, 1H); 13C NMR 6CDCl3) d 114.3, 117.6, 119.0, 126.3,
126.7, 136.9, 145.5, 168.2. Anal. Calcd for C8H5N5O:
C, 51.34; H, 2.69; N, 37.42. Found: C, 51.49; H, 2.68; N,
37.42.
1
145 6100), 117 640), 90 624); H NMR 6CDCl3) d 1.43 6t,
3H, Jˆ7 Hz), 4.41 6q, 2H, Jˆ7 Hz), 7.38 6d, 1H, Jˆ7 Hz),
7.70 6s, 1H), 7.79 6s, 1H), 8.18 6d, 1H, Jˆ7 Hz), 8.37 6s,
1H); 13C NMR 6CDCl3) d 14.2, 61.5, 111.6, 113.7, 120.5,
125.3, 126.2, 135.9, 144.4, 165.2. Anal. Calcd for
C10H10N2O2: C, 63.15; H, 5.30; N, 14.73. Found: C,
62.91; H, 5.28; N, 14.68.
4.3.6. 7-1Ethoxycarbonyl)aminoimidazo[1,2-a]pyridine
14b). A solution of 3b 611.1 g, 59.3 mmol) in EtOH
6200 mL) was re¯uxed for 4.5 h. The white precipitate
was ®ltered and washed with EtOH 630 mL) to give amide
4b 67.97 g). The ®ltrate was concentrated in vacuo and the
crude product was chromatographed 6neutral Al2O3,
CH2Cl2). The ®rst fraction gave 1b 63.20 g, 28%), The
®nal elution gave amide 7-=ethoxycarbonyl)amino-
imidazo[1,2-a]pyridine 64b) 60.81 g) overall yield 672%);
mp 162±1648C; IR 6KBr) 3205, 1720, 1601, 1273, 1254,
1069 cm21; MS m/z 205 6M1, 100), 177 624), 159 650), 132
674), 105 672), 79 635), 52 651); 1H NMR 6DMSO-d6) d 1.28
6t, 3H, Jˆ7 Hz), 4.18 6q, 2H, Jˆ7 Hz), 6.95 6d, 1H,
Jˆ7 Hz), 7.44 6s, 1H), 7.73 6s, 1H), 7.79 6s, 1H), 8.43 6d,
1H, Jˆ7 Hz), 9.95 6brs, 1H); 13C NMR 6DMSO-d6) d 14.4,
60.6, 101.1, 106.4, 112.0, 127.0, 133.0, 136.2, 145.2, 153.5.
Anal. Calcd for C10H11N3O2: C, 58.53; H, 5.40; N, 20.48.
Found: C, 58.67; H, 5.39; N, 20.41.
4.3.2. 7-Carbohydrazidoimidazo[1,2-a]pyridine 12b). A
mixture of ester 1b 617.5 g, 92.1 mmol) and hydrazine
monohydrate 627.6 g, 553 mmol) in EtOH 6180 mL) was
re¯uxed for 60 h. After cooling at rt the solvent was
concentrated under vacuo, the precipitate was ®ltred and
washed with CH2Cl2 to give 2b 615.0 g, 92.5%); mp
277±2798C; IR 6KBr) 3305, 3251, 1647, 1550,
1342 cm21; MS m/z 176 6M1, 22), 145 6100), 117 664), 90
649), 63 624); 1H NMR 6DMSO-d6) d 4.61 6brs, 2H), 7.31 6d,
1H, Jˆ7 Hz), 7.72 6s, 1H), 8.07 6s, 1H), 8.08 6s, 1H), 8.62
6d, 1H, Jˆ7 Hz), 9.99 6s, 1H); 13C NMR 6DMSO-d6) d
110.0, 114.2, 115.6, 126.6, 128.7, 134.9, 143.6, 164.3.
Anal. Calcd for C8H8N4O: C, 54.54; H, 4.58; N, 31.80.
Found: C, 54.68; H, 4.60; N, 31.69.
4.3.3. 2-Carbohydrazidoimidazo[1,2-a]pyridine 12f).
This was prepared according to the procedure used for the
synthesis of compound 2b. From ester 1f14 628.5 g,
150 mmol) using 618.8 g, 376 mmol) of hydrazine 6reaction
time 60 h). The precipitate was washed with a small quan-
tity of EtOH and dried in vacuo to yield 2f 624.1 g, 91%);
4.3.7. 2-1Ethoxycarbonyl)aminoimidazo[1,2-a]pyridine
14f). This was prepared according to the procedure used
for the synthesis of compound 4b. From 3f 619.6 g,
105 mmol) 6reaction time 3.5 h) 17.8 g of amide 4f was
collected and chromatography gave in order of elution: 1f
60.42 g, 3%) and 7-=ethoxycarbonyl)aminoimidazo[1,2-
a]pyridine 64f) 60.50 g) overall yield 685%); mp 223±
2258C; IR 6KBr) 3182, 1712, 1258 cm21; MS m/z 205
6M1, 50), 159 627), 133 6100), 105 657), 78 660), 51 646);
1H NMR 6DMSO-d6) d 1.27 6t, 3H, Jˆ7 Hz), 4.17 6q, 2H,
Jˆ7 Hz), 6.86 6t, 1H, Jˆ6.5 Hz), 7.21 6m, 1H), 7.41 6d, 1H,
Jˆ9 Hz), 7.88 6s, 1H), 8.53 6d, 1H, Jˆ6.5 Hz), 10.34 6brs,
1H); 13C NMR 6DMSO-d6) d 14.6, 60.4, 98.9, 111.5, 115.0,
124.1, 126.4, 141.2, 142.5, 153.4. Anal. Calcd for
C10H11N3O2: C, 58.53; H, 5.40; N, 20.48. Found: C,
58.72; H, 5.41; N, 20.45.
mp 198±2008C; IR 6KBr) 3430, 1679, 1568, 1475 cm21
;
MS m/z 176 6M1, 87), 145 6100), 117 650), 90 657), 78
688), 63 638), 51 633); H NMR 6DMSO-d6) d 4.30 6brs,
1
2H), 6.76 6t, 1H, Jˆ7 Hz), 7.12 6brs, 1H), 7.38 6d, 1H,
Jˆ9 Hz), 8.17 6s, 1H), 8.37 6d, 1H, Jˆ7 Hz), 9.35 6s, 1H);
13C NMR 6DMSO-d6) d 113.0, 114.4, 117.3, 126.2, 127.5,
138.8, 144.0, 161.5. Anal. Calcd for C8H8N4O: C, 54.54; H,
4.58; N, 31.80. Found: C, 54.48; H, 4.56; N, 31.91.
4.3.4. 7-Carbazidoimidazo[1,2-a]pyridine 13b). A stirred
solution of 2b 624.1 g, 137 mmol) in 2N HCl 680 mL) was
diluted with cold H2O 6500 mL). An aqueous solution of
NaNO2 614.18 g, 206 mmol) was added dropwise, maintain-
ing the temperature below 158C. The solution was stirred at
rt for 2 h, neutralized with Na2CO3 and extracted with
CH2Cl2. After drying, the organic layers were concentrated
under vacuo. The crude precipitate was washed with Et2O
630 mL) to afford 3b 619.6 g, 76%); mp 123±1258C 6note:
explosion hazards!);26 IR 6KBr) 2155, 1687, 1323, 1220,
1125 cm21; MS m/z 187 6M1, 20), 159 695), 131 6100),
4.3.8. 7-Aminoimidazo[1,2-a]pyridine 15b). A stirred
solution of 4b 62.00 g, 9.76 mmol) in 5N aqueous NaOH
6100 mL) was heated under re¯ux for 7 h. The solution
was diluted with H2O 6100 mL), extracted with CH2Cl2,
dried with Na2SO4 and concentrated in vacuo. The crude
product was chromatographed 6neutral Al2O3, CH2Cl2/
EtOH, 99/1, v/v) to afford 5b 61.21 g, 93%); mp 139±
1418C; IR 6KBr) 3421, 2924, 1656 cm21; MS m/z 133
1
1
104 665), 77 685), 52 686); H NMR 6CDCl3) d 7.37 6d,
6M1, 100), 106 618), 79 637), 52 635); H NMR 6CDCl3) d
1H, Jˆ7 Hz), 7.74 6s, 1H), 7.84 6s, 1H), 8.19 6d, 1H,
Jˆ7 Hz), 8.36 6s, 1H); 13C NMR 6CDCl3) d 110.8, 114.4,
120.9, 125.6, 126.1, 136.70, 144.0, 170.9. Anal. Calcd for
C8H5N5O: C, 51.34; H, 2.69; N, 37.42. Found: C, 51.54; H,
2.70; N, 37.28.
4.55 6s, 2H), 6.20 6dd, 1H, Jˆ2, 7 Hz), 6.54 6d, 1H,
Jˆ2 Hz), 7.19 6s, 1H), 7.24 6s, 1H), 7.69 6d, 1H, Jˆ7 Hz);
13C NMR 6CDCl3) d 94.5, 106.7, 110.3, 125.8, 131.4, 142.2,
147.2. Anal. Calcd for C7H7N3: C, 63.14; H, 5.30; N, 31.56.
Found: C, 62.91; H, 5.30; N, 31.45.

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J. M. Chezal et al. / Tetrahedron 58 =2002) 295±307
4.3.9. 2-Aminoimidazo[1,2-a]pyridine 15f).13 This was
prepared according to the procedure used for the synthesis
of compound 5b. From 4f 60.50 g, 2.44 mmol) to afford 5f
60.26 g, 80%) 6note: these amine was unstable and
decomposed at rt).
NMR 6CDCl3) d 113.1, 115.4, 117.9, 118.6, 127.7, 134.5,
142.7. Anal. Calcd for C7H5N5: C, 52.83; H, 3.17; N, 44.00.
Found: C, 52.95; H, 3.17; N, 44.10.
4.4.4. 5-Azidoimidazo[1,2-a]pyridine 16d). Reaction time
12 h, yield: ,1% as an brown oil; IR 6KBr) 2140, 1500,
4.3.10. 3-Amino-2-14-bromophenyl)imidazo[1,2-a]pyri-
dine 122). To a cold solution 608C) of 3-nitroso compound
2117 64.00 g, 13.2 mmol) in concentrated HBr 648%,
50 mL), tin powder in small portion 64.00 g, 33.6 mmol)
was added. The solution was stirred at rt for 3 h. After cool-
ing, H2O 6100 mL) was added, the solution was neutralized
with Na2CO3 and concentrated in vacuo. The crude product
was chromatographed 6neutral Al2O3, CH2Cl2) to give 22
62.40 g, 63%); mp 150±1528C; IR 6KBr) 3200±2900,
1480 cm21; MS m/z 289 6M112, 96), 287 6M1, 100), 261
610), 259 610), 181 637), 104 624), 79 687), 78 675), 51 623);
1H NMR 6CDCl3) d 3.38 6brs, 2H), 6.83 6t, 1H, Jˆ6.8 Hz),
7.14 6m, 1H), 7.53 6m, 3H), 7.89 6d, 2H, Jˆ8.5 Hz), 7.96 6d,
1H, Jˆ6.8 Hz); 13C NMR 6CDCl3) d 111.9, 117.3, 121.1,
121.9, 123.6, 128.4, 128.5 62C), 131.7 62C), 132.4, 133.4,
141.1. Anal. Calcd for C13H10N3Br: C, 54.19; H, 3.50; N,
14.58. Found: C, 54.21; H, 3.48; N, 14.62.
1290, 1140 cm21 1H NMR 6CDCl3) d 6.59 6d, 1H,
;
Jˆ7.5 Hz), 7.25 6dd, 1H, Jˆ9, 7.5 Hz), 7.47 6d, 1H,
Jˆ9 Hz), 7.62 6s, 1H), 7.66 6s, 1H). Anal. Calcd for
C7H5N5: C, 52.83; H, 3.17; N, 44.00. Found: C, 52.80; H,
3.18; N, 44.17.
4.5. Method A: General procedure for the preparation of
iminophosphoranes using amino compounds
To a solution of the appropriate amine 5 619.5 mmol) in
CH3CN 650 mL), Et3N 633 mL), CCl4 621 mL) and PPh3
62 equiv.) were added. The solution was stirred at rt for
24 h, concentrated in vacuo, and chromatographed 6neutral
Al2O3, AcOEt/hexanes, 8/2, v/v) to afford 7a±e, 23.
4.6. Method B: General procedure for the preparation of
iminophosphoranes using azido compounds
4.4. General procedure for the preparation of azido
compounds 6a±d
To a solution of the appropriate azide 6a±c 61.26 mmol) in
dry CH2Cl2 620 mL), PPh3 60.36 g, 2.74 mmol) was added.
The solution was stirred at rt for 4 h. The solvent was
evapored and the crude product was chromatographed
6neutral Al2O3, CH2Cl2) to give iminophosphoranes 7a±c.
To a cold solution 6258C) of the appropriate amine
622.5 mmol) in mixture of H2O 6150 mL) and concentrated
HCl 637%, 9 mL), a solution of NaNO2 61.72 g, 24.9 mmol)
in H2O 630 mL) was added dropwise, keeping the tempera-
ture of the reaction below 08C. After 10 min, a solution of
NaN3 63.66 g, 56.3 mmol) in H2O 635 mL) was added drop-
wise to the cooled reaction mixture. The solution was stirred
at rt until completion 61±12 h). The mixture was neutralized
with Na2CO3, extracted with CH2Cl2, dried, and concen-
trated in vacuo. The residue was puri®ed by chromato-
graphy 6neutral Al2O3, CH2Cl2) to give azides 6a±d. All
azido compounds are light sensitive and must be kept cold
under argon.
4.6.1. 8-1Triphenylphosphoranylidene)aminoimidazo-
[1,2-a]pyridine 17a). Method A: yield: 23%; Method B:
yield: 67%; mp 164±1668C; IR 6KBr) 1517, 1482, 1341,
1127 cm21; MS m/z 393 6M1, 100), 369 645), 238 612),
1
183 633); H NMR 6CDCl3) d 6.00 6d, 1H, Jˆ7 Hz), 6.35
6t, 1H, Jˆ7 Hz), 7.53 6m, 12H), 7.92 6m, 6H); 13C NMR
3
6CDCl3) d 108.1 6d, JP±Cˆ13 Hz), 112.5, 113.2, 115.1,
3
1
125.6 6d, JP±Cˆ11 Hz, 6C), 130.0 6d, JP±Cˆ100 Hz, 3C),
131.8, 131.8 63C), 132.8 6d, 2JP±Cˆ10 Hz, 6C), 141.8, 146.1
6d, 3JP±Cˆ27 Hz). Anal. Calcd for C25H20N3P: C, 76.32; H,
5.12; N, 10.68. Found: C, 76.35; H, 5.10; N, 10.68.
4.4.1. 8-Azidoimidazo[1,2-a]pyridine 16a). Reaction time
1 h, yield: 76%; mp 59±618C; IR 6KBr) 2060, 1720,
4.6.2. 7-1Triphenylphosphoranylidene)aminoimidazo-
[1,2-a]pyridine 17b). Method A: yield: 49%; Method B:
yield: 61%; mp 161±1638C; IR 6KBr) 1640, 1464, 1323,
1131 cm21; MS m/z 393 6M1, 100), 316 617), 208 616),
1
1530 cm21; H NMR 6CDCl3) d 6.72 6m, 2H), 7.63 6m,
2H), 7.95 6m, 1H); 13C NMR 6CDCl3) d 111.7, 112.1,
113.6, 122.2, 129.0, 133.0, 140.1. Anal. Calcd for
C7H5N5: C, 52.83; H, 3.17; N, 44.00. Found: C, 52.65; H,
3.16; N, 43.99.
1
183 620); H NMR 6CDCl3) d 6.54 6s, 1H), 6.68 6d, 1H,
Jˆ7 Hz), 7.25 6s, 1H), 7.31 6s, 1H), 7.49 6m, 6H), 7.57 6t,
3H, Jˆ7 Hz), 7.81 6m, 7H); 13C NMR 6CDCl3) d 103.0 6d,
3JP±Cˆ13 Hz), 109.9, 116.1 6d, 3JP±Cˆ26 Hz), 124.8, 128.8
4.4.2. 7-Azidoimidazo[1,2-a]pyridine 16b). Reaction time
2 h, yield: 60%; mp 132±1348C; IR 6KBr) 2110, 1644,
3
1
6d, JP±Cˆ12 Hz, 6C), 129.6 6d, JP±Cˆ99 Hz, 3C), 132.1
1
2
1522, 1471, 1308, 1278, 1143 cm21; H NMR 6CDCl3) d
64C), 132.6 6d, JP±Cˆ10 Hz, 6C), 148.2, 149.7. Anal.
6.38 6d, 1H, Jˆ7 Hz), 7.12 6s, 1H), 7.46 6s, 1H), 7.50 6s,
1H), 7.98 6d, 1H, Jˆ7 Hz); 13C NMR 6CDCl3) d 104.7,
106.3, 112.0, 126.5, 134.1, 137.2, 145.2. Anal. Calcd for
C7H5N5: C, 52.83; H, 3.17; N, 44.00. Found: C, 53.02; H,
3.16; N, 44.08.
Calcd for C25H20N3P: C, 76.32; H, 5.12; N, 10.68. Found:
C, 76.44; H, 5.14; N, 10.66.
4.6.3. 6-1Triphenylphosphoranylidene)aminoimidazo-
[1,2-a]pyridine 17c). Method A: yield: 36%; Method B:
yield: 50%; mp 152±1548C; IR 6KBr) 1506, 1437, 1358,
1295, 1204 cm21; MS m/z 393 6M1, 100), 208 612), 183
4.4.3. 6-Azidoimidazo[1,2-a]pyridine 16c). Reaction time
2 h, CH2Cl2/EtOH, 98/2, v/v, yield: 63%; mp 71±738C; IR
1
631); H NMR 6CDCl3) d 6.92 6d, 1H, Jˆ9.5 Hz), 7.21 6s,
6KBr) 2110, 1530, 1310, 1260, 1140 cm21
;
1H NMR
1H), 7.29 6d, 1H, Jˆ9.5 Hz), 7.40 6s, 1H), 7.45 6m, 10H),
7.75 6m, 6H); 13C NMR 6CDCl3) d 111.4, 115.1 6d,
6CDCl3) d 6.97 6dd, 1H, Jˆ2, 9.5 Hz), 7.56 6s, 1H), 7.62
6d, 1H, Jˆ9.5 Hz), 7.65 6s, 1H), 7.90 6d, 1H, Jˆ2 Hz); 13C
3JP±Cˆ18 Hz), 116.1, 127.6 6d, JP±Cˆ16 Hz), 128.6 6d,
3

J. M. Chezal et al. / Tetrahedron 58 =2002) 295±307
303
1
3JP±Cˆ12 Hz, 6C), 130.2 6d, JP±Cˆ100 Hz, 3C), 131.8
Pd/C were added. The mixture was re¯uxed until no more
substrate was observed by TLC. The solvent was evaporated
and the crude product was chromatographed 6neutral Al2O3,
CH2Cl2).
2
63C), 132.0, 132.3 6d, JP±Cˆ9.5 Hz, 6C), 137.9, 142.2.
Anal. Calcd for C25H20N3P: C, 76.32; H, 5.12; N, 10.68.
Found: C, 76.12; H, 5.13; N, 10.71.
4.6.4. 5-1Triphenylphosphoranylidene)aminoimidazo-
[1,2-a]pyridine 17d). Method A: yield: 48%; mp 193±
1958C; IR 6KBr) 1577, 1439, 1352, 1274, 1110 cm21; MS
m/z 393 6M1, 1), 369 6100), 292 612), 260 612), 183 643),
Method C: General procedure using iminophosphoranes
compounds. To a stirred solution of the appropriate imino-
phosphorane 62.03 mmol) in dry nitrobenzene 615 mL),
acrolein 63 equiv.) in nitrobenzene 65 mL) was added. The
solution was heated at 958C for 20 h, and re¯uxed for 3 h.
The solvent was removed under vacuo and the crude
product was chromatographed 6neutral Al2O3, AcOEt/
hexanes, 9/1, v/v).
1
109612); H NMR 6CDCl3) d 5.78 6d, 1H, Jˆ7.5 Hz), 6.32
6d, 1H, Jˆ7.5 Hz), 7.18 6t, 1H, Jˆ7.5 Hz), 7.46 6m, 8H),
7.53 6m, 3H), 7.86 6dd, 6H, Jˆ7, 12 Hz); 13C NMR 6CDCl3)
3
d 96.3, 106.9 6d, JP±Cˆ21.5 Hz), 128.3 68C), 130.7 6d,
2
1JP±Cˆ100 Hz, 3C), 131.4 63C), 133.1 6d, JP±Cˆ10 Hz,
3
6C), 138.6, 156.6, 162.6 6d, JP±Cˆ5 Hz). Anal. Calcd for
4.7.1. Imidazo[1,2-h][1,7]naphthyridine 18a). From
acrolein: Method A: 64 equiv., reaction time 18 h), Method
B: 6reaction time 5 h), Method C: 6eluate with CH2Cl2/
EtOH, 99/1, v/v) as an oil; IR 6KBr) 1520, 1480, 1410,
1390, 1330 cm21; MS m/z 169 6M1, 100), 142 629), 129
614), 115 617); 1H NMR 6CDCl3) d 6.99 6d, 1H,
Jˆ7.2 Hz), 7.49 6dd, 1H, Jˆ4.3, 8 Hz), 7.65 6s, 1H), 7.72
6s, 1H), 8.00 6d, 1H, Jˆ7.2 Hz), 8.02 6d, 1H, Jˆ8 Hz), 8.97
6d, 1H); 13C NMR 6CDCl3) d 111.5, 115.0, 122.8, 124.0,
124.7, 132.6, 134.5, 140.6, 142.8, 150.6. Anal. Calcd for
C10H7N3: C, 70.99; H, 4.17; N, 24.84. Found: C, 70.73; H,
4.18; N, 24.85.
C25H20N3P: C, 76.32; H, 5.12; N, 10.68. Found: C, 76.28; H,
5.14; N, 10.69.
4.6.5. 3-1Triphenylphosphoranylidene)aminoimidazo-
[1,2-a]pyridine 17e). Method A: yield: 36%; mp 129±
1318C; IR 6KBr) 1540, 1438, 1292, 1184, 1119 cm21; MS
m/z 393 6M1, 71), 288 68), 262 6100), 183 662), 108 641), 78
623), 51 620); 1H NMR 6CDCl3) d 6.71 6t, 1H, Jˆ7 Hz), 6.95
6m, 1H), 7.42 6d, 1H, Jˆ9 Hz), 7.50 6m, 6H), 7.58 6t, 3H,
Jˆ7 Hz), 7.83 6m, 6H), 8.35 6d, 1H, Jˆ7 Hz); 13C NMR
6CDCl3) d 110.1, 115.7, 117.0, 120.8, 122.5, 128.8 6d,
1
3JP±Cˆ12 Hz, 6C), 129.7 6d, JP±Cˆ101 Hz, 3C), 132.2
2
2
63C), 132.5 6d, JP±Cˆ10 Hz, 6C), 133.4 6d, JP±Cˆ9.5 Hz,
C), 139.9. Anal. Calcd for C25H20N3P: C, 76.32; H, 5.12; N,
10.68. Found: C, 76.59; H, 5.11; N, 10.66.
4.7.2. 9-Methylimidazo[1,2-h][1,7]naphthyridine 18b).
From crotonaldehyde: Method A: 64 equiv., reaction time
19 h), Method B: 6reaction time 2.5 h); mp 132±1348C; IR
6KBr) 1600, 1480, 1420, 1390, 1320, 1140 cm21; MS m/z
183 6M1, 100), 182 648), 157 620); 1H NMR 6CDCl3) d 2.77
6s, 3H), 6.89 6d, 1H, Jˆ7 Hz), 7.30 6d, 1H, Jˆ8 Hz), 7.57 6s,
1H), 7.64 6s, 1H), 7.84 6d, 1H, Jˆ8 Hz), 7.89 6d, 1H,
Jˆ7 Hz); 13C NMR 6CDCl3) d 25.0, 111.4, 114.8, 122.4,
123.1, 123.2, 132.2, 134.7, 139.8, 142.7, 160.0. Anal. Calcd
for C11H9N3: C, 72.11; H, 4.95; N, 22.94. Found: C, 72.32;
H, 4.96; N, 22.86.
4.6.6. 3-1Triphenylphosphoranylidene)amino-2-14-bromo-
phenyl)imidazo[1,2-a]pyridine 123). Method A: yield:
99%; mp 197±1998C; IR 6KBr) 1541, 1438, 1341,
1114 cm21; MS m/z 549 6M112, 43), 547 6M1, 41), 288
1
613), 262 6100), 183 647), 108 630), 78 628); H NMR
6CDCl3) d 6.43 6t, 1H Jˆ7 Hz), 6.89 6m, 1H), 7.21 6d,
2H, Jˆ8 Hz), 7.41 6m, 7H), 7.50 6m, 3H), 7.59 6m, 6H),
7.78 6d, 1H, Jˆ7 Hz), 7.83 6d, 2H, Jˆ8 Hz); 13C NMR
6CDCl3) d 110.0, 116.6, 118.8, 121.4, 122.4, 128.2 6d,
From ethanal: Method A: 62 equiv., reaction time 19 h),
Method B: 6reaction time 3.5 h).
1
3JP±Cˆ10 Hz, 6C), 128.4 62C), 129.6 6d, JP±Cˆ100 Hz,
2
3C), 129.6 6d, JP±Cˆ8.5 Hz), 130.2 62C), 131.7 6d,
2
4JP±Cˆ3 Hz, 3C), 131.9 6d, JP±Cˆ10 Hz, 6C), 133.0,
4.7.3. 9-Ethyl-8-methylimidazo[1,2-h][1,7]naphthyridine
18c). From propanal: Method A: 62.2 equiv., reaction time
19 h). The ®rst fraction gave =^)-9-ethyl-9,10-dihydro-8-
methylimidazo[1,2-h][1,7]naphthyridine 6^)-69) as an oil;
3
4
134.5 6d, JP±Cˆ3 Hz), 139.5 6d, JP±Cˆ1.5 Hz). Anal.
Calcd for C31H23N3BrP: C, 67.89; H, 4.23; N, 7.66.
Found: C, 68.02; H, 4.22; N, 7.64.
1
IR 6KBr) 3500, 1630, 1540, 1480, 1330 cm21; H NMR
6CDCl3) d 0.87 6t, 3H, Jˆ7.4 Hz), 1.39 6m, 1H), 1.59
6hept., 1H, Jˆ7.2 Hz), 4.12 6m, 1H), 5.48 6s, 1H), 5.96 6s,
1H), 6.23 6d, 1H, Jˆ6.7 Hz), 7.24 6d, 1H, Jˆ6.7 Hz), 7.28
6s, 1H), 7.37 6s, 1H); 13C NMR 6CDCl3) d 8.1, 20.5, 27.5,
57.1, 109.0, 111.83, 112.6, 113.2, 119.8, 130.3, 131.5,
137.9. Anal. Calcd for C13H15N3: C, 73.21; H, 7.09; N,
19.70. Found: C, 73.50; H, 7.06; N, 19.65. The second
fraction gave 9-ethyl-8-methylimidazo[1,2-h][1,7]naph-
thyridine 68c); mp 183±1858C; IR 6KBr) 1510, 1480,
1410, 1390, 1320, 1140 cm21; MS m/z 211 6M1, 96), 210
6100), 183 644); 1H NMR 6CDCl3) d 1.44 6t, 3H, Jˆ7.5 Hz),
2.51 6s, 3H), 3.09 6q, 2H, Jˆ7.5 Hz), 6.93 6d, 1H, Jˆ7 Hz),
7.60 6d, 1H, Jˆ1 Hz), 7.68 6d, 1H, Jˆ1 Hz), 7.73 6s, 1H),
7.93 6d, 1H, Jˆ7 Hz); 13C NMR 6CDCl3) d 12.9, 19.0, 29.3,
111.3, 114.9, 123.1, 123.2, 131.1, 132.2, 135.0, 138.4,
143.1, 164.0. Anal. Calcd for C13H13N3: C, 73.91; H, 6.20;
4.7. Reactivity of amines with carbonyl compounds
Method A: General procedure in 1,2-dichlorobenzene. To a
solution of the appropriate amine 67.52 mmol) in dry 1,2-
dichlorobenzene 640 mL) a solution of the suitable carbonyl
reagent in the same solvent 610 mL) was added. The mixture
was re¯uxed until no more substrate was observed by TLC.
The solvent was evapored and the crude product was
chromatographed 6neutral Al2O3, CH2Cl2).
Method B: General procedure in 1,2-dichlorobenzene with
10% Pd/C. To a solution of the appropriate amine
67.52 mmol) in dry 1,2-dichlorobenzene 640 mL) a solution
of the suitable carbonyl reagent 64 equiv. for acetaldehyde
and propanal, and 2 equiv. for acrolein and crotonaldehyde)
in the same solvent 610 mL), and a small quantity of 10%

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J. M. Chezal et al. / Tetrahedron 58 =2002) 295±307
N, 19.89. Found: C, 74.12; H, 6.22; N, 19.83. Method B:
6reaction time 2.5 h) to give 8c.
2H, Jˆ9.5 Hz), 8.00 6s, 1H), 8.08 6d, 1H, Jˆ8.5 Hz); 13C
NMR 6CDCl3) d 24.5, 111.5, 120.7, 122.9, 123.0, 127.0,
127.1, 133.3, 140.3, 143.3, 156.3. Anal. Calcd for
C11H9N3: C, 72.11; H, 4.95; N, 22.94. Found: C, 72.24; H,
4.94; N, 22.95.
4.7.4. Imidazo[2,1-f][1,6]naphthyridine 110a). From
acrolein: Method A: 64 equiv., reaction time 14 h, eluate
with CH2Cl2/EtOH, 99/1, v/v). Method B 6reaction time
4 h, eluate with CH2Cl2/EtOH, 99/1, v/v), Method C: 6eluate
with AcOEt/hexanes, 8/2, v/v) as a yellow oil; IR 6KBr)
1635, 1522, 1320, 805 cm21; MS m/z 169 6M1, 100), 142
From ethanal: Method A: 62 equiv., reaction time 9 h),
Method B: 6reaction time 3 h).
1
648), 129 616), 115 627); H NMR 6CDCl3) d 7.31 6d, 1H,
4.7.9. 7-Ethyl-8-methylimidazo[1,2-a][1,5]naphthyridine
111c). From propanal: Method A: 62 equiv., reaction time
20 h). Method B: 6reaction time 3 h); mp 163±1658C; IR
6KBr) 1600, 1510, 1310, 1280, 1210, 1180 cm21; MS m/z
Jˆ7.5 Hz), 7.53 6dd, 1H, Jˆ4.5, 8 Hz), 7.62 6s, 1H), 7.64 6s,
1H), 8.12 6d, 1H, Jˆ7.5 Hz), 8.88 6m, 2H); 13C NMR
6CDCl3) d 114.5, 114.6, 119.9, 122.8, 126.5, 131.1, 132.7,
142.1, 146.5, 150.7. Anal. Calcd for C10H7N3: C, 70.99; H,
4.17; N, 24.84. Found: C, 71.09; H, 4.18; N, 24.92.
1
211 6M1, 100), 210 698), 194 69), 183 623); H NMR
6CDCl3) d 1.39 6t, 3H, Jˆ7.5 Hz), 2.56 6s, 3H), 2.98 6q,
2H, Jˆ7.5 Hz), 7.69 6s, 1H), 7.72 6s, 2H), 7.93 6s, 1H),
8.00 6s, 1H); 13C NMR 6CDCl3) d 12.8, 19.4, 28.8, 111.3,
119.5, 123.5, 127.3, 127.5, 131.5, 133.3, 138.5, 143.6,
160.1. Anal. Calcd for C13H13N3: C, 73.91; H, 6.20; N,
19.89. Found: C, 73.63; H, 6.22; N, 19.82.
4.7.5. 8-Methylimidazo[2,1-f][1,6]naphthyridine 110b).
From crotonaldehyde: Method A: 64 equiv., reaction time
36 h, eluate with CH2Cl2/EtOH, 99/1, v/v). Method B:
6reaction time 4 h, eluate with CH2Cl2/EtOH, 99/1, v/v);
mp 116±1188C; IR 6KBr) 1638, 1560, 1321 cm21; MS m/z
183 6M1, 100), 182 622), 142 616); 1H NMR 6CDCl3) d 2.57
6s, 3H), 7.04 6d, 1H, Jˆ7.5 Hz), 7.22 6d, 1H, Jˆ8 Hz), 7.43
6s, 1H), 7.45 6s, 1H), 7.92 6d, 1H, Jˆ7.5 Hz), 8.58 6d, 1H,
Jˆ8 Hz); 13C NMR 6CDCl3) d 24.7, 113.9, 117.2, 122.8
62C), 126.1, 130.9, 131.1, 142.0, 145.7, 159.8. Anal.
Calcd for C11H9N3: C, 72.11; H, 4.95; N, 22.94. Found: C,
72.22, H, 4.94; N, 22.86.
4.7.10. Imidazo[1,2-a][1,8]naphthyridine7g 112a). From
acrolein: Method A: 65 equiv., reaction time 6 h, eluate
with CH2Cl2/EtOH, 99/1, v/v). Method B: 6reaction time
19 h, eluate with CH2Cl2/EtOH, 99/1, v/v); mp 90±928C
6lit. 91±938C).
4.7.11. 8-Methylimidazo[1,2-a][1,8]naphthyridine7b 112b).
From crotonaldehyde: Method A: 64 equiv., reaction time
24 h). Method B: 6reaction time 20 h); mp 100±1028C 6lit.
101±1038C).
From ethanal: Method A: 68 equiv., reaction time 14 h,
eluate with CH2Cl2/EtOH, 99/1, v/v). Method B: 6reaction
time 5 h, eluate with CH2Cl2/EtOH, 99/1, v/v).
From ethanal: Method A: 68 equiv., reaction time 35 h).
Method B: 6reaction time 23 h).
4.7.6. 8-Ethyl-9-methylimidazo[2,1-f][1,6]naphthyridine
110c). From propanal: Method A: yield: 68 equiv., reaction
time 14 h, eluate with CH2Cl2/EtOH 99/1, v/v). Method B:
6reaction time 5 h, eluate with CH2Cl2/EtOH 99/1, v/v); mp
89±918C; IR 6KBr) 1639, 1546, 1321 cm21; MS m/z 211
6M1, 94), 210 6100), 183 625), 51 612); 1H NMR 6CDCl3) d
1.40 6t, 3H, Jˆ7.5 Hz), 2.55 6s, 3H), 3.00 6q, 2H, Jˆ7.5 Hz),
7.29 6d, 1H, Jˆ7.5 Hz), 7.59 6s, 1H), 7.62 6s, 1H), 8.07 6d,
1H, Jˆ7.5 Hz), 8.63 6s, 1H); 13C NMR 6CDCl3) d 12.8,
19.1, 29.3, 114.2, 114.5, 118.2, 125.4, 131.3, 131.5, 132.0,
142.5, 144.4, 163.8. Anal. Calcd for C13H13N3: C, 73.91; H,
6.20; N, 19.89. Found: C, 73.61; H, 6.18; N, 19.97.
4.7.12. 1^)-6-Ethyl-5,6-dihydro-4-methylpyrido[6,1,2-
cd]-2,3a,5-triazaazulene 1^)-113). From propanal: Method
A: 63 equiv., reaction time 20 h) as an oil; IR 6KBr) 3290,
1634, 1540, 1456, 1379, 1274, 1149 cm21; MS m/z 213
6M1, 63), 198 633), 184 6100), 143 630); 1H NMR
6CDCl3) d 1.04 6t, 3H, Jˆ7 Hz), 1.38 6m, 1H), 1.70 6m,
1H), 2.02 6s, 3H), 3.68 6m, 1H), 5.45 6brs, 1H), 6.12 6d,
1H, Jˆ7 Hz), 6.44 6s, 1H), 7.10 6t, 1H, Jˆ7 Hz), 7.18 6d,
1H, Jˆ7 Hz), 7.47 6s, 1H); 13C NMR 6CDCl3) d 10.7, 24.07,
28.7, 64.4, 97.9, 108.6, 114.1, 123.3, 126.4, 133.5, 133.8,
143.1, 148.5. Anal. Calcd for C13H15N3: C, 73.21; H, 7.09;
N, 19.70. Found: C, 73.33; H, 7.11; N, 19.74.
4.7.7. Imidazo[1,2-a][1,5]naphthyridine 111a). From
acrolein: Method A: 65 equiv., reaction time 18 h), Method
B: 6reaction time 3 h); mp 145±1478C; IR 6KBr) 1528,
1454, 1316 cm21; MS m/z 169 6M1, 100), 142 616), 129
4.7.13. Dipyrido[1,2-a;20,30-d]imidazole 116a). From
acrolein: Method A: 64 equiv., reaction time 20 h). Method
B: 6reaction time 20 h); mp 199±2018C; IR 6KBr) 1497,
1408 cm21; MS m/z 169 6M1, 100), 168 622), 142 611), 78
644), 51 637); 1H NMR 6CDCl3) d 6.96 6t, 1H, Jˆ7 Hz), 7.30
6dd, 1H, Jˆ4.5, 8 Hz), 7.54 6m, 1H), 7.80 6d, 1H, Jˆ9 Hz),
8.23 6d, 1H, Jˆ8 Hz), 8.51 6d, 1H, Jˆ7 Hz), 8.83 6d,
Jˆ4.5 Hz); 13C NMR 6CDCl3) d 111.3, 115.9, 118.3,
118.7, 121.1, 125.8, 130.7, 148.7, 149.6, 156.3. Anal.
Calcd for C10H7N3: C, 70.99; H, 4.17; N, 24.84. Found: C,
71.22; H, 4.16; N, 24.79.
1
631), 115 617); H NMR 6CDCl3) d 7.52 6dd, 1H, Jˆ4.5,
8.5 Hz), 7.68 6s, 1H), 7.73 6AB system, 2H, Jˆ9.5 Hz), 8.04
6s, 1H), 8.19 6d, 1H, Jˆ8.5 Hz), 8.77 6d, 1H, Jˆ4.5 Hz); 13C
NMR 6CDCl3) d 111.7, 120.9, 122.5, 122.6, 127.4, 128.9,
133.5, 141.0, 143.3, 147.3. Anal. Calcd for C10H7N3: C,
70.99; H, 4.17; N, 24.84. Found: C, 70.92; H, 4.16; N, 24.85.
4.7.8. 7-Methylimidazo[1,2-a][1,5]naphthyridine 111b).
From crotonaldehyde: Method A: 64 equiv., reaction time
7 h), Method B: 6reaction time 3 h); mp 166±1688C; IR
6KBr) 1520, 1450, 1420, 1310 cm21; MS m/z 183 6M1,
4.7.14. 4-Methyldipyrido[1,2-a;20,30-d]imidazole 116b).
From crotonaldehyde: Method A: 65 equiv., reaction time
17 h). Method B: 6reaction time 20 h); mp 192±1948C; IR
1
100), 156 611), 129 610); H NMR 6CDCl3) d 2.72 6s,
3H), 7.38 6d, 1H, Jˆ8.5 Hz), 7.67 6s, 1H), 7.70 6AB system,

J. M. Chezal et al. / Tetrahedron 58 =2002) 295±307
305
6KBr) 1500, 1483, 1278, 1124 cm21; MS m/z 183 6M1,
100), 182 634), 168 68), 155 612), 78 637), 51 633); H
for C11H11N3: C, 71.33; H, 5.99; N, 22.69. Found: C, 71.21;
H, 5.99; N, 22.77.
1
NMR 6CDCl3) d 2.81 6s, 3H), 6.80 6t, 1H, Jˆ7 Hz), 6.88
6d, 1H, Jˆ5 Hz), 7.37 6m, 1H), 7.64 6d, 1H, Jˆ9 Hz), 8.50
6d, 1H, Jˆ5 Hz), 8.52 6d, 1H, Jˆ7 Hz); 13C NMR 6CDCl3) d
18.7, 111.1, 117.9, 118.4, 120.5, 127.8, 130.8, 132.7, 147.9,
149.1, 155.7. Anal. Calcd for C11H9N3: C, 72.11; H, 4.95; N,
22.94. Found: C, 71.88; H, 4.95; N, 22.99.
4.7.19. 2-Methyldipyrido[1,2-a;30,20-d]imidazole1 117c).
From ethanal: Method A: 64 equiv., reaction time 16 h).
Method B: 6reaction time 2.5 h); mp 150±1528C 6lit. 149±
1518C).
4.7.20. 2-Ethyl-3-methyldipyrido[1,2-a;30,20-d]imidazole
117d). From propanal: Method A: 62.2 equiv., reaction time
7 h). Method B 6reaction time 4 h); mp 108±1108C; IR
6KBr) 1639, 1571, 1493, 1397, 1134 cm21; MS m/z 211
4.7.15. 2-Methyldipyrido[1,2-a;20,30-d]imidazole 116c).
From ethanal: Method A: 66 equiv., reaction time 22 h).
Method B: 6reaction time 20 h); mp 220±2228C; IR 6KBr)
3043, 1596, 1498, 1409, 1350, 1242 cm21; MS m/z 183
1
6M1, 66), 196 6100), 149 616), 78 655), 51 624); H NMR
1
6M1, 100), 182 644), 155611), 78 629), 51 626); H NMR
6CDCl3) d 1.37 6t, 3H, Jˆ7.5 Hz), 2.47 6s, 3H), 2.93 6q, 2H,
Jˆ7.5 Hz), 6.80 6t, 1H, Jˆ7 Hz), 7.38 6m, 1H), 7.58 6d, 1H,
Jˆ9 Hz), 7.88 6s, 1H), 8.72 6d, 1H, Jˆ7 Hz); 13C NMR
6CDCl3) d 12.9, 19.6, 28.7, 110.2, 117.8, 124.4, 127.8,
129.5, 129.9, 135.1, 139.8, 147.9, 155.4. Anal. Calcd for
C13H13N3: C, 73.91; H, 6.20; N, 19.89. Found: C, 74.18;
H, 6.22; N, 19.84.
6CDCl3) d 2.77 6s, 3H), 6.89 6t, 1H, Jˆ7 Hz), 7.14 6d, 1H,
Jˆ8 Hz), 7.47 6m, 1H), 7.74 6d, 1H, Jˆ9 Hz), 8.03 6d, 1H,
Jˆ8 Hz), 8.44 6d, 1H, Jˆ7 Hz); 13C NMR 6CDCl3) d 25.1,
111.0, 116.0, 118.2, 118.7, 119.1, 125.6, 130.0, 149.3,
156.1, 157.9. Anal. Calcd for C11H9N3: C, 72.11; H, 4.95;
N, 22.94. Found: C, 72.08; H, 4.94; N, 23.01.
4.7.16. 2-Ethyl-3-methyldipyrido[1,2-a;20,30-d]imidazole
116d) and 3-ethyl-2-methyldipyrido[1,2-a;20,30-d]imida-
zole 116e). From propanal: Method A: 62.2 equiv., reaction
time 17 h) gave compound 16d; mp 219±2218C; IR 6KBr)
1609, 1504, 1449, 1402, 1354, 1256 cm21; MS m/z 211
4.7.21. 2-14-Bromophenyl)-5,6-dihydropyrido[6,1,2-cd]-
2,3a,8-triazaazulene 124a). From acrolein: Method A:
610 equiv., reaction time 24 h). Method B: 6reaction time
30 h). Method C: 6using dry 1,2-dichlorobenzene 640 mL)
as solvent, 908C for 20 h and re¯ux for 4 h) yield: 13%; mp
124±1268C; IR 6KBr) 1470, 1340, 1010 cm21; MS m/z 327
6M112, 96), 325 6M1, 100), 312 68), 246 612), 117 616), 91
1
6M1, 74), 210 6100), 183 621), 78 628), 51 618); H NMR
6CDCl3) d 1.43 6t, 3H, Jˆ7 Hz), 2.54 6s, 3H), 3.02 6q, 2H,
Jˆ7 Hz), 6.87 6t, 1H, Jˆ6.5 Hz), 7.44 6m, 1H), 7.74 6d, 1H,
Jˆ9 Hz), 7.92 6s, 1H), 8.39 6d, 1H, Jˆ6.5 Hz); 13C NMR
6CDCl3) d 12.7, 19.4, 29.2, 110.6, 117.9, 119.2, 119.3,
123.9, 125.5, 129.2, 148.6, 154.5, 161.3. Anal. Calcd for
C13H13N3: C, 73.91; H, 6.20; N, 19.89. Found: C, 73.98;
H, 6.21; N, 19.84. Method B: 6reaction time 20 h) yield in
order to elution 16d and 16e; mp 178±1808C; IR 6KBr)
1639, 1495, 1357, 1321 cm21; MS m/z 211 6M1, 100),
1
643), 64 613); H NMR 6CDCl3) d 2.96 6m, 2H), 3.19 6m,
2H), 6.65 6d, 1H, Jˆ6.5 Hz), 7.22 6m, 1H), 7.55 6d, 1H,
Jˆ9 Hz), 7.61 6d, 2H, Jˆ7.5 Hz), 7.70 6t, 1H, Jˆ4 Hz),
8.38 6d, 2H, Jˆ7.5 Hz); 13C NMR 6CDCl3) d 30.8, 34.65,
112.1, 115.9, 122.3, 126.0, 128.5, 130.6 62C), 131.3 62C),
133.1, 139.0, 141.9, 144.8, 154.9. Anal. Calcd for
C16H12N3Br: C, 58.91; H, 3.71; N, 12.88. Found: C,
59.04; H, 3.70; N, 12.83.
1
196 629), 182 623) 169 67), 78 62); H NMR 6CDCl3) d
1.28 6t, 3H, Jˆ7.5 Hz), 2.40 6s, 3H), 3.07 6q, 2H,
Jˆ7.5 Hz), 6.81 6t, 1H, Jˆ7 Hz), 7.36 6m, 1H), 7.67 6d,
1H, Jˆ9 Hz), 8.46 6s, 1H), 8.48 6d, 1H, Jˆ7 Hz); 13C
NMR 6CDCl3) d 12.7, 15.7, 21.2, 111.2, 118.3, 119.8,
124.0, 127.7, 129.2, 136.7, 149.1, 150.0, 155.1. Anal.
Calcd for C13H13N3: C, 73.91; H, 6.20; N, 19.89. Found:
C, 73.98; H, 6.19; N, 19.92.
4.7.22. 1^)-2-14-Bromophenyl)-5,6-dihydro-6-methyl-
pyrido[6,1,2-cd]-2,3a,8-triazaazulene 124b). From croton-
aldehyde: Method A: 64 equiv., reaction time 5 h) yield 2-=4-
bromophenyl)-3-=but-2-eneimino)imidazo[1,2-a]pyridine
625a); mp 108±1108C; IR 6KBr) 1580, 1480, 1340,
1220 cm21; MS m/z 341 6M112, 27), 339 6M1, 29), 325
610), 261 630), 78 6100), 51 616); 1H NMR 6CDCl3) d 2.02
6dd, 3H, Jˆ1.5, 7 Hz), 6.29 6sex., 1H, Jˆ7, 15.5 Hz), 6.51
6ddd, 1H, Jˆ15.5, 1.5, 9 Hz), 6.87 6t, 1H, Jˆ7 Hz), 7.24 6m,
1H), 7.58 6d, 1H, Jˆ9 Hz), 7.59 6d, 2H, Jˆ8.5 Hz), 7.71 6d,
2H, Jˆ8.5 Hz), 8.27 6d, 1H, Jˆ7 Hz), 8.32 6d, 1H, Jˆ9 Hz);
13C NMR 6CDCl3) d 18.9, 112.4, 117.4, 121.7, 123.10,
125.0, 129.8 62C), 131.9 62C), 132.9, 133.9, 142.8, 144.2,
161.9. Anal. Calcd for C17H14N3Br: C, 60.02; H, 4.15; N,
12.35. Found: C, 59.96; H, 4.14; N, 12.38. Method A:
66 equiv., reaction time at 1058C for 7.5 h, and under re¯ux
for 17 h). The ®rst eluate gave 6^)-24b; mp 155±1578C; IR
6KBr) 1620, 1500, 1470, 1340, 1300, 1230 cm21; MS m/z
341 6M112, 100), 339 6M1, 94), 326 655), 324 657), 244
614), 123 617), 104 648), 78 618); 1H NMR 6CDCl3) d 1.24
6d, 3H, Jˆ7 Hz), 2.63 6d, 1H, Jˆ15.5 Hz), 2.98 6dt, 1H,
Jˆ15.5, 6 Hz), 3.54 6m, 1H), 6.69 6d, 1H, Jˆ7 Hz), 7.22
6dd, 1H, Jˆ7, 9 Hz), 7.55 6d, 1H, Jˆ9 Hz), 7.60 6d, 2H,
Jˆ8.5 Hz), 7.62 6m, 1H), 8.29 6d, 2H, Jˆ8.5 Hz); 13C
NMR 6CDCl3) d 20.4, 36.3, 40.1, 110.9, 115.7, 122.2,
125.9, 128.4, 130.6 62C), 131.2 62C), 133.1, 141.8, 143.6,
4.7.17. Dipyrido[1,2-a;30,20-d]imidazole1 117a). From
acrolein: Method A: 64 equiv., reaction time 7 h) yield 6%.
Method B: 6reaction time 3.5 h). Method C: 6using dry 1,2-
dichlorobenzene 640 mL) as solvent, 908C for 21 h and
re¯ux for 3 h); mp 125±1278C 6lit. 129±1318C).
4.7.18. 4-Methyldipyrido[1,2-a;30,20-d]imidazole1 117b).
From crotonaldehyde: Method A: 64 equiv., reaction time
23 h); mp 134±1368C 6lit. 143±1458C). Method B: 6reaction
time 11 h) gave =^)-5,6-dihydro-6-methylpyrido[6,1,2-cd]-
2,3a,8-triazaazulene 620) as an oil; IR 6KBr) 1627, 1521,
1500, 1453, 1294 cm21; MS m/z 185 6M1, 90), 170 6100),
1
157 650), 104 655), 78 641), 63 620), 51 639); H NMR
6CDCl3) d 1.19 6d, 3H, Jˆ6.5 Hz), 2.58 6d, 1H, Jˆ16 Hz),
2.93 6td, 1H, Jˆ6.5, 16 Hz), 3.52 6quint., Jˆ6.5 Hz), 6.70
6d, 1H, Jˆ7 Hz), 7.19 6dd, 1H, Jˆ7, 8 Hz), 7.52 6m, 2H),
7.85 6s, 1H); 13C NMR 6CDCl3) d 20.1, 36.2, 40.0, 110.7,
116.0, 125.3, 132.5, 135.9, 143.3, 146.4, 152.7. Anal. Calcd

306
J. M. Chezal et al. / Tetrahedron 58 =2002) 295±307
144.9, 152.7. Anal. Calcd for C17H14N3Br: C, 60.02; H,
4.15; N, 12.35. Found: C, 60.21; H, 4.16; N, 12.33. The
second eluate gave 25a. Method B: 6reaction time for
30 h) yields compound 6^)-24b.
was chromatographed 6neutral Al2O3, CH2Cl2) to yield
17c 670 mg, 14%).
4.8.1. 3-1But-2-eneimino)imidazo[1,2-a]pyridine 119). To
a solution of 5e 60.70 g, 5.26 mmol) in dry toluene 630 mL),
a solution of crotonaldehyde 60.74 g, 10.6 mmol) in the
same solvent 65 mL) was added. The mixture was stirred
at 708C for 10 h. The solvent was evaporated and the crude
product was chromatographed 6neutral Al2O3, CH2Cl2) to
yield 19 60.75 g, 77%); mp 116±1188C; IR 6KBr) 1637,
1583, 1485, 1338, 1302, 1250 cm21; MS m/z 185 6M1,
32), 169 616), 107 634), 78 6100), 51 642); 1H NMR
6CD3OD) d 1.92 6d, 3H, Jˆ6 Hz), 6.42 6m, 2H), 6.90 6t,
1H, Jˆ7 Hz), 7.24 6m, 1H), 7.43 6d, 1H, Jˆ9 Hz), 7.59 6s,
1H), 8.33 6d, 1H, Jˆ7 Hz), 8.38 6d, 1H, Jˆ8.5 Hz); 13C
NMR 6CDCl3) d 18.8, 112.2, 117.7, 119.2, 123.0, 124.5,
132.9, 134.4, 142.3, 144.1, 156.9. Anal. Calcd for
C11H11N3: C, 71.33; H, 5.99; N, 22.69. Found: C, 71.42;
H, 5.97; N, 22.71.
From acetaldehyde: Method A: 64 equiv., reaction time
28 h) gave 6^)-24b. Method B: 6reaction time 30 h) gave
6^)-24b.
4.7.23. 1^)-2-14-Bromophenyl)-6-ethyl-5,6-dihydro-5-
methylpyrido[6,1,2-cd]-2,3a,8-triazaazulene 1^)-124c).
From propanal: Method A: 68 equiv., reaction time 31 h).
The ®rst eluate gave 6^)-24c as an oil; yield: 6%; IR
6KBr) 1620, 1500, 1470, 1350, 1300, 1240 cm21; MS m/z
369 6M112, 82), 367 6M1, 82), 340 697), 338 6100), 311
616), 118 621), 104 618), 78 613); 1H NMR 6CDCl3) d 0.82
6t, 3H, Jˆ7 Hz), 1.10 6m, 1H), 1.55 6d, 3H, Jˆ7.5 Hz), 1.64
6m, 1H), 2.27 6qd, 1H, Jˆ7.5, 2 Hz), 3.05 6d, 1H,
Jˆ11.5 Hz), 6.65 6d, 1H, Jˆ6.5 Hz), 7.24 6dd, 1H, Jˆ6.5,
9 Hz), 7.37 6d, 1H, Jˆ2 Hz), 7.58 6d, 1H, Jˆ9 Hz), 7.61 6d,
2H, Jˆ8.5 Hz), 8.30 6d, 2H, Jˆ8.5 Hz); 13C NMR 6CDCl3)
d 11.9, 17.8, 22.1, 42.3, 51.3, 112.8, 115.7, 122.3, 125.3,
128.1, 130.6 62C), 131.3 62C), 133.1, 140.8, 141.9, 145.1,
158.3. Anal. Calcd for C19H18N3Br: C, 61.97; H, 4.93; N,
11.41. Found: C, 62.11; H, 4.94; N, 11.36. The second
eluate gave 2-=4-bromophenyl)-3-=2-methylpent-2-ene-
imino)imidazo[1,2-a]pyridine 625b) as an oil; yield: 7%;
IR 6KBr) 1580, 1470, 1340, 1220 cm21; MS m/z 369
6M112, 18), 367 6M1, 18), 354 637), 352 637), 289 610),
4.9. Thermolysis of 19
To a solution of 19 60.20 g, 1.08 mmol) in dry 1,2-dichloro-
benzene 615 mL), a small quantity of 10% Pd/C was added.
The solution was stirred under re¯ux for 20 h. The solvent
was evaporated and the crude product was chromatographed
6neutral Al2O3, CH2Cl2) to yield 17b 622 mg, 11%).
1
261 616), 259 616), 78 6100), 51 618); H NMR 6CDCl3) d
References
1.11 6t, 3H, Jˆ7.5 Hz), 2.08 6s, 3H), 2.37 6m, 2H), 5.94 6t,
1H, Jˆ7 Hz), 6.85 6t, 1H, Jˆ6.6 Hz), 7.22 6m, 1H), 7.57 6m,
3H), 7.73 6d, 2H, Jˆ8.5 Hz), 8.28 6d, 1H, Jˆ6.6 Hz), 8.32
6s, 1H); 13C NMR 6CDCl3) d 10.9, 13.4, 22.4, 112.3, 117.4,
121.5, 123.1, 124.8, 129.7 62C), 131.0, 131.3, 131.8 62C),
134.00, 142.7, 148.0, 136.3, 164.4. Anal. Calcd for
C19H18N3Br: C, 61.97; H, 4.93; N, 11.41. Found: C,
61.81; H, 4.91; N, 11.46. Method A: 618 equiv., reaction
time 45 h) gave 6^)-24c. Method B: 6reaction time 30 h)
gave 6^)-24c.
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Â
È
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60.45 g, 94%) as an oil; IR 6KBr) 1633, 1501, 1357 cm21
;
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MS m/z 159 6M1, 100), 105 615), 79 618); 1H NMR 6CDCl3)
d 2.20 6d, 3H, Jˆ5 Hz), 6.79 6t, 1H, Jˆ7 Hz), 7.12 6m, 1H),
7.48 6s, 1H), 7.50 6d, 1H, Jˆ9 Hz), 8.22 6q, 1H, Jˆ5 Hz),
8.31 6d, 1H, Jˆ7 Hz); 13C NMR 6CDCl3) d 23.2, 112.2,
117.5, 118.7, 122.7, 124.2, 134.1, 143.6, 158.7. Anal.
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68.11; H, 5.71; N, 26.32.
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