Chloroformamidinium salts: Efficient reagents for preparation of 2-aminobenzoimidazole, 2-aminobenzoxazole, and 2-aminobenzothiazole derivatives

Article abstract of DOI:10.1002/jhet.5570430312

A Reaction involving chloroformamidinium salts (TCFH 1a, BTCFH 1b, DmCFH 1c, DmPCFH 1d, BPCFH 1e) and 2-aminophenol 9a, benzene-1,2-diamine 9b, and 2-aminothiophenol 9c afforded 2-aminobenzoxazole 13, 2-aminobenzoimidazole 14, and 2-aminobenzothiazole 15 derivatives, respectively as major products, due to the in situ heterocyclization with dimethylamine acting as the better leaving group. Attempts for preparation of 13-15 from the reaction of N,N-dimethyl carbomyl chloride 16 with 2-aminophenol 9a, benzene-1,2-diamine 9b, and 2-aminothiophenol 9c were unsuccessful, and gave the unexpected products benzoxazol-2-ol 18a, benzoimidazol-2-one 18b, and S-(2-amino-phenyl) N,N-dimethylthiocarbamate 19 respectively. On the other hand reaction of chloroformamidinium salts 1a-e with 3-benzyl-2-hydrazinoquinoxaline 3 and 1-hydrazinophthalazine hydrochloride 4 in the presence of triethylamine as a base, afforded the [1,2,4]triazolo derivatives 6 and 7 respectively in good yield and purity. These triazole derivatives were formed due to the strong tendency towards heterocyclization and substitution of dimethylamine group as a better leaving group.

Full text of DOI:10.1002/jhet.5570430312

May-Jun 2006
599
Chloroformamidinium Salts: Efficient Reagents for Preparation of 2-
Aminobenzoimidazole, 2-Aminobenzoxazole, and 2-
Aminobenzothiazole Derivatives
Ayman El-Faham*[a], Mohamed Chebbo [b], Mohamed Abdul-Ghani [b],
and Ghassan Younes [b]
[[a] Alexandria University, Faculty of Science, Chemistry Department,
P. O. Box 426, 21321 Ibrahimia, Alexandria, Egypt;
E mail: Aymanel_faham@hotmail.com
[b] Beirut Arab University, Faculty of Science, Chemistry Department,
P. O. Box 11-5020, Beirut, Lebanon.
Received July 26, 2005
R2
R3
XH
R1
R3
N
X
N
Et3N / DMF
PF6
Cl
N
N
NH2
R4
R4
1
13-15
9
X= O; R3 = R4 = -CH3; 13a
X= O; R3, R4 = -(CH2)4; 13b
X= O; R3, R4 = -(CH2)5; 13c
X= NH; R3= R4 = -CH3; 14a
X= NH; R3, R4 = -(CH2)4; 14b
X= NH; R3, R4 = -(CH2)5; 14c
X= S; R3 = R4 = -CH3; 15a
X= S; R3, R4 = -(CH2)4; 15b
R1= R2 = R3 = R4 = -CH3; 1a
R1,R2 = R3,R4 = -(CH2)4; 1b
R1 = R2 = -CH3, R3,R4 = -(CH2)4; 1c
R1 = R2 = -CH3, R3,R4 = -(CH2)5; 1d
R1,R2 = R3,R4 = -(CH2)5; 1e
A Reaction involving chloroformamidinium salts (TCFH 1a, BTCFH 1b, DmCFH 1c, DmPCFH 1d,
BPCFH 1e) and 2-aminophenol 9a, benzene-1,2-diamine 9b, and 2-aminothiophenol 9c afforded 2-
aminobenzoxazole 13, 2-aminobenzoimidazole 14, and 2-aminobenzothiazole 15 derivatives, respectively
as major products, due to the in situ heterocyclization with dimethylamine acting as the better leaving
group. Attempts for preparation of 13-15 from the reaction of N,N-dimethyl carbomyl chloride 16 with 2-
aminophenol 9a, benzene-1,2-diamine 9b, and 2-aminothiophenol 9c were unsuccessful, and gave the
unexpected products benzoxazol-2-ol 18a, benzoimidazol-2-one 18b, and S-(2-amino-phenyl) N,N-
dimethylthiocarbamate 19 respectively. On the other hand reaction of chloroformamidinium salts 1a-e with
3-benzyl-2-hydrazinoquinoxaline 3 and 1-hydrazinophthalazine hydrochloride 4 in the presence of
triethylamine as a base, afforded the [1,2,4]triazolo derivatives 6 and 7 respectively in good yield and
purity. These triazole derivatives were formed due to the strong tendency towards heterocyclization and
substitution of dimethylamine group as a better leaving group.
J. Heterocyclic Chem., 43, 599 (2006).
2-Aminobenzothiazoles are broadly found in bio-
hydrazino derivatives such as 3-benzyl-2-hydazinoquin-
organic and medicinal chemistry with application in drug
discovery and development for the treatment of diabetes
[1], epilepsy [2], inflammation [3], amyotrophic lateral
sclerosis [4], analgesia [5], tuberculosis [6], and viral
infection [7]. Investigations into the preparation of 2-
aminobenzothiazoles can be traced to the early 1900s with
the work of Hugeschoff, who found that an arylthiourea
can be cyclized by treatment with bromine in chloroform
to form a 2-aminobenzothiazole [8]. Several drawbacks
are associated with the use of bromine, which is a highly
toxic and corrosive reagent, and can be difficult to
manipulate on small scale. Recently [9] an organic
ammonium tribromides have been used as alternative
reagents to bromine.
oxaline 3, 1-hydrazinophthalazine hydrochloride 4, and 6-
benzyl-5-hydrazino-2H-[1,2,4]triazin-3-one
5
to give
[1,2,4]triazolo derivatives 6-8 respectively in high yields
and purity, due to in situ heterocyclization and substitution
of one of the dialkylamino groups (Scheme I) [11].
R2
NH
R1
R3
N
N
R1
R2
N
PF6
Cl
N
R3
N
R4
R4
R1= R2 = R3 = R4 = CH3; 1a
R1,R2 = R3,R4 = (CH2)4; 1b
2
Figure 1
In recent work [10] we reported the reaction of chloro-
formamidinium salts 1a and 1b with aryl hydrazine
derivatives to give 4-amino-1,1,3,3-tetrasubstituted guan-
idines 2 (Figure 1), as well as reaction with heterocyclic
The present work reports a novel and an efficient
procedure for preparation of 2-aminobenzoxazole 13, 2-
aminobenzoimidazole 14, and 2-aminobenzothiazole 15

600
A. El-Faham, M. Chebbo, M. Abdul-Ghani, and G. Younes
Vol 43
derivatives as well as fused [1,2,4]triazolo derivatives 6-8,
which involve the use of chloroformamidinium salts
(TCFH, 1a), (BTCFH, 1b), (DmTCFH, 1c), (DmPCFH,
1d), and (BPCFH, 1e) (Figure 2).
chloroformamidinium salts 1, to afford intermediate 11
from which a penta-substituted guanidine intermediate 12
is formed which then undergoes in situ intramolecular
cyclization [11] to afford the azole derivatives 13 and 14,
Scheme I
N
N
C6H5
NH2
C6H5
N
H
3
N
N
N
R3
N
N
R4
6
N
R2
R4
R1
R3
N
N
4
N
Et3N
NHNH2.HCl
PF6
Cl
R3
N
N
N
R4
N
7
N
HN
C6H5
R1= R2 = R3 = R4 = CH3; 1a
R1,R2 = R3,R4 = (CH2)4; 1b
N
N
HN
C6H5
O
N
NHNH2
5
O
N
N
R3
N
R4
8
R3, R4 = CH3 or (CH2)4
R2
as in case of the reaction of 2-aminophenol 9a and
benzene-1,2-diamine 9b with the chloroformamidinium
salts 1 (Scheme II).
XH
R1
R3
N
PF6
Cl
N
NH2
R4
On the other hand, reaction of chloroformamidinium
salts 1a and 1b with benzene 1,2-diamine 9b in
dichloromethane (DCM) or dimethylformamide (DMF) as
a solvent at room temperature affords a mixture of
gaunidine derivatives 12 as major products, while the
benzoimidazole derivatives 14 were minor. This was not
the case in the reaction with o-aminophenol 9a and o-
aminothiophenol 9c.
1
9
X = O, 9a; NH, 9b, or S, 9c
R1= R2 = R3 = R4 = -CH3; 1a
R1,R2 = R3,R4 = -(CH2)4; 1b
R1 = R2 = -CH3, R3,R4 = -(CH2)4; 1c
R1 = R2 = -CH3, R3,R4 = -(CH2)5; 1d
R1,R2 = R3,R4 = -(CH2)5; 1e
Figure 2
Results and Discussion.
Attempts to prepare of the azole derivatives 13-15 from
the reaction of N,N-dimethyl carbamoyl chloride 16 under
the same conditions used above were not successful.
Reaction of 16 with o-aminophenol 9a and benzene-1,2-
diamine 9b afforded benzoxazol-2-ol 18a and 1,3-
dihydrobenzoimidazol-2-one 18b as a major product and
2-(N,N-dimethyl)aminobenzoxazole 13a and 2-(N,N-
dimethyl) aminobenzoimidazole 14a as a minor product
in 2% yield, respectively (Scheme III). This is due to the
lone pair of the anilino nitrogen atom firstly attacked the
carbonyl carbon atom of 16 forming the intermediate 17
and then undergoing in situ intramolecular cyclization
with loss of the dimethylamine as a better leaving group
to afford 18a and 18b as observed from their spectral
data. On the other hand, reaction of N,N-dimethyl
carbamoyl chloride 16 with o-aminothiophenol 9c gave S-
(2-aminophenyl)-N,N-dimethyl thiocarbamate 19, due to
the lone pair of the sulfur atom firstly attacking the
Chloroformamidinium salts 1a-e were prepared as
described previously described [12] and allowed to react
with o-substituted aniline derivatives 9 to afford the 2-
aminobenzoxazole, 2-aminobenzothiazole and 2-amino-
benzimidazole derivatives 13-15. Compounds 13-15 could
be formed by two alternative routes (A or B), depending
on the nucleophicity of the X substituent of 9. Route A, if
X is more nucleophilic than the anilino nitrogen atom, the
lone pair of X would first attack the central carbon atom
of the chloroformamidinium salts 1 displacing the
chloride ion to form intermediate 10 which then under-
goes the in situ heterocyclization with the loss of
dimethylamine as a better leaving group to afford the
expected product 15, as in the case of the reaction of o-
aminothiophenol 9c with the chloroformamidinium salts
1. Otherwise, route B, the lone pair of the anilino nitrogen
atom will first attack the central carbon atom of the

May-Jun 2006
Chloroformamidinium Salts: Efficient Reagents
601
Scheme II
A
Cl
XH
R3
R1
N
N
PF6
NH2
R2
R4
B
9
1
Et3N / DMF
R1
N R2
B
XH
NH
A
R1
N
R2
PF6
R4
X
PF6
X=NH, O
X= S
N R4
R4
N
NH2
R3
11
10
XH
R1
R1
R2
X
N
N
R2
C
N
N
R4
N
R4
N
H
R3
12
R3
X = NH, R1=R2=R3 =R4= CH3,12a
X = NH, R1=R2= CH3, R3,R4= (CH2)4, 12b
- R1R2NH
R3
X
N
- R1R2NH
N
R4
X= O; R3 = R4 = CH3; 13a
X= O; R3, R4 = (CH2)4; 13b
X= O; R3, R4 = (CH2)5; 13c
X=NH; R3= R4 = CH3; 14a
X=NH; R3, R4 = (CH2)4; 14b
X=NH; R3, R4 = (CH2)5; 14c
X= S; R3 = R4 = CH3; 15a
X= S; R3, R4 = (CH2)4; 15b
Scheme III
1
XH
H3C
Cl
CH3
O
N
NH2
2
9
16
Et3N
CH3
XH
2
1
X
N
O
CH3
NH
X=O, 9a; NH, 9b
O
X= S, 9c
CH3
N
NH2
17
H3C
19
CH3
X
X
O
X
-NHMe2
O
N
+
N
CH3
NH
N
H
N
CH3
CH3
X = O, 13a; X = NH; 14a
X
N
(minor)
OH
X = O, 18a; X = NH, 18b
(major)

602
A. El-Faham, M. Chebbo, M. Abdul-Ghani, and G. Younes
Vol 43
carbonyl carbon atom of 16 forming 19 as a major
product based on its spectral data (Scheme III).
The ir spectrum of 19 showed two absorption peaks at
3440 and 3340 cm-1 due to the -NH2 group, and an
absorption peak at 1660 cm-1 expected for the C=O
group. The 1H NMR spectrum showed a multiplet
(ꢀ=7.13-7.09), a doublet of doublets (ꢀ=6.72, Jortho=8.4
Hz, Jmeta=1.3 Hz), and a triplet of doublets (ꢀ=7.50,
Jortho=7.4 Hz, Jmeta=1.3 Hz) corresponding to the four
The ir spectrum of 18a showed two absorption peaks at
3500 and 1640 cm-1 corresponding to the hydroxyl and the
imine groups, respectively. The 1H NMR spectrum of 18a
showed a doublet of doublet (ꢀ=7.26, Jortho=7.2 Hz,
Jmeta=1.5 Hz) corresponding to the aromatic hydrogen in
the ortho position with respect to the oxygen atom. A
multiplet corresponding to the three aromatic hydrogen
atoms was also observed in the region ꢀ 7.16-7.03. The
hydrogen of the hydroxyl group was observed by a broad
singlet at ꢀ 3.48. The 13C NMR spectrum of 18a showed
the expected signals. The imine carbon was observed at ꢀ
155.05, while six signals corresponding to the six
aromatic carbons were located in the region ꢀ 143.53-
109.80. Mass spectral analysis of 18a showed an ion peak
at 135 amu corresponding to the molecular weight of 18a.
The ir spectrum of compound 18b showed one NH
absorption at 3170 cm-1 and strong absorption for the
carbonyl group at 1760 cm-1. Also the 1H NMR
spectrum was consistent with the suggested structure. A
singlet due to the hydrogen of the two NH groups was
observed at ꢀ 10.57. Another singlet assigned to the
four aromatic hydrogen atoms was observed at ꢀ 6.91.
The 13C NMR spectrum of 18b showed four resolved
carbon signals. The low-field carbon signal at ꢀ 154.12
was assigned to the carbonyl carbon. Three signals were
aromatic hydrogen atoms.
A singlet at ꢀ 5.26
corresponding to the two hydrogen atoms of the -NH2
group was observed. The two methyl groups were
observed as two 3-proton singlets (ꢀ=3.05 and 2.90).
The 13C NMR spectrum of 19 showed eight resolved
carbon signals. The carbonyl carbon signal was
observed at ꢀ 165.65, while six signals corresponding to
six aromatic carbon atoms were located in the region ꢀ
150.79-110.35. A signal for the two methyl groups was
observed at ꢀ 36.89. Mass spectral analysis of 19 gave
an ion peak at 196.15 amu corresponding to the
molecular weight of 19.
Chloroformamidinium salts (DmTCFH, 1c) and
(DmPCFH, 1d) also, reacted with 3-benzyl-2-hydrazino-
quinoxaline 3 and 1-hydrazinophthalazine hydrochloride
4 in the presence of triethyl amine as a base, to afford the
[1,2,4]triazolo derivatives 6 and 7, respectively in good
yield and purity (Scheme IV). These triazole derivatives
have been prepared previously [10], and formed due to
the strong tendency towards heterocyclization [11] and
Scheme IV
N
N
C6H5
NH2
C6H5
N
H
3
N
N
N
R4
N
R2
R4
R3
R1
R3
N
N
6
PF6
Cl
Et3N
N
N
R3
N
N
R1= R2 =CH3; R3,R4 = (CH2)4; 1c
R1= R2 =CH3; R3,R4 = (CH2)5; 1d
N
N
R4
4
N
NHNH2.HCl
7
R3,R4 = (CH2)4; 6a and 7a
R3,R4 = (CH2)5; 6b and 7b
observed in the aromatic region at ꢀ 128.02, 119.37 and
107.44 assigned each to the two quaternary, two ortho
and meta carbon atoms of the aromatic ring,
respectively. Mass spectral analysis of 18b gave an ion
peak at 134.05 amu, corresponding to the molecular
weight of 18b which is consistent with the assigned
structure.
substitution of the diemthylamine group which acted as
the better leaving group verified by their spectroscopic
data, mass spectra, and elemental analysis.
Conclusions.
We have successfully demonstrated the versatility of
chloroformamidinium salts 1a-e as useful reagents for the

May-Jun 2006
Chloroformamidinium Salts: Efficient Reagents
603
General Procedure for Preparation of Chloroformamidinium
salts (1) [12].
synthesis of 2-aminobenzoxazole 13, 2-aminobenzi-
midazole 14, and 2-aminobenzothiazole 15 derivatives as
well as [1,2,4]triazolo derivatives 6 and 7.
Oxalyl chloride (8.59 ml, 100 mmoles) was added dropwise
to a solution of urea derivative (100 mmoles) in dry CH2Cl2 (300
ml) at room temperature over a period of 5 min. The reaction
mixture was stirred under reflux for 3 hours, and then the
solvent was removed under reduced pressure. The residue was
washed twice with anhydrous ether (100 ml), and then flashed
with nitrogen to remove the excess of ether. The residue
obtained was dissolved in CH2Cl2, and a saturated aqueous
solution of potassium hexafluorophosphate (KPF6, 18.4 g, 100
mmoles) was added at room temperature with vigorous stirring
for 10-15 minutes. The organic layer was collected, washed once
with water (100 ml), dried over MgSO4 anhydrous, filtered, the
solvent removed under reduced pressure and the crude product
was recrystallized from CH2Cl2/ether.
EXPERIMENTAL
General.
Abbreviation used in the text: TCFH = 1,1,3,3-tetramethyl-
chloroformamidinium hexafluorophosphate; BTCFH = bis-
(tetramethylene)chloroformamodinium hexafluorophosphate;
BPCFH = bis-(pentaramethylene) chloroformamodinium hexa-
fluorophosphate DmTCFH = 1,1-dimethyl- 3,3-tetramethylene
chloroformamidinium hexafluorophosphate; DmPCFH = 1,1-
dimethyl-3,3-pentamethylene chloroformamidinium hexa-
fluorophosphate; DMF
= dimethylformamide; DCM =
dichloromethane; Et3N = triethylamine.
1,1-Dimethyl-3,3-tetramethylene-2-chloroformamidinium
Hexafluorophosophate (DmTCFH, 1c) [12c].
Column chromatography was performed using silica gel 60
obtained from Fluka Chemie (CH-9470, Mesh <230 ASTM). TLC
was performed using silica 8ꢀ4 cm plates from Albet using
suitable solvent systems with spots being visualized by a
Spectroline UV Lamp Model CM-10 (254 nm). All solvents used
for recrystallization, extraction, column chromatography and TLC
were commercial grade, and distilled before use. Melting points
were obtained in open capillary tubes using Gallenkamp Sanyo
melting point apparatus and were uncorrected. Infrared spectra (IR)
were recorded in KBr pellets on a Shimadzu 8300 series Fourier
Transformer Instrument. Ultraviolet (UV) spectra were taken with a
Helios ꢀ-Spectronic Unicam spectrophotometer using a quartz
sample cell of 1 cm path length. NMR spectra were recorded on a
Bruker Avance 300 MHz spectrometer at ambient temperature.
Tetramethylsilane (TMS) was used as reference for all NMR spectra
with chemical shifts reported as ppm relative to TMS. Mass spectra
(MS) [m/z (% rel. int.)] were recorded on Shimadzu GC-MS QP
5050 A spectrometer using electron impact (EI) at 70 eV. Elemental
analyses were carried out at the University of Cairo Microanalytical
Laboratories.
The product was obtained as a white solid in yield of 82%
(25.1 g), m.p. 118-119 ºC. 1H nmr (CD3CN): ꢁ 1.98-2.04 (p, 4 H,
2 CH2), 3.29 (s, 6 H, 2 CH3), 3.76-3.81 (t, 4 H, 2 CH2) ppm. 13C
nmr (CD3CN): 25.66, 44.09, 55.9, 155.95. ms: m/z 161 (M+)
163.10 (15.42, [M+2-PF6]+); 161.10 (44.38, [M-PF6]+); 70.10
(100, [M-C3H6NClPF6]+).
Anal. Calcd for C7H14N2ClPF6 (306.5): C, 27.56; H, 4.50; N,
9.29. Found: C, 27.40; H, 4.56; N, 9.13.
1,1-Dimethyl-3,3-pentamethylene-2-chloroformamidinium
Hexafluorophosphate (DmPCFH, 1d).
The product was obtained as a sticky solid in yield of 61%
(19.7 g). 1H nmr (CD3CN): ꢁ 1.68-1.79 (m, 6 H, 3 CH2), 3.27 (s,
3 H, 1 CH3), 3.28 (s, 3 H, 1 CH3), 3.65-3.68 (m, 4 H, 2 CH2)
ppm.
Anal. Calcd for C8H16N2ClPF6 (320.5): C, 29.95; H, 4.99; N,
8.73. Found: C, 30.15; H, 5.00; N, 8.91.
General Procedure for Reaction of (1a-e) with o-Substituted
Aniline.
General Procedure for Preparation of Urea Derivatives [12].
The salt 1a-e (5 mmoles) was added to a solution of o-
substituted aniline 9 (5 mmoles) and triethylamine (10 mmoles)
in DMF (10 ml) and the reaction mixture was refluxed for 16-24
h on a water bath. Afterwards, the mixture was left to reach
room temperature, and then poured into 50 ml of cold water. The
solid formed was collected by filtration and washed with water.
If precipitation did not take place, the aqueous solution was
extracted with dichloromethane (3x100 ml). The organic layer
was collected and washed with water (50 ml), saturated NaCl
(50 ml), dried MgSO4, filtered and then the solvent was removed
under reduced pressure. The crude product was recrystallized
twice from the indicated solvent.
N,N-Dimethyl carbamoyl chloride 16 (55.05 ml, 0.6 moles)
was added dropwise to a stirred mixture of a secondary amine
(0.5 moles) and triethylamine (69.6 ml, 0.5 moles) in dry
methylene chloride (400 ml) at 0 ºC. When the addition was
completed, the mixture was stirred overnight at room
temperature. The reaction mixture was then washed with water
(100 ml), 10% HCl (100 ml), saturated sodium carbonate
solution (100 ml), water (100 ml), and then saturated sodium
chloride (100 ml), dried over anhydrous Na2SO4, filtered, and
then the solvent removed under reduced pressure. The oily
residue product was purified by simple or vacuum distillation.
1,1-Dimethyl-3,3-tetramethylene Urea (DmTU) [12c].
2-(N, N-Dimethyl)amino benzoxazole (13a).
The product obtained as yellow oil in yield of 77.5%, b.p. 144
-147 ºC. 1H nmr (CDCl3): ꢁ 1.80-2.10 (m, 4 H, 2 CH2), 2.72 (s, 6
H, 2 CH3), 3.27-3.49 (m, 4 H, 2 CH2) ppm.
The product was obtained as a red solid in yield of 62% (0.5
g) from ethanol, m.p. 93-95 ºC. Rf: 0.84 (CH2Cl2/MeOH 9:1); ir
(potassium bromide): 3050-2850 (C-H), 1655 (C=N), 1590-1475
(C=C aromatic), 1270 (C-O), 1240 (C-N) cm-1. 1H nmr (DMSO-
d6): ꢁ 3.11 (s, 6 H, 2 CH3), 6.94-6.99 (t, 1 H, aromatic), 7.02-
7.14 (t, 1 H, aromatic), 7.23-7.26 (d, 1 H, aromatic), 7.35-7.38
(d, 1 H, aromatic) ppm. 13C nmr (DMSO-d6): ꢁ 37.58, 109.03,
1,1-Dimethyl-3,3-pentamethylene Urea (DmPU) [12c].
The product obtained as yellow oil in yield of 77.5%, b.p.
147-151 ºC. 1H nmr (CDCl3): ꢁ 1.47-1.48 (m, 6 H, 3 CH2), 2.72
(s, 6 H, 2 CH3), 3.07-3.09 (m, 4 H, 2 CH2) ppm.

604
A. El-Faham, M. Chebbo, M. Abdul-Ghani, and G. Younes
Vol 43
1
115.77, 120.29, 124.14, 143.85, 148.96, 163.02 ppm. ms: m/z
162 (M+): 163 (18.25, [M+1]+); 162.05 (100, [M]+); 161 (28.14,
M-H); 147.10 (49.05, [M-CH3]+); 132.80 (27.49, [M-C2H5]+);
119.80 (19.56, [M-C2H4N]+); 104.05 (19.93, [M-C2H4NO]+);
77.05 (17.24, [M-C3H5N2O]+); 55.10 (88.03, [M-C5H3N2O]+).
Anal. Calcd for C9H10N2O (162): C, 66.66; H, 6.17; N, 17.28.
Found: C, 66.81; H, 6.00; N, 17.46.
max =251 nm (ꢁ =8500); ꢀ max =289 nm (ꢁ =12250). H nmr
(DMSO-d6): ꢂ 1.92-1.96 (p, 4 H, 2 CH2), 3.41-3.45 (t, 4 H, 2
CH2), 6.85-6.87 (d, 2 H, aromatic), 7.12-7.15 (d, 2 H, aromatic),
11.10 (s br, 1 H, 1 NH) ppm. . 13C NMR (DMSO-d6): ꢂ 25.43,
47.71, 111.82, 119.90, 138.29, 154.06 ppm.
Anal. Calcd for C11H13N3: C, 70.58; H, 6.95; N, 22.45. Found:
C, 70.81; H, 7.20; N, 22.73.
2-Piperidin-1-yl-1H-benzoimidazole (14c).
2-Pyrrolidin-1-yl-benzoxazole (13b).
The product was obtained as a pale yellow solid in yield of
44% (0.4 g) from CH2Cl2/n-hexane, m.p. 143 ºC (dec). Rf: 0.37
(CH2Cl2/MeOH 9:1). 1H nmr (DMSO-d6): ꢂ 1.56-160 (m, 6 H, 2
CH2), 3.45-3.48 (m, 4 H, 2 CH2), 6.87-6.89 (d, 2 H, aromatic),
7.13-7.15 (d, 2 H, aromatic), 11.23 (s br, 1 H, 1 NH) ppm. ms:
m/z 201 (M+): 201.20 (36.27, [M]+); 200.20 (11.08, [M-H]+);
145.95 (38.60, [M-C4H7]+); 119 (14.57, [M-C5H8N]+); 104
(17.78, [M-C5H9N2]+); 55.10 (100, [M-C8H8N3]+).
The product was obtained as a reddish brown solid in yield of
70% (0.7 g) from CH2Cl2/n-hexane, m.p. 136-138 ºC. Rf: 0.75
(CH2Cl2/MeOH 9:1). UV/VIS (Ethanol): ꢀ max=210 nm (ꢁ
=20360); ꢀ max =249 nm (ꢁ =19310); ꢀ max=283 nm (ꢁ
=12060). UV/VIS (CH3CN): ꢀ.max=209 nm (ꢁ =23410); ꢀ
1
max=253 nm (ꢁ =18960); ꢀ max=286 nm (ꢁ =12330). H nmr
(DMSO-d6): ꢂ 1.91-1.99 (p, 4 H, 2 CH2), 3.51-3.55 (t, 4 H, 2
CH2), 6.93-6.99 (t, 1 H, aromatic), 7.08-7.14 (t, 1 H, aromatic),
7.23-7.26 (d, 1 H, aromatic), 7.36-7.38 (d, 1 H, aromatic) ppm.
ms: m/z 188 (M+): 189.25 (7.66, [M+1]+); 188.15 [50.72, [M]+);
187.15 (7.35, [M-H]+); 161.05 (4.63, [M-C2H3]+); 147.10 (4.70,
[M-C3H5]+); 133.05 (29.18, [M-C4H7]+); 120.05 (3.25, [M-
C4H6N]+); 83.90 (100, [M-C6H2NO]+); 77.05 (3.21, [M-
C5H7N2O]+); 70.05 (14.32, [M-C7H4NO]+); 55.10 (22.27, [M-
C7H5N2O]+).
Anal. Calcd for C12H15N3 (201): C, 71.64; H, 7.46; N, 20.89.
Found: C, 71.80; H, 7.69; N, 21.00.
2-(N, N-Dimethyl)aminobenzothiazole (15a).
The product was purified through silica gel column using
CH2Cl2/MeOH (9:1) as eluent, and the fractions with the same
Rf values were collected and the solvent was removed in vacuo
to give 0.4 g (44%) of the off-white solid, m.p. 90-92 ºC. Rf :
0.91 (CH2Cl2/ MeOH 9:1); ir (potassium bromide): 3050-2850
(C-H), 1600 (C=N), 1570-1550 (C=C aromatic), 1300 (C-N) cm-
Anal. Calcd for C11H12N2O (188): C, 70.21; H, 6.38; N, 14.89.
Found: C, 70.46; H, 6.20; N, 15.10.
2-Piperidin-1-yl-benzoxazole (13c).
1. H nmr (DMSO-d6): ꢂ 3.13 (s, 6 H, 2 CH3), 7.00-7.05 (t, 1 H,
1
aromatic), 7.22-7.27 (t, 1 H, aromatic), 7.41-7.44 (d, 1 H,
aromatic), 7.72-7.74 (d, 1 H, aromatic) ppm. 13C NMR (CDCl3):
ꢂ 40.50, 119.14, 121.00, 121.13, 126.30, 131.52, 153.64, 169.11
ppm. ms: m/z 178 (M+): 180.15 (4.59, [M+2]+); 179.10 (10.51,
[M+1]+); 178.10 (100, [M]+); 177.15 (4.52, [M-H]+); 163.05
(62.33, [M-CH3]+); 149.05 (89.76, [M-C2H5]+); 136.05 (35.53,
[M-C2H4N]+); 121.80 (1.26, [M-C3H6N]+); 107.85 (12.54, [M-
C3H6N2]+); 55.10 (5.13, [M-C5H3N2S]+).
The product was obtained as an orange solid in yield of 59%
(0.6 g) from ethanol, m.p. 75-77 ºC. Rf: 0.89 (CH2Cl2/MeOH
9:1). 1H nmr (DMSO-d6): ꢂ 1.58-1.61 (m, 6 H, 3 CH2), 3.58-3.59
(m, 4 H, 2 CH2), 6.98-7.00 (tt, 1 H, aromatic), 7.09-7.14 (tt, 1 H,
aromatic), 7.23-7.26 (ddd, 1 H, aromatic), 7.35-7.37 (dd, 1 H,
aromatic) ppm.
ms: m/z 202 (M+): 203.35 (11.58, [M+1]+); 202.2 (62.87,
[M]+); 201.05 (12.85, [M-H]+); 147.10 (35.44, [M-C4H7]+); 133
(18.06, [M-C5H9]+); 92 (11.40, [M-C6H10N2]+); 57.10 (100, [M-
C8H5N2O]+); 55.10 (90.68, [M-C8H7N2O]+).
Anal. Calcd for C9H10N2S (178): C, 60.67; H, 5.61; N, 15.73.
Found: C, 60.89; H, 5.43; N, 15.96.
Anal. Calcd for C12H14N2O (202): C, 71.28; H, 6.93; N, 13.86.
Found: C, 71.50; H, 6.85; N, 14.08.
2-Pyrrolidin-1-yl-benzothiazole (15b).
The product was purified through silica gel column using
CH2Cl2/MeOH (9:1) as eluent, and the fractions with the same
Rf values were collected and the solvent was removed in vacuo
to give 0.5 g (48%) of the off-white solid, m.p. 101-103 ºC. Rf:
0.89 (CH2Cl2/MeOH 9:1). UV/VIS (Ethanol): ꢀ max =225 nm (ꢁ
2-(N,N-Dimethyl)aminobenzoimidazole (14a).
The product was obtained as beige-brown crystals in yield of
47% (0.37 g) from CH2Cl2/n-hexane, m.p. 204 ºC (dec). Rf: 0.22
(CH2Cl2/MeOH 9:1); ir (potassium bromide): 3120 (NH), 3060-
2800 (C-H), 1645 (C=N), 1600-1575 (C=C aromatic), 1300 (C-
1
=24830); ꢀ max =271 nm (ꢁ =15160). H nmr (DMSO-d6): ꢂ
1
N) cm-1. H nmr (DMSO-d6): ꢂ 3.03 (s, 6 H, 2 CH3), 6.86-6.88
1.97-2.02 (p, 4 H, 2 CH2), 3.45-3.50 (t, 4 H, 2 CH2), 6.99- 7.04
(t, 1 H, aromatic), 7.22-7.27 (t, 1 H, aromatic), 7.42-7.45 (d, 1
H, aromatic), 7.72-7.74 (d, 1 H, aromatic) ppm. ms: m/z 204
(M+): 206.10 (5.07, [M+2]+); 205.10 (14.14, [M+1]+); 204.10
(100, [M]+); 203.10 (11.49, [M-H]+); 177.05 (11.75, [M-C2H3]+);
163 (10.87, [M-C3H5]+); 149 (64.77, [M-C4H7]+); 136 (6.87, [M-
C4H6N]+); 121.95 (1.42, [M-C5H8N]+); 107.95 (8.69, [M-
C5H8N2]+); 55.10 (2.70, [M-C7H5N2S]+).
(d, 2 H, aromatic), 7.13-7.16 (d, 2 H, aromatic), 11.22 (s br, 1 H,
1 NH) ppm. 13C nmr (CD3OD): ꢂ 39.03, 113.19, 121.67, 158.62
ppm. ms: m/z 161 (M+): 162 (5.22, [M+1]+); 161.10 (28.71,
[M]+); 160 (5.45, [M-H]+); 146.05 (24.84, [M-CH3]+); 132.05
(14.48, [M-C2H5]+); 119 (8.11, [M-C2H4N]+); 105 (5.62, [M-
C3H6N]+); 77.15 (6.58, [M-C3H6N3]+); 55.10 (100, [M-
C5H4N3]+).
Anal. Calcd for C11H12N2S (204): C, 64.70; H, 5.88; N, 13.72.
Found: C, 64.99; H, 5.61; N, 13.98.
Anal. Calcd for C9H11N3: C, 67.08; H, 6.83; N, 26.08. Found:
C, 67.31; H, 7.00; N, 26.32.
N''-(2-Aminophenyl)-N,N,N',N'-tetramethylguanidinium hexa-
fluorophosphate (12a).
2-Pyrrolidin-1-yl-1H-benzoimidazole (14b).
The product was obtained as a beige solid in yield of 43%
(0.35 g) CH2Cl2/n-hexane, m.p. 229 ºC (dec). Rf: 0.33 (CH2Cl2/
MeOH 9:1). UV/VIS (Ethanol): ꢀ max = 220 nm (ꢁ =22900); ꢀ
The product was obtained as a white solid in 34% yield (0.35
g), m.p. 124-125 ºC. Rf: 0.39 (CH2Cl2/ MeOH 9:1). ir

May-Jun 2006
Chloroformamidinium Salts: Efficient Reagents
605
(potassium bromide): 3480 (NH), 3390-3360 (NH2), 3050-2900
(C-H), 1640 (C=N), 1565-1510 (C=C aromatic), 1310 (C-N)
cm-1. 1H nmr (DMSO-d6): ꢀ 2.86 (s, 12 H, 4 CH3), 5.19 (s, 2 H, 1
NH2), 6.56-6.62 (t d, 1 H, aromatic), 6.74-6.80 (m, 2 H,
aromatic), 6.98-7.04 (t d, 1 H, aromatic), 9.03 (s br, 1 H, 1 NH)
ppm. 13C nmr (DMSO-d6): ꢀ 34.72, 116.32, 117.34, 119.86,
124.79, 127.76, 142.63, 160.09 ppm.
The product from the aqueous layer was obtained as a white
solid in yield 2% (0.2 g), m.p.155-157 ºC. Rf : 0.27 (CH2Cl2/
MeOH 9:1). 1H nmr (DMSO-d6): ꢀ 2.99 (s, 3 H, 1 CH3), 3.03 (s,
3 H, 1 CH3), 7.08-7.12 (m, 4 H, aromatic), 11.14 (s, 1 H, 1 NH)
ppm. This compound was identified as 2-(N,N-dimethyl)amino-
benzoimidazole 14a.
S-(2-aminophenyl)-N,N-dimethylthiocarbamate (19).
Anal. Calcd for C11H19 F6N4P (352.3): C, 37.51; H, 5.44; N,
15.90. Found: C, 37.69; H, 5.58; N, 16.13.
The product was obtained as white needles in 30 % yield (3
g), m.p. 62-64 ºC. Rf: 0.93 (CH2Cl2/MeOH 9:1); ir (potassium
bromide): 3440-3340 (NH2), 3080-2950 (C-H), 1660 (C=O),
N''-[(2-Aminophenylamino)-N,N-dimethyl-N',N'-tetramethylene-
guanidiniumhexa-fluorophosphate (12b).
1
1580-1480 (aromatic), 1260 (C-N) cm-1. H nmr (DMSO-d6): ꢀ
2.90 (d, 3 H, 1 CH3), 3.05 (d, 3 H, 1 CH3), 5.26 (s, 2 H, 1 NH2),
6.49-6.54 (t d, 1 H, aromatic), 6.71-6.74 (d d, 1 H, aromatic),
7.09-7.13 (m, 2 H, aromatic) ppm. 13C nmr (DMSO-d6): ꢀ 36.89,
110.35, 115.35, 117.17, 131.51, 138.01, 150.79, 165.65 ppm.
ms: m/z 196 (M+): 196.15 (11.10, [M]+); 104 (8.42, [M-
C6H6N]+); 72.05 (100, [M-C6H6NS]+); 55.05 (100, [M-
C5H5N2OS]+); 53.10 (3.79, [M-C5H7N2OS]+).
The product was obtained as an off white solid in 27% yield
(0.3 g), m.p. 134-136 ºC. Rf : 0.50 (CH2Cl2/ MeOH 9:1). 1H nmr
(DMSO-d6): ꢀ 1.85-1.87 (m, 4 H, 2 CH2), 2.72 (s, 3 H, 1 CH3),
2.84 (s, 3 H, 1 CH3), 3.44-3.46 (m, 4 H, 2 CH2), 5.17 (s, 2 H, 1
NH2), 6.56-6.62 (t d, 1 H, aromatic), 6.76-6.79 (d d, 1 H,
aromatic), 6.81-6.84 (d d, 1 H, aromatic), 6.98-7.04 (t d, 1 H,
aromatic), 8.81 (s br, 1 H, 1 NH) ppm.
Anal. Calcd for C9H12N2OS (196.3): C, 55.08; H, 6.16; N,
14.27. Found: C, C, 55.28; H, 6.19; N, 14.32.
Anal. Calcd for C13H21F6N4P (378.3): C, 41.27; H, 5.60; N,
14.81. Found: C, 41.43; H, 5.68; N, 14.99.
General Procedure for Reaction of 1a-e with Hydrazine
Derivatives.
General Procedure for the Reaction of N,N-Dimethyl Carbamoyl
Chloride with o-Substituted Aniline.
The salt 1a-e (5 mmoles) was added to a solution of hydrazine
derivatives (5 mmoles) and triethylamine (10 mmoles) in DMF
(10 ml) and the reaction mixture was stirred at room temperature
overnight. Afterwards, the mixture was left to reach room
temperature, and then poured into 50 ml of cold water. The solid
formed was filtered directly and washed with water. If
precipitation did not take place, the aqueous solution was
extracted with dichloromethane (3x100 ml). The organic layer
was collected and washed with water (50 ml), saturated NaCl
(50 ml), dried MgSO4, filtered and then the solvent was removed
under reduced pressure. The crude product was recrystallized
from the indicated solvent.
N,N-Dimethylcarbamoyl chloride 14 (5.5 ml, 60 mmoles) was
added to a mixture of o-substituted aniline 9 (50 mmoles) and
triethylamine (13.9 ml, 100 mmoles) in DMF (50 ml). The
reaction mixture was refluxed for 12-18 h. After cooling, the
reaction mixture was poured into 100 ml of water. The solid was
collected by vacuum filtration, and then washed with water. The
crude product was recrystallised from 1,4-dioxane. The aqueous
layer was extracted with 200 ml of CH2Cl2. Then the organic
layer was washed with 100 ml of water, dried over anhydrous
MgSO4. The solvent was removed under high pressure. The
crude product was crystallized from CH2Cl2/n-hexane.
Benzoxazol-2-ol (18a).
4-Benzyl-1-(N,N-dimethylamino)-[1,2,4]triazolo[4,3-a]quinoxaline
(6a) [10].
The product was obtained as brown solid in 15% yield (1 g),
m.p. 130-132 ºC. Rf : 0.66 (CH2Cl2/MeOH 9:1); ir (potassium
bromide): 3500 (-OH), 3100-3050 (C-H), 1640 (C=N), 1600-
1475 (C=C aromatic), 1310 (C-O), 1260 (C-N) cm-1. H nmr
(CDCl3): ꢀ 3.48 (s br, 1 H, 1 OH), 7.03-7.16 (m, 3 H, aromatic),
7.25-7.28 (d d, 1 H, aromatic) ppm. C-NMR (DMSO-d6): ꢀ
109.80, 110.20, 122.38, 124.22, 130.33, 143.53, 155.05 ppm.
ms: m/z 135 (M+): 135 (100, [M]+); 84 (19.53, [M-C4H3]+);
53.10 (11.08, [M-C3NO2]+).
Anal. Calcd for C7H5NO2(135.12): C, 62.22; H, 3.73; N,
10.37. Found: C, 62.34; H, 3.79; N, 10.49.
The product was obtained as an orange solid in 61% yield (0.9
g) from ethanol, m.p. 166-167 ºC. Rf: 0.83 (CH2Cl2/MeOH 9:1);
ir (potassium bromide): 3100-2900 (C-H), 1620 (C=N), 1540-
1
1
1500 (C=C aromatic), 1480 (-CH2-), 1300 (C-N) cm-1. H nmr
13
(DMSO-d6): ꢀ 2.93 (s, 6 H, 2 CH3), 4.48 (s, 2 H, 1 CH2), 7.20-
7.27 (t t, 1 H, aromatic), 7.29-7.32 (m, 2 H, aromatic), 7.45-7.48
(d d, 2 H, aromatic), 7.59-7.64 (td, 1 H, aromatic), 7.67-7.73 (td,
1 H, aromatic), 7.96-7.99 (dd, 1 H, aromatic), 8.41-8.45 (dd, 1
H, aromatic) ppm. ms: m/z 303 (M+): 304.15 (14.98, [M+1]+);
303.20 (61.11, [M]+); 302.20 (50.96, [M-H]); 274.05 (15.28,
[M-C2H5]+); 233.10 (19.64, [M-C3H6N2]+); 77.10 (7.05, [M-
C12H12N5]+); 55.15 (100, [M-C14H10N5]+).
1,3-Dihydrobenzoimidazol-2-one (18b).
The product was obtained as white crystals in 32% yield (2 g),
m.p. 240 ºC (dec). Rf: 0.50 (CH2Cl2/MeOH 9:1); ir (potassium
bromide): 3170 (NH), 3100-3050 (C-H), 1760 (C=O), 1630-
4-Benzyl-1-pyrrolidin-1-yl-[1,2,4]triazolo[4,3-a]quinoxaline
(6b)[10].
1
1480 (C=C aromatic), 1265 (C-N) cm-1. H nmr (DMSO-d6): ꢀ
The product was obtained as beige solid in 83% yield (1.4 g)
C from ethanol, m.p. 144-145 ºC. Rf : 0.86 (CH2Cl2/MeOH 9:1).
UV/VIS (Ethanol): ꢁ max =219 nm (ꢂ = 21050); ꢁ max=260 nm
(ꢂ=13410); ꢁ max =327 nm (ꢂ=5290). UV/VIS (CH3CN): ꢁ max
=207 nm (ꢂ=23560); ꢁ max = 258 nm (ꢂ=13020); ꢁ max =327
nm (ꢂ=4970); ir (potassium bromide): 3100-2860 (C-H), 1620
(C=N), 1525-1500 (C=C aromatic), 1460 (-CH2-), 1300 (C-N)
6.91 (s, 4 H, aromatic), 10.57 (s, 2 H, 2 NH) ppm. 13C NMR
(DMSO-d6): ꢀ 107.44, 119.36, 128.02, 154.12 ppm. ms: m/z 135
(M+): 135 (9.44, [M+1]+); 134.05 (100, [M]+); 132.95 (10.72,
[M-H]+); 53 (13.64, [M-C3HN2O]+).
Anal. Calcd for C7H6N2O (134.14): C, 62.68; H, 4.51; N,
20.88. Found: C, 62.79; H, 4.59; N, 21.00.

606
A. El-Faham, M. Chebbo, M. Abdul-Ghani, and G. Younes
Vol 43
cm-1. H nmr (CDCl3): ꢀ 2.07-2.12 (p, 4 H, 2 CH2), 3.51-3.55 (t,
4 H, 2 CH2), 4.59 (s, 2 H, 1 CH2), 7.21-7.23 (m, 1 H, aromatic),
7.27-7.32 (m, 2 H, aromatic), 7.53-7.57 (m, 2 H, aromatic),
7.64-7.66 (m, 2 H, aromatic), 8.00-8.04 (m, 1 H, aromatic),
8.36-8.39 (m, 1 H, aromatic) ppm. 13C nmr (CDCl3): ꢀ 24.75,
40.24, 51.91, 116.00, 126.73, 126.77, 128.15, 128.40, 129.60,
129.75, 136.44, 136.70, 142.89, 154.50, 155.50 ppm. ms: m/z
329 (M+): 330.25 (7.49, [M+1]+); 329.25 (26.85, [M]+); 328.20
(14.96, [M-H]+); 302.25 (9.58, [M-C2H3]+); 274.20 (14.33, [M-
C4H8]+); 232.20 (13.43, [M-C5H9N2]+); 219.10 (7.05, [M-
C5H8N3]+); 83.95 (100, [M-C15H9N4]+); 70.10 (33.38, [M-
C16H11N4]+); 55.10 (40.39, [M-C16H12N5]+).
1
REFERENCES
[1] H. Suter and H. Zutter, Helv. Chim, Acta., 50, 1084
(1967)
[2a] S. J. Hays, M. J. Rice, D. F. Ortwine, G. Johnson, R. D.
Schwartz, D. K. Boyed, L. F. Copeland, M. G. Vartanian, and P. A.
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M. Barreau, J. C. Blanchard, A. Boireau, Y. Bour, M. A. Coleno, A.
Doble, G. Doerflinger, C. D. Huu, M. H. Donat, J. M. Duchesne, P.
Ganil, C. Gueremy, E. Honore, B. Just, R. Kerphirique, S. Gontier,
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C, Nemecek, P. M. Pasquet, O. Piot, J. Pratt, J. Rataud, M. Reibaud,
J. M. Stutzmann, and S. Mignani, J. Med. Chem., 42, 2828 (1999);
[c] Y. He, A. Benz, T. Fu, M. Wang, D. F. Covey, C. F. Zorumski,
and S. Mennick, Neuropharmacology, 42, 199 (2002).
[3] S. N. Sawhney, S. K. Arora, J. V. Singh, O. P. Bansal,
and S. P. Singh, Indian J. Chem.,16, 605 (1978)
3-Pyrrolidin-1-yl-[1,2,4]triazolo[3,4-a]phthalazine (7a) [10].
The product was obtained as deep yellow solid in 66% yield
(0.8 g) from CH2Cl2/n-hexane, m.p. 119 ºC (dec). Rf: 0.65
(CH2Cl2/MeOH 9:1); UV/VIS (Ethanol): ꢁ max = 217 nm (ꢂ =
25590); ꢁ max = 278 nm (ꢂ = 20170); ꢁ max = 321 nm (ꢂ =
4420);ir (potassium bromide): 3100-2880 (C-H), 1610 (C=N),
[4] G. Bensimon, L. Lacomblez, and V. Meininger, New
Engl. J. Med., 330, 585 (1994)
[5] G. Foscolos, G. Tsatsas, A. Champagnac, and M.
Pommier, Ann. Pharm. Fr., 35, 295 (1977)
1590-1550 (C=C aromatic), 1475 (-CH2-), 1340 (C-N) cm-1. H
1
nmr (DMSO-d6): ꢀ 2.02-2.06 (p, 4 H, 2 CH2), 3.82-3.87 (t, 4 H,
2 CH2), 7.96-8.07 (m, 2 H, aromatic), 8.14-8.18 (d, 1 H,
aromatic), 8.32-8.36 (d, 1 H, aromatic), 8.99 (s, 1 H, 1 CH) ppm.
13C nmr (DMSO-d6): ꢀ 22.88, 47.75, 119.27, 120.52, 121.49,
127.49, 130.83, 132.88, 137.20, 143.54, 146.45 ppm. ms: m/z
239 (M+): 239.15. MS (EI): 239.15 (5.06, [M]+); 184.15 (7.13,
[M-C4H7]+); 169.10 (7.14, [M-C4H8N]+); 57.15 (100, M-
C9H4N5]+); 55.10 (49.81, [M-C9H6N5]+).
[6] V. G. Shirke, R. P. Bhamaria, B. G. Khadse, and S. R.
Sengupta, Indian Drugs, 27, 350 (1990)
[7] C. J. Paget, K. Kisner, R. L. Stone, and D. C. Delong, J.
Med. Chem., 12, 1016 (1969)
[8a] H. Hugerschoff, Chem. Ber., 34, 3130 (1901); [b] H.
Hugerschoff, Chem. Ber., 36, 3121 (1903); [c] J. M. Sprague, A. H.
Land (Eds), In Heterocyclic Compounds, R. C. Elderfield, J. Wiley,
New York, 1957, Vol. 5, Chapter 8, pp 484-721.
[9] A. D. Jordan, C. Luo, and A. B. Reitz, J. Org. Chem., 68,
8693 (2003)
3-Piperidin-1-yl-[1,2,4]triazolo[3,4-a]phthalazine (7b) [10].
[10] M. Abdul-Ghani, Sh. N. Khattab, A. M. El-Massry, A.
El-Faham, and Adel Amer, Org. Prep. Proced. Int., 36, 121 (2004)
[11] E. W. Douglas and S. Hamilton, J. Org. Chem., 67, 7553
(2002).
[12a] A. El-Faham, Chemistry Lett., 671 (1998); [b] A. El-
Faham, Org. Prep. Proced. Int., 30, 477 (1998); [c] L. A. Carpino
and A. El-Faham, J. Am. Chem. Soc., 117, 5401 (1995); [d] A. El-
Faham, Sh. N. Khattab, M. Abdul-Ghani, and F. Albericio, Eur. J.
Org. Chem., In press.
The product was obtained as yellow solid in 70% yield (0.9 g)
from ethanol, m.p. 130 ºC. Rf: 0.61 (CH2Cl2/MeOH 9:1). 1H nmr
(DMSO-d6): ꢀ 1.60 - 1.67 (m, 6 H, 3 CH2), 3.47-3.5 (t, 4 H, 2
CH2), 7.77-7.82 (t, 1 H, aromatic), 7.91-7.96 (t, 1 H, aromatic),
8.05-8.08 (d, 1 H, aromatic), 8.31-8.34 (d, 1 H, aromatic), 8.83
(s, 1 H, 1 CH) ppm. 13C NMR (DMSO-d6): ꢀ 21.83, 22.80,
46.90, 119.48, 120.30, 121.32, 126.79, 128.36, 131.98, 138.44,
144.48, 150.78 ppm.