Synthesis and Spectral Investigation of Heterocycles
Containing
Di and Tri- Heteroatoms
Dr. Nagham Mahmood Aljamali1* , Dr. Shireen Ridha Rasool2,
Rana Neama Atiya3
1Assist. Professor, Dept. of Chem., Educt. College, Kufa Univ., Iraq
2Lecturer, Dept of Chem., Science College, Babylon Univ., Iraq
3M.Sc.,
College of Pharmacy, Univ. Kufa, Iraq
*Corresponding Author E-mail: dr.nagham_mj@yahoo.com
ABSTRACT:
The aim of this work , synthesis
of mono cycles containing di and tri-hetero atoms from((N, S ,O and Se)
via reaction between di ester
compounds with di hetero atoms compounds like ( alkyl di
amine, ethylene glycol ,ethylene di thiol, sodium hydro selenium with di
chloro ethylene )., and synthesis some of them via reaction of di
carbonyl compounds with di hetero atoms
compounds to give cycles included
two or more heteroatoms (N, S ,O and Se) by
several steps via condensation
reactions. All formatted compounds have been investigated using
several spectral techniques (elemental analysis (C.H.N), 1H.NMR–spectra
, FT.IR–spectra) and measurement of melting points.
KEYWORDS: alkyl di amine , tri heteroatoms,
sodium hydride , alkyl dichloride.
INTRODUCTION:
Heteroatoms compounds are
essential to life in various field, because of variety of microbial activities
associated with structure of these compounds, which considered as intermediate of many reactions and
synthesis of new compounds..
Some of these compounds which containing
sulfur or nitrogen atom were used as analgesic and in other medicinal applications(1-5).
Heteroatom–epane and epine
compounds are one a class of organic heterocyclic compounds containing a six or
seven-member saturated and unsaturated ring structure composed of two heteroatoms (selenium , sulphur, nitrogen , oxygen), which
are named by addition of suffix (-epane) such as (selenepane, thiepane, azepane, oxepane) in this paper,
some of these compounds contain two lactam groups
which explain their biological applications(6-12)and pharmaceutical drugs,these activities due to the presence of (-N=C–S)
moiety and lactam cycle in these compounds .
So many attempts were carried out every where to incorporate structural
modification in order to get compounds of potential activity.
These properties predetermine them inter alia for the preparation of
wide spectrum of medicinal drugs(13-18)
.
EXPERIMENTAL:
All chemical used were supplied from Fluka and BDH – Chemical Company
Apparatus: All measurements were carried out by Melting
points: electro thermal 9300, melting point engineering Ltd., U.K., FT.IR-spectra: Fourier Transform Infrared Shimadzu 8300–(FT.IR),
KBr disc was performed by CO.S.Q.C. Iraq, Elemental
Analysis (C.H.N): EA-017, H.NMR-spectra: (300MHZ) in DMSO as solvent.
Synthesis of hetro atoms –epane cycles
compounds [1-4]:
A mixture of (0.01mole, 1.6g) of diethyl malonate was refluxed with one of compounds
[(0.01mole,0.6g) of ethelynediamine, (0.01 mole,
0.94g) of ethylenedithiol, (0.01mole, 0.62g) of
ethylene glycol] respectively for (2hrs), the precipitate was filtered off and recrystallized to produce (86%, 84%, 87%) of compounds [1-3]
respectively .While (0.01 mole , 1.6 g ) of diethyl malonate
was reacted with (0.02mole, 2.05g) of NaHSe, the
precipitate was filtered off then (0.01mole, 2.73g) from this precipitate was reacted with (0.01mole, 0.99g)
of ethylene dichloride ,the precipitate was filtered off and recrystallized to produce 86% of compound [4]:
Compound [1]: 1,4-diazepane -5,7-dione .
Compound [2]: 1,4-dithiepane-5,7-dione .
Compound [3]: 1,4-dioxepane-5,7-dione.
Compound [4]: 1,4-diselenepane-5,7-dione.
Reaction Scheme (1): synthesis of compounds [1-5]
Synthesis of 2,2-(ethane-1,2-diyl)bis(4H-1,3,4-thiadiazine-5(6H)-one) [6]:
A mixture of (0.01 mole, 1.74 g) of diethylmalate and (0.02 mole, 0.64 g) of hydrazine were
refluxed for (2 hrs ) , after cooling , the
precipitate was filtered off, then (0.01 mole, 1.46 g) from this precipitate[5]
was reacted with (0.02 mole, 2.21 g) of thi acetyl
chloride by cyclocondensation, after cooling, the
precipitate was filtered off and recrystallized to produce 87% of compound [6].
Synthesis of 1-(2-benzo[d]thiazol-2-ylthio)-1,4-diazepane–2,5-dione) [7-9]:
(0.01 mole,
1.67 g) of 2-thiolbenzothiazol was condensed with (0.01 mole , 0.79 g) of
2-aminoethylene chloride in filtered off, then (0.01 mole, 2.1g) of this
precipitate [7] was reacted with (0.01 mole, 0.93 g) of amino acetoyl chloride for (2hrs ) refluxing, the
precipitate filtered off , then (0.01
mole, 1.9 g) of compound [8] was cyclized with (0.01
mole ,1.6 g) of diethyl malonate upon heating, the
precipitate was filtered off and recrystallized to give 83% of compound [9]
Synthesis of 5,7-(diphenyl)2,4-dihydro-1,4-thiazepine [10] :
(0.01 mole, 1.68g) of dibenzoylmethylen
was reacted with (0.01 mole, 0.7g) of thiol amino
ethylene in refluxing absolute ethanol , the precipitate formed and filtered
off , recrystallized from ethanol to yield 85% of
compound [10]
Synthesis of 3-methyl-6-tolyl-2,7-dihydro-1,4,5-thidiazepine
[ 11 ,12]:
Compound[12] was also formed
by heating of (0.01 mole, 1.6 g) of toluiyl chloride
with (0.01 mole, 0.9g) of thio acetone for (2hrs) in
presence of ethanol, after cooling , the precipitate [11] was filtered off,
then (0.01 mole, 2.2g) of this precipitate [11] was cyclised with (0.01 mole,
0.32g) of hydrazine, the precipitate was filtered off and recrystallized
to produce 86% of compound [12].
Reaction Scheme (2 ):
synthesis of compounds [6-12]
RESULTS AND DISCUSSION:
This research contained synthesized two series, one
series synthesized from treatment of diethyl malonate
with ethylene dihetro atom derivatives gave 1,
4-diepane.5, 7-dione derivatives (1-4) as shown in schem
(1) in (84-87)%. The structures of these products
[1-12] were established from their melting points and spectroscopic methods (FT.IR-
spectra, (C.H.N)-analysis
H.NMR-spectra):
FT.IR-Spectra: All FT. IR spectra
showed in figure (1-6). All the I.R spectra showed a peak at (1660-1710) cm-1
which appeared due to carbonyl group (-C=O) stretching. In compound [1] the
FT.IR-spectra showed a peak at (3276) cm-1 due to amide group. while the (C-S)(14) stretching in compound [2]
showed at (663) cm-1.The compound [3] showed peak in (1166) cm-1
due to (C-O) stretching. In compound [4] showed peak in (1610) cm-1
due to (C-Se) (14).
The two series
contained synthesized compounds [6, 9, 10 and 12 ] as shown in scheme (2) in
(87 , 83 , 85 and 86) % respectively .the structures of these products were
established from their spectroscopic
methods (FT.IR- spectra, (C.H.N)-analysis H.NMR-spectra): all the I.R-spectra
showed a peak at (1681-1685) cm-1 due to carbonyl group in compounds
[6,9] .while the (N-H) stretching(14-16) showed at (3340-3355) cm-1
in compounds [6,9] .the (C=N) stretching showed in (1537-1615) cm-1
in compounds [6,10 and 12] and (CH=CH) at (3080) cm-1in compound [10
].while other peaks explain in table (1).
Table (1): FT.IR data (cm-1) of compounds
[1-12]
|
Comp
No.
|
Structural
formula
|
|
-CO-S
|
|
|
N-H
|
C-S
|
C-Se
|
C=N
|
|
[1]
|
|
1695
|
---
|
----
|
-----
|
3276
|
----
|
----
|
----
|
|
[2]
|
|
----
|
1660
|
-----
|
----
|
----
|
663,
1436
|
-----
|
----
|
|
[3]
|
|
----
|
----
|
1711
|
-----
|
----
|
----
|
----
|
----
|
|
[4]
|
|
----
|
----
|
-----
|
1686
|
-----
|
----
|
1610
|
----
|
|
[6]
|
|
1685
|
-----
|
------
|
-----
|
3355
|
661
|
-----
|
1460
|
|
[9]
|
|
1681
|
-----
|
-----
|
-----
|
3340
|
682
|
-----
|
1537
|
|
[10]
|
|
-------
|
-----
|
-----
|
-----
|
-------
|
642
|
-----
|
1615
|
|
[12]
|
|
----
|
-----
|
-----
|
----
|
-----
|
-----
|
-----
|
1615
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Fig
(1): FT.IR- Spectra of Compound [ 1 ]
Fig
(2): FT.IR- Spectra of Compound [ 2 ]
Fig
(3): FT.IR- Spectra of Compound [ 6 ]
Fig
(4): FT.IR- Spectra of Compound [ 9 ]
Fig
(5): FT.IR- Spectra of Compound [ 10 ]
Fig
(6): FT.IR- Spectra of Compound [ 12 ]
Fig
(7): 1H.NMR - Spectra of Compound [ 1
]
1H.NMR- Spectrum : all the 1H.NMR-Spectra
showed in figures (9-11) and table (2) .all the H1.NMR-Spectra of diepane compounds[1-4] by the presence of protons at
(9.32-9.9)ppm
since the proton of (N-H) of amide group .the CH2 protons in
compounds[1-4] showed singlet signal within the region (4.3-4.9)ppm .the four
protons of (CH2-S) endo cyclic(14) showed singlet signal in the region (3.35)ppm .the protons of CH2 in (S-CH2-CH2-N)
group showed two bands ,one band showed triplet signals within the region
(3.5-3.8)ppm due to (S-CH2) group in
compounds[9,10] .The (CH2) protons in (-CH2-CH2-)
group exocyclic showed singlet signals in the
region 2.3 ppm
.,Table (2) and figures (7-11).
Table(2):1H.NMR-data(ppm) of compounds[1-12]
|
Comp. No.
|
(NH-CO-)
|
(S-CH2)
|
(Se-CH2)
|
(O-CH2)
|
N-CH2CH2-
|
(C=CH) Alkene
|
Phenyl rings
|
|
[1]
|
9.32
|
----
|
---
|
---
|
4.62
|
---
|
----
|
|
[2]
|
----
|
4.3
|
----
|
----
|
----
|
---
|
-----
|
|
[3]
|
---
|
----
|
----
|
4.73
|
-----
|
---
|
-----
|
|
[4]
|
----
|
----
|
4.90
|
----
|
---
|
---
|
----
|
|
[6]
|
9..82
|
----
|
----
|
----
|
3.35
|
---
|
7.267
|
|
[9]
|
9.96
|
----
|
--
|
----
|
3.55
|
----
|
7.26 ,7.79
,7.82
|
|
[10]
|
----
|
-----
|
----
|
----
|
3.80
|
1.95
|
6.34 , 6.37
,7.26
|
|
[12]
|
---
|
3.65
|
----
|
---
|
---
|
----
|
6.34 , 6.37
,7.26
|
Fig
(8): 1H.NMR - Spectra of Compound [ 3
]
Fig
(9): 1H.NMR - Spectra of Compound [ 4
]
Fig
(10): 1H.NMR - Spectra of Compound [ 6
]
Fig
(11): 1H.NMR - Spectra of Compound [ 9
]
(C.H.N)– Analysis :
(C.H.N)-analysis ,from compared the calculated data with found data of
these compounds , the results were comparable, the data of analysis, and
physical properties are listed in
table(3) .
Table (3) :melting points, M.F & (C.H.N)–Analysis of
compounds[1-12]
|
Comp. No.
|
M.F
|
M.p(C°)
|
Calc./ Found C%
|
H%
|
N%
|
|
[1]
|
C5H8N2O2
|
198
|
46.875 /46.718
|
6.290 /
6.122
|
21.860 /
21.734
|
|
[2]
|
C5H6O2S2
|
224
|
37.020
/ 36.958
|
3.730 /
3.617
|
------
|
|
[3]
|
C5H6O4
|
215
|
46.160 /
46.107
|
4.650 /
4.506
|
------
|
|
[4]
|
C5H6O2Se2
|
236
|
23.460 /23.316
|
2.360 /
2.225
|
------
|
|
[6]
|
C8H10N4O2S2
|
178
|
37.200 / 37.096
|
3.900 /
3.724
|
21.690 / 21.626
|
|
9]
|
C14H15N3O2S2
|
223
|
52.320 /52.057
|
4.700 /
3.982
|
13.070 / 12.904
|
|
[10]
|
C17H15NS
|
220
|
76.940
/ 76.837
|
5.700 / 5.489
|
5.280 / 5.115
|
|
[12]
|
C12H14N2S
|
215
|
66.020 / 65.909
|
6.460 / 6.284
|
12.830 / 12.677
|
CONCLUSION:
All results of spectral studies are evidences of
synthesized compounds via shift of frequency of some bands of reactant
compounds and formation of other bands in formatted compounds.
ACKNOWLEDGEMENT:
I would like to express my thanks for Mr. Audaiin Jordan for providing
{(C.H.N)-element analytical
,H.NMR-spectra and Melting points} and Zaidan Company
for supplied of materials.
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