Synthesis of Various
–Membered Rings from (aze-cycles)
Dr. Nagham Mahmood Aljamali
Assistant Professor,
Chemistry Department, Kufa University, Iraq
*Corresponding Author E-mail: Dr.Nagham_mj@yahoo.com
ABSTRACT:
Series compounds
containing heterocyclic compounds (various membered
ring) and formazane have been synthesized in present
work. Some of these compound used imine and amino
compounds as starting materials in their synthesis like compounds [1-4] to
prepare cycles. This work involved , synthesis of oxazepine
compounds [9] as (seven–membered ring), which is used
in synthesis of tri azeocine compounds [10] as
(eight–membered ring), bi cyclic compounds [11] , di azepine compounds [12,13], di azetidine–thione and di azrine as (four or (three–membered ring) linked . with di azepine (seven–ring) like compounds [13 , 15] , formazane (azo –imine ) like compounds [6 , 22] .
The structure of
these compounds were characterized by (H.NMR, FT.IR, C.H.N) –Techniques and
their melting points.
KEYWORDS: Various–membered
, various rings , various cycles.
INTRODUCTION:
A large number of heterocycles have been synthesized and studied for their
interesting and important properties in a several fields(1-3) .
Heterocyclic compounds are very widely distributed in nature and are essential
to life in many applications(4,5) .
In this study,
(three, Four, five, six, seven, eight)–membered ring
and bicyclic ring system containing at least two or
more of different kinds of hetero atoms in ring (Sulfur, Nitrogen, Oxygen).
Which have numerous pharmaceutical
activities like antimicrobial(6) , antidiabetic,
anticancer, antioxidant, treatment of various diseases(7,8), some of
them are used for thyroid drugs and leukemia, antihyperlipidemic
activity, anti–HIV agents(9) and large number of synthetic drugs and
dyes included hetero cyclic ring systems which consider important intermediate
in synthesis(10-14) .
Formazane compounds contain of
imine compound on the other hand , the incorporation
of imine compound with azo
compound at same carbon atom of imine group which
give compound named (formazane compound)(15),
these compounds involved any imine compounds bearing azo group.
EXPERIMENTAL:
Melting point were
recorded with–stuart melting point apparatus and were
uncorrected. Infra red spectra (FT.IR) were recorded on Shimadzu FT.IR -8300 spectro photometer, H.NMR spectra were recorded on a
Bruker-400 MHZ –Operating at 300 MHZ with tetramethylsilane
as internal standard in DMSO –d6 as a solvent , measurements were made in
Malaysia. Element Analysis (C.H.N) was carried out in Malaysia. Thin layer
chromatography (TLC) was carried out by using alumina plates percolated with
silica –gel, supplied by Merck Comp. spots were detected with iodine vapour.
Synthesis of
compounds [1-4] :
A mixture of p–hydroxybenzaldehyde (0.02 mole) anddichloro methylene (0.01 mole) was refluxed for (4hrs) , then the precipitate was
filtered off and re crystallized to yield 80% of compound [1] , which (0.01 mole) reacts with p–formal diazonium
salt to produce 88% of compound [2] , which (0.01 mole)
refluxed with hydrazine (0.03 mole) for (3hrs) with
drops of glacial acetic acid , after precipitate dried to give 83% of compound
[3] , which (0.01 mole) reacts with oxalic acid (0.03
mole) to give cyclic compound 84% of compound [4] .
Synthesis of
compounds [5-7] :
To P–methoxybenzaldehyde (0.02 mole)
dissolved in absolute ethanol , hydrazine hydrate (0.01 mole)
was added with stirring and the mixture was refluxed for (3hrs) then filtered ,
dried and re crystallized from ethanol
to give 81% of compound [5] . According to procedure(15) to synthesis formazane
derivatives [6] by reaction compound [5] with P–methyl phenyl diazonium salt to yield 91% of compound [6] which named formazane derivative , while (0.01 mole)
of compound [5] reacts with (0.02 mole) of malonic acid to produce 86% of seven –membered
ring from compound [7] according to procedure(15) .
Synthesis of
compounds [8-11] :
The equimolar mixture of benzaldehyde
(0.01 mole ) and P –toluidine
. in absolute ethanol was refluxed for (3hrs) in present of drops of glacial
acetic acid, after filtered and dried with re crystallized from ethanol to give
81% of compound [8], which (0.01 mole) refluxed with
(0.01 mole) of maleic
anhydride in dry benzene. To give 80% of compound [9], which (0.01) mole reacts
with (0.01 mole) of hydrazine according procedure(15).
To yield eight–membered ring 79% of compound
[10] , which reacts with oxalic acid to produce bi cyclic compound
82% from compound [11] .
Synthesis of
compounds [12, 13]:
A mixture of compound [9] andthiosemicarbazide
(equimolar) was refluxed for (8hrs) with stirring,
the precipitate filtered and dried to give 84% of diazepine
derivative of compound [12] , which cyclized with dichloro methylene to give four –membered ring 81% of
compound [13] .
Synthesis of compounds [14,15] :
The aquimolar of
compound [9] (0.01 mole) with glycine was
refluxed with stirringby using mechanical stirring,
the precipitate was filtered off and re crystallized to give 84% of compound
[14], which cyclized with hydrazine to produce three–membered ring 81% of
compound [15] .
Synthesis of compound
[16, 18]:
Equimolar mixture of melamine
(0.01 mole)
and benzaldehyde was refluxed for (3hrs) in
presence of absolute ethanol with stirring to give 86% of compound [16], which reacts with cystaine acid to produce 79% of compound [17], which (0.01 mole) reacts with
(0.03 mole) of succinic
acid to produce many of rings in same
compounds (five and eight–membered ring) 79%
of compound [18].
Synthesis of compounds [19-22]:
According to
procedure(15), (0.01 mole) of melamine dissolved in (3ml) of
hydrochloric acid with sodium nitrite to give diazonium
salt ,named compound [19], which added
to (0.03 mole) of [(P–methyl phenyl)–benylidine or P–tuluidine]
respectively to produce formazane(15) derivatives
of compounds [20 ,22] respectively.
Compound [20] was cyclized in presence of copper
acetate to produce 81% of compound [21].
Scheme of Reactions:
RESULTS AND DISCUSSION:
Various
compounds are used as starting material to synthesis (3,4,5,6.7.8)–membered ring like (imine compounds, hydrazo imine , oxazepine , …) in
synthesis of di azepine
(seven membered ring) di azirine (three membered ring), di azetine (four membered ring), thiazocineand tri
azocine (eight membered
ring), tri azolandpyrazole (five membered
ring) , bi cycle compounds like compound [9] and compound [18] .
Formazane is one of synthesized compounds in this paper named
compound [6] and compound [22] which contain azo
group linked with imine group at same carbon atom of imine group in same compound. All synthesized compounds
[1-22] have been characterized by their melting points and spectroscopic
methods like (FT.IR) and (C.H.N) –analysis and some of them by ('H.NMR)
–spectra.
FT.IR –spectra, showed an absorption band
at (1710 , 1612) cm-1 due to carbonyl group of aldehyde
in compounds [1,2] respectively, which disappeared and other bands appeared at
(1629)cm-1 due to (CH =N) imine group in
compound [3] and bands at [1685 to
(–CO–NH) ., 3280 to(-NH) of amid., (1240) to
(-N –N =C-)endo cycle(16) ofpyrazole) in
compound [4] .
Absorption band at [1640 to (C=N) imine group and(1460 , 1438) to azo group )(15)
at same compound [6]., bands at (1720 to (CO-) carbonyl of ketone , (C=N –N-)endo cycle:
1265 cm-1) in compound [7]., band at (1638 to CH=N imine group ) in compound [8] , which disappeared and
others bands appeared like [1690 to (–NH–CO-)lactame
and 1725 to (–CO–O-) lactone]
in compound [9] oxazepine., bands at (1695 to –CO –NH
and -HN –NH- in tri azocine
cycle: 3280) in compound [10] which disappeared and other bands appeared like
(1689 cm-1 to CO –N) in compound [11] ., (1695 to –CO –N- , 3455 and
3299 to NH2 , 1305 to C=S ) in compound [12]., (1320 to C=S, 3295 to
NH in compound [13]., [1725 to (–CO–O-)
carbonyl of carboxyl group, 3470 cm-1 to (-OH) of carboxyl group ] in compound [14]
which disappeared and other bands appeared like [1288 to (N–N=C-) endo cycle of di azirine, 3295 to (-NH)] in compound [15]., [1630 cm-1
to (CH=N) imine group, ( 3390 and 3360) to( NH2)
amine, (N–C=N)- endo
cycle of melamine: 1240] in compound [16], (2570 to –SH thiol(17),
1690 to –CO –N- amide., 3392 and 3360 to NH2 imine
group, 1245 to N–C=N- endo cycle of melamine) in compound [17]., [1322 to(15)
(S –CH2), 490 to(16)(C–S), 1698 to (–CO–N-) amide,
1240 cm-1(–N–N=C)- endo cycle of melamine]
in compound [18]., [(1480 and 1537) to (–N=N-) azo
group, (3453 and 3312) to (–NH2)
imine group] in compound [20], which disappeared and
other band appeared at 1608 to (C=N–N–N) of tri azole(15)
. cycle in compound [21]., [1634 to (C=N) imine group
linked(15) with (–N=N-) azo group at 1433
and 1488 due to formation of formazane compound in
compound [22]., and other data in table (1) 'H.NMR –spectrum showed signal at
(8.89) due to (CH=N) proton of imine group in
compound [5] which disappeared, this due
to formation formazane. compound in compound [6].,
signals ( 3 to (N–CH–N) proton(15) of tri azocine
cycle., (3.5 and 3.6) to (–CO–CH2–CH2–CO)
in same cycle ) in compound [11] ., signals at ( 3.5 and 3.65 to (CO–CH2–CH2–CO)
, 3.0 to (N–CH–N )proton of di azepine cycle, 4.0 to(NH–CH2–N) proton of di azetidine cycle ) in
compound [13] ., signals at (3.0 and 3.4) to (CO–CH2–CH2–CO)
, 4.2 to
(N–CH–N) , (4.6, 4.7, 4.85 ) protons(15) of (N–CH–CH2–CH2–S) of thiozocane cycle) in
compound [18]., signal at (8.3 to (NH2) proton of amine group
in compound [20] which disappeared
in compound [21]., and other peaks shown
in table (2) .
Their (C.H.N) –analysis and melting
points, it was found from compared the calculated data with experimentally data
of these compound, the results compactable, the data of analysis, M.F and
melting points are listed in table (3) .
ACKNOWLEDGEMENT:
I would like to express my thanks to Mr.
Ahmed in Malaysia for providing (C.H.N) elements analytical and 'H.NMR–spectra.
and melting points and express my thanks to (United Arabic Company) and (Zaidan company of chemical) for supplied some materials .
Table (1): FT.IR –data (cm-1)
of compounds [1-22] .
|
Comp. No. |
I.R(KBr) (only important groups) |
|
[1] |
(-CHO-) carbonyl of aldehyde
: (1710) , (C-O-C) ether :1140. |
|
[2] |
(-CHO) carbonyl of aldehyde
: (1712) , (NH) of amine : (3310) , (C-O-C) ether :1144. |
|
[3] |
(CH=N) imine group : 1629
, (NH2) amine (3479 , 3312) , (C-O-C) ether :1140. |
|
[4] |
(-CO-NH) carbonyl of amide : 1685 , (NH) of amide :
3280 , (N-N=C) endocycle of pyrazole
: 1240 . |
|
[5] |
(CH=N) imine group : 1630
, (-OCH3) ether :1160 . |
|
[6] |
(C=N) imine group : 1640 ,
(-N=N-) azo group : 1460 , 1438, (-OCH3)
ether :1166 . |
|
[7] |
(-CO-) ketone : 1720 ,
(C=N-N) endo cycle : 1265 , (-OCH3) :
1165 . |
|
[8] |
(CH=N) imine group : 1638
. |
|
[9] |
(-CO-N-) carbonyl of amide (lactame):1690
, (-CO-O-) carbonyl of lactone in oxazepine : 1725 |
|
[10] |
(CO-N-) carbonyl of amide in tri azocine
cycle : 1695 ,(NH-NH-) in tri azocine cycle : 3280
. |
|
[11] |
(CO-N) carbonyl of amide :1689 . |
|
[12] |
(CO-N-) carbonyl of amide : 1695 , (NH2)
: (3455 , 3299) ., (C=S) thion group : 1305 . |
|
[13] |
(CO-N) carbonyl of amide : 1685 , (NH) : 3295 ,
(C=S) thion group : 1320 . |
|
[14] |
(CO-N) carbonyl of amide : 1690 .,(-CO-O-)carbonyl
of carboxyl group :1725 , (-OH) hydroxyl of carboxyl group : 3470 . |
|
[15] |
(CO-N-) carbonyl of amide :1694 , (NH) : 3295 .,
(N-N=C) endo cycle of di azirine : 1288 , (CH) aliphatic : 2986 . |
|
[16] |
(CH=N) imine group : 1630
, (NH2) amine : (3390 , 3366) , (N-C=N-) endo
cycle of melamine : 1240 . |
|
[17] |
(CO-N) carbonyl of amide :1690 , (NH2)
amine :(3392 , 3360) , (N-C=N-) endo cycle of melamine :1245 ., (SH) thiol
: 2570 . |
|
[18] |
(CO-N) carbonyl of amide : 1698 , (S-CH2)
: 1322 , (C-S-C) endo cycle : 490 ., (N-C=N-) endo cycle of melamine : 1240 . |
|
[20] |
(-N=N-) azo group : (1486
, 1537) , (N-C=N) endo cycle of melamine compound :
(1232) , NH2 : (3453 , 3312) . |
|
[21] |
(C=N-N-N) endo cycle of
tri azole ring : 1608 , (-N-C=N-) endo cycle of melamine : 1248 . |
|
[22] |
(C=N) imine group :1634 ,
(-N=N-) azo group : 1433 , 1488 , (N-C=N-) endo cycle of melamine : 1232 . |
Table (2) : 'H.NMR –data (ppm .,
DMSO) of some compounds .
|
Comp.No. |
H.NMR (only important peaks) |
|
[5] |
8.89 (CH=N) proton of imine
group ., 3.10 (-OCH3) protons of methoxy
group . |
|
[6] |
1.31 (-CH3) protons of methyl ., 3.0
(-OCH3) protons of methoxy group ., (7.4
, 7.3 ) doublet –doublet of signals of protons of phenyl groups on azo groups . |
|
[11] |
3 (N-CH-N) proton of tri azocine
cycle ., (3.5 , 3.6) (CO –CH2CH2CO)., 1.5 (CH3)
protons of methyl group . |
|
[13] |
5.55 (-NH-) proton of amine ., (3.5 , 3.65) protons
of (CO-CH2-CH2-CO) ., 3.0 (N-CH-N) proton of di
azepinecycle ., 4.0 (NH-CH2-N) protons
of di azetidine cycle .,
1.5 (CH3) protons of methyl group . |
|
[18] |
3.0 , 3.4 (CO-CH2-CH2-CO) .,
4.6 (N-CH-N) ., (4.6 , 4.7 , 4.85) protons of (N-CH-CH2-CH2-S)
of cycle ., (4.0 , 4.10) protons of (CO-CH2-CH2-CO) of
cycle ., 1.3 (-CH3)
protons of methyl . |
|
[20] |
8.3 (NH2) protons of amine group ., (1.3)
protons of methyl group . |
|
[21] |
1.4 (CH3) protons of methyl group . |
Table (3) : physical properties and
(C.H.N) analysis of compounds [1-22].
|
Comp No. |
M.F |
M.P C0(+2) |
Name of Compounds |
Calc./Found |
||
|
C% |
H% |
N% |
||||
|
[1] |
C15H12O4 |
184 |
Bis(4–formal phenoxy)methylene . |
70.31 70.08 |
4.68 4.49 |
/ |
|
[2] |
C22H16N2O5 |
205 |
Bis(4–formal phenoxy )imine hydrazo–benzaldehyde . |
68.04 67.91 |
4.12 4.00 |
7.21 7.14 |
|
[3] |
C22H22N8O2 |
253 |
Bis(4–hydrazo imine phenoxy )-4 –(hydrazobenzylidine)hydrazo imine . |
61.39 61.20 |
5.11 5.02 |
26.04 25.97 |
|
[4] |
C28H16N8O8 |
265 |
Tris(4–pyrazol-3,4–dione phenyl) di
oxo -hydrazo imine . |
56.75 56.63 |
2.70 2.64 |
18.91 18.78 |
|
[5] |
C16H16N2O2 |
160 |
Bis (4 –methoxy phenyl) hydrazo di imine
. |
71.64 71.50 |
5.97 5.83 |
10.44 10.36 |
|
[6] |
C30H28N6O2 |
240 |
Bis[(4–methoxyphenyl)(4methyl(phenyl azo)]-hydrazo di imine . |
71.42 71.31 |
5.55 5.40 |
16.66 16.59 |
|
[7] |
C19H16N2O4 |
182 |
3,7–bis(4–methoxy phenyl)–di
azepine-4,6–dione . |
67.85 67.72 |
4.76 4.60 |
8.33 8.20 |
|
[8] |
C14H13N |
151 |
(4–methoxy phenyl)–phenyl imine
. |
86.15 86.07 |
6.66 6.54 |
7.17 7.04 |
|
[9] |
C18H15NO3 |
198 |
3-(4–methoxy
phenyl)-2-phenyl-1,3–oxazepine-4,7–dione . |
73.72 73.58 |
5.11 5.01 |
4.77 4.56 |
|
[10] |
C18H17N3O2 |
182 |
3 –phenyl -4- (4 –methyl benzene) -1,2 -4 –tri azocine -5,8 –dione . |
70.35 70.21 |
5.53 5.38 |
13.68 13.50 |
|
[11] |
C20H15N3O4 |
204 |
3–phenyl-4-(4–methyl phenyl)-1,2 –bicycle(di azetidine-3,4,dione)-1,2-4–tri azocine
-5,8–dione . |
66.48 66.32 |
4.15 4.03 |
11.63 11.50 |
|
[12] |
C19H18N4O2S |
196 |
2–(phenyl)-3-(4–methyl benzene)-1 –(thiourea)-1,3–diazepine-4,7–dione . |
62.29 62.17 |
4.91 4.78 |
15.30 15.19 |
|
[13] |
C20H18N4O2S |
202 |
2–(phenyl)-3-(4–methyl phenyl)-1–(di azetidine-2–thione)-1,3–di azepine-4,7–dione . |
63.49 63.32 |
4.76 4.61 |
14.81 14.67 |
|
[14] |
C20H18N2O4 |
215 |
2–(phenyl)-3-(4–methyl phenyl)-1–(aceticacid)-1,3–diazepine-4,7–dione . |
68.57 68.38 |
5.14 5.03 |
8.0 7.89 |
|
[15] |
C20H18N4O2 |
186 |
2–(phenyl)-3-(4–methyl phenyl)-1 –(di azirine-methyl)-1,3–di azepine -4,7–dione . |
69.36 69.21 |
5.20 5.05 |
16.18 16.02 |
|
[16] |
C10H10N6 |
<350 |
2 –(phenyl imine)–melamine
. |
56.07 56.09 |
4.67 4.48 |
39.25 39.11 |
|
[17] |
C13H15N7OS |
<350 |
2–(2--phenyl-4--methyl
thiol–imidazole-5–one)–melamine . |
49.21 49.08 |
4.73 4.57 |
30.91 30.70 |
|
[18] |
C26H23N7O7S |
<350 |
5,4–bis(pyrolidine-2,5–dione)-2–(4-,3--thiazocane-2-,5--dione)-2–phenyl(imidazolidine-5–one)–melamine . |
54.07 53.95 |
3.98 3.76 |
16.98 16.79 |
|
[20] |
C24H24N12 |
<350 |
2,4,6–Tris(2–(4–methyl amino benzene)azo) melamine . |
60.0 59.89 |
5.0 4.91 |
35.0 34.90 |
|
[21] |
C24H18N12 |
<350 |
2,4,6–Tris(3–methyl benzotriazole)
melamine . |
60.75 60.58 |
3.79 3.61 |
35.44 35.32 |
|
[22] |
C45H36N12 |
<350 |
2,4,6–Tris[(4–methyl phenyl) phenyl imine–azo] –melamine . |
72.58 72.34 |
4.83 4.68 |
22.58 22.45 |
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Received on
12.03.2014 Modified on 26.03.2014
Accepted on
31.03.2014 ©A&V Publications All right reserved
Research J. Science and Tech. 6(1): Jan.-Mar.
2014; Page 42-52