J. of university of anbar for pure science : Vol.3: No.
2 : 2009
ISSN: 1991-8941
Synthesis ,Characterization and Identification of New
Oxazepine,Oxazepane and Oxazinane Compounds from reaction of
Some (Z)-2-((2-hydroxybenzylideneamino)methyl)-2(hydroxymethyl)propane-1,3-diol Derivatives with some
cycloanhydrides.
Waleed F. Hammadi*
Khalid,F.Abdul-Gaffor** Hameed M. Al-Kubaisi **
*University of Anbar - College of Education for women
**University of Anbar - College of Science
Abstract:- Z)-2- ((2-hydroxybenzylideneamino)methyl -2 -(hydroxy)propane -1,3-diol,(E) -4- (3-hydroxy-2,2bis (hydroxyl methyl) propylimino)pentan-2-one, -2- ((4-(hydrazonopentane -2-ylideneamino methyl)-2 -(hydroxyl
methyl)propane-1,3-diol and (Z)-2-((4-amino-1,5-dimethyl-2-phenyl-1H pyrazol-3(2H)-ylideneamino)methyl)-2(hydroxymethyl)propane-1,3-diol were prepared by condensation of 2-(aminomethyl)-2-(hydroxymethyl)propane1,3-diol with 2-hydroxy benzaldehyde, pentane-2,4-dione, (E)-4-hydrazonopentan-2-one and 4-amino-1,5-dimethyl2-phenyl-1H-pyrazol-3(2H)-one .These Schiff- bases were reacted with Succinic, Maleic and Malonic anhydride in
absolute ethanol to give 6,7-membered heterocyclic ring system Oxazepine,Oxazepane,Oxazinan.The Schiff-bases
and the final products were identified by their melting points, elemental analysis, FT-IR and UV-Visible spectra.
Keywords :Schiffbases;Oxazepine,Oxazepane,Oxazinan Synthesis ;Properties; Identification Studies.
Diketene reacts with N,N-diphenyl guanidine to
give the tranquilizer ketazolam and N-substituted
tetrahydro-1,3-oxazine-4-one respectively [9,10]. The
reaction of diketene with isocyanic acid , cyanamides
and flouro sulphinyl isocyanate afforded the
corresponding 1,3-oxazine-2,4-diones [11-13].
Furthermore,
thermal
rearrangement
of
ketovinylazirines gave substituted 1,3-oxazepines. [914]
N-acyl immonium ions have been the most
commonly used dienes to effect [4+2] cycloaddition
as 4 components with substituted 1,3-butadienes. It
is found that N-acylimines or immonium ions that are
capable of tautomerization undergo intermolecular
Diels-alder reaction to give dihydro-1,3-oxazines
[17].
The reaction of N-Benzylidene 1,5-dimethyl-2phenylpyrazolonamines
(Schiff
bases
with
Cyclopentane -1,1-dicarboxylic anhydride to give 2aryl-3-3(1,5-dimethyl-2-phenylpyrazolo)-1-(5)
spirocyclopentyltetra hydro-1,3-oxazine-4,6-diones
[18]. Synthesis and characterization of 8-(4-dimethyl
amino-phenyl)-9-(6-R- benzothiazol-2-yl)-7-oxa-9aza-spiro[4.5]decane-6,10-dione[19].
Introduction
The synthesis of 2-phenyl -1,3-oxazepine by
irradiation of 4-phenyl-2-oxa-3-aza bicyclo[3.2.0]hepta-3,6-diene was studied by Toshio Makai with
other workers[1].The discovery of the central nervous
system(CNS) activity of 1,4- benzodiazepine [2]
encourage the chemists to look for more effective
ways to build up the 7- membered heterocyclic ring
systems from already available materials.The Sixmembered heterocyclic ring system: 1,3-oxazine has
already been reported and thorouly reviewed in the
literature [1-4] . Maleic, arylmaleic and substituted
maleic anhydrides react with trimethylsilyl azide to
give 4- and 5-substituted ((oxauraciles)) dihydro-1,3oxazine-2,6-diones [5,6].
Both 2- methoxy pyrroline and 2-methoxy
piprdinine react with diketene
under neutral
conditions at 0c to give the corresponding, 2methoxy dihydro 1,3-oxazine-4-ones [7,8].
One of these ways which has been discovered
recently involves direct addition of maleic anhydride
to the (C=N) double bond of Schiff - bases and
anumber of 2,3-diaryl-2,3-dihydro-1,3-oxazepine4,7-diones were prepared and characterized.[5-8]
32
J. of university of anbar for pure science : Vol.3: No.2 : 2009
of
(Z)-2-((2-hydroxybenzylideneamino)methyl)-2(hydroxymethyl)propane-1,3-diol and 0.01 mol (
0.98g)of maleic anhydride in 20ml of absolute
ethanol. The reaction mixture was refluxed in water
bath at 78C for 2hr., the solvent was then removed
and the resulting solid was recrystallized from
anhydrous THF. Compounds 8,11,14 preparation in
same of method.
Preparation
of
3-(3-hydroxy-2,2bis(hydroxymethyl)propyl)-2-(2-hydroxyphenyl)1,3-oxazepane-4,7-dione:
In a 100 ml round bottom flask equipped with a
double surface condenser fitted with calcium chloride
guard tube, was placed a mixture of 0.01mol (2.39g)
of
(Z)-2-((2-hydroxybenzylideneamino)methyl)-2(hydroxymethyl)propane-1,3-diol and 0.01 mol (
1.0g)of succin anhydride in 20ml of absolute ethanol.
The reaction mixture was refluxed in water bath at
78C for 2hr., the solvent was then removed and the
resulting solid was recrystallized from anhydrous
THF. Compounds 9,12,15 preparation in same of
method.
Preparation
of
(
R)-3-(3-hydroxy-2,2bis(hydroxymethyl)propyl)-2-methyl-2-(2oxopropyl)-1,3-oxazinane-4,6-dione: In a 100 ml
round bottom flask equipped with a double surface
condenser fitted with calcium chloride guard tube,
was placed a mixture of 0.01mol ( 1.35g)
(E)-4-(3-hydroxy-2,2bis(hydroxymethyl)propylimino)pentan-2-one0.01
mol(0.86g)
of malonic anhydride in 20ml of
absolute ethanol. The reaction mixture was refluxed
in water bath at 78C for 3hr., the solvent was then
removed and the resulting solid was recrystallized
from anhydrous 1,4-Dioxan. Compounds 10,13,16
preparation in same of method.
Extensive synthesis and testing of the barbiturates
over a long time span has produced well-defined
structure activity relationships. Which have been
summarized. [20] .
Materials and methods
Melting points were recorded with
Gallenkamp Melting point Apparatus and were
uncorrected. Elemental analysis were carried out with
perkin-Elmer,2400;CHN Elemental Analyzer. FT-IR
spectra were recorded on FT-IR spectrophotometer 8400s Shimadza (KBr) in Chemistry department of
Education for women college AL-Anbar and UVVisible spectra were recorded (in ethanol) on
Schimadza Reco- 160 Spectrophotometer.
Preparation
of
(Z)-2-((2hydroxybenzylideneamino)methyl)-2(hydroxymethyl)propane-1,3-diol: A mixture of
0.01 mole( 1.35
g) of 2-(amino methyl)-2(hydroxymethyl)propane-1,3-diol and 0.01 mole
(1.22 g) of o-hydroxy benzaldehyde in 20 ml of
absolute ethanol, was refluxed in a water bath for 1h,
then left to cool in ice-water bath whereby yellow
crystalline solid was precipitated. The solid was
filtered, recrystallized twice from ethanol.
Preparation
of
(E)-4-(3-hydroxy-2,2bis(hydroxymethyl)propan-2-one: A mixture of
0.01 mole( 1.35 g) of 2-(amino methyl)-2(hydroxymethyl)propane-1,3-diol and 0.01 mole ( 1.0
g) of acetyl acetone in 20 ml of absolute ethanol, was
refluxed in a water bath for 1h, then left to cool in
ice-water bath whereby yellow crystalline solid was
precipitated. The solid was filtered, recrystallized
twice from ethanol.
Preparation of
2-((4- hydrazonopentan-2ylideneamino)methyl)-2-(hydroxymethyl)propane1,3-diol: A mixture of 0.01 mole(2.17 g) of (E)-4(3-hydroxy-2,2-bis(hydroxymethyl)propan-2-one and
0.01 mole (0.5 g) of hydrazine hydrate in 20 ml of
absolute ethanol, was refluxed in a water bath for
1.5h, then left to cool in ice-water bath whereby
yellow crystalline solid was precipitated. The solid
was filtered, recrystallized twice from ethanol.
Preparation
of(E)-4-((3-hydroxy-2,2bis(hydroxymethyl)propylimino)methyl)-5methyl-2phenyl-1H-pyrazol-3(2H)-one : A mixture
of 0.01 mole(1.35)of 2-(amino methyl)-2(hydroxymethyl)propane-1,3-diol and 0.01 mole
(2.03g)of 4-aminoanti pyrine in 20 ml of absolute
ethanol, was refluxed in a water bath for 1h, then left
to cool in ice-water bath whereby pink crystalline
solid was precipitated. The solid was filtered,
recrystallized twice from ethanol.
Preparation
of
3-(3-hydroxy-2,2bis(hydroxymethyl)propyl)-2-(2-hydroxyphenyl)2,3-dihydro-1,3-oxazepine-4,7-dione:
In a 100 ml round bottom flask equipped with a
double surface condenser fitted with calcium chloride
guard tube, was placed a mixture of 0.01mol (2.39g)
Results and Discussion
Schiff bases (1-4) are prepared by condensation of
2-(amino
methyl)-2-(hydroxymethyl)propane-1,3diol with salicyldehyde, acetyl acetone and 4-amino
antipyrine .
It is known that Schiff bases react smoothly with
acid chlorides and anhydrides
to give the
corresponding addition products[21-24].
This is indicated by the appearance of the
characteristic C=O (lacton-lactam) absorption band at
(1665-1680)cm-1 in the FT-IR spectra of addition
products (3).
It is impressive to note that the two absorption
band at (1800-1950)cm-1 in the FT-IR spectra of
pure Maleic ,Succinic and Malonic anhydride have
diappeared when the anhydride became of the 6,7membered ring system of the3-(3-hydroxy-2,2-bis
(hydroxymethyl)
propyl)-2-phenyl-1,3-oxazepane4,7-dione,3-(3-hydroxy-2,2bis(hydroxymethyl)propyl)-2-phenyl-1,3-oxazepine4,7-dion and 2-(4-(dimethylamino) phenyl)-3-(3hydroxy-2,2- bis (hydroxymethyl) propyl)-1,3oxazinane -4,6-dione. The new absorption bands of
33
J. of university of anbar for pure science : Vol.3: No.2 : 2009
cyclic 6,7- membered lactone-lactam combined
structure [3]. and positive Br2/CCl4 and KMNO4
tests.
In this paper , the reaction of the Maleic,
Succinic and Malonic anhydride with (1-4) Schiff
bases gives the dipolar intermediate [2] which
collapses to 6,7-membered heterocyclic ring system.
[3] is presented.
the (C=O) group in the FT-IR spectra of the addition
products (3) appear at (1665-1685)cm-1 , this
attributed to the fact that the structures of the addition
products are combination of the lacton-lactam
structure [25]
Furthermore, the UV-Visible spectra of
Oxazepine, Oxazinane derivatives show absorption
maxima at( 240-350)nm due to charge transfer of the
O
N
OH
2
OH
OH
OH
HO
OH
Absolute ethano l
Water bath / ref lux
OH
N
O OH
O
O
(1 )
(2)
OH
OH
HO
O
N
O OH
(3)
The reaction of maleic , succinic and malonic
cycloaddition in terms the number of the new bond.
anhydride with various Schiff bases is a sort of
The ring size of the product, and the number of atoms
cycloaddition reaction. Cycloaddition is a ring
in the components taking part in the cycloaddition.
formation that results from the addition of bonds to
This cycloaddition reaction is classified as a 2+5-7,
either or with formation of new bonds. This
and it is the first cycloaddition of this type , although
class of reactions and its reverse encompasses a large
in principle, one would predict that the butadiene
number of individual types.Huisgen (20)
cation might add to an olefin through a (4n+2)
formulated
useful
classification
of
has
diverse
transition state to yield the cyclohexenyl cation.
34
J. of university of anbar for pure science : Vol.3: No.2 : 2009
Table (1) Melting points, yield, Molecular formula[M.F], elemental analysis of New Schiff bases(1-4)
O
OH
OH
H 3C
OH OH
(1)
CH 3
N
HO
OH
OH
H 2N
CH3 CH 3
(2)
Compound
m.p/Co
%Yield
1
2
3
4
242-244
136-138
175-177
256-258
78
69
81
73
HO
N
O
OH
OH
N
N
H 3C
(3)
Molecular
Formula
C12H17NO4
C10H19NO4
C10H21N3O3
C16H24N4O3
OH
OH
N
HO
CH 3
(4)
C
60.24
55.28
51.93
59.98
Calc.
H
7.16
8.81
9.15
7.55
N
5.85
6.45
18.17
17.49
C
59.99
55.01
51.69
60.10
Found
H
7.00
8.77
9.03
7.40
N
5.70
6. 32
18.02
17. 30
Table (2) The major FT-IR absorptions (cm-1) of New Schiff bases (1-4)
Compound
O-H str.
N-H str.
1
2
3
4
3540
3460
3510
3470
3450,3310
3430,3280
C-H str.
Aromatic
3050
3070
3090
3065
C=O .
str.
1690
1680
C=N str.
1610
1605
1620
1610
C=C str.
Aromatic
1580
1585
1580
1590
C-O str.
1310
1320
1310
1330
Table (3) The UV-Visible absorption maxima /nm of New Schiff bases(1-4)
Compound
UV-Visible absorption maxima /nm
1
380,300,266.225.220
2
275,226,220
3
280,244,222
4
375,320,260,251,226
35
C-H bend.
Aromatic
1010,770
1020,870
1010,900
1020,870
J. of university of anbar for pure science : Vol.3: No.2 : 2009
Comp
m.p/c
5
6
7
8
9
10
11
12
13
14
15
16
177-175
190-188
211-209
240-238
166-164
170-168
246-244
188-186
165-163
154-152
206-104
258-256
Table( 4) Melting point ,percentage yield, molecular formula and elemental analysis of compounds (5-16)
Yield%
M.F
Calc.
C
H
N
C
72
C16H19NO7
56.97
5.68
4.15
56.68
66
C16H21NO7
56.63
6.24
4.13
56.45
68
C15H19NO7
55.38
5.89
4.31
55.12
65
C14H21NO7
53.33
6.71
4.44
53.19
80
C14H23NO7
52.99
7.31
4.41
53.04
71
C13H21NO7
51.48
6.98
4.62
51.29
67
C18H25N3O9
50.58
5.90
9.83
50.41
70
C18H29N3O9
50.11
6.78
9.74
50.02
66
C16H25N3O9
47.64
6.25
10.42
47.46
67
C20H26N4O6
57.41
6.26
13.39
57.31
59
C20H28N4O6
57.13
6.71
13.33
57.03
57
C19H26N4O6
56.15
6.45
13.79
56.01
Comp.
O-H str.
NH2 str.
5
6
7
8
9
10
11
12
13
14
15
16
3510,3470
3520,3480
3540,3470
3570
3560
3555
3530
3560
3540
3550
3560
3540
3410,3360
3430,3320
3430,3290
3420,3280
3415,3275
3450,3300
Table(5)The major IR absorption (cm-1)of compounds (5-16)
C=O str.
C=O str.
C=N str.
Lacton, lactam
1710
1700
1705
-
1680
1680
1670
1685
1670
1675
1670
1665
1680
1670
1670
1675
36
1430
1435
1450
1440
1430
1450
1480
1460
1450
1430
1460
1450
Found
H
5.55
6.18
5.80
6.65
7.16
6.80
5.74
6.51
6.23
5.99
6.52
6.28
N
4.01
3.98
4.21
4.20
4.23
4.54
9.70
9.48
10.28
13.10
13.08
13.62
C=C str.
Olefin
C=C str.
Aromatic
C-O-C str.
1600
1610
1610
-
1580,1560
1580,1540
1580,1560
1580,1555
1580,1565
1580,1565
1190
1180
1170
1200
1210
1200
1190
1210
1200
1190
1180
119
1600
-
J. of university of anbar for pure science : Vol.3: No.2 : 2009
Table (6) Uv-spectra of compounds (5-16)
Comp.
5
6
7
8
9
10
11
12
13
14
15
16
UV-Visible absorption maxima /nm
320,300,266,230.221
315,255,243,229
333,265,251,243,223
285,265,239,224
289,269,241,236,222
285,240,225,220
275,250,235,226
295,250,235,222
290,269,240,235,220
310,300,276,220.
325,235,223
330,285,261,243,223
[11]-Gunav,V.I;Mikhailopulo,I- A;Ovechkina
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[12]Ficini,
J.
and
Genet,J.P;Soc.Chim.Fr.,1974,2086.
[13]-Fietch,H.;Glauss,K.;Schmidt,
E
and
Jensen,H.;Chem.Abst.,1976,84,13568f.
[14]- Kato,T,;Ymamota,Y., Chem.Pharm.Bull.
,1967,15,1334.[15]Kato,T
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Sakamoto, T.,Chem.Abst.,1968,68,11452.
[16]-Matsuda,I.,;Yamato,S.,and
Ishii,Y.;
J.Chem.Soc . perkin Trans. (1)
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[17]-Eckhardt, H.H and Perst,H. ;Tet.Lett
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[18]- Obaid, H., A; National J. ,Chem. Vol.
(7),446-460,(2002).
[19]- W.F. Alhity; ), Journal of Um-Salama for
Science Vol.
3,No. 1, (2005), pp. 93102.
[20]- Hou, J. P., and Poole, J. W.: J. Pharm .
Sci. 58:1150,1969
[21]- Waleed,F.Al-hiti and Mohammad,A.AlHadithi
(Synthesis
and
characterization of Oxazepine,Oxazepane
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Approach,)
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(1975).
References:[1]-Toshio Makai, Tsutomu Kumagai, and
Osamu
Sashimoto1977,
(photochemical and thermal reactions of
some heterocycles containing C=N-O and
N=C-O group ) Pure and Appl.
Chem.Vol.49,pp.287-308
[ 2]- Cheesman,G.W.H.and Greenberg ,S.G.
1979, (Synthesis of 5,6-dihydro-4Hpyrrolo[1,2-] [1,4] benzodiazepines), J.
Heterocyclic Chem. 16,241
[3]- Schiff ,H.. 1864,Ann, 131,118
[4]- Clifford J. Crewell, Olaf, A. Rungvist, and
Malcolm M. Campbell 1972, ( Spectral
analysis of organic compounds),2nd ed.,
Longman.
[5]
J.
Macmillan,
S.Washburen,
J.
HeterocyclicChem.,Vol.1, No.6, (1975)
pp.1215.
[6] J. H. Macmillan.,OrganicPreparation
proceed.Int.,Vol.9,No.2,(1977) ,pp.87.
[7]
H.Uchida,
H
Iwasawa,.and
M.Ohta,Synthesis and cycloaddition
reaction
of
1,3oxazepine,
Chem.Soc.Jpn.,Vol.46,No.1,(1 973) ,pp.
3277 .
[8] T,Kato and M. Kando, Synthesis and
cycloaddition reaction of di and trisubstituted-1,3-oxazepine,
Hetrocycles,Vol.1,No.3,(1975),pp.927
[9] R. N.Lacey, Thermal Rearrangement of
Tetraphenyl-(Z)ketovinylazirine
J.Chem.Soc,Vol.1,No.3,(1954) ,pp.839.
[10] A. Maujean, and J.Chuche, Condensation
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Trimethyl amine, Tet.Lett.,Vol.1,No.1,
(1976) ,pp. 2905-8.
37
J. of university of anbar for pure science : Vol.3: No.2 : 2009
No.
Name of compounds
Structure
NH2
OH
N
HO
CH3
HO
N
CH3
HO O
N
HO
HO
38
O
OH
J. of university of anbar for pure science : Vol.3: No.2 : 2009
10
11
O
HO O
O
N
HO
HO
O
O
H2N
N
O
12
13
39
J. of university of anbar for pure science : Vol.3: No.2 : 2009
14
15
16
) ,1-, 3( --2- ( ((Z)-2 ))- 2
Email scianb@yahoo.con
-:
)-2 ))- 2-(Z ( ( ) -2- ( 3 ,1-, -2 ))- 2-(Z)
( ( ) -2- ( 3 ,1-, ) -4)) 2-(Z ( ( (-2-
) ( -3,1-
.
FT-IR ). (C.H.N.
40
