J. Chem. Sci.
(2 02 0) 13 2: 90
P age 3 of 7
90
2
. 2 f N-hydroxy-3-(4-methylphenoxy)propanamide
wi t h di chl or om et ha ne and t he com b in e d or gan i c l ay e r wa s
was h ed wi t h wat er and dr ied ove r Na S O . Th e s ol v e nt wa s
eva por at ed and t he res u l ta nt cru de pr oduc t was pur i fie d b y
(7f): C o mp o u n d 7f w as pr ep a r ed in 56 % yi e ld fr om
2
4
m eth y l -3 - (4 -m e th y l ph en ox y ) pr op ano a te us i ng gen eral
p r oc ed u re A. W hi t e s ol id . M. p.: 13 6- 1 3 8 °C. I R (K B r):
col um n chr om at ogr aphy t o fu rni s h t he req ui re d pr od u ct 8a
-
0 3 , 8 2 1 , 1 2 4 0 , 1 5 10 , 16 35 , 31 74 cm ; H N MR (3 00
1
1
(
0 .21 g, 24% ) as a wh it e s ol i d. M. p: 166 -16 8 °C (l i t 1 68 - 17 2
5
1 5 -1
C ) ; IR (K Br ): 748 , 104 7, 140 2 , 150 0, 170 5, 298 2 c m ;
°
M Hz , DM SO -d ): d 10 .5 5 ( s , 1H ) , 8. 88 ( s , 1H ) , 7. 0 7 (d , J =
6
1
H NMR (3 00 MHz , C DC l ): d 9. 10 (s , 1H ) , 7. 06- 6 . 91 ( m,
8
. 4 Hz , 2 H) , 6 .7 9 (d d , J = 9. 6, 2. 7 H z, 2H ) , 4. 11 ( t, J = 6 Hz,
3
1
H ), 6. 93- 6 . 80 (m , 1H ) , 4. 65 (s , 2H ); C NM R (75 MHz ,
3
1
3
H), 2 .4 0 (t , J = 6 H z, 2H ) , 2. 22 ( s , 3H ) ; C N MR (7 5
3
2
C DC l ): d 166 .3 2, 143 .6 4, 12 6. 03, 124 .2 5, 122 .7 3, 1 16 . 77 ,
1
M Hz , DM SO -d ): d 16 6. 66 , 15 6. 24 , 12 9. 78 , 12 9. 2 2, 114 .1 8,
6
cal c d . fo r (M ?Na )21 8. 0 79 3; F o un d: 21 8. 07 94 .
3
6
?
16 .0 9, 67. 15 ; MS (7 0eV) : m / z 149 (M ).
?
3 . 63 , 3 2 .5 5 , 2 0 .0 2 ; MS ( 70 eV ) : m /z 19 5( M ) ; HR MS
2
.
3
b
6
-
m
e
t
h
y
l
-
2
H
-
1
,
4
-
b
e
n
z
o
x
a
z
i
n
-
3
(
4
H
)
-
o
n
e
(
8b): C om pou nd 8b was pr epare d i n 24% yi el d f ro m N-
2
(
. 2 g N-hydroxy-3-(4chlorophenoxy)propanamide
7g): C o mp o u n d 7g w as pr ep a r ed in 52 % yi e ld fr om
m eth y l -3 - (4 -c h l o ro p hen ox y) p ro pan oa te us i ng gen eral
p r oc ed u re A. W hi t e s ol id . M. p.: 12 5- 1 2 6 °C; I R (K B r):
hyd rox y- 2-(4 - m et hyl phe n oxy ) acet am i de us i ng g en er a l
pr oced ur e B. Wh it e s ol i d. M. p. : 207 -20 9 °C ; IR ( K Br ) :
-1 1
00 , 104 5, 121 9, 140 0, 149 2, 151 9, 170 1 cm ; H N M R
8
-
1
1
(
3
0
0
M
H
z
,
C
D
C
l
)
:
d
9
.
2
6
(
s
,
1
H
)
,
6
.
9
4
-
6
.
6
3
(
m
,
3
H
)
,
4
.
6
2
3
6
5
7
,
8
1
9
,
1
2
3
6
,
1
4
9
2
,
1
6
3
1
,
3
1
6
3
c
m
;
H
N
M
R
(
3
0
0
1
3
(
s
,
2
H
)
,
2
.
3
0
(
s
,
3
H
)
;
C
N
M
R
(
7
5
M
H
z
,
C
D
C
l
)
:
d
1
6
6
.
5
5
,
3
M
H
z
,
D
M
S
O
-
d
)
:
d
1
0
.
5
5
(
s
,
1
H
)
,
8
.
8
8
(
s
,
1
H
)
,
7
.
3
2
(
d
d
,
6
141 .4 6, 132 .5 5, 125 .7 4, 124 .6 8, 116 . 43, 67. 25 , 20. 6 4; MS
(7 0eV) : m / z 1 63 (M ).
J = 6 .6 , 2 .1 Hz , 2 H) , 6. 94 ( dd , J = 6. 6, 2. 1 H z, 2H ) , 4. 16 (t ,
?
1
3
J = 6 Hz , 2 H), 2 .4 1 ( t, J = 6 H z, 2H ) ; C N MR ( 7 5 MHz ,
DM S O- d ): d 1 6 6 .4 6, 15 7. 21 , 12 9. 25 , 12 4. 36 , 116 .1 7,
6
6
?
4 . 09 , 3 2 .5 3 ; M S( 70 eV ) : m /z 21 5( M ) ; H RMS ca lc d. fo r
M ?Na ) 2 3 8 .0 2 4 7 ; F ou nd : 23 8. 02 47 .
2
.
3
c
6
-
c
h
l
o
r
o
-
2
H
-
1
,
4
-
b
e
n
z
o
x
a
z
i
n
-
3
(
4
H
)
-
o
n
e
(
(8c): C om pou nd 8c was pr epa red i n 31% yi el d f ro m N-
hyd rox y- 2-(4 - chl or ophe nox y) acet am i de us i n g g en er a l
pr oced ur e B. Wh it e s ol i d. M. p. : 217 -21 8 °C . IR ( K Br ) :
2
(
. 2 h N-hydroxy-3-(4-bromophenoxy)propanamide
7h): C o mp o u n d 7h w as pr ep a r ed in 48 % yi el d fr om
m eth y l -3 - (4 -b r om o p he no x y) p ro pan oa te u s in g gen eral
p r oc ed u re A. W hi t e s ol id . M. p. 13 5- 1 3 6 °C: I R (K B r):
-
1 1
729 , 860 , 104 1, 121 1, 139 8, 149 2, 170 1, 295 8 cm ; H
NMR (3 00 MH z, DMS O- d ): d 10. 81 (s , 1H ), 7. 00- 6. 84 ( m,
6
1
3
3H ), 4. 59 (s , 2H ); C NMR (7 5 MHz , DMS O -d ) : d
6
-
1
1
164 .6 5, 142 .1 3, 128 .6 8, 125 .6 7, 122 .3 6, 1 17. 58 , 1 15 . 15 ,
6
8
1 3 , 1 0 5 1 , 1 2 3 6 , 1 48 3, 16 29 , 31 59 cm ; H N MR (3 00
?
6. 64 ; MS (7 0eV) : m / z 183 (M ).
M Hz , DM S O- d ): d 10 .5 6 ( s , 1H ) 8. 89 ( s , 1H ) , 7. 42 (t , J =
6
8
2
1
. 7 Hz , 2 H), 6 .8 9 (d , J = 8. 7 H z, 2H ) , 4. 16 ( t, J = 6 H z, 2H ),
1
3
2
.3 d 6-bromo-2H-1,4-benzoxazin-3(4H)-one
. 4 2 (t , J = 6 Hz , 2 H ) ; C N MR ( 75 MH z, D MSO -d ): d
6
6 6 .4 5 , 1 5 7 .5 5 , 13 2. 09 , 11 6. 67 , 11 1. 94 , 63 .9 3, 32. 30 ; (8d): C om pou nd 8d was pr epare d i n 48% yi el d f ro m N-
?
M S ( 7 0 e V): m / z 2 5 9 , 26 1( 1 :1) ( M ) ; H RMS ca l cd. fo r hyd rox y- 2-(4 - br om ophe nox y) acet am i de us i n g g en er a l
M ?Na )2 8 1 .9 7 4 2 ; F ou nd : 28 1. 97 51 .
pr oced ur e B. Wh it e s ol i d. M. p. : 222 -22 4 °C ; IR ( K Br ) :
(
-1 1
02 , 121 7, 149 2, 168 1 cm ; H NMR (3 00 MHz , CD Cl ) :
8
3
d 8. 45 (s , 1H ) , 7. 09 (d d, J = 8. 7, 2. 1 Hz, 1H ), 6. 97 ( d, J =
1
3
1. 8 Hz, 1 H) , 6. 86 (d , J = 8. 4 Hz, 1H ), 4. 62 (s , 2 H);
C
2 . 3 General procedure B for the cyclisation
of hydroxamic acids using PPA
NMR (7 5 MHz , C DC l3 , DM S O-d ): d 16 4. 91, 1 42 . 47 ,
6
128 .2 3, 125 .7 7, 118 .6 9, 117 .6 3, 114 .1 4, 6 6. 92; MS ( 70 eV ):
m / z 230 , 232 (1 :1 ) (M ).
?
Th e fo l l o wi n g p re p a r ati on of 8a is r epr es e nt at ive .
2
.3 e 2,3-dihydro-1,5-benzoxazepin-4(5H)-one
O
O
PPA
(8e): C om pou nd 8e was pr epa red i n 48% yi el d f ro m N-
hyd rox y- 3-ph enox ypr opa nam i de us i n g g ene ral pr oc e du re
B. Wh it e s ol i d. M. p. 130 .5 - 131 .5 °C ; IR (K Br ): 5 2 6, 7 52 ,
HN
HO
O
N
H
O
7
a
8a
-1 1
788 , 121 9, 139 4, 149 8, 169 9 cm ; H NMR (3 00 MHz ,
C DC l ): d 8. 90 (s , 1H ), 7. 11- 6 . 97 (m , 4H ), 4. 47 (t , J = 5 .7
3
1
Hz, 2H ), 2. 88 (t , J = 5. 7 Hz, 2H ); C NM R (7 5 MHz ,
3
C DC l ): d 173 .2 7, 148 .6 5, 12 8. 92, 125 .3 5, 123 .7 6, 1 22 . 08 ,
1
2 . 3 a 2H-1,4-benzoxazin-3(4H)one (8a): A m i xt ure
o f th e N-h y d r o x y -2 - ph en ox y ac eta mi de ( 1.0 g, 6. 0 m m ol )
3
?
21 .7 7, 68. 74 , 37. 06 ; MS (7 0eV ): m / z 163 (M ).
an d p o l y p h o s p h o ric ac id ( PP A ) ( 5.0 g) w as s t ir red
v i go r o us l y a t 1 0 0 °C f or 5 h. A ft er co m pl e ti on of t he 2.3 f 7-methyl-2,3-dihydro-1,5-benzoxazepin-4(5H)-
r eact i o n (b y TLC ) t h e r eac ti on m i xt ur e w as co ol ed to 70 °C , one (8f): C om pou nd 8f was pr epa red i n 45% yi e ld f ro m
d i lu te d wi t h wa t e r ( 10 0 m L) an d co ol ed to ro om N-h ydr oxy -3- (4- m et hyl phe n oxy )
t emp e r a tu r e. Th e di lu te d r eac tio n m ix tu re w as ext ra cte d gen eral pr ocedu re B. Wh i t e s ol i d. M. p. 130 .5 -131 . 6 °C;
pr opa nam i de
u si n g