Note: Descriptions are shown in the official language in which they were submitted.
BACKGROUND OF THE INVENTION
This invention relates to a novel process for prepar-
ing anthranylaldehyde derivatives.
More particularly, it relates to a process for
preparing anthranylaldehyde derivatives of following formula
(I):
zl
~NH~ (I)
Z CHO
wherein, zl and z2 are same or different each other and
each represent ahydrogen atom, a halogen atom, a methyl group
oratrifluoromethyl group; zl is attached to ortho position
to the amino group and z2 may be positioned at any of 3-,
.,
4-, 5- and 6-positions.
Compounds of formula (I) are expected to be used
in various organic reactions as they have an aldehyde group,
~; :
and therefore, it is quite important to develop an advantag-
eous process for preparing the same. Among compounds of
formula (I) obtained by the process of the invention, N-(
2,6-dichlorophenyl)anthranylaldèhyde having following formula
:... , :
: ~ - ~ -: . .
. .
3 2~)
(II) is an important material for preparing o-(2,6-dichloro-
anilino)phenylacetic acid having formula (III) (hereinafter
referred to as "Dichlofenac"), known as an anti-inflammatory
and analgesic agent.
Cl
-
NH ~ (II)
ClCHO
Cl
NH ~ (III)
2COOH
Known processes for the production of compound (III)
include, for instance, those disclosed in Japanese Patent
Publication Specifications 42-23418, 44-27374, 44-27573
and 45-11295. None of these methods, however, involves
the aldehyde (II) as the starting material. ~he applicant
has already developed a process for preparing Dichlofenac
by using the aldehyde (II) as the starting material in
Japanese Provisional Publication n 53-84940 dated July 26,
1978~
Heretofore, very few reports may be found regarding
proce~ for preparaing aldehydes of formula (I), particularly
- 2 -
' -- ' , .
~;. .'
'
- :- - :
312~)
aldehyde (II), with an exception of Japanese Patent Publi-
cation Sepcification 47-20220 wherein there are disclosed
a method of reducing N-(2,6-dichlorophenyl)anthranylic acid,
a method of oxidizing o-(2,6-dichloroanilino)benzyl alcohol
and a method of reducing N-(2,6-dichlorophenyl)anthranylic ha-
lide. The Specification, however, discloses no yield of
the aldehyde (II).
~NU~ ~ NU~
Cl COOH Cl CHO
`: ~
SOC12
:~ ~1 Cl -
NH ~ ~ NH
Cl C~Cl : Cl CH2OH
The inventors have tried to produce the desired
compound (I) di~rectly by the condensation reaction of o-
halogenobenzaldehyde with an aniline derivative haviny
foliowing formula (IV) but failed to succeed.
it ~
- '
~- '
NH2 (IV~
(wherein, zl and z2 are as defined above.).
After further studies, the inventors have found that
a condensation product may be formed in good yield by using
an o-halogenoaldehyde, the aldehyde group of which is protected
with a specific group, and that the protected group may
readily be converted to free aldehyde group with an acid.
`: '
BRIEF SUMMARY OF THE INVENTION
.
It is, therefore, an object of the invention to
provide a compound (I) in good yield.
Other objects of the invention will become clear as
- the description proceeds.
According to the method of the invention, compounds
(I) may be prepared by reactingan o-halogenobenzaldehyde
having formula (V):
CHO
',~ ' ~ X (V) ''
(wherein, X represents a halogen atom.j with an alkylamine
derivative having formula (VI):
~, ~
4 -
. ~ .
. - : . . . ... _ .
. ~
:~ ~ , - . . ' . - : ., . . ' ' - :
- . .: ' , . ,
. : . . - . . -~ - . . : - - .
- . . - . - .
- .
R \ /(R )n
/ N(CH2)m Y (VI)
(wherein, R and Rl each represent a lower alkyl group;
Y represents nitorgen, oxygen or sulfur atom m represents
an integer of 2 or 3; and n represents O or 1, provided that
n is 1 when Y is nitrogen atom and n is O when Y is oxygen
or sulfur atom.) to give a compound of formula (VIl):
R
--~/ N ~
CH (CH2)m (VII)
~ \ I
(Rl)
(wherein, X, Y, R, Rl, m and n are as defined above.~,
then by reacting the compound (VII) with an aniline derivative
(IV)~ giving a condensation product having the following
formula:
NH ~ R
~¦ ~ Z CH N ~
Y (C112)m (VIII)
l ~ n
wherein y~ zl, z , R, Rl, m and n are defined as above.), and
finally by treating the thus obtained product with an acid.
5 _
-: - ~ ., - : , .
-
: : :. . - . .
- . -. . . . : :
DETAILED DESCRIPTION OF THE INVENTION
In the above formulae, X represents a halogen atom,
preferably bromine or iodine atom.
o-Halogenobenzaldehydes include o-chlorobenzaldehyde,
o-bromobenzaldehyde and o-iodobenzaldehyde.
In alkylamine derivatives (VI), R and Rl each repre-
sent alower alkyl group having from 1 to 5 carbon atoms,
such as methyl, ethyl, propyl and butyl. Examples of alkyl-
amine derivatives (VI) are diamines such as N,N'-dimethyl-
ethylenediamine, N,N'-diethyleth~lenediamine, N,N'-dipropyl-
ethylenediamine and N,N'-dimethyl-1,3-propanediamine; amino-
alcohols such as N-methylaminoethanol, N-ethylaminoethanol,
N-propylaminoethanol and N-methylamino-3-propanol; and amino-
thiols such as N-methylaminoethylthiol, N-ethylaminoethyl-
thiol, N-propylaminoethylthiol and N-methylamino-3-propyl-
thiol.
TXe condensation reaction of o-halogenobenzaldehyde
(V) with amine derivative (VI) may be performed by mixing
them at ambient temperature and then by heating them in a
solvent capable of forming an azeotropic mixture with water,
while removing the water formed in situ.
Examples of solvents capable of forming an azeotropic
mixture are benzene and toluenê.
The condensation reaction proceeds almost quantitatively
,`~ : .
~ - 6 -
_ , , , , , , . . _ ,
: : . :- . . - .. . . . :.;.. , . - , . - . , : -
, . '~ . ' ~ ' ' ' - ,
.. . . . . . .
31~3
The subsequent condensation reaction of the compound (VII)
with aniline derivative (IV) is performed in the presence
of a base and a copper compound. There is no specific limit-
ation as to the nature of base to be used in the process of
the invention as far as it acts as a usual hydrogen halide
eliminating agent. The base includes alkali carbonates such
as sodium carbonate and potassium carbonate and alkali hydrogen
carbonates such as sodium hydrogen carbonate and potassium
hydrogen carbonate. Copper catalyst includes copper powder;
various copper salts such as cuprous chloride, cupric chloride,
cuprous bromide, curpic bromide and cuprous iodide; copper
oxides such as cuprous oxide and cupric~oxide; copper compounds
with organic acids such as coppér acetate; and copper chelate
compounds such as acetylacetonatocopper.
Although the reaction may ~e performed in the absence of
a solvent, it is prefer~ble to employ a solvent in order to
control the reaction temperature. The solvent includes non-
polar solvent, for example,satùrated hydrocarbons such as
octane and nonane and aromatic hydrocarbons such as ben~ene
and toluene. It also includes ethers such as dinormalhutyl, eit
:
diisobutyl ether, diisoamyl ether, ethyl amyl ether and
anisole; and dimethylformamide and dimethyl sulfoxide. The
-
~ reaction may be promoted in the presence of a tertiary amine,
~ . ,
for example, N-alkylmorpholines such as N-methylmorpholine,
N-ethylmorpholine, N-propylmorpholine and N-butylmorpholine.
~,-
~ .. .
- ? -
~:
- - :, . : . ' -: .
,.......... . . . . .
- .: :- : . ~ . -
- -
-~ ;- . .- , - :
:~ . . ~ : .
.,
. . ' . ~
2~
The reaction may be promoted by refluxing a reaction
mixture at a boiling point of the solvent used, and by removing
water formed from an azeotropic mixture.
The period required for cd~pletion of the reaction
will vary, depending on varisous conditions such as amount
of catalyst to be used, species of solvent and molar ratio ~-
of reactants; hut it will be suitably from 4 to 14 hours.
The reaction may preferably be performed at 80-180C.
Equimolar amounts of compound (VII) and aniline compound
(IV) are used, in general. Ho~ever, it is preferable that
a little excess of aniline compound (IV) is used than the
compound (VII).
The condensation product obtained by the above reaction
:: has the following structure (VIII): ~
zl (VIII)
Z CH N
\y (CH2)m
(R )n
. (wherein, y~ zl, z2, R, Rl, m a~d n are as defined above.).
~ The compound (vlII)may react with excess aniline compound
.~ '. . . .
(IV) by further heating, giving a compound of the following
8 -
-: . .
,, . - : : . . .... . .. _.. _ __ __
. . . , .. ~ , .. . .
. -. . , . . :': ' . , : , -
~ :' . ' ' ' -. .' ' '.'' . : ' . ' - .
--
z~
formula (IX):
~z l
CH ~ z2
(wherein, zl and z2 are as defined above.).
The compound (IX) also gives the aimed anthranylaldehyde
derivative (I) by treating it with an acid.
After the condensation reaction, the compound (VIII)
may be isolated by conventional methods. For example, the
solid residue is removed by fl1tration, the solvent is
evaporated by distillation under reduced pressure, and crystals
are separated. The yield of the condensation reaction is
usually from 65 to 95%.
.
The compound (VIII)may readily be decomposed by maintain-
ing it in a water-miscible org~nic solvent or aqueous solvent
at an acidic condition to give the desired anthranylaldehyde
derivative (1).
There is no specific limitation as to the nature of
the organic solvent or aqueous solvent as far as it dissolves
the~compound ~VIII).~
9 -_
` -7~
..- . . : : :
: ,: ,~. : ~ . ':
- : ' ' ,~:: -
; .' ' ~ ' ': '
~$~
Acid to maintain acidic condition includes inorganic
acids such as hydrochloric acid, sulfuric acid and phosphoric
acid; acidic salts such as sodium hydrogen sulfate, sodium
hydrogen sulfite and ammonium chloride; and strong organic
acids such as sulfonic acids and monochloroacetic acid.
The reaction usually proceeds at ambient temperature;
but heating at 40-70C is sometimes required, depending on
the species of compounds to be decomposed.
The period required for completion of the reaction
will vary from 10 minutes to 5 hours, preferably from 20 minutes
to 1 hour.
Usually, the reaction is performed at ambient temperature
under stirring for period mentioned above.
After completion of the reaction, the reaction mixture
~; is extracted with a solvent such as benzene. Subsequently,
the extract is dried and the solvent is removed to give ~ -
compound (I) in the form of an oil or solid.
As mentioned above, the compound (VIII)may once be
isolated~for acid decomposition. Alternatively, compound
may also be obtained by acidifying the reaction mixture
without~isolation of compound (VIII).
As~clear from tHe foregoing descriptions, the process
of the invention provides anthranylaldehyde derivative
I) by USiDg a readily available o-halogenobenzaldehyde as
the starting material, with high yield, under quite easy
"~
- . . - , :. - . -
--: ~ . , . . - . .. .
,, . ,,, , ~ , . ,, ~ . ..... :
:, : , . " : , .
- ~ . . : - . -
. . - ~ . .
. .
~3iZ~
operations.
The invention is further illustrated by the following
working examples, which by no means restrict the scope of
the invention.
Example 1.
9.0 g (0.01 mol.) of N,N'-dimethylethylenediamine
was added dropwise to a solution of 18.5 g (0.10 mol.)
of o-bromobenzaldehyde in 50 ml of toluene at 30-40C, and
the mixture was stirred for 2 hours at ambient temperature.
Water was removed by azeotropic distillation with
benzene, and the benzene was evaporated ~y distillation
under reduced pressure. The resulting residue was distilled
at 78-81C/0.4 mmHg, in a strèam of nitrogen, affording 23.8 g
of a pale yellow oil, which was confirmed to be 1,3-dimethyl-
, ~
2-(o-bromophenyI)imidazolidine by IR (dissipation of carbonyl
absorption of starting material) and NMR analyses.
yield=93~.
NMR (CDCl3) :~2.20 s (6H), 2330-3.45 m (4H), 4.03 s (lH),
6.90-7.80 m (4H).
Example 2.
12.7 g of 1,3-dimethyl-2-~o-bromophenyl)imidazolidine (
O~.OSO~mol.), 16~.~2 g (O.lO~mol.~ of 2,6-dichloroaniline~ 30 ml
of~N-isobutylmorpholine, 22.0 g (0.16 mol.) of pulverized
~ .
. :
.
'-': . ' ' ' :
1~31Z~
potassium carbonate and 1.2 g (0,015 mol.) of cupric
oxide were added to 50 ml of n-nonane. The mixture
was refluxed for 6.5 hours, while removing water formed
}n situ by azeotropic distillation. After cooling and
filtration, the n-nonane, N-isobutylmorpholine and 2,6-
dichloroaniline were evaporated by distillation under reduced
pressure of 0.5 mmHg, leaving a residue. The residue was
dissolved in hot hexane, treated with charcoal and recrysta-
llized, gi~ing 13.5 g o~ pale yellow crystals. The compound
was confirmed to be 1,3-dimethyl-2-[o-(2,6-dichloroanilino)-
phenyl]imidazolidine by IR, NM~ and mass spectrometric anal-
yses. yield=80%.
m.p.=114-116C
IR (KBr) : 2950-2600, 1596, 1530, 1460, 1350, 895, 770,
745, 710 cm~
NMR (CDC13); ~2.27 s (6H), 2.S0-3.40 m (4H), 3.54 s (lH),
6.30-7.45 m (7H)
MS (20 eV) : m/e 337 (M+ + 2, 36.9%), 336 (M~ + 1, 26.0%),
335 (M+, 57.7%), 334 (28.4%), 332 (65.0~),
- 321 (13.9%), 32Q (base peak), 293 (40.7%),
. 292 (8.3 %), 291 (67.4%).
. .
~ ; 12 -
. ~ .
., .. .. ,. ._. . _. _ . . . . .... . . . _ . .... _ _ _ . _
~ . . ~ . - . . - .
. . .. . - .- - . . . . .
2~
Example 3.
3.4 g (0.010 mol.) of 1l3-dimethyl-2-1O-(2,6-dichloro-
anilino)phenyl~imidazolidine obtained in Example 2 was
dissolved in 30 ml of benzene. 10 mlofa 5% hydrochloric
acid was added and the mixture was stirred for 30 minutes
at ambient temperature. After separating the two layers,
the benzene layer was dried with anhydrous sodium sulfate
and the benzene was evaporated ~y distillation, leaving
yellow crystals. The crystals were recrystallized from `
hexane to give 2.5 g of pale yeilow crystals which were conf-
irmed to be N-(2,6-dichlorophe~l)anthranylaldehyde by IR
and NMR analyses. yield=94~.
m.p.=110-112-C
IR ~KBr) : 1665, 1590, 1508, 1455, 1400, 772, 752 cm 1
NMR (CDC13): ~ 6.25-7.60 m (7H), 9.85 s (lH)
Example 4.
9.0 g (0.10 mol.) of N,N'-dimethylethylenediamine
was added to a solution of 18.5 g (0.10 mol.) of o-bromo-
benzaldehyde in 50 ml of xylene, and the mixture was stirred
, ~ ~
for~2 hours;at ambient temperature. Then the mixture was
heated~and water formed in the system was removed by azeotropic
dlstillation.~ The xylene~solution was cooled and 32.4 g (
0.20~mol.) of 2,6-dichloroanillne, 30 ml of N-ethylmorpholine
s~
: - . :..... . ~ : .: . . . -
- : , ,,
'-'- ' : ` :., ; ` - ': ` ' - . ,
and 30 g (0.22 mol.) of pulverized anhydrous potassium
carbonate were added. The mixture was again heated for
2 hours to remove water by azeotropic distillation. A~ter
cooling, 2.8 ~ (0.020 mol.) of cu~rous oxide was added
and the mixture was refluxed for 6 hours, while removing
water formed in situ by azeotropic distillation. After
cooling and filtration, 100 ml of xylene was further added
and then 50 mlofa 5% hydrochloric acid was added, and the
mixture was stirred for 1 hour at 30-40C. The xylene layer
was separated, washed with water, dried over anhydrous
sodium sulfate and subjected to distillation under reduced
pressure at 160-168DC/0.4 mmHg to give 16.8 g of a yellow
oil. After allowing to stand at ambient temperature, the oil
turned to crystals which ~e confirmed to be N-(2,6-dichlorQ-
phenyl)anthranylaldehyde by IR and NMR analyses. yield=63%.
Example 5.
18.5 g (0.10 mol.) of o-bromobenzaldehyde was added
(0.10 mol.)
to a solution of 9.0 g/of N ,h ~ -dimethylethylenediamine in
50 ml of xylene, and the mixture was stirred for 2 hours
at ambient temperature. The mixture was then heated to
remove water in the system by azeotropic distillation.
The xylene solution was cooled and 64.8 g (0.40 mol.)
:: ..
of 2,6-dichloroaniline, 30 ml of N-isobutylmorpholine and
14 -
, ~ .: . . - . . . . . . .
- . . . : . . ..
. -
, ' - ' ' '' ' ' ' ' '" .
. , . ~ . .
. ~ ~. . .
.. . . . . .
.
j
:
(0.33 mol.)
45 g~of pulverized anhydrous potassium carbonate were added.
The mixture was heated, with stirring, for 2 hours
again to remove water in the system by azeotropic distill-
ation. After cooling, 2.4 g (0.030 mol) of cupric oxide
was added, and the mixture was refluxed for 4 hours, while
removing water formed in situ by azeotropic distillation.
The mixture was cooled to ~0C, and excess amount of
potassium carbonate and potassium bromide formed were dissol-
ved by addition of 200 ml of water and stirring. The organic
layer was separated and evaporated by distillation under
reduced pressure. The bath tèmperature was maintained at
140C and the pressure was slowly rèduced to remove a fract-
ion distilled out at 0.5 mmHg. The residue was dissolved in
150 ml of benzene, and àfter addition of 50 mlof a5~ hydro-
chloric acid, the mixture was stirred and separated. The
benzene layer was dried with anhydrous sodium sulfate and
~ .
the benzene was evaporated by d~stillation under reduced
; pressure. The residue was recrystallized from hexane, afford-
ing 19.2 g of N-(2,6-dichloroph~nyl)anthranylaldehyde.
yield=72%~
: -. - , .
.~. . .-; . :~' -
. ~ - : - .
- ~ - .
~3~2~
Example 6.
Following substantially the same procedures as in
Example 4, except that 1.4 g (0.01 mol.) of cuprous bromide
was used in place of cuprous oxide, there ~7as obtained
10.2 g of N-(2,6-dichlorophenyl)anthranylaldehyde.
yield=38~.
Example 7.
9.3 g (0.050 mol.) of o-bromobenzaldehyde
was added to a solution of 6.0 g (0.052 mol.) of N,N'-diethyl-
ethylenediamine in 30 ml of xyle~e, and the mixture was ~tirred
for 5 houmæ at ambient temperature. The mixture was heated
to remove water in the system by azeotroic distillation. The
xylene solution was cooled and 16.2 g (0.10 mol.) of 2,6-
dichloroaniline, 15 ml of N-iso~utylmorpholine and 15 g (
0.11 mol.) of pulverized anhydrous potassium carbonate were
added. The mixture was again heated for 2 hours to remove
water in the system by azeotroic disti~lation. After cool-
ing, 1.4 g (0.010 mol.) of cupric oxide was added and the
mixture was refluxed for îs hours to remove water formed
in situ. By subjecting the reacti~on mixture to acid decomp-
osltion in the similar manner as in Example 5, there was
obtained 7.5 g of N-(2,6-dichlorophenyl)anthranylaldehyde.
ld=56~
16 _
.. . . .
`~-- ' ' . : `
.,: ' .: . '
. ~ \
Example 8.
9.3 g of o-bromobenzaldehyde (0.050 mol.) was added
to a solution of 3.8 g (0.050 mol.) of N-methylaminoethanol
in 30 ml of xylene, and the mixture was stirred for 8 hours
at ambient temperature. The mixture waa heated to remove
water in the system by azeotropic distillation. The xylene
solution was cooled and 16.2 g (0.10 mol.) of 2,6-dichloro-
aniline, 15 ml of N-isobutylmorpholine and 22 g (0.16 mol.)
of pulverized anhydrous potassium carbonate were added. The
mixture was refluxed fo~ 2 hours to remove water in the
system by azeotropic distillatioh. After cooling, 1.2 g (
0.015 mol. ) of cupric oxide was added and the mixture was
refluxed for 7.5 hours to remove water formed in situ. By
subjecting the reaction mixture to acid decomposition in
the similar procedures as in Example 5, there was obtained
6.5 g of N-~2,6-dichlorophenyl)anthranylaldehyde. yield=49%.
,~ ,
Example 9.
23.1 g (0.10 mol.) of o-iodobenzaldehyde was added to
a solution of 9.0 g ()0.10 mol.) of N,N'-dimethylethylenediamine
in 50 ml of toluene, and the mixture was stirred for 8 hours
,,
at ambient temperature. The mixture was heated to remove
water in the system by azeotr~pic distillation. The xylene
solution was cooled and 48.6 g (0.30 mol.) of 2,6-dichloro-
' - 17 - -
. , - ~ ~
- : - ~ - . .
~ 5L`3:~%~
aniline, 30 ml of N-isobutylmorpholine and 30 g (0.22 mol.)
of pulverized anhydrous potassium carbonate were added. The
mixture was again heated for 2 hours to remove water in
the system by azeotropic distillation. After cooling,
2.4 g (0.030 mol.) of cupric oxide was added and the mixture
was refluxed to remove water formed ln situ. By subjecting
the reaction mixture to acid decomposition in the similar
manner as in Example 4, there was obtained 20 g of N-t2,6-
dichlorophenyl)anthranylaldehyde. yield=75%. -
Example 10.
A mixture of 92.5 g (0.50 mol.) of o-bromobenzaldehyde
and 41.3 g (0.55 mol.) of N-metH~laminoethanol in 300 ml --
~ ~ .
of benzene was refluxed for 2 hours, while removing water
formed in situ. The benzene waS evaporated by distillation
under reduced~pressure, and the residue was subjected to
distillation at 100-102C/l.0 mmHg under nitrogen stream
to give 115.0 g of a colorless oil. The compound was
confirmed to be 2-(o-bromophenyl)-3-methyloxazolidine
by IR analysis on the basis of dissipation of carbonyl
absorption shown in the starting material. yield=95%.
NMR (CDC13): ~ 2.30 s (3H), 2.45-3.37 m (2H), 3.87-4.10 m (2H),
5.15 s (lN), 6.90-7~.70 m (4~)
z~
Example 11.
A mixture of 24.2 g (0.10 mol.) of 2-(o-bromophenyl)-
3-methyloxazolidine, 32.4 g (0.20 mol.) of 2,6-dichloroaniline,
41.4 g (0.30 mol.) of pulverized anhydrous potassium carbonate
and 2.4 g (0.030 mol.) of cupric oxide in 150 ml of di-n-
butyl ether was refluxed for 6.5 hours, with vigorous stirring,
while removing water formed in situ. After cooling and
filtration, 100 mlofa 15% hydrochloric acid was added to the
filtrate and the mixture was heated for 2 hours at 80-85C,
with stirring. After cooling, the organic layer was separated
and subjected to distillation under reduced pressure to
remove the di-n-butyl ether and 2,6-dichloroaniline. The
resulting residue was added to methanol to precipitate 17.3 g
of the desired N-~2,6-dichlorophenyl)anthranylaldehyde in the
form of pale yellow crystals. The filtrate was condensed
and lS ml of di-n-butyl ether was added, and the mixture was
allowed to stand for 3 days,giving further 7.9 g of
N-(2,6-dichlorophenyl)anthranylaldehyde. yield=72%.
;- -
.
,'; ' ~ ' . .
.~ . .
19- ~
., `, . ~... . .
. ' '. ' ' ' '
,' ,
. . ' ~ ~ ' ,
Example 12.
A mixture of 48 h g (0.20 mol.) of 2-(o-bromophenyl)-
3-methyloxazolidine, 51.0 g (0.~0 mol.) of o-chloroaniline,
83.0 g (0.60 mol.) of pulverized anhydrous potassium carbonate
and 4.8 g (0.06 mol.) of cupric oxide in 350 ml of di-n-
butyl ether was refluxed for 7 hours, with vigorous stirring,
while removing water formed _ situ. After cooling and filt-
ration, the filtrate was washed with water, dried over anhyd-
rous sodium sulfate and subjected to distillation, maintair.ing
the bath temperature at 140C. The pressure was gradually
reduced, and a fraction evaporated at 0.5 mmHg was separated.
The residue was dissolvea in 130 ml of toluene, 40 ml
ofa8% hydrochloric acid was added, and the mixture was heated
for 2 hours at 60-70C with stirring. After cooling, aqueous
ammonia was added until pH of ~hé aqueous layer reached 3-5
and the mixture was shaken. T~e toluene layer was separated,
washed in turn with water,a10% àqueous sodium hydrogen sulfite
solution and water and dried over anhydrous sodium sulfate.
The toluene was evaporated by distillation under reduced
pressure and the resid~é was subjected to distillation under
reduced pressure at 172-178C/0.7-0.8 mmHg, affording 19.4 g
of N-(o-chlorophenyl)anthranylàldehyde in the form of a pale ye-
: ~
~w oil, the chemical structure of which was confirmed by
IR and NMR analyses. yield=42%.
IR ~Deat): 3250, 166Q, 1530, 1320, 742, 650 cm 1
NMR (CDC13): ~6.65-7.70 m (8H), 9.84 (lH)
- 20--
~, ~; : , _ __ , . . ... _
... . . . .
.
- :
,
2~3
Example 13.
Following substantially the same procedures as in
Example 12, except that 65 g (0.40 mol.) of m-trifluoromethyl-
aniline and 51.0 g (0.20 mol.) of 1,3-dimethyl-2-(o-bromo- -
phenyl)imidazolidine were used in pl~ace of o-chloroaniline
and 2-(o-bromophenyl)-3-methyloxazolidine, respectively, there
was obtained 26.6 g of N-(m-trifluoromethylphenyl)anthranyl-
aldehyde, boiling at 150-156C/0.6 mmHg. yield=50~.
IR (KBr) : 3250, 1660, 1580, 1332, 1120, 795, 750, 690 cm 1
NMR (CDC13): ~6.70-7.60 m (8H), 9.80 (lH)
~-
Example 14.
Following similar procedures as in the first step of
Example 12 and using 10.6 g (0.10 mol.) of o-toluidine and
12.7 g (0.050 mol.) of 1,3-dimethyl-2-(o-bromophenyl)imidaz-
olidine, a mixture was refluxea for 4 hours. The reaction
product was confirmed to be 1,3-dimethyl-2-[o-(o-methylanilino)-
phenyl]imidazolidine by combined gaschromatographic and mass
spectrometric analyses. The compound was then subjected to
acid decomposition, giving N-(o-methylphenyl)anthranylaldehyde,
the yield of which was 40~ based on 1,3-dimethyl-2-(o-bromo-
phenyl)imidazolidine reacted.
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