Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
l~gZ8~4
BACKGROUND OF THIS INVENTION
1. Field of This Invention
This invention relates to a process for the production
- of 1,2-dihydro-2-oxo-4-methyl-7-amino-quinoline. This
invention also relates to a process for the production of
1,2-dihydro-2-oxo-4-methyl-7-acetoacetic acid amido quinoline.
2. Prior Art
1,2-dihydro-2-oxo-4-methyl-7-amino-quinoline has been
produced from m-phenylene diamine and acetoacetic ester by
heating at 130C. for 19 hours in an autoclave - a 45 to
60 percent yield resulted (Chemisches Zentralblatt, Vol.
109, (1938), page 4240.) Nowadays acetoacetic acid ester
is obtained most economically from diketene.
An object of this invention is the production of
1,2-dihydro-2-oxo-4-methyl-7-amino-quinoline or 1,2-dihydro-
2-oxo-4-methyl-7-acetoacetic acid amido quinoline by the
reaction of diketene with m-phenylene diamine.
SUMMARY OF THE INVENTION
.
According to the invention, about one mole of
diketene can be reacted with about one mole of
m-phenylene diamine to produce 1,2-dihydro-2-oxo-4-methyl-
7-amino-quinoline or about two moles of diketene can be
reacted with about one mole of m-phenylene diamine to produce
1,2-dihydro-2-oxo-4-methyl-7-acetoacetic acid amido quinoline.
The above reactions are carried out at a temperature below
100C., at about or below atmospheric pressure and in the
presence of catalytic amounts of acetic acid.
The first embodiment of this invention involves a
process for producing 1,2-dihydro-2-oxo-4-methyl-7-amino- ~-
quinoline. The process includes reacting about one mole
of diketene with about one mole of m-phenylene diamine.
- 2 -
.~ ~;
1~4Z894
The phrase "about one mole" includes the range of 0.9 to
1.1 mole. Preferably one mole of diketene is reacted with
one mole of m-phenylene diamine. In such a case, yields of
70-to 80 percent are obtained.
The reaction can be conducted in water in the
presence of a catalytic amount of acetic acid. Pre-
ferably the amount of acetic acid present is 10 percent by
weight of the mixture of water and acetic acid.
- 3 -
;&~ '
1~4Z894
The reaction can be conducted in en organic solvent in the
presence of about 5 percent by weight of the mixture of the
or~anic solvent and th~ acetic acid. That amount of acetic acid
is catalytic to the subject reaction. The starting materials
are soluble in the organic solvent. Examples of the organic
solvent are methanol, butyl acetate, carbon tetrachloride and
toluene.
The reaction can also be conducted in glacial acetic acid.
The reaction is conducted at a temperature below 100C. and
at about or below atmospheric pressure. Preferably the reaction
temperature is between 60 and 65C. Also, under certain
circumstances the reaction can be conducted under reflux (reflux
i9 the highest temperature which should normally be used).
This embodiment of this invention allows the production of
7-amino-lepidone directly from diketene (in~tead of through
acetoacetic ester) using a process which is carried out at
considerably lower temperatures than prior process and without
pressure, but with better yields.
The second embodiment of this invention involves a process
for producing 1,2-dihydro-2-oxo-4-methyl-7-acetoacetic acid
amido-quinoline. The process involves reacting about two moles of
diketene with about one m~le of m-phenylene diamine. The phrase
"about one mole" includes the range of 0.9 to 1.1 mole and the
phrase "about two moles" includes the range of 1.9 to 2.1 moles.
Preferably two moles of diketene is reacted with one mole of
m-phenylene diamine. In such a case, better results are obtained. ~-~
-4-
1~42894
The reaction can be conducted in water in the presence of
a catalytic amount of acetic acid. Preferably the amount of
acetic acid present is 10 percent by weight of the mixture of
water and acetic acid.
The reaction can be conducted in an organic solvent in the
presence of about 5 percent by weight of the mixture of the
.~ ,
organic solvent and the acetic acid. That amount of acetic acid
is catalytic, to the subject reaction. The starting materials
are soluble in the organic solvent.
The reaction can also be cor.ducted in glacial acetic acid.
The reaction is conducted at a temperature below 100C.
and at about or below atmospheric pressure. Preferably the
reaction temperature is between 60 and 65C. Also, the reaction
can be conducted under reflux (reflux is the highest temperature
which should normally be used).
,.: .
,; :. .
~,.' . .. .
'.'' ' '':
-5-
''" :'
" '
.. . .
1~4Z894
DETAILED DESCRIPTION OF THIS INVENTION
1,2-dihydro-2-oxo-4-methyl-7-amino-quinoline is also
termed 7-amino-2-oxy-lepidine or 7-amino-lepidone. 7-amino-
lepidone is a intermediate from which valuable pharmaceuticals
..~.
are and can be made.
1,2-dihydro-2-oxo-4-methyl-7-acetoacetic acid amido-
quinoline is also termed 7-acetoacetylamino-4-mehhyl-quinolone-
(2) or 7-acetoacetylamino-lepidone. 7-acetoacetylamino-lepidone
is an intermediate from which special pigments are and can be
made-
All, parts, ratios, percentages and proportions herein are
on a weight basis, unless otherwise stated or obvious to one
ordinarily skilled in the art from this disclosure.
EXAMPLE 1
This example is the preferred mode of the first embodiment
of this invention.
43.2 gm. of at least 98 percent pure 1,3-phenylene diamine
(melting point: 60 to 62C) and 100 ml of 10 percent acetic acid
are placed in a sù~f~rizing flask equipped with an anchor bolt,
reflux coo~e~, dr~pping funnel, ther meter and water bath.
35.2 gm. of diketene were allowed to drip into the reaction
mixture over the course of about 20 minutes at room temperature.
The reaction mixture was stirred during the addition. The
temperature was allowed to rise with the aid of the reaction heat -
to 60 to 65C. After completion of the addition of diketene, the
reaction was allowed to continue for another hour at 60 to 65C.
After cooling to about 15C. the resultant precipitate was
-6- -
~42~94 :~:
separated out and dried under vacuum at 60 to 70C until the
precipitate reached a constant weight. 49.2 gm. of yellow,
disc~lored l,2-dihydro-2-oxo-4-methyl-7-amino-quinoline with
a melting point of 268 to 269C were obtained, which corresponded -~
to a yield of 70.7 percent, based on the m-phenylene diamine.
After a single recrystallization from dimethylformamide/H20
(1:1), the product was colorless and had a melting point of
274.6 1:o 2~5.4C. ``
The example was repeated, except that the single
10 recrystallization was done using 50 percent acetic acid. The
product was colorless and had a melting point of 274.0 to
274.8C.
EXAMPLE 2
This example i9 the preferred mode of the second :" `
embodiment of this invention.
129.6 gm of at least 98 percent pure 1,3-phenylene diamine
(melting point: 60 to 62C) and 750 ml of 10 percent acetic
acid were placed in a sulfurizing flask, equipped with an
anchor bolt, reflux cooler, drip funnel, thermometer and water ;
20 bath. 211.2 gm of diketene were allowed to drip into the reaction
mixture over the course of 1.5 hours at room temperature. The
reaction was stirred during the addition. The temperature, with
the aid of the reaction heat, was allowed to rise to 60 to 65C.
After completion of the addition of diketene, the mixture was `
allowed to continue for another hour at 60 to 65C. and was then
cool~td to about 15C, The precipitated product was then ~
separated out and dried udder vacuum at 60 to 70C. until the ~ -
--7--
1s~4Z894
precipate reached a constant weight. 257 gm. of raw, almost
colorless, l,2-dihydro-3-oxo-4-methyl-7-acetoacetamino-quinoline
was obtained having a melting point of about 238C. This
corresponded to a yield of about 83 percent, based on the
m-phenylene diamine. After a single recrystallization from 67
percent acetic acid, the product had a melting point of 246.0
to 247.0C. After one more recrystallization from the diluted
acetic acid, the melting point was found not to have changed.
-8-
