Патент USA US2522164

Patented Sept. 12, 1950
2,522,163
UNITED STATES PATENT OFFICE
2,522,163
PROCESS OF MANUFACTURING
PYRIDINECARBOXYLIC ACIDS
Wheeler, In
dianapolis, lnd., assigners toR.Reilly
Tar &
Francis E. Cislak and William
Chemical Corporati on, Indianapolis, [nd., a
corporation of Indiana
No Drawing. Application March 25, 1942,
Serial No. 438.168
21 Claims. ( Cl. ZED-295.5)
2
Our invention relates to a process of manu
i’acturing pyridinecarboxylic acids by the oxida
To this end, add about 25 co. more concentrated
nitric acid. Re?ux the solution for about 2—3
hours. Distill oil the water, and the remaining
nitric acid.
Repeat the procedure of the immediately pre
oline, and alkyl quinolines.
Heretofore pyrldinecarboxylic acids have been
prepared by the oxidatio
alkyl pyridines, quin
oline, isoquinoline, or alkyl quinolines with potas
ceding paragraph until a total of about 275 cc.
of the concentrated nitric acid has been put
through. When the last distillation has been
The preparation of pyri
this manner is costly and 10 completed, remove any remaining traces of nitric
acid from the residue in the flask by aerating
the hot solution.
Then cool the said residue and dilute it with
about 700 cc. of water.
a
‘
If it is desired to eliminate sulfuric acid, add
the calculated amount
20
oxidation of the above-mentioned pyridine-ring
containing compounds.
talline nicotinic acid in known manner.
Example 2.—In place of intermittently add
Fundamentally, our process consists in oxidiz
ing the sulfates of the said pyridine-ring-con
taining compounds with nitric acid at elevated
temperatures, with or without oxidation cat
alysts; if desired, with subsequent elimination of
sulfuric acid.
ing small portions of nitric acid to the 3-picoline
sulfate, re?uxing, and distilling, as in Example 1,
The preferred manner in which our invention
may be practiced is described
trated, in the following examples.
Example 1.-—In a one-liter ?ask, form a solu
tion of 47 grams of 96% 3-picoline, 50 cc. of con
centrated sulfuric acid (96%), and 25 cc. of con
centrated nitric acid (70%). Re?ux this solu
tion for about 2-3 hours; and then distill off the
water formed by the oxidation (as well as the
IO
the water and excess nitric acid.
The entering nitric-acid vapor may be mixed
with oxygen or air; in which case the amount
of nitric acid required is diminished.
In a one-liter ?ask form a solution of 47 grams
of 93% 3-picoline and 92 grams of 96% sulfuric
acid. Heat this solution to a temperature of
about 150-250” 0., preferably about 170° C., and
maintain it at this temperature. Slowly (over a
-10 period of 15 to 25 hours) vaporize 300
the nitric acid). and
with it any remaining nitric acid. It is desir
able to stop the distillation when the tempera~
, aerate the hot solution
to remove residual traces of nitric acid.
ture of the liquid remaining in the ?ask reaches
about 200° C.
Cool and dilute the picoline-sulfate solution,
and ii’ desired separate the nicotinic acid, as in
Now cool the contents of the ?ask to about
Example
1.
120° 0., and repeat the nitric-acid oxidation. 50
Example 3.-—In place of the 3-picoline of E‘ -
2,522, 168
4
boxylic acid as described in claim 8, in which
the pyridine-ring-containing compound is 3
use any of the other alkyl
picoline.
10. The method of producing a pyridinecar
pyridines, such as Z-picoline. 4-picoline, 2,6
lutidlne, 2-ethyl pyridine. etc.. to obtain corre
sponding
pyridinecarboxylic acids.
Example 4.-In place 0! the a-picoline
boxylic acid as described in claim 8, in which the
pyridine-ring-containlng compound is quinoline.
01 Ex
11. The method of producing a pyridinecar
boxylic acid as described in claim 8, in which the
amples l and 2. we can use quinoline or iso
quinoline, to obtain pyridinedicarboxyilc acids.
pyridine-ring-containing compound is z-picoline.
or we can use alkyl quinolines to obtain pyridine
dicarboxylic acids or alkyl pyridinedicarboxylic
12. The method of producing a pyridinecar
i0 boxylic acid as described in claim 8, in which the
pyridine-ring-containing compound is 4-picoline.
acids.
For instance, a solution of 64.5 g. of quinoline
and 110 g. of 98% sulfuric acid is placed in any
suitable vessel for bringing about intimate con
tact of gas and liquid. and heated to 150-230" 0..
preferably about 180° 0.: and the vapor of 500
to 800 cc. oi’ nitric acid (‘10%) is passed through
over a period of 24-48 hours. The reaction mix
ture is cooled. and diluted with water‘, where
upon any small
.
13. The method of producing a pyridinecar
boxylic acid as
in claim 6, with the
addition 01.’ the step of eliminating sulfuric acid.
14. The method of producing a pyrldinecar
boxylic acid which comprises oxidizing a sul
fate of alkyl pyridine with nitric acid at ele
vated temperatures and recovering the pyridine
carboxylic
20
15. The acid.
method of producing pyridinecar
ouinolines precipitate and are ?ltered oil. The
?ltrate is made alkaline. and more lay-product
nitro-cornpounds are precipitated and removed
boxylic acids which comprises oxidizing a sul
fate of the following compounds
by ?ltration. The remaining alkaline solution
contains a salt of quinolinic acid. 0n acidifying
this alkaline solution with acetic acid, and treat
ing with a solution of copper sulfate. green cop
per ouinolinate is precipitated. From this cop
where R. is alkyl and
per salt ouinolinic acid mayY be prepared by sat
urating its aqueous suspension with hydrogen 30
sul?de. filtering of! the precipitated copper sul
fide. and evaporating the filtrate until quinolinlc
acid
separates.
‘if desired, we can use oxidation catalysts. such
as vanadium or manganese salts. in anv of thoset35
Examples 1 to 4. with bene?cial results:
those catalysts are not necessary.
We claim as our invention:
1. The method of producing a ovridinecar
hnxylic acid. which comprises oxidizing a sul
fate of a nvridine-ring-containinq compound 01’
the class consisting of alkvl nvridines. ouinoiine.
with nitric acid at elevated
the pyridine ring, recovering a pyrldinecar
temperatures and
boxylic
16. Inacid.
the catalytic oxidation to a pyridine
carboxylic acid
N-heteroarylgrouping
compound
at
tached to the nitrogen-containing aromatic
nucleus by one or more carbon-to-carbon link
ages, the improvement which comprises con
ducting the oxidation by reacting nitric acid with
iqnnuinoline. and aikvl ouinolines. with nitric
the N-heteroaryi compound in the presence of a
acid at an elevated temperature sufficiently high
to vannrize nitric acid and recovering the pyri 45 relatively small amount of the catalyst and sul
{uric
dinpr-orhoxvlic acid.
1'1. acid.
The process which comprises mixing sul
2.1‘he method of producing a pvridinecar
furic
acid
and a compound of the class consist
hnszvlic acid as described in claim‘ 1. in which
ing of alkyl pyridines and compounds having the
the ovridine-ring-containing compound is 3
50 structure
picoiine.
3. The method of producing a nvridinecar
hnxviic acid as described in claim 1. in which the
pyridine-rine-cootaining compound is ouinoline.
4. The method of producing a nyridinecar
_N,
hoxvlic acid as descrihed in claim 1. in which the 55 where R is selected from the group consisting
pvridine-ring-rontaining compound is Z-nicoiine.
of hydrogen and alkyl and N is the pyridine
ring, and reacting the resultant mixture with
nitric acid at elevated temperatures and recov
5. The method of producing pvridinecar
hoxylic acid as described in claim 1. in which
the ovridine-ring-containing compound is 4
nicoline.
6. The method of producing pyridinecar
hoazviic acid as described in claim 1. in which the
60
ering the so formed pyridinecarboxylic acid.
18. The process which comprises mixing sul
turic acid and qulnoline, reacting the resultant
mixture with nitric acid at elevated tempera
ovridine-ring-containing compound is an alkyl
turgs and recovering the so formed nicotinic
ouinoline.
'1. The method of producing a pyridinecar 65 aci19.. In the catalytic oxidation to a pyridine
boxvlic acid as described in claim 1, with the
carboxylic acid of an N-heteroaryl compound
addition of the step of eliminating sulfuric acid.
containing an oxidizable organic grouping at
8. The method of producing a pyridinecar
tached to the nitrogen-containing aromatic
boxylic acid. which comprises treating a pyridine
nucleus by one or more carbon-to-carbon link
ring-containlne compound of the class consist
ages. the improvement which comprises con
‘mg of allryl pyridines, quinoline, isoquinoline.
ducting the oxldation by adding nitric acid to
and alkvl quinolines. with sulfuric acid and
nitric acid at an elevated temperature will
ciently high to vaporize nitric acid and recov
ing the pyridinecarboxylic acid.
9. The method of producing a pyridinecar
a solution containing the N-heteroaryl com
pound and a relatively small amount of the cata
75 lyst dissolved in sulfuric acid.
2,898, 188
20. m the catalytic oxidation to a pyridine
carboxyiic acid of an N-heteroaryl compound
containing an oxidizable organic grouping at
tached to the nitrogen-containing aromatic
nucleus by one or more carbon-to-carbon link
ages, the improvement which comprises con
ducting the oxidation by reacting nitric acid
pyridine-?ug-containing compound is an mm
quinoline.
FRANCIS E- CISLAK.
wnimam R. WHEELER.
REFERENCES CITED
The following references are of record in the
tile of this patent:
with a sulfuric acid solution of the N-heteroaryl
compound in the presence of a catalyst.
Mater, "Das Pyridine und Seiner Derivatives,"
10
21. The method of producing a pyridinecar
193‘. 90888 212, 222, 230, 237, 241, 248, 249, 251,
264
bosyiic acid as described in claim 8. in which the