CA2128951A1 - Preparation of aromatic carboxylic acids - Google Patents
Preparation of aromatic carboxylic acidsInfo
- Publication number
- CA2128951A1 CA2128951A1 CA 2128951 CA2128951A CA2128951A1 CA 2128951 A1 CA2128951 A1 CA 2128951A1 CA 2128951 CA2128951 CA 2128951 CA 2128951 A CA2128951 A CA 2128951A CA 2128951 A1 CA2128951 A1 CA 2128951A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- preparation
- carboxylic acids
- quinoline
- aromatic carboxylic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
- C07C51/27—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with oxides of nitrogen or nitrogen-containing mineral acids
- C07C51/275—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with oxides of nitrogen or nitrogen-containing mineral acids of hydrocarbyl groups
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/16—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of arsenic, antimony, bismuth, vanadium, niobium, tantalum, polonium, chromium, molybdenum, tungsten, manganese, technetium or rhenium
- B01J23/20—Vanadium, niobium or tantalum
- B01J23/22—Vanadium
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
- C07B41/08—Formation or introduction of functional groups containing oxygen of carboxyl groups or salts, halides or anhydrides thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Quinoline Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Preparation of Aromatic Carboxylic Acids Abstract of the disclosure:
Preparation of aromatic carboxylic acids of the formula I
Ar(COOH)n (Ar = isoaromatic or heteroaromatic radicals, n = 1 to 4) by oxidation of a compound II
Ar(CH3)n II
using an oxidizing nitrogen/oxygen compound (III) in the presence of sulfuric acid and a vanadium compound (IV) at from 120° to 180°C in the liquid phase, in which for each mole of compound II present in the reaction mixture, from 20 to 100 mol% of vanadium compound (IV) are available for the oxidation.
Preparation of aromatic carboxylic acids of the formula I
Ar(COOH)n (Ar = isoaromatic or heteroaromatic radicals, n = 1 to 4) by oxidation of a compound II
Ar(CH3)n II
using an oxidizing nitrogen/oxygen compound (III) in the presence of sulfuric acid and a vanadium compound (IV) at from 120° to 180°C in the liquid phase, in which for each mole of compound II present in the reaction mixture, from 20 to 100 mol% of vanadium compound (IV) are available for the oxidation.
Description
I~ASFAltTlEN~lESEL~SCHAFT ~ J~ ! 1 02 ~o~o/4421~
1 . , .
Preparation of Aromatic Carboxylic Acids The present invention relates to an improved process for the preparation of aromatic carboxylic acids o~ the formula I
Ar(COOH)n 1, s in which Ar denotes an isoaromatic or heteroaromatic radical, which can be unsubstituted or which can carry inert substituents, and in which n is squal to 1 to 4, by oxidation of a compound of the formula II
Ar(CH3)n 11 using an oxidizing nitrogen/oxygen compound (III) in the presence of sulfuric acid and a vanadium compound (IV) at a temperature of from 120 to 180C in the liquid phase.
The preparation of aromatic carboxylic acids by direct oxidation of methyl- -substituted aromatics is well known in nun erous forms. ûue to their importance as - -intermediates for numerous dyestuffs, pharmaceuticals, and plant protectants, the heteroaromatic carboxylic acids are of special interest here.
This particularly applies to quinoline carboxylic acids, which are important intermediates for the synthesis of pharmaceutical~. The halogen-substituted ~ -quinoline-8-carboxylic acids described in EP-B 277,631 are used as plant protect~nts.
~: :
J. Am. Chem. Soc. 68, 2721 (1946) discloses that compounds such as quinoline-5-,-6- and -7-carboxylic acids as well as 2-phenylquinoline-5-carboxylic acid serveas starting cornpounds for the preparation of -(2-piperidyl)-quinoline methanols which are effective against malaria. The synthesis of the quinoline carboxylic acids 30 takes place by oxidation of relevant methylquinolines, in which process arsenic acid and chromium trioxide are used as oxidizing agents, however the yields and selectivities are unsatisfactory, while there is also the fact that the use of these -oxidizing agents presents considerable technological problems. -35 EP-A 282,778 describes the preparation of 7-chloroquinoline-8-carboxylic acidas well as its derivalives substituted in position 3 by chlorine or methyl, which are obtained by direct oxidation of the relevant 8-methylquinoline with nitric acid or ` il'~5:1 ~ASFAl~T~ es~lLscHAn o,z.oo50~ 21~
nitrogen dioxide in the presence ot sulfuric acid and vanadium pentoxlde actln~ as catalyst. Since nitroquinoline carboxylic acids and methylquinolines nltrated on tho nucleus are formed under the selected reaction conditions as by-products, thls reaction does not take place w~th suffic~ently high yields and selectivities.
s lt is thus an ob~ect of the present invention to overcome the aforementioned drawbacks and to render the aromatic carboxylic acids I available in a simpler and more economical manner than hitherto.
.0 Accordingly, we have found a process for the preparation of aromatic carboxylic acids of the formula I
Ar~OOOH)n 1, 15 in which Ar denotes an isoaromatic or heteroaromatic radical, which can be unsubstituted or can carry inert substituents and in which n is equal to 1 to 4, by oxidation of a compound II
Ar(CH3)n - ~
using an oxidking nitrogen/oxygen cornpound (III) in the presence of sulfuric acid --and a vanadium compound (IV) at from 120 to 180C in the liquid phase, wherein for each mole of compound Il in the reaction mixture, from 20 to 1 00mol% of vanadium compound (IV) are available for the oxidation.
' 2S
We have also found that th~s process achieves a h~gh degree of success in the - ~ -case of heteroaromatic carboxylic acids, and that it achieves a very high degree of success when it is applied to the synthes~s of quinoline carboxylic acids of the -formula v ~ V
in particular quinoline-6-carboxylic acid. ; --Suitable radicals Ar in the end products I and starting compounds II respectively are, for example, those derived from - isoaromatic cornpounds such as benzene, naphthalene, anthracene, andphenanthrene as well as condensed polycyclic arornatics such as chrysene and benzanthracene, and .
, , .. . - . .. - .- -. .. ,~.. ~.. - .. . .... . .... .. . .. ..
BASFAI~TIEN(~ESELLSCHAF~ o.z.oo~o/4421ff . ~
- heteroaromatic compounds such as furan, thioph~ne, pyrrob, oxazole, isoxazole, oxadiazoles, thiazole, isothiazole, thiadiazoles, pyrazole, imidazole, triazoles, pyridine, pyridazine, pyrimidine, and pyrazine as parent substances.
5 Particularly suitable heteroaromatics are those which carry anellated rings as in, primarily, quinoline and isoquinoline, and also in benzofuran, isobenzofuran, benzothiophene, indole, isoindole, benzisoxazole, benzoxazole, benzisothiazole, benzothiazole, indazole, purine, quinoxaline, quinazoline, phthalazine, indoline, isoindoline, chroman, and isochroman.
From 1 to 4 methyl groups are linked to radical Ar in the corresponding startingcompounds ll, the preferred number o~ methyl groups being 1 or 2, especially 1.
Where Ar stands for a heteroaromatic parent substance having one anellated ring,preferably at least one methyl group is linked to the anellated ring.
~s The remaining C atoms can carry arbitrary inert substituents, ie, intrinsically non-oxidizable radicals, for example fluorine, chlorine, bromine, iodine, nitro, carboxyl and hydroxy as well as aryl such as phenyl, -naphthyl and ~-naphthyl and aralkyl such as benzyl as well as 1- und 2-phenylethyl.
Also C~-c6 alkyl groups and - cycloalkyl such as cyclopentyl and cyclohexyl, 2~ - cycloalkyl-substituted alkyl such as 1- und 2-cyclohexylethyl, ~ ~
, .
- oxacycloalkyl such as 2- und 3-oxacyclopentyl, 2-, 3- and 4-oxacyclohexyl, and - ~.
30 - Cl~4alkoxy such as methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, sec-butyloxy, and tert-butyloxy may be suitable provided they are inert or substantially inert under the reaction conditions. These substituents are frequently inert in anellated heteroaromatic rings, particular when they are linked to the heteroaromatic parent substances.
Moreover the inert substituents may be themselves substituted, for example, by halogen, nitro, cyano and alko)~y.
Preferred starting compounds ll are methyl-substituted heteroaromatics. Due to the fact that quinoline carboxylic acids V are the desired end products, the BASF~l~TlENaeSeLLSCHAFT o.z oo~o/44210 methylquinolines of th~ formula ll' -s N~ CH3 ll are particularly preferred, the compound 6-methylquinoline being particularly preferred when it is desired to synthesize quinoline-6~carboxylic acid.
The starting compounds ll are commercially availabb or can be prepared by 10 conventionai methods ( J. Am. Chem. Soc. 66, 396 (1944)).
The starting compounds 5-, 6-, 7-, and 8-methylquinoline which are particularly important when producing quinoline carboxylic acids as the end products are described in J. Chem. Soc. 3645 (1962), Monthyl l~sue No. 2,139 (1881~ and 15 British Patent 198,462 and can be prepared according to the methods indicated therein.
The processes for the synthesis of compounds 1 are carried out by conventional tschniques in the liquid phase batchwis~ or continuously. When the process is 20 carried out batchwise, the oxidation of compound II to form compound I takes place in a stirred boiler by mixing all of the reactants. It may be recommendable, in order to increase the selectivity toward compound 1, to limit the conversion of compound II to approximately 50 % and preferably 80 ~. Usually, good selectivi~
ties are achieved even when the conversion is quantitative.
When the proc0ss is carried out continuously, the reaction can take place, for example, in a stirr~d boiler upstream of a tubular reactor, in a cascade of stirred boil~rs, or in a tubular reactor.
30 Oxidizing nitrogen/oxygen compounds (Ill) serve as oxidizing agents, nitric acid being chiefly suitable. It may be used in concentrated form or diluted with water.
Furthermore nitrogen/oxygen compounds such as dinitrogen pentoxide and, in particular, nitrogen dioxide and dimeric dinitrogen tetroxide are suitable. Moreover it is possible to use oxygen as weil as the nitrogen oxide-containing reaction off-35 gases formed during conversion of compound ll to compound I together withcompound lll as oxidizing agents. Oxygen can be used as pure substance and in ths form of air. Generally speaking, it causes an increase in the reaction rate.
To convert compound ll to compound 1, it is advantag~ous to use from 2 to 8 and 40 especially from 5 to 7 mol of compound III per mole of starting material ll.
r ~i KTleN~es~lLSCN~T o z oo~o/4421~
The process is usually carried out under atmospheric pressure. When gaseous n~trogen/oxygen compounds are used, it is advisable to carry out the reaction at a slightly elevated pressure of up to approximately 10 bar.
5 Cornpounds (IV) of pentavalent vanadium are used as oxidation catalysts, preferably such as are soluble in sulfuric acid and mixtures of sulfuric acid and n~tr~c ac~d. Bes~des the sulfate, n~trate, and acetate, vanadium pentox~de and ammonium polyvanadate are used, in particular. One essential feature of the invention is that it makes it possible to use higher amounts of compound IV thannormally necessary for catalytic reactions. By ~higher amounts" we mean that in the preparation of compound I there are used from 0.1 to 0.6kg and preferably from 0.2 to 0.5kg of vanadium compound (IV) per kilogram of compound ll. When smaller amounts of compound IV are used, a drop in selectivity is generally observable due to side reactions such as nitration.
:~
Sulfuric acid serves as the reaction medium and can be used in concentrations of ~ -from ca 50 to 90 ~ and preferably from 70 to 85 ~o. Usually, it is advantageous for the reactiwl to be carried out at a rate of from 2 to 1Okg of sulfuric acid per ; --kilogram of compound ll.
The reaction temperature is from 120 to 180C and preferably from 130 to 1 70C. - --, In other respects, the reaction takes place in a manner knownper se by dissolving 25 compound II in sulfuric acid, subsequently admixing this solution with the vanadium compound (IV) and then adding cwmpound lll. For pur~fication purposes, the reaction mixture is usually cooled, diluted with water and adjusted to a pH of approximately 0.5 to 5.0 with a base such as sodium hydroxide, thus causing the end product I to precipitate. This can then be isolated by usual methods such as30 filtration and recrystallisation and purified.
In the case of heteroaromatic end products, especially quinoline carboxy!ic acids V, these may fwm immediately following dilution with water, in the fwm of the~r sulfuric salts. Advantageously they can be separated from the reaction solution by ,~ filtration. The salts can then be converted to the correspond~ng base in conventional manner in aqueous solution by means of an alkaline solution such asa caustic soda solution.
Another advantage is that the sulfuric acid formed during the wwking up process 40 and the filtrate containing the vanadium cwmpound (IV) can be used a number of ~ :-.3 ~ ~
I~ASFAKTlENl~ESELLSCHArr o,z.o~o/4421~
times.
Aromatic carboxylic acids I prepared in the process of the invention are valuable products for a large number of applications. Particularly the quinoline carboxylic acids V are of interest, since they are important intermediates for pharmaceuticals.
Of very great significance are the processes of the invention for the preparation of quinoline-6-carboxylic acid.
Preparation of quinolin~-6-carboxylic acid Example 1 A solution of 106g ~0.74mol) of 6-methylquinoline in 600g of 60%strength sulfuric acid was admixed with 37 g (0.2 mol) of vanadium pentoxide and heated to a temperatur~ of ca 133C. Over a period of 8h 619g (6.4mol) of 65%strength nitric acid were added thereto. At the same time. 380mL Of 35%strength nitric acid were rGmoved by distillation. Following cooling to 50C, the reaction mixture was diluted with 420mL of water and stirred for a furtner 10h at 25C. 114g of the sulfate of quinoline-6-carboxylic acid were then r0moved by filtration.
The filtrate thus produced, containing diluted vanadium pentoxide and dissolved sulfuric acid, was concentrated so as to have the original concentration of 60%strength sulfuric acid. There were obtained 570g of a solution of vanadium pentoxide in 60 ~ strength sulfuric acid.
The sulfuric salt of th~ quinoline-6-carboxylic acid in 800mL of water was converted to quinoline-6-carboxylic acid using concentrated caustic soda solution at 40C up to a pH of ca 3.5 to 4 with stirring. Following cooling of this solution.
the precipitated product was removed by filtration.
Yield: 83g of quinoline-6-carboxylic acid (65 ~ oftheoly) Example 2 36 106g (0.74mol) of 6-m~thylquinoline were dissolved in a mixture of 98g of concentrated sulfuric acid and 570g o~ vanadium pentoxide-containing 60%
strength sulfuric acid ~concentrated filtrate as described in Example 1). Following heating to 1 35C, 542 g (5.6mol) of 65 ~ostrength nitric acid were introduced over a period of 7h. The manner in which the process was carried out and the purification of the product were as describ~d in Example 1.
.
, r~ r~ ~
SF~KTlEN~iESELLSCHAFT o,z.o~so/442111 Yield: 95 g of quinoline-6-carboxylic acid ~74 Example 3 The preparation of quinoline-6-carboxylic acid took place as described in Exampb1. During the addition of the 65 % strength nitric acid, air was also introduced at a rate of 5 L per hour.
Yield: 97 g ( 76 ~) ,0 ample 4 -The preparation of quinoline-6-carboxylic acid took place as described in Example 1 . During the addition of the 65 % strength nitric acld, the nitrogen oxide-containing 15 reaction off-gas formed during the reaction was recycled and fed to the reaction solution.
Yield: 97g (76 ~) 20 Example 5 A solution of 106g (0.74mol) of 6-msthylquinolins in 600g of 60%strength sulfuric acid was admixed with 37 g l0.2 mol) of vanadium pentoxide and heated to a temperature of ca 130C. Nitrogen dioxide was then introduced to establish a 25 superatmospheric pressure of up to 0.2bar. Thereafter oxygen was continuouslyfed in in such a manner that a constant overpressure of 0.5bar was maintained.
When no more oxygen was consumed ~after 9h), the reaction mixture was worked up as described in Example 1.
30 Yield: 90 g of quinoline-6-carboxylic acid ( 70 ~) - - - 7 . ~ ~ -
1 . , .
Preparation of Aromatic Carboxylic Acids The present invention relates to an improved process for the preparation of aromatic carboxylic acids o~ the formula I
Ar(COOH)n 1, s in which Ar denotes an isoaromatic or heteroaromatic radical, which can be unsubstituted or which can carry inert substituents, and in which n is squal to 1 to 4, by oxidation of a compound of the formula II
Ar(CH3)n 11 using an oxidizing nitrogen/oxygen compound (III) in the presence of sulfuric acid and a vanadium compound (IV) at a temperature of from 120 to 180C in the liquid phase.
The preparation of aromatic carboxylic acids by direct oxidation of methyl- -substituted aromatics is well known in nun erous forms. ûue to their importance as - -intermediates for numerous dyestuffs, pharmaceuticals, and plant protectants, the heteroaromatic carboxylic acids are of special interest here.
This particularly applies to quinoline carboxylic acids, which are important intermediates for the synthesis of pharmaceutical~. The halogen-substituted ~ -quinoline-8-carboxylic acids described in EP-B 277,631 are used as plant protect~nts.
~: :
J. Am. Chem. Soc. 68, 2721 (1946) discloses that compounds such as quinoline-5-,-6- and -7-carboxylic acids as well as 2-phenylquinoline-5-carboxylic acid serveas starting cornpounds for the preparation of -(2-piperidyl)-quinoline methanols which are effective against malaria. The synthesis of the quinoline carboxylic acids 30 takes place by oxidation of relevant methylquinolines, in which process arsenic acid and chromium trioxide are used as oxidizing agents, however the yields and selectivities are unsatisfactory, while there is also the fact that the use of these -oxidizing agents presents considerable technological problems. -35 EP-A 282,778 describes the preparation of 7-chloroquinoline-8-carboxylic acidas well as its derivalives substituted in position 3 by chlorine or methyl, which are obtained by direct oxidation of the relevant 8-methylquinoline with nitric acid or ` il'~5:1 ~ASFAl~T~ es~lLscHAn o,z.oo50~ 21~
nitrogen dioxide in the presence ot sulfuric acid and vanadium pentoxlde actln~ as catalyst. Since nitroquinoline carboxylic acids and methylquinolines nltrated on tho nucleus are formed under the selected reaction conditions as by-products, thls reaction does not take place w~th suffic~ently high yields and selectivities.
s lt is thus an ob~ect of the present invention to overcome the aforementioned drawbacks and to render the aromatic carboxylic acids I available in a simpler and more economical manner than hitherto.
.0 Accordingly, we have found a process for the preparation of aromatic carboxylic acids of the formula I
Ar~OOOH)n 1, 15 in which Ar denotes an isoaromatic or heteroaromatic radical, which can be unsubstituted or can carry inert substituents and in which n is equal to 1 to 4, by oxidation of a compound II
Ar(CH3)n - ~
using an oxidking nitrogen/oxygen cornpound (III) in the presence of sulfuric acid --and a vanadium compound (IV) at from 120 to 180C in the liquid phase, wherein for each mole of compound Il in the reaction mixture, from 20 to 1 00mol% of vanadium compound (IV) are available for the oxidation.
' 2S
We have also found that th~s process achieves a h~gh degree of success in the - ~ -case of heteroaromatic carboxylic acids, and that it achieves a very high degree of success when it is applied to the synthes~s of quinoline carboxylic acids of the -formula v ~ V
in particular quinoline-6-carboxylic acid. ; --Suitable radicals Ar in the end products I and starting compounds II respectively are, for example, those derived from - isoaromatic cornpounds such as benzene, naphthalene, anthracene, andphenanthrene as well as condensed polycyclic arornatics such as chrysene and benzanthracene, and .
, , .. . - . .. - .- -. .. ,~.. ~.. - .. . .... . .... .. . .. ..
BASFAI~TIEN(~ESELLSCHAF~ o.z.oo~o/4421ff . ~
- heteroaromatic compounds such as furan, thioph~ne, pyrrob, oxazole, isoxazole, oxadiazoles, thiazole, isothiazole, thiadiazoles, pyrazole, imidazole, triazoles, pyridine, pyridazine, pyrimidine, and pyrazine as parent substances.
5 Particularly suitable heteroaromatics are those which carry anellated rings as in, primarily, quinoline and isoquinoline, and also in benzofuran, isobenzofuran, benzothiophene, indole, isoindole, benzisoxazole, benzoxazole, benzisothiazole, benzothiazole, indazole, purine, quinoxaline, quinazoline, phthalazine, indoline, isoindoline, chroman, and isochroman.
From 1 to 4 methyl groups are linked to radical Ar in the corresponding startingcompounds ll, the preferred number o~ methyl groups being 1 or 2, especially 1.
Where Ar stands for a heteroaromatic parent substance having one anellated ring,preferably at least one methyl group is linked to the anellated ring.
~s The remaining C atoms can carry arbitrary inert substituents, ie, intrinsically non-oxidizable radicals, for example fluorine, chlorine, bromine, iodine, nitro, carboxyl and hydroxy as well as aryl such as phenyl, -naphthyl and ~-naphthyl and aralkyl such as benzyl as well as 1- und 2-phenylethyl.
Also C~-c6 alkyl groups and - cycloalkyl such as cyclopentyl and cyclohexyl, 2~ - cycloalkyl-substituted alkyl such as 1- und 2-cyclohexylethyl, ~ ~
, .
- oxacycloalkyl such as 2- und 3-oxacyclopentyl, 2-, 3- and 4-oxacyclohexyl, and - ~.
30 - Cl~4alkoxy such as methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, sec-butyloxy, and tert-butyloxy may be suitable provided they are inert or substantially inert under the reaction conditions. These substituents are frequently inert in anellated heteroaromatic rings, particular when they are linked to the heteroaromatic parent substances.
Moreover the inert substituents may be themselves substituted, for example, by halogen, nitro, cyano and alko)~y.
Preferred starting compounds ll are methyl-substituted heteroaromatics. Due to the fact that quinoline carboxylic acids V are the desired end products, the BASF~l~TlENaeSeLLSCHAFT o.z oo~o/44210 methylquinolines of th~ formula ll' -s N~ CH3 ll are particularly preferred, the compound 6-methylquinoline being particularly preferred when it is desired to synthesize quinoline-6~carboxylic acid.
The starting compounds ll are commercially availabb or can be prepared by 10 conventionai methods ( J. Am. Chem. Soc. 66, 396 (1944)).
The starting compounds 5-, 6-, 7-, and 8-methylquinoline which are particularly important when producing quinoline carboxylic acids as the end products are described in J. Chem. Soc. 3645 (1962), Monthyl l~sue No. 2,139 (1881~ and 15 British Patent 198,462 and can be prepared according to the methods indicated therein.
The processes for the synthesis of compounds 1 are carried out by conventional tschniques in the liquid phase batchwis~ or continuously. When the process is 20 carried out batchwise, the oxidation of compound II to form compound I takes place in a stirred boiler by mixing all of the reactants. It may be recommendable, in order to increase the selectivity toward compound 1, to limit the conversion of compound II to approximately 50 % and preferably 80 ~. Usually, good selectivi~
ties are achieved even when the conversion is quantitative.
When the proc0ss is carried out continuously, the reaction can take place, for example, in a stirr~d boiler upstream of a tubular reactor, in a cascade of stirred boil~rs, or in a tubular reactor.
30 Oxidizing nitrogen/oxygen compounds (Ill) serve as oxidizing agents, nitric acid being chiefly suitable. It may be used in concentrated form or diluted with water.
Furthermore nitrogen/oxygen compounds such as dinitrogen pentoxide and, in particular, nitrogen dioxide and dimeric dinitrogen tetroxide are suitable. Moreover it is possible to use oxygen as weil as the nitrogen oxide-containing reaction off-35 gases formed during conversion of compound ll to compound I together withcompound lll as oxidizing agents. Oxygen can be used as pure substance and in ths form of air. Generally speaking, it causes an increase in the reaction rate.
To convert compound ll to compound 1, it is advantag~ous to use from 2 to 8 and 40 especially from 5 to 7 mol of compound III per mole of starting material ll.
r ~i KTleN~es~lLSCN~T o z oo~o/4421~
The process is usually carried out under atmospheric pressure. When gaseous n~trogen/oxygen compounds are used, it is advisable to carry out the reaction at a slightly elevated pressure of up to approximately 10 bar.
5 Cornpounds (IV) of pentavalent vanadium are used as oxidation catalysts, preferably such as are soluble in sulfuric acid and mixtures of sulfuric acid and n~tr~c ac~d. Bes~des the sulfate, n~trate, and acetate, vanadium pentox~de and ammonium polyvanadate are used, in particular. One essential feature of the invention is that it makes it possible to use higher amounts of compound IV thannormally necessary for catalytic reactions. By ~higher amounts" we mean that in the preparation of compound I there are used from 0.1 to 0.6kg and preferably from 0.2 to 0.5kg of vanadium compound (IV) per kilogram of compound ll. When smaller amounts of compound IV are used, a drop in selectivity is generally observable due to side reactions such as nitration.
:~
Sulfuric acid serves as the reaction medium and can be used in concentrations of ~ -from ca 50 to 90 ~ and preferably from 70 to 85 ~o. Usually, it is advantageous for the reactiwl to be carried out at a rate of from 2 to 1Okg of sulfuric acid per ; --kilogram of compound ll.
The reaction temperature is from 120 to 180C and preferably from 130 to 1 70C. - --, In other respects, the reaction takes place in a manner knownper se by dissolving 25 compound II in sulfuric acid, subsequently admixing this solution with the vanadium compound (IV) and then adding cwmpound lll. For pur~fication purposes, the reaction mixture is usually cooled, diluted with water and adjusted to a pH of approximately 0.5 to 5.0 with a base such as sodium hydroxide, thus causing the end product I to precipitate. This can then be isolated by usual methods such as30 filtration and recrystallisation and purified.
In the case of heteroaromatic end products, especially quinoline carboxy!ic acids V, these may fwm immediately following dilution with water, in the fwm of the~r sulfuric salts. Advantageously they can be separated from the reaction solution by ,~ filtration. The salts can then be converted to the correspond~ng base in conventional manner in aqueous solution by means of an alkaline solution such asa caustic soda solution.
Another advantage is that the sulfuric acid formed during the wwking up process 40 and the filtrate containing the vanadium cwmpound (IV) can be used a number of ~ :-.3 ~ ~
I~ASFAKTlENl~ESELLSCHArr o,z.o~o/4421~
times.
Aromatic carboxylic acids I prepared in the process of the invention are valuable products for a large number of applications. Particularly the quinoline carboxylic acids V are of interest, since they are important intermediates for pharmaceuticals.
Of very great significance are the processes of the invention for the preparation of quinoline-6-carboxylic acid.
Preparation of quinolin~-6-carboxylic acid Example 1 A solution of 106g ~0.74mol) of 6-methylquinoline in 600g of 60%strength sulfuric acid was admixed with 37 g (0.2 mol) of vanadium pentoxide and heated to a temperatur~ of ca 133C. Over a period of 8h 619g (6.4mol) of 65%strength nitric acid were added thereto. At the same time. 380mL Of 35%strength nitric acid were rGmoved by distillation. Following cooling to 50C, the reaction mixture was diluted with 420mL of water and stirred for a furtner 10h at 25C. 114g of the sulfate of quinoline-6-carboxylic acid were then r0moved by filtration.
The filtrate thus produced, containing diluted vanadium pentoxide and dissolved sulfuric acid, was concentrated so as to have the original concentration of 60%strength sulfuric acid. There were obtained 570g of a solution of vanadium pentoxide in 60 ~ strength sulfuric acid.
The sulfuric salt of th~ quinoline-6-carboxylic acid in 800mL of water was converted to quinoline-6-carboxylic acid using concentrated caustic soda solution at 40C up to a pH of ca 3.5 to 4 with stirring. Following cooling of this solution.
the precipitated product was removed by filtration.
Yield: 83g of quinoline-6-carboxylic acid (65 ~ oftheoly) Example 2 36 106g (0.74mol) of 6-m~thylquinoline were dissolved in a mixture of 98g of concentrated sulfuric acid and 570g o~ vanadium pentoxide-containing 60%
strength sulfuric acid ~concentrated filtrate as described in Example 1). Following heating to 1 35C, 542 g (5.6mol) of 65 ~ostrength nitric acid were introduced over a period of 7h. The manner in which the process was carried out and the purification of the product were as describ~d in Example 1.
.
, r~ r~ ~
SF~KTlEN~iESELLSCHAFT o,z.o~so/442111 Yield: 95 g of quinoline-6-carboxylic acid ~74 Example 3 The preparation of quinoline-6-carboxylic acid took place as described in Exampb1. During the addition of the 65 % strength nitric acid, air was also introduced at a rate of 5 L per hour.
Yield: 97 g ( 76 ~) ,0 ample 4 -The preparation of quinoline-6-carboxylic acid took place as described in Example 1 . During the addition of the 65 % strength nitric acld, the nitrogen oxide-containing 15 reaction off-gas formed during the reaction was recycled and fed to the reaction solution.
Yield: 97g (76 ~) 20 Example 5 A solution of 106g (0.74mol) of 6-msthylquinolins in 600g of 60%strength sulfuric acid was admixed with 37 g l0.2 mol) of vanadium pentoxide and heated to a temperature of ca 130C. Nitrogen dioxide was then introduced to establish a 25 superatmospheric pressure of up to 0.2bar. Thereafter oxygen was continuouslyfed in in such a manner that a constant overpressure of 0.5bar was maintained.
When no more oxygen was consumed ~after 9h), the reaction mixture was worked up as described in Example 1.
30 Yield: 90 g of quinoline-6-carboxylic acid ( 70 ~) - - - 7 . ~ ~ -
Claims (4)
1. A process for the preparation of an aromatic carboxylic acid of the formula I
Ar(COOH)n I
in which Ar denotes an isoaromatic or heteroaromatic radical, which can be unsubstituted or can carry inert substituents and in which n is equal to 1 to 4, by oxidation of a compound II
Ar(CH3)n II
using an oxidizing nitrogen/oxygen compound (III) in the presence of sulfuric acid and a vanadium compound (IV) at from 120° to 180°C in the liquid phase, wherein for each mole of compound II in the reaction mixture, from 20 to 100mol% of vanadium compound (IV) are available for the oxidation.
Ar(COOH)n I
in which Ar denotes an isoaromatic or heteroaromatic radical, which can be unsubstituted or can carry inert substituents and in which n is equal to 1 to 4, by oxidation of a compound II
Ar(CH3)n II
using an oxidizing nitrogen/oxygen compound (III) in the presence of sulfuric acid and a vanadium compound (IV) at from 120° to 180°C in the liquid phase, wherein for each mole of compound II in the reaction mixture, from 20 to 100mol% of vanadium compound (IV) are available for the oxidation.
2. A process for the preparation of an aromatic carboxylic acid (I) as claimed in claim 1 which is applied to the synthesis of heteroaromatic carboxylic acids.
3. A process for the preparation of an aromatic carboxylic acid (I) as claimed in claim 2 which is applied to the synthesis of quinoline carboxylic acids of formula V.
4. A process for the preparation of aromatic carboxylic acids (I) as claimed in claim 3 which is applied to the synthesis of quinoline-6-carboxylic acid.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19934326288 DE4326288A1 (en) | 1993-08-05 | 1993-08-05 | Process for the production of aromatic carboxylic acids |
| DEP4326288.0 | 1993-08-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2128951A1 true CA2128951A1 (en) | 1995-02-06 |
Family
ID=6494515
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2128951 Abandoned CA2128951A1 (en) | 1993-08-05 | 1994-07-27 | Preparation of aromatic carboxylic acids |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0639570A1 (en) |
| JP (1) | JPH0769936A (en) |
| CA (1) | CA2128951A1 (en) |
| DE (1) | DE4326288A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103467226A (en) * | 2013-08-12 | 2013-12-25 | 浙江工业大学 | Method for synthesis of aromatic carboxylic acid by selective catalytic oxidation of alkyl aromatic compound |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4757146A (en) * | 1986-08-29 | 1988-07-12 | American Cyanamid Company | Method for the preparation of quinoline-2,3-dicarboxylic acid |
| EP0282778B1 (en) * | 1987-03-03 | 1992-05-13 | BASF Aktiengesellschaft | Process for the preparation of 7-chloro-quinoline-8-carboxylic acids |
-
1993
- 1993-08-05 DE DE19934326288 patent/DE4326288A1/en not_active Withdrawn
-
1994
- 1994-07-27 CA CA 2128951 patent/CA2128951A1/en not_active Abandoned
- 1994-07-29 EP EP94111824A patent/EP0639570A1/en not_active Withdrawn
- 1994-08-03 JP JP18253794A patent/JPH0769936A/en not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103467226A (en) * | 2013-08-12 | 2013-12-25 | 浙江工业大学 | Method for synthesis of aromatic carboxylic acid by selective catalytic oxidation of alkyl aromatic compound |
| CN103467226B (en) * | 2013-08-12 | 2015-08-05 | 浙江工业大学 | A kind of method of selective catalytic oxidation alkyl-aromatic compounds synthetic aroma carboxylic acid |
Also Published As
| Publication number | Publication date |
|---|---|
| DE4326288A1 (en) | 1995-02-09 |
| JPH0769936A (en) | 1995-03-14 |
| EP0639570A1 (en) | 1995-02-22 |
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