CA1225094A - Process for the production of tetronic acid - Google Patents
Process for the production of tetronic acidInfo
- Publication number
- CA1225094A CA1225094A CA000473780A CA473780A CA1225094A CA 1225094 A CA1225094 A CA 1225094A CA 000473780 A CA000473780 A CA 000473780A CA 473780 A CA473780 A CA 473780A CA 1225094 A CA1225094 A CA 1225094A
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- Prior art keywords
- ester
- acid
- chloroacetoacetic
- thermal treatment
- temperature
- Prior art date
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D307/60—Two oxygen atoms, e.g. succinic anhydride
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Furan Compounds (AREA)
- Cephalosporin Compounds (AREA)
Abstract
PROCESS FOR THE PRODUCTION OF TETRONIC ACID
ABSTRACT OF THE DISCLOSURE
A process is disclosed for the production of tetronic acid from a 4-chloroacetoacetic ester. The 4-chloroacetoacetic ester is converted by chlorination into the corresponding 2,4-dichloro-acetoacetic ester. The latter is converted by thermal treatment at a temperature of 110° to 160°C. into 3-chlorotetronic acid.
Then the 3-chlorotetronic acid is converted into tetronic acid by hydration by means of hydrogen in the presence of a platinum metal catalyst.
ABSTRACT OF THE DISCLOSURE
A process is disclosed for the production of tetronic acid from a 4-chloroacetoacetic ester. The 4-chloroacetoacetic ester is converted by chlorination into the corresponding 2,4-dichloro-acetoacetic ester. The latter is converted by thermal treatment at a temperature of 110° to 160°C. into 3-chlorotetronic acid.
Then the 3-chlorotetronic acid is converted into tetronic acid by hydration by means of hydrogen in the presence of a platinum metal catalyst.
Description
lZ~51)94 .
This invention relates to a process for the predilection of tetronic acid.
hitherto, tetroni~ acid has been produced starting prom acetoacetlc ester by way of 2,4-dlbromoacetoacetlc ester and 3-bromotetronlc acld~wlth subsequent hydration using sodium amalgam [Wolff and Schwab, Ann. 291 (1896), 231, and W. D.
Kumler, J. Am. Chum. Sock 60 (1938) 863]. The yield of tetronlc¦
acid based on the starting material was 18 percent.
Since such process way un~atlsfactory, an entire series of other pro cases was developed. According to Swiss Patent No.
503,722, for example, 4-chloroacetoacetlc ester is converted with an aromatic amine into 3-arylaminocrotolactone and from such material the tetronlc acid it liberated by treatment with mineral cold. The disadvantage of this method is that isolation of the tetronlc cold can only be achieved by high vacuum 3ublimatlon. According to Swiss Patent No. 529,128, the starling 4-haloacetoacetic acid it converted with alkali in an aqueous ~olutlon, By treatment with mineral cold, the tetronlc cold it liberated. In itch gage also, the isolation of the tetronic cold mutt be accomplished by way of high vacuum sublimation; moreover, the realizable yield is only 43 to 44 percent.
According to US. Patent 4,421,922, a 4-haloaceto-acetic ester is first converted into the corresponding 4- i benzyloxyacetoacetic ester and the corresponding 4-hydroxyacetoacetic ester is formed therefrom by hydrogenolysis as an intermediate product. The I
, 17~Z5094 ester 19 converted into tetronl¢ cold by treatment with cold.
In the case of such process, the 4-hydroxyacetoacetlc ester can be isolated and, after isolation, the treatment with acid can be carried out. But it it also possible to carry out the hydrogenolysis in the presence of acid. In that case, the primary 4-hydroxyacetoacetic ester, formed in situ, is converted¦
directly into the tetronlc cold. The disadvantage of such process ties in the fact that it has to be carried out by way of expensive, intermediate product. Rob Schmidt and Zlmmer then tried again to improve the tetronlc cold synthesis starling out from acetoacetlc ester by way of 3-bromotetronic cold [Sync.
Comma 11 (5) 1981, 383-390~ The bromation of the acetoacetic ester and the conversion of such product into 3-bromotetronlc acid was carried out according to W. D. Kumler, J. Am. Chum.
Sock 60 (1938) 859. The hydration however, was undertaken by means of Ho and Pd/C. The improvement lay in such step, 31nce a yield¦
of 82 to 94 percent was achieved. The yield, however, is related to the 3-bromotetronic acid. If the yield is related to the entire reaction scheme, that is, inclusive of the synthesis of the 3-bromotetronlc acid from acetoacetlc ester (according to Kumler about 36%), then the yield also is only 29 to 34 percent.
A further disadvantage of the prior art process is the fact that in consequence of organic salts obtained, the tetronlc acid can be recovered only by a lengthy extraction procedure.
An object of the invention is to provide a process which avoids or mitigates the above-mentioned disadvantages of the prior processes.
` ..., l;~Z5~94 .1 1 .
I
if Al.
The invention thus involves prepaying tetronic acid, i.e.
This invention relates to a process for the predilection of tetronic acid.
hitherto, tetroni~ acid has been produced starting prom acetoacetlc ester by way of 2,4-dlbromoacetoacetlc ester and 3-bromotetronlc acld~wlth subsequent hydration using sodium amalgam [Wolff and Schwab, Ann. 291 (1896), 231, and W. D.
Kumler, J. Am. Chum. Sock 60 (1938) 863]. The yield of tetronlc¦
acid based on the starting material was 18 percent.
Since such process way un~atlsfactory, an entire series of other pro cases was developed. According to Swiss Patent No.
503,722, for example, 4-chloroacetoacetlc ester is converted with an aromatic amine into 3-arylaminocrotolactone and from such material the tetronlc acid it liberated by treatment with mineral cold. The disadvantage of this method is that isolation of the tetronlc cold can only be achieved by high vacuum 3ublimatlon. According to Swiss Patent No. 529,128, the starling 4-haloacetoacetic acid it converted with alkali in an aqueous ~olutlon, By treatment with mineral cold, the tetronlc cold it liberated. In itch gage also, the isolation of the tetronic cold mutt be accomplished by way of high vacuum sublimation; moreover, the realizable yield is only 43 to 44 percent.
According to US. Patent 4,421,922, a 4-haloaceto-acetic ester is first converted into the corresponding 4- i benzyloxyacetoacetic ester and the corresponding 4-hydroxyacetoacetic ester is formed therefrom by hydrogenolysis as an intermediate product. The I
, 17~Z5094 ester 19 converted into tetronl¢ cold by treatment with cold.
In the case of such process, the 4-hydroxyacetoacetlc ester can be isolated and, after isolation, the treatment with acid can be carried out. But it it also possible to carry out the hydrogenolysis in the presence of acid. In that case, the primary 4-hydroxyacetoacetic ester, formed in situ, is converted¦
directly into the tetronlc cold. The disadvantage of such process ties in the fact that it has to be carried out by way of expensive, intermediate product. Rob Schmidt and Zlmmer then tried again to improve the tetronlc cold synthesis starling out from acetoacetlc ester by way of 3-bromotetronic cold [Sync.
Comma 11 (5) 1981, 383-390~ The bromation of the acetoacetic ester and the conversion of such product into 3-bromotetronlc acid was carried out according to W. D. Kumler, J. Am. Chum.
Sock 60 (1938) 859. The hydration however, was undertaken by means of Ho and Pd/C. The improvement lay in such step, 31nce a yield¦
of 82 to 94 percent was achieved. The yield, however, is related to the 3-bromotetronic acid. If the yield is related to the entire reaction scheme, that is, inclusive of the synthesis of the 3-bromotetronlc acid from acetoacetlc ester (according to Kumler about 36%), then the yield also is only 29 to 34 percent.
A further disadvantage of the prior art process is the fact that in consequence of organic salts obtained, the tetronlc acid can be recovered only by a lengthy extraction procedure.
An object of the invention is to provide a process which avoids or mitigates the above-mentioned disadvantages of the prior processes.
` ..., l;~Z5~94 .1 1 .
I
if Al.
The invention thus involves prepaying tetronic acid, i.e.
2,4-dioxo-tetrahydrofurclll, from a 4-chloroacetoacetic ester.
The inventive process involves chlorinating a 4-chloroacetoacetlc ester to provide the corre~pondlng 2,4-dlchloroacetoacetic ester, converting the 2,4-dichloroacetoacetlc ester by thermal treatment at a temperature of 110 to 160C. into 3-chlorotetronlc acid, and converting the 3-chlorotetronic cold by hydration by means of hydrogen in the presence of a platinum metal catalyst into tetronlc cold.
Basically, any ester moiety can be used in the 4-chloroacetoacetlc ester. Effectively, useful esters include those of alcohols having 1 to 6 carbon atoms and the bouncily ester. Preferably 4-chloroacetoacetlc cold ethyl ester I used.
The chlorination of the 2-chloroacetoacetlc ester into the 2,4-dlchloroacetoacetic ester can be carried out according to known methods. Preferably the chlorination is carried out by means of sulfuryl chloride in an organic solvent or mixture of organic solvents. Examples of suitable organic solvents are chlorinated aliphatlc carbohydrate, such as, ethylene chloride, chloroform and carbon tetrachloride, and aromatic hydrocarbons, such as Tulane Preferably, however, ethylene ¦
chloride is used as the organic solvent. Advantageously, 200 to 1000 grams of solvent are used per mole of 4-chloroacetoacetlc ester. The mole ratio of chlorination agent to chlorates o ester is preferably I to 1. rho Temperature at which the chlorination step is conducted can vary, but advantageously the chlorination step is operated at 0 to 40C.
The 2,4-dichloroacetoacetic ester obtained after chlorination is usually available dissolved in the solvent.
Prior to further processing, the 2,4-dichloroacetoacetic ester is advantageously freed of the solvent and is then subjected to the thermal treatment. Effectively one proceeds in such a way that the 2,4-dichloroacetoacetic ester, after removal of the solvent, is dried and then heated at 110 to 160C., preferably at 130 to 150C. The thermal treatment is carried out under reflex conditions under reduced or normal pressure, preferably under normal pressure.
After the reaction is completed in the thermal treatment step, the 3 chlorotetronic acid present as a solid-flied product is cleaned, preferably with an aromatic hydra-carbon, and is subsequently subjected to the hydrogenation step.
The hydrogenation advantageously takes place in water. For this purpose, the aqueous solution of sheller-tetronic acid is hydrogenated in the presence of a platinum metal catalyst, such as platinum, palladium or rhodium in a quantity of 2 to 10 weight percent on a carrier material such as pumice, alumina, silica gel or charcoal, with hydrogen under pressure at a temperature of 0 to 30C. Preferably the hydrogenation step is run at ambient temperature with a catalyst which is 5 percent of palladium on coal. The hydrogenation pressure can be between 3.5 and 20 atmospheres; low pressures mean longer hydrogenation times. Effectively 3.0 to 8.0 grams, preferably about 4.0 grams, of the palladium catalyst is used 3Q per mole of 3-chlorotetronic acid in the hydrogenation step.
The process of the invention has -the following advantages as compared to the known prior art processes set out above:
ox - i - The 2,4-chloroacetoacetlc ester can be produced almost quantitatively prom industrially-available sheller-acetoacetic ester and requires no clistlllatlve cleaning (purlfication)prlor to the further conversion thereof.
- The yield Or 3-chlorotetronlc cold (65 to 75 percent) in the thermal cycllzatlon Or the 2,4-dlchloroacetoacetlc ester is twice as high a that Or 3-bromotetronlc acid prom the corresponding dlbromoacetoacetlc ester. I
- In the case Or the reduction of the 3-chlorotetronlc cold to tetronlc acid, the operation can be conducted without the addition of bases. Thus, an expensive separation of tetronlc acid and organic salts is omitted or avoided.
By way of summary, tetronic acid is produced by the invention process from a 4-chloroacetoacetlc ester by way Or the¦
corresponding 2>4-dichloroacetoacetlc ester, then
The inventive process involves chlorinating a 4-chloroacetoacetlc ester to provide the corre~pondlng 2,4-dlchloroacetoacetic ester, converting the 2,4-dichloroacetoacetlc ester by thermal treatment at a temperature of 110 to 160C. into 3-chlorotetronlc acid, and converting the 3-chlorotetronic cold by hydration by means of hydrogen in the presence of a platinum metal catalyst into tetronlc cold.
Basically, any ester moiety can be used in the 4-chloroacetoacetlc ester. Effectively, useful esters include those of alcohols having 1 to 6 carbon atoms and the bouncily ester. Preferably 4-chloroacetoacetlc cold ethyl ester I used.
The chlorination of the 2-chloroacetoacetlc ester into the 2,4-dlchloroacetoacetic ester can be carried out according to known methods. Preferably the chlorination is carried out by means of sulfuryl chloride in an organic solvent or mixture of organic solvents. Examples of suitable organic solvents are chlorinated aliphatlc carbohydrate, such as, ethylene chloride, chloroform and carbon tetrachloride, and aromatic hydrocarbons, such as Tulane Preferably, however, ethylene ¦
chloride is used as the organic solvent. Advantageously, 200 to 1000 grams of solvent are used per mole of 4-chloroacetoacetlc ester. The mole ratio of chlorination agent to chlorates o ester is preferably I to 1. rho Temperature at which the chlorination step is conducted can vary, but advantageously the chlorination step is operated at 0 to 40C.
The 2,4-dichloroacetoacetic ester obtained after chlorination is usually available dissolved in the solvent.
Prior to further processing, the 2,4-dichloroacetoacetic ester is advantageously freed of the solvent and is then subjected to the thermal treatment. Effectively one proceeds in such a way that the 2,4-dichloroacetoacetic ester, after removal of the solvent, is dried and then heated at 110 to 160C., preferably at 130 to 150C. The thermal treatment is carried out under reflex conditions under reduced or normal pressure, preferably under normal pressure.
After the reaction is completed in the thermal treatment step, the 3 chlorotetronic acid present as a solid-flied product is cleaned, preferably with an aromatic hydra-carbon, and is subsequently subjected to the hydrogenation step.
The hydrogenation advantageously takes place in water. For this purpose, the aqueous solution of sheller-tetronic acid is hydrogenated in the presence of a platinum metal catalyst, such as platinum, palladium or rhodium in a quantity of 2 to 10 weight percent on a carrier material such as pumice, alumina, silica gel or charcoal, with hydrogen under pressure at a temperature of 0 to 30C. Preferably the hydrogenation step is run at ambient temperature with a catalyst which is 5 percent of palladium on coal. The hydrogenation pressure can be between 3.5 and 20 atmospheres; low pressures mean longer hydrogenation times. Effectively 3.0 to 8.0 grams, preferably about 4.0 grams, of the palladium catalyst is used 3Q per mole of 3-chlorotetronic acid in the hydrogenation step.
The process of the invention has -the following advantages as compared to the known prior art processes set out above:
ox - i - The 2,4-chloroacetoacetlc ester can be produced almost quantitatively prom industrially-available sheller-acetoacetic ester and requires no clistlllatlve cleaning (purlfication)prlor to the further conversion thereof.
- The yield Or 3-chlorotetronlc cold (65 to 75 percent) in the thermal cycllzatlon Or the 2,4-dlchloroacetoacetlc ester is twice as high a that Or 3-bromotetronlc acid prom the corresponding dlbromoacetoacetlc ester. I
- In the case Or the reduction of the 3-chlorotetronlc cold to tetronlc acid, the operation can be conducted without the addition of bases. Thus, an expensive separation of tetronlc acid and organic salts is omitted or avoided.
By way of summary, tetronic acid is produced by the invention process from a 4-chloroacetoacetlc ester by way Or the¦
corresponding 2>4-dichloroacetoacetlc ester, then
3-chlorotetronlc cold and subsequently hydration thereof provides tetronic cold. The invention also involves a process Or prod~clng tetronlc acid starling from the 2,~-dichloro-acetoacetlc ester.
The following Examples illustrate the invention. As used herein all parts, percentages ratios and proportions are on a weight basis unless otherwise stated or otherwise obvious to one skilled in the art.
I¦ 335.90 g (2.00 mole) of 4-chloroacetoacetic acid ethyl Al ester was dissolved in 1000 ml of ethylene chloride. To this, 287.12 g (2.04 mole) of sulfuryl chloride was slowly added drop by drop at ambient temperature over a 2.5 hour period. The development of gas was complete after about 10 hours.
lZ~5094 Subsequently, the solvent was distilled off on a notation evaporator and the yellow, oily reaction product was dried under high vacuum. 405.30 g of 2,4-dichloroacetoacetic cold ethyl ester was obtained with a content (GO) of 96.1 percent.
The 2,4-dichloroacetoacetic acid ethyl ester was heated for¦
2.5 hours at 140C. under reflex. This boiling temperature was achieved by the fact that the reaction was carried out under reduced pressure Since the 2,4-dlchloroacetoacetic ester was consumed during the reaction, a constant reaction temperature was obtained only by continuous diminution of the pressure (beginning with 90 mar and ending with 30 mar). The reaction ¦
was completed when no further reflex was observed. The reaction mixture way allowed to cool, whereby the solution solidified. As a result Or the addition of 300 ml of Tulane, this mixture was again made storable. The deposited 3-chlorotetronic acid way drained off, washed with 500 ml of Tulane and dried under high vacuum. 185.20 g of slightly browni3h-colored microcrystalline 3-chlorotetronic acid having a melting point of 206C. was obtained. The content of the 3-chlorotetronlc cold, according to potentiometric NaOH-titratlon, was 99.3 percent. This corresponded to a yield of 68.4 percent, based on the 4-chloroacetoacetic acid ethyl ester. To achieve recrystallization, 107 e of 3-chlorotetronlc acid in 3400 ml ox acid ester was dissolved hot and the ablution way boiled with 20 g of activated charcoal for ¦
2 hours under reflex. The hot solution was filtered off and the¦
resultant yellowlsh-colored solution was concentrated to 100 ml.
The precipitate obtained was subjected to suction, washed with 100 ml of acetic ester and dried under high vacuum 166 g of a white microcrystalline 3-chlorotetronic acid having a melting point of 206C. was isolated with a content of 99.4 percent. The mother liquor of the reaction solution was con-cent rated and distilled under high vacuum. From the first fraction, 12.4~ g of unconverted 2,4-dichloroacetoacetic ester was recovered.
50.0 g (0.37 mole) of 3-chlorotetronic acid (content 99.4 percent) was dissolved in 400 ml of water and mixed with 1.45 g of palladium on coal to percent). The 3-chlorotetronic 10 acid was hydrogenated at a constant pressure of 5 bar and at ambient temperature using hydrogen gas. After 7 hours the hydrogenation absorption was completed. The catalyst was filtered out of the solution containing the tetronic acid and cay 3 % hydrochloric acid. The catalyst, while on the filter 15 as a residue, was washed with 100 ml of water The aqueous hydrochloric tetronic acid solution from the filtration pro-seedier and the water from the washing step (which may contain a small amount of tetronic acid) were collected together. The aqueous hydrochloric acid was distilled off on a rotation 20 evaporator at a bath temperature of 30C. The slightly-yellowish crude acid was dried for 3 hours under high vacuum.
The yield was 36.5 g of white crystalline tetronic acid, having a con-tent (HPLC) of 99,2 percent. The total yield of tetronic acid, based on the 4-chloroacetoacetic ethyl ester 25 used, was 65.6 percent.
As in Example l, 1 mole of 4-chloroacetoacetic acid methyl ester was chlorinated with an equivalent quantity of sulfuryl chloride at ambient temperature. The convention 30 into 2,4-dichloroacetoaceticacid methyl ester was quantitative, the content (GO) of which amounted to 93 percent. The sub-sequent heating lZZ5094 for 3 hours under reflex at 140C. under vacuum (95 to 70 mm Hug) i produced 3-chlorotetronic acid at 75.5 percent yield with a content of 100 percent. The reprocessing was accomplished as in i Example 1. Upon dlstlllatlon of the mother liquor, 11.8 percent of educe was recovered.
As in Example 1, 1 mole ox 4-chloroacetoacetic acid bouncily ester way chlorinated with an equivalent quantity of sulfuryl chloride at ambient temperature. The conversion into 2,4-dlchloroacetoacetlc cold bouncily ester was quantitative.
Subsequent heating for 2 hours under reflex at 130C. under , vacuum (25 to 60 mm Hug) produced 3-chlorotetronic acid at a yield of 66.3 percent with a content of 99.9 percent.
As in example 1, 1 mole of 4-chloracetoacetic acid ethyl ester was chlorinated with an equivalent quantity of sulfurylchlo~
ride at ambient temperature. The conversion into 2,4-dichloroace-¦
¦ to acetic acid ethyl ester was quantitative.
Subsequent heating for 4 hours at 140C under normal pressure produced 3-chlorotetronic acid atayield of 84,6 percent with a content of 100 percent.
¦ Further conversion into tetronic acid, as in Example 1 ¦ produced tetronic acid at a yield of 74 percent, based on the 4-chloraceto-cetic acid ethyl ester.
, I 9 Al I
The following Examples illustrate the invention. As used herein all parts, percentages ratios and proportions are on a weight basis unless otherwise stated or otherwise obvious to one skilled in the art.
I¦ 335.90 g (2.00 mole) of 4-chloroacetoacetic acid ethyl Al ester was dissolved in 1000 ml of ethylene chloride. To this, 287.12 g (2.04 mole) of sulfuryl chloride was slowly added drop by drop at ambient temperature over a 2.5 hour period. The development of gas was complete after about 10 hours.
lZ~5094 Subsequently, the solvent was distilled off on a notation evaporator and the yellow, oily reaction product was dried under high vacuum. 405.30 g of 2,4-dichloroacetoacetic cold ethyl ester was obtained with a content (GO) of 96.1 percent.
The 2,4-dichloroacetoacetic acid ethyl ester was heated for¦
2.5 hours at 140C. under reflex. This boiling temperature was achieved by the fact that the reaction was carried out under reduced pressure Since the 2,4-dlchloroacetoacetic ester was consumed during the reaction, a constant reaction temperature was obtained only by continuous diminution of the pressure (beginning with 90 mar and ending with 30 mar). The reaction ¦
was completed when no further reflex was observed. The reaction mixture way allowed to cool, whereby the solution solidified. As a result Or the addition of 300 ml of Tulane, this mixture was again made storable. The deposited 3-chlorotetronic acid way drained off, washed with 500 ml of Tulane and dried under high vacuum. 185.20 g of slightly browni3h-colored microcrystalline 3-chlorotetronic acid having a melting point of 206C. was obtained. The content of the 3-chlorotetronlc cold, according to potentiometric NaOH-titratlon, was 99.3 percent. This corresponded to a yield of 68.4 percent, based on the 4-chloroacetoacetic acid ethyl ester. To achieve recrystallization, 107 e of 3-chlorotetronlc acid in 3400 ml ox acid ester was dissolved hot and the ablution way boiled with 20 g of activated charcoal for ¦
2 hours under reflex. The hot solution was filtered off and the¦
resultant yellowlsh-colored solution was concentrated to 100 ml.
The precipitate obtained was subjected to suction, washed with 100 ml of acetic ester and dried under high vacuum 166 g of a white microcrystalline 3-chlorotetronic acid having a melting point of 206C. was isolated with a content of 99.4 percent. The mother liquor of the reaction solution was con-cent rated and distilled under high vacuum. From the first fraction, 12.4~ g of unconverted 2,4-dichloroacetoacetic ester was recovered.
50.0 g (0.37 mole) of 3-chlorotetronic acid (content 99.4 percent) was dissolved in 400 ml of water and mixed with 1.45 g of palladium on coal to percent). The 3-chlorotetronic 10 acid was hydrogenated at a constant pressure of 5 bar and at ambient temperature using hydrogen gas. After 7 hours the hydrogenation absorption was completed. The catalyst was filtered out of the solution containing the tetronic acid and cay 3 % hydrochloric acid. The catalyst, while on the filter 15 as a residue, was washed with 100 ml of water The aqueous hydrochloric tetronic acid solution from the filtration pro-seedier and the water from the washing step (which may contain a small amount of tetronic acid) were collected together. The aqueous hydrochloric acid was distilled off on a rotation 20 evaporator at a bath temperature of 30C. The slightly-yellowish crude acid was dried for 3 hours under high vacuum.
The yield was 36.5 g of white crystalline tetronic acid, having a con-tent (HPLC) of 99,2 percent. The total yield of tetronic acid, based on the 4-chloroacetoacetic ethyl ester 25 used, was 65.6 percent.
As in Example l, 1 mole of 4-chloroacetoacetic acid methyl ester was chlorinated with an equivalent quantity of sulfuryl chloride at ambient temperature. The convention 30 into 2,4-dichloroacetoaceticacid methyl ester was quantitative, the content (GO) of which amounted to 93 percent. The sub-sequent heating lZZ5094 for 3 hours under reflex at 140C. under vacuum (95 to 70 mm Hug) i produced 3-chlorotetronic acid at 75.5 percent yield with a content of 100 percent. The reprocessing was accomplished as in i Example 1. Upon dlstlllatlon of the mother liquor, 11.8 percent of educe was recovered.
As in Example 1, 1 mole ox 4-chloroacetoacetic acid bouncily ester way chlorinated with an equivalent quantity of sulfuryl chloride at ambient temperature. The conversion into 2,4-dlchloroacetoacetlc cold bouncily ester was quantitative.
Subsequent heating for 2 hours under reflex at 130C. under , vacuum (25 to 60 mm Hug) produced 3-chlorotetronic acid at a yield of 66.3 percent with a content of 99.9 percent.
As in example 1, 1 mole of 4-chloracetoacetic acid ethyl ester was chlorinated with an equivalent quantity of sulfurylchlo~
ride at ambient temperature. The conversion into 2,4-dichloroace-¦
¦ to acetic acid ethyl ester was quantitative.
Subsequent heating for 4 hours at 140C under normal pressure produced 3-chlorotetronic acid atayield of 84,6 percent with a content of 100 percent.
¦ Further conversion into tetronic acid, as in Example 1 ¦ produced tetronic acid at a yield of 74 percent, based on the 4-chloraceto-cetic acid ethyl ester.
, I 9 Al I
Claims (19)
PROPERTY OR PRIVILEGE IS ClAIMED ARE DEFINED AS FOLLOWS:
1. A process for the production of tetronic acid, which comprises chlorinating a 4-chloroacetoacetic ester to produce the corresponding 2,4-dichloroacetoacetic ester, converting the 2,4-dichloroacetoacetic ester by thermal treatment at a temperature of 110° to 160°C. into 3-chlorotetronic acid, and converting the 3-chlorotetronic acid into tetronic acid by hydration by means of hydrogen in the presence of a platinum metal catalyst.
2. A process as claimed in Claim l, wherein the 4-chloroacetoacetic ester has an ester moiety containing from l to 6 carbon atoms.
3. A process as claimed in Claim l, wherein the 4-chloroacetoacetic ester is -the ethyl ester of 4-chloroaceto-acetic acid.
4. A process as claimed in Claim l, wherein the 4-chloroacetoacetic ester is the benzyl ester of 4-chloroaceto-acetic acid.
5. A process as claimed in Claim 1, wherein chlorination is carried out by means of sulfuryl chloride at a temperature of from 0° to 40°C.
6. A process as claimed in Claim 5, wherein the 4-chloroacetoacetic ester is present in an organic solvent.
7. A process as claimed in Claim 6, wherein the organic solvent is a chlorinated hydrocarbon or an aromatic hydro-carbon.
8. A process as claimed in Claim 6 or 7, wherein from 200 to l,000 grams of the organic solvent is used per mole of 4-chloroacetoacetic ester.
9. A process as claimed in Claim 5, 6 or 7, wherein the chlorination is conducted at room temperature.
10. A process as claimed in Claim 6 or 7, wherein the result-ant 2,4-dichloroacetoacetic ester is removed from the organic solvent and dried before being subjected to the thermal treatment.
11. A process as claimed in Claim 1, wherein the thermal treatment step is conducted at a temperature of 130° to 150°C.
12. A process as claimed in Claim 1 or 11, wherein the thermal treatment step is conducted under reflux conditions under reduced or normal pressure.
13. A process as claimed in Claim 1 or ll, wherein the thermal treatment step is conducted under normal pressure.
14. A process as claimed in Claim 1, wherein the hydro-genation is conducted in water.
15. A process as claimed in Claim 14, wherein the hydrogena-tion is carried out at a temperature of from 0° to 30°C.
16. A process as claimed in Claim 14 or 15, wherein the hydrogenation is carried out at a hydrogenation pressure of from 3.5 to 20 atmospheres.
17. A process as claimed in Claim 14 or 15, wherein from 3.0 to 8.0 grams of catalyst are used per mole of 3-chlorotetronic acid
18. A process as claimed in Claim 14 or 15, wherein the pla-tinum metal catalyst is palladium, platinum or rhodium.
19. A process as claimed in claim 14 or 15, wherein the plati-um metal catalyst is palladium, platinum or rhodium in a quantity of from 2 to 10 weight percent on a carrier material which is pumice, alumina, silica gel or charcoal.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH604/84A CH658056A5 (en) | 1984-02-09 | 1984-02-09 | METHOD FOR PRODUCING TETRONIC ACID. |
| CH604/84 | 1984-02-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1225094A true CA1225094A (en) | 1987-08-04 |
Family
ID=4190834
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000473780A Expired CA1225094A (en) | 1984-02-09 | 1985-02-07 | Process for the production of tetronic acid |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0153615B1 (en) |
| JP (1) | JPS60184073A (en) |
| AT (1) | ATE42550T1 (en) |
| CA (1) | CA1225094A (en) |
| CH (1) | CH658056A5 (en) |
| DD (1) | DD229126A5 (en) |
| DE (1) | DE3569735D1 (en) |
| HU (1) | HU196066B (en) |
| IL (1) | IL74131A (en) |
| IN (1) | IN162567B (en) |
| MX (1) | MX156171A (en) |
| SU (1) | SU1436868A3 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8344151B2 (en) | 2009-12-23 | 2013-01-01 | Bayer Cropscience Ag | Process for the preparation of 4-aminobut-2-enolides starting from 4-alkoxyfuran-2(5H)-one or 4-arylalkoxyfuran-2(5H)-one |
| US8487112B2 (en) | 2007-09-18 | 2013-07-16 | Bayer Cropscience Ag | Method for producing 4-aminobut-2-enolides |
| US8680286B2 (en) | 2009-03-16 | 2014-03-25 | Bayer Cropscience Ag | Method for producing enaminocarbonyl compounds |
| US8680285B2 (en) | 2009-03-16 | 2014-03-25 | Bayer Cropscience Ag | Method for producing enaminocarbonyl compounds |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63112883U (en) * | 1987-01-13 | 1988-07-20 | ||
| JPH0525919Y2 (en) * | 1987-11-30 | 1993-06-30 | ||
| CA2210821A1 (en) * | 1996-09-04 | 1998-03-04 | Lonza Ag | Process for the preparation of an arylazotetronic acid derivative |
| CA2211503A1 (en) * | 1996-09-04 | 1998-03-04 | Josef Schroer | Process for the preparation of tetronic acid derivatives |
| AUPQ841900A0 (en) * | 2000-06-28 | 2000-07-20 | Unisearch Limited | Synthesis of cyclic compounds |
| EP2042496A1 (en) | 2007-09-18 | 2009-04-01 | Bayer CropScience AG | Method for manufacturing 4-aminobut-2-enolids |
| JP2010070460A (en) | 2008-09-16 | 2010-04-02 | Daicel Chem Ind Ltd | Method for producing tetronic acid |
| TW201111370A (en) | 2009-08-18 | 2011-04-01 | Bayer Cropscience Ag | Novel process for the preparation of 4-aminobut-2-enolides |
| CN106632081A (en) * | 2016-12-14 | 2017-05-10 | 四川同晟生物医药有限公司 | 5-chloro-6-(chloromethyl) uracil and preparation method thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH529128A (en) * | 1970-09-04 | 1972-10-15 | Lonza Ag | Process for the production of tetronic acid |
| CH649294A5 (en) * | 1981-06-17 | 1985-05-15 | Lonza Ag | METHOD FOR PRODUCING TETRONIC ACID. |
| CH649996A5 (en) * | 1981-06-17 | 1985-06-28 | Lonza Ag | PROCESS FOR THE PRODUCTION OF TETRONIC ACID. |
-
1984
- 1984-02-09 CH CH604/84A patent/CH658056A5/en not_active IP Right Cessation
-
1985
- 1985-01-14 HU HU85132A patent/HU196066B/en not_active IP Right Cessation
- 1985-01-18 DD DD85272648A patent/DD229126A5/en not_active IP Right Cessation
- 1985-01-22 IL IL74131A patent/IL74131A/en unknown
- 1985-01-22 IN IN52/MAS/85A patent/IN162567B/en unknown
- 1985-02-04 EP EP85101150A patent/EP0153615B1/en not_active Expired
- 1985-02-04 DE DE8585101150T patent/DE3569735D1/en not_active Expired
- 1985-02-04 AT AT85101150T patent/ATE42550T1/en not_active IP Right Cessation
- 1985-02-06 MX MX204247A patent/MX156171A/en unknown
- 1985-02-07 CA CA000473780A patent/CA1225094A/en not_active Expired
- 1985-02-08 SU SU853853848A patent/SU1436868A3/en active
- 1985-02-08 JP JP60023386A patent/JPS60184073A/en active Granted
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8487112B2 (en) | 2007-09-18 | 2013-07-16 | Bayer Cropscience Ag | Method for producing 4-aminobut-2-enolides |
| US8680286B2 (en) | 2009-03-16 | 2014-03-25 | Bayer Cropscience Ag | Method for producing enaminocarbonyl compounds |
| US8680285B2 (en) | 2009-03-16 | 2014-03-25 | Bayer Cropscience Ag | Method for producing enaminocarbonyl compounds |
| US8344151B2 (en) | 2009-12-23 | 2013-01-01 | Bayer Cropscience Ag | Process for the preparation of 4-aminobut-2-enolides starting from 4-alkoxyfuran-2(5H)-one or 4-arylalkoxyfuran-2(5H)-one |
Also Published As
| Publication number | Publication date |
|---|---|
| ATE42550T1 (en) | 1989-05-15 |
| MX156171A (en) | 1988-07-19 |
| JPS6156232B2 (en) | 1986-12-01 |
| EP0153615A1 (en) | 1985-09-04 |
| JPS60184073A (en) | 1985-09-19 |
| IL74131A (en) | 1988-11-30 |
| CH658056A5 (en) | 1986-10-15 |
| EP0153615B1 (en) | 1989-04-26 |
| SU1436868A3 (en) | 1988-11-07 |
| DE3569735D1 (en) | 1989-06-01 |
| IN162567B (en) | 1988-06-11 |
| HU196066B (en) | 1988-09-28 |
| DD229126A5 (en) | 1985-10-30 |
| HUT39441A (en) | 1986-09-29 |
| IL74131A0 (en) | 1985-04-30 |
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