CA1291142C - O-pyrones and a process for their preparation and the use thereof - Google Patents
O-pyrones and a process for their preparation and the use thereofInfo
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Abstract
.alpha.-Pyrones and a process for their preparation and the use thereof Abstract of the Disclosure Alkoxymethyleneaconitic acid triesters of formula I
(I), wherein R1, R2, R3 and R4 are each independently unsubstituted or substituted aliphatic hydrocarbon radicals, can be obtained by reacting aconitic acid triesters with formates in the presence of TiCl4, a tertiary amine and a complexing solvent.
Enol ethers of formula I can be cyclised in the presence of strong anhydrous acids, in a manner which is known per se, to 2-oxo-2H-pyran-4,5-dicarboxylic acid diesters of formula V
(I), wherein R1, R2, R3 and R4 are each independently unsubstituted or substituted aliphatic hydrocarbon radicals, can be obtained by reacting aconitic acid triesters with formates in the presence of TiCl4, a tertiary amine and a complexing solvent.
Enol ethers of formula I can be cyclised in the presence of strong anhydrous acids, in a manner which is known per se, to 2-oxo-2H-pyran-4,5-dicarboxylic acid diesters of formula V
Description
6-15288/+ /B
~-Pyrones and a process for their preparation _ The present invention relates to 2-oxo-2H-4,5-dicarboxylic acid diesters (hereinafter also referred to as a-pyrone-4,5-dicarboxylic acid diesters), to a process for their preparation and to the US8 thereof as diene components in Diels-Alder reactions.
It is known that a number of aliphatic aldehydes and ketones react withCH acidic compounds, e.g. malonates, in the presence of TiCl4, an ether and a tertiary amine, in a Knoevenagel condensation, to give the corresponding alkylidene compounds (q.v. W. Lehnert, Tetrahedron Letters 54, 4723-4724 (1970), Tetrahedron 28, 663-666 (1972), Tetra-hedron 29, 635-638 (1973), Tetrahedron 30, 301-305 (1974).
It is also known from N.P. Shusherina, Russian Chemical Reviews 43 (10), 197~, pp. 851-861, that e.g. methyl 2-oxo-2H-pyran-5-carboxylate can be reacted as diene component in Diels-Alder reactions with different dienophiles. ~-Pyrones having two ester groups in the 4-and 5-positions are not known. It is, however, desirable to provide these compounds, as the two functional groups permit their wide-ranging use as intermediates.
An object of the present invention are ~-Pyrone-4,5-dicarboxylic acid diesters of formula ~l ooc~
i! ! (v)~
'o' ~o wherein R' and R~ are each independently of the other an aliphatic hydrocarbon radical of l to 20 carbon atoms which are unsubstituted or substituted by cyano, halogen or Cl-Clzalkoxy.
Rl and R~ have the same preferred meanings as indicated hereinafter.
The compounds of the present invention can be obtained by cyclising alkoxymethyleneaconitic acid triesters of formula I in a manner which is known per se.
Yet a further object of the invention is a process for the preparation of ~-pyrones of formula V, whlch comprises cyclislng an alkoxymethyl-eneaconitic acid triester of formula I
OOR~
RlOOC\ ~ ~ ~CoOR3 (I), 0-R~
wherein Rl, R2, R3 and R4 are each independently aliphatic hydrocarbon radicals of 1 to 20 carbon atoms, which are unsubstituted or substi-tuted by cyano, halogen or Cl-C12alkoxy in the presence of a strong anhydrou3 acid at elevated temperature, and isolatlng the resultant compound of ormula Y in a manner known per se.
It i5 preferred to use strong anhydrous acids, preferably organic acids, in the reaction, with the preferred temperature range being from 50 to 200C, in particular from 70 to 150C. Illustrative of organic acids are: formic acid, propionic acid, butyric acid, fluorosulfonic acid, chlorosulfonic acid, methanesulfonic acid, toluenesulfonic acid and benzenesulfonic acid. The reaction is preEerably carried out in formic acid or acetic acid and without the addition of a solvent.
Rl, R2, R3 and R4 as hydrocarbon radicals each independently contain preferably 1 to 12, carbon atoms, and are each independently preferably unsubstituted or substituted linear or branched alkyl, cycloalkyl, alkylcycloalkyl, aralkyl or a1karalkyl.
R1, R`2, R3 and R~ as alkyl each lndependently contain 1 to 18, in particular 1 to 12 and, most preferably, l to 6 carbon atoms. Exemplary of alkyl groups are: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl, pentyl, hexyl, octyl, 2-ethyl-n-hexyl, nonyl, decyl, undecyl, dodecyl, tetradecyl and octadecyl.
In a particularly preferred embodiment of the compounds of formula I, R1, R2, R3 and R~ are each independently methyl or ethyl.
Rl, R2, R3 and ~4 as cycloalkyl may each independently contain from 3 to 12, preferably 3 to ~ and, most preferably, 4 to 6, ring carbon atoms. Examples of cycloalkyl groups are: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclo-decyl, cyclododceyl, with cyclopentyl or cyclohexyl being preferred.
R1, R~, R3 and R~ as alkylcycloalkyl each independently contain from 4 to 24 carbon atoms. Examples are the above mentioned cycloaliphatlc groups which are substituted by linear or branched alkyl, preferably by methyl, ethyl or propyl.
R~, R2, R3 and R4 as a~alkyl and alkaralkyl each independently contaln monocyclic or polycyclic condensed aromatic hydrocarbon radicals.
Aralkyl contains 7 to 15 carbon atoms and alkaralkyl contains 8 to 15 carbon atoms. The aromatic hydrocarbon moiety of aralkyl and alkaralkyl is preferably phenyl or naphthyl. Examples of such radicals are ben~yl, phenylethyl, 2-phenylpropyl, naphthylmethyl, methylbenzyl and ethyl-benzyl.
The aliphatic hydrocarbon radicals Rl, R2, R3 and R~ may each lndepen-dently be substituted by one or more, preferably by one to three, identical or different groups. Suitable substituents of Rl to R4 are those which do not react with TiCl~, under the reaction conditions.
Suitsble substituents are: cyano, halogen, in particular F, Cl, Br, preferably F and Cl, and alkoxy. Alkoxy ~ubstituents contain from 1 to 12, preferably from 1 to 4, carbon atoms. In a preferred embodiment of the compounds of formula I, Rl to R~ are substituted by an alkoxy or a cyano group or by one or more halogen atoms.
- 4 - ~ ~9~
As halogen-substituted groups, Rl, R2, R3 and R4 are preferably each independently haloalkyl which is not substituted by halogen in the ~-position.
Rl, R2, R3 and R4 as haloalkyl each independently contain prefarably from 2 to 6 carbon atoms. Examples are: l-chloroeth-2-yl, 1-bromo-eth-2-yl, 1-fluoroeth-2-yl, 2-chloroprop-2-yl, 1,1-dichloroeth-2-yl, 1,1-difluoroeth-2-yl, 1~1,1-trichloroeth-2-yl, l,l,1-trichloroprop-3-yi, 1,1,1-trifluoroeth-2-yl, 1,1,1-trifluoro-2,2-dichloroprop-3-yl.
In a preferred embodiment of the enol ethers of formula I, the radicals Rl, R2, R3 and R4 are identical.
The compounds of formula I are novel affd can be prepared by a novel process by reacting carbonyl compounds with CH acidic bonds and an ester in the presence of TiCl4, a tertiary amine and a complexing solvent, which process comprises reacting, as carbonyl compound, an sconitic acid triester of formula II
ÇOOR~
C~ CoOR3 (II), RlOOC-C~2~C ~
wherein Rl, R2, R~ and R~ are each independently unsubstituted or substituted aliphatic hydrocarbon radicals, and, as ester, a formate of formula III
H-C~O (III), o_R4 wherein R~ independently has the same ~eaning as Rl, to give the enol ether of formula I.
The formate acts as an aldehyde during the reaction and forms an enol ether with the aconitic acid triester, with the elimination of water.
The reaction is preferably carried out in the temperature range from _20V to +SOC, in particular from 0 to +30VC, and the reaction time may be several hours.
~ .
~ 5 --Some of the compounds of formula III are commercially available or theycan be obtained by methods which are known per se by transesterifica-tion from the commercially avai]able formates. The compounds oE
formula II are known and can be prepared e.g. by elimination of water from citrates.
An equimolar amount or an excess of the formate of formula III can be used, based on the aconitic acid triester of formula II. The excess may be chosen such that the formate simultaneously acts as solvent. The formate of formula III is suitably employed in a 2- to 8-fold excess, preferably in a 2- to S-fold exc~ss In a preferred embodiment of the process, the aliphatic hydrocarbon radicals R3 and R4 are each independently of the other Cl-C6alkyl, preferably methyl or ethyl.
A particularly advantageous embodiment of the process is that wherein the radicals R1, R2, R3 and R~ are iden-tical, as a transesterification possible under the indicated reaction conditions is avoided and a homogeneous reaction product is thereby obtained.
The tertiary amine may be e.g. a mono-, di- or triamine whose N-atoms are alkylated.
Preferred tertiary amines are amines of formula IV
: s R6 - i (IV) wherein Rs, R6 and R7 are each independently branched or unbranched alkyl of preferably 1 to 2U, most preferably 1 to 12, carbon atoms, aralkyl or aryl of preferably 7 to lS and 6 to 15 carbon atoms respectively, or cycloalkyl of preferably 4 to 7 ring carbon atoms.
Aralkyl is preferably benzyl and aryl is preferably phenyl.
- 6 - ~9~
~urther suitable tertary amines are heteroaromatic amines or N-alkylated, preferably N-methylated1 aliphatic-heterocyclic amines. The heteroaromatic amines preferably contain 5 or 6 ring members. The aliphatic-heterocyclic amines preferably contain 3 to 7, most prefer-ably 5 to 7, ring members. They may contain further hetero atoms, in particular N, 0 and S.
E~amples of such tertiary amines are: trimethylamine, triethylamine, methyl diethylamine, tri-n-propylamine, triisopropylamine, methyl diisopropylamine, tri-n-butylamine, triisobutylamine, tri-tert-butyl-amine, trihexylamine, dimethyl cyclohexylamine, pyridine, quinoline, diamines of the general formula (alkyl~2-N-(CHz)n-N(alkyl)2, where n = 2 to 6, N-alkylpiperidine, N-alkylpyrrolidine, N-alkylmorpholine, N-alkylpyrazoline, N,N'-dialkylpiperazine, wherein the alkyl moiety contains 1 to 4 carbon atoms and is preferably methyl.
It is most preferred to use N-methylmorpholine as tertiary amine.
An equimolar amount or an excess of tertiary amine may be used, based on the aconltic acid triester. The excess may be chosen such that the tertiary amine simultaneously acts as solvent. A 2- to 20-fold, preferably a 4- to 12-fold, exces~ may suitably be used.
An approximately equimolar amount or a slight excess of TiCl4 can be used, based on the formate. It i9 preferred to use an equimolar amount.
It is advantageous to use at least 2 moles of complexing solvent per mole of TiCl~. The complexing solvent can simultaneously be the solvent for the reaction.
Suitable complexing solvents for TiCl4 are for example solvents that contain nitrogen, oxygen or sulfur atoms and which are able to co-ordinate their hetero atoms with the titanium through free pairs of electrons. It is preferred to use ethers, in particular aliphatic etherY.
The following ethers are illustrative of those which may be suitably employed: dlethyl ethers, di-n-propyl ather, diisopropyl ether, di-n-butyl ether, diisobutyl ether, di-tert-butyl ether, dihexyl ether, tetrahydrofuran, dioxane, glycol ethers of the general forrnula R8-O-(CH2)n-O-R8, where n is 2 to 6 and ~ i5 C1-C,,alkyl, preferably methyl or ethyl, e.g. ethylene glycol dimethyl ether or ethylene glycol diethyl ether.
~urther suitable ethers are e.g. polyalkylene glycol diethers which may correspond to the formula R8-O-(CnH2n-O~--R8, wherein R8 is Cl-C4alkyl, preferably methyl or ethyl, n is 2 to 6, preferably 2 to 4, and x is 2 to 4. Exemplary of such ethers are: diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, dipropylene glycol dimethyl ether and dibutylene glycol diethyl ether.
A preferred embodiment of the process of the invention comprises carrying out the reaction in the presence of an additional inert solvent, preferably a polar aprotic solvent. Illustrative of such solvents are halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1,1-tri-chloroethane, 1,1,2,2-tetrachloroethane, or substituted benzenes such as chlorobenzene, toluene or xylene.
The compounds of formula Y are useful polyfunctional intermediates for synthesising organic compounds. Thsy can be used e.g. as diene com-ponents in Diels-Alder reactions using different dienophiles. In such resctions ~hey can be reacted under milder reaction conditions than the ~-pyrone monocarboxylic acid methyl ester. Owing to the functional groups present therein, such Diels-Alder adducts can be converted e.g.
into polycyclic compounds.
A further ob~ect of t~e invention concerns the use of 2-oxo-2H-pyran-4,5-dicarboxylic acid diesters of formula V as diene components in Diels-Alder reactions.
The invention is illustrated in more detail by the following Examples.
Example 1: Preparation of ~-p~rone-4,5-dicarboxvlic acid diethyl ester With stirring, a solutlon of 113.14 g (0.6 mole) of titanium tetra-chloride in 150 ml of tetrachloromethane is added dropwise at 2G-3~C
over 40 minutes to 1200 ml of tetrahydrofuran. After one hour, 44.16 g (0.6 mole? of ethyl formate and 38.7 g (0.15 mole) of aconitic acid triethyl ester are added in succession at the same temperature.
Finally, 120.93 g (1.2 moles) of N-methylmorpholine in 210 ml of tetrahydrofuran are added over 45 minutes. After 15 minutes the reaction mixture is poured, with efficient stirring, into 1500 ml of H~O, 200 g of sodium bicarbonate and 1400 ml of methylene chloride. The batch is stirred until the evolution of C02 has ceased. The resultant suspension is first filtered and the two pha~es of the filtrate are separated. The aqueous phase is extracted with two 300 ml portions of methylene chloride and the combined methylene chloride extracts are dried over sodium sulfate and concentrated by evaporation. ~nreacted constituents are distilled o~f from the resultant crude product (44.95 g; 95.4 %) under a high vacuum at 61UC, affording 31.38 g (66.6 ~) of ethoxymethyleneaconitic acid triethyl ester. ~H-NMR
spectrum (in CdCl3): 6.85 (lH singlet), 7.5 (lH singlet). The product is further processed direct.
31.38 g (0.1 mole) of ethoxymethyleneaconitic acid triethyl ester are heated in 314 ml of formic acid for 1 hour at 95C. The formic acid is then distilled off under a water pump vacuum. Distillation of the resldue under high v~cuum yields 10.00 g (62.4 %) o~ ~-pyrone-4,5-dicarboxylic acid diethyl ester (b.p. 82C/1.2 x 10 2 mbar). lH-NMR
spectrum (in CdC13): 6.40 (lH, singlet, 8.25 (lH singlet).
~g~2 Use Examples Example 2: Preparation of anthracene-9,10-quinone-2,3-dicarboxylic aciddiethyl ester With stirring, 45.79 g ~0.1908 mole) of ~-pyrone-4,5-dicarboxylic acid diethyl ester and 25.15 g (0.1590 mole) of naphthoquinone are refluxed in 150 ml of xylene for 17 hours. The hydroquinone initially formed ls unstable in air ln the reaction medium employed and oxidises sponta-neously to quinone.
The xylene is distilled off and the dlstillation residue is dissolved hot in 300 ml of methanol. The solution is cooled to 20VC and the crystalline crude product is flltered with suction, dissolved in 300 ml of chloroform and filtered over 100 g of silica gel, affording 20.73 g ~37 %) of anthracene-9,10-quinone-2,3-dicarboxylic acid diethyl ester of m.p. 153-155~C (recrystallisation from ethanol).
H-NMR spectrum (in CdCl3): 8.88 (singlet), ~.40 (multiplet), 7.73 (multiplet).
Example 3: Preparation of naphthacene-5,12-quinone-2,3-dicarboxylic acid diethyl ester In an autoclave, 15~91 g ~0.076 mole) of 1,4-anthraquinone and 18.42 g (0.076 mole) of ~-pyrone-4,5-dicarboxylic acid diethyl ester are heated in 34 ml of xylene for 24 hours to 160C. The xylene is then distilled off. The distillation residue is dissolved in chloroform and the solution is filtered over 1.2 g of silica gel (particle size:
0.040-0.063 mm) and the silica gel i9 rinsed with chloroform, affording 19.7 g of a crude dark brown substance which is sub~ected to subli-mation at 220C under a high vacuum. Yield: 6.3 g (30 %~ of naphtha-cene-5,12-quinone-2,3-dicarboxylic acid diethyl ester with a melting point of 208-209C. Mas3 spectrum: M+ = 402. The yield is quantitative with the recovery of unreacted a-pyrone-4,5-dicarboxylic acid diethyl e3ter.
1~9~
Example 4: Preparation of naphthalbne-1,4-quinone-6,7-dicarboxylic aclddiethyl ester With stirring, 2.4 g (0.01 mole) of a-pyrone-4,5-dicarboxylic acid diethyl ester and 5.4 g ~0.05 mole) of 1,4-benzoquinone are refluxed in 7 ml of 1,2-dichlorobenzene for 12 hours and the mixture i8 then allowed to stand for 5 hours at room temperature. The preclpitated black crystals are washed with dichlorobenzene and the combined dark dichlorobenzene solution is chromatographed over 36 g of silica gel (eluant: methylene chloride). The methylene chloride solution is evaporated to dryness in a rotary evaporator. Excess 1,4-benzoquinone also sublimes at a water bath temperature of 90C. Upon addition of 1 ml of ethyl ether, 1.1 g (36.4 %) of naphthalene-1,4-quinone-6,7-dicarboxylic acid diethyl ester (m.p. 59-62C) crystallises from the oily distillation residue. A further crop of crystals can be obtained from the mother liquors. lH-NMR spectrum (in CdCl3): 8.42 (singlet), 5.06 (singlet). Mass spectrum: M = 302.
~-Pyrones and a process for their preparation _ The present invention relates to 2-oxo-2H-4,5-dicarboxylic acid diesters (hereinafter also referred to as a-pyrone-4,5-dicarboxylic acid diesters), to a process for their preparation and to the US8 thereof as diene components in Diels-Alder reactions.
It is known that a number of aliphatic aldehydes and ketones react withCH acidic compounds, e.g. malonates, in the presence of TiCl4, an ether and a tertiary amine, in a Knoevenagel condensation, to give the corresponding alkylidene compounds (q.v. W. Lehnert, Tetrahedron Letters 54, 4723-4724 (1970), Tetrahedron 28, 663-666 (1972), Tetra-hedron 29, 635-638 (1973), Tetrahedron 30, 301-305 (1974).
It is also known from N.P. Shusherina, Russian Chemical Reviews 43 (10), 197~, pp. 851-861, that e.g. methyl 2-oxo-2H-pyran-5-carboxylate can be reacted as diene component in Diels-Alder reactions with different dienophiles. ~-Pyrones having two ester groups in the 4-and 5-positions are not known. It is, however, desirable to provide these compounds, as the two functional groups permit their wide-ranging use as intermediates.
An object of the present invention are ~-Pyrone-4,5-dicarboxylic acid diesters of formula ~l ooc~
i! ! (v)~
'o' ~o wherein R' and R~ are each independently of the other an aliphatic hydrocarbon radical of l to 20 carbon atoms which are unsubstituted or substituted by cyano, halogen or Cl-Clzalkoxy.
Rl and R~ have the same preferred meanings as indicated hereinafter.
The compounds of the present invention can be obtained by cyclising alkoxymethyleneaconitic acid triesters of formula I in a manner which is known per se.
Yet a further object of the invention is a process for the preparation of ~-pyrones of formula V, whlch comprises cyclislng an alkoxymethyl-eneaconitic acid triester of formula I
OOR~
RlOOC\ ~ ~ ~CoOR3 (I), 0-R~
wherein Rl, R2, R3 and R4 are each independently aliphatic hydrocarbon radicals of 1 to 20 carbon atoms, which are unsubstituted or substi-tuted by cyano, halogen or Cl-C12alkoxy in the presence of a strong anhydrou3 acid at elevated temperature, and isolatlng the resultant compound of ormula Y in a manner known per se.
It i5 preferred to use strong anhydrous acids, preferably organic acids, in the reaction, with the preferred temperature range being from 50 to 200C, in particular from 70 to 150C. Illustrative of organic acids are: formic acid, propionic acid, butyric acid, fluorosulfonic acid, chlorosulfonic acid, methanesulfonic acid, toluenesulfonic acid and benzenesulfonic acid. The reaction is preEerably carried out in formic acid or acetic acid and without the addition of a solvent.
Rl, R2, R3 and R4 as hydrocarbon radicals each independently contain preferably 1 to 12, carbon atoms, and are each independently preferably unsubstituted or substituted linear or branched alkyl, cycloalkyl, alkylcycloalkyl, aralkyl or a1karalkyl.
R1, R`2, R3 and R~ as alkyl each lndependently contain 1 to 18, in particular 1 to 12 and, most preferably, l to 6 carbon atoms. Exemplary of alkyl groups are: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl, pentyl, hexyl, octyl, 2-ethyl-n-hexyl, nonyl, decyl, undecyl, dodecyl, tetradecyl and octadecyl.
In a particularly preferred embodiment of the compounds of formula I, R1, R2, R3 and R~ are each independently methyl or ethyl.
Rl, R2, R3 and ~4 as cycloalkyl may each independently contain from 3 to 12, preferably 3 to ~ and, most preferably, 4 to 6, ring carbon atoms. Examples of cycloalkyl groups are: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclo-decyl, cyclododceyl, with cyclopentyl or cyclohexyl being preferred.
R1, R~, R3 and R~ as alkylcycloalkyl each independently contain from 4 to 24 carbon atoms. Examples are the above mentioned cycloaliphatlc groups which are substituted by linear or branched alkyl, preferably by methyl, ethyl or propyl.
R~, R2, R3 and R4 as a~alkyl and alkaralkyl each independently contaln monocyclic or polycyclic condensed aromatic hydrocarbon radicals.
Aralkyl contains 7 to 15 carbon atoms and alkaralkyl contains 8 to 15 carbon atoms. The aromatic hydrocarbon moiety of aralkyl and alkaralkyl is preferably phenyl or naphthyl. Examples of such radicals are ben~yl, phenylethyl, 2-phenylpropyl, naphthylmethyl, methylbenzyl and ethyl-benzyl.
The aliphatic hydrocarbon radicals Rl, R2, R3 and R~ may each lndepen-dently be substituted by one or more, preferably by one to three, identical or different groups. Suitable substituents of Rl to R4 are those which do not react with TiCl~, under the reaction conditions.
Suitsble substituents are: cyano, halogen, in particular F, Cl, Br, preferably F and Cl, and alkoxy. Alkoxy ~ubstituents contain from 1 to 12, preferably from 1 to 4, carbon atoms. In a preferred embodiment of the compounds of formula I, Rl to R~ are substituted by an alkoxy or a cyano group or by one or more halogen atoms.
- 4 - ~ ~9~
As halogen-substituted groups, Rl, R2, R3 and R4 are preferably each independently haloalkyl which is not substituted by halogen in the ~-position.
Rl, R2, R3 and R4 as haloalkyl each independently contain prefarably from 2 to 6 carbon atoms. Examples are: l-chloroeth-2-yl, 1-bromo-eth-2-yl, 1-fluoroeth-2-yl, 2-chloroprop-2-yl, 1,1-dichloroeth-2-yl, 1,1-difluoroeth-2-yl, 1~1,1-trichloroeth-2-yl, l,l,1-trichloroprop-3-yi, 1,1,1-trifluoroeth-2-yl, 1,1,1-trifluoro-2,2-dichloroprop-3-yl.
In a preferred embodiment of the enol ethers of formula I, the radicals Rl, R2, R3 and R4 are identical.
The compounds of formula I are novel affd can be prepared by a novel process by reacting carbonyl compounds with CH acidic bonds and an ester in the presence of TiCl4, a tertiary amine and a complexing solvent, which process comprises reacting, as carbonyl compound, an sconitic acid triester of formula II
ÇOOR~
C~ CoOR3 (II), RlOOC-C~2~C ~
wherein Rl, R2, R~ and R~ are each independently unsubstituted or substituted aliphatic hydrocarbon radicals, and, as ester, a formate of formula III
H-C~O (III), o_R4 wherein R~ independently has the same ~eaning as Rl, to give the enol ether of formula I.
The formate acts as an aldehyde during the reaction and forms an enol ether with the aconitic acid triester, with the elimination of water.
The reaction is preferably carried out in the temperature range from _20V to +SOC, in particular from 0 to +30VC, and the reaction time may be several hours.
~ .
~ 5 --Some of the compounds of formula III are commercially available or theycan be obtained by methods which are known per se by transesterifica-tion from the commercially avai]able formates. The compounds oE
formula II are known and can be prepared e.g. by elimination of water from citrates.
An equimolar amount or an excess of the formate of formula III can be used, based on the aconitic acid triester of formula II. The excess may be chosen such that the formate simultaneously acts as solvent. The formate of formula III is suitably employed in a 2- to 8-fold excess, preferably in a 2- to S-fold exc~ss In a preferred embodiment of the process, the aliphatic hydrocarbon radicals R3 and R4 are each independently of the other Cl-C6alkyl, preferably methyl or ethyl.
A particularly advantageous embodiment of the process is that wherein the radicals R1, R2, R3 and R~ are iden-tical, as a transesterification possible under the indicated reaction conditions is avoided and a homogeneous reaction product is thereby obtained.
The tertiary amine may be e.g. a mono-, di- or triamine whose N-atoms are alkylated.
Preferred tertiary amines are amines of formula IV
: s R6 - i (IV) wherein Rs, R6 and R7 are each independently branched or unbranched alkyl of preferably 1 to 2U, most preferably 1 to 12, carbon atoms, aralkyl or aryl of preferably 7 to lS and 6 to 15 carbon atoms respectively, or cycloalkyl of preferably 4 to 7 ring carbon atoms.
Aralkyl is preferably benzyl and aryl is preferably phenyl.
- 6 - ~9~
~urther suitable tertary amines are heteroaromatic amines or N-alkylated, preferably N-methylated1 aliphatic-heterocyclic amines. The heteroaromatic amines preferably contain 5 or 6 ring members. The aliphatic-heterocyclic amines preferably contain 3 to 7, most prefer-ably 5 to 7, ring members. They may contain further hetero atoms, in particular N, 0 and S.
E~amples of such tertiary amines are: trimethylamine, triethylamine, methyl diethylamine, tri-n-propylamine, triisopropylamine, methyl diisopropylamine, tri-n-butylamine, triisobutylamine, tri-tert-butyl-amine, trihexylamine, dimethyl cyclohexylamine, pyridine, quinoline, diamines of the general formula (alkyl~2-N-(CHz)n-N(alkyl)2, where n = 2 to 6, N-alkylpiperidine, N-alkylpyrrolidine, N-alkylmorpholine, N-alkylpyrazoline, N,N'-dialkylpiperazine, wherein the alkyl moiety contains 1 to 4 carbon atoms and is preferably methyl.
It is most preferred to use N-methylmorpholine as tertiary amine.
An equimolar amount or an excess of tertiary amine may be used, based on the aconltic acid triester. The excess may be chosen such that the tertiary amine simultaneously acts as solvent. A 2- to 20-fold, preferably a 4- to 12-fold, exces~ may suitably be used.
An approximately equimolar amount or a slight excess of TiCl4 can be used, based on the formate. It i9 preferred to use an equimolar amount.
It is advantageous to use at least 2 moles of complexing solvent per mole of TiCl~. The complexing solvent can simultaneously be the solvent for the reaction.
Suitable complexing solvents for TiCl4 are for example solvents that contain nitrogen, oxygen or sulfur atoms and which are able to co-ordinate their hetero atoms with the titanium through free pairs of electrons. It is preferred to use ethers, in particular aliphatic etherY.
The following ethers are illustrative of those which may be suitably employed: dlethyl ethers, di-n-propyl ather, diisopropyl ether, di-n-butyl ether, diisobutyl ether, di-tert-butyl ether, dihexyl ether, tetrahydrofuran, dioxane, glycol ethers of the general forrnula R8-O-(CH2)n-O-R8, where n is 2 to 6 and ~ i5 C1-C,,alkyl, preferably methyl or ethyl, e.g. ethylene glycol dimethyl ether or ethylene glycol diethyl ether.
~urther suitable ethers are e.g. polyalkylene glycol diethers which may correspond to the formula R8-O-(CnH2n-O~--R8, wherein R8 is Cl-C4alkyl, preferably methyl or ethyl, n is 2 to 6, preferably 2 to 4, and x is 2 to 4. Exemplary of such ethers are: diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, dipropylene glycol dimethyl ether and dibutylene glycol diethyl ether.
A preferred embodiment of the process of the invention comprises carrying out the reaction in the presence of an additional inert solvent, preferably a polar aprotic solvent. Illustrative of such solvents are halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1,1-tri-chloroethane, 1,1,2,2-tetrachloroethane, or substituted benzenes such as chlorobenzene, toluene or xylene.
The compounds of formula Y are useful polyfunctional intermediates for synthesising organic compounds. Thsy can be used e.g. as diene com-ponents in Diels-Alder reactions using different dienophiles. In such resctions ~hey can be reacted under milder reaction conditions than the ~-pyrone monocarboxylic acid methyl ester. Owing to the functional groups present therein, such Diels-Alder adducts can be converted e.g.
into polycyclic compounds.
A further ob~ect of t~e invention concerns the use of 2-oxo-2H-pyran-4,5-dicarboxylic acid diesters of formula V as diene components in Diels-Alder reactions.
The invention is illustrated in more detail by the following Examples.
Example 1: Preparation of ~-p~rone-4,5-dicarboxvlic acid diethyl ester With stirring, a solutlon of 113.14 g (0.6 mole) of titanium tetra-chloride in 150 ml of tetrachloromethane is added dropwise at 2G-3~C
over 40 minutes to 1200 ml of tetrahydrofuran. After one hour, 44.16 g (0.6 mole? of ethyl formate and 38.7 g (0.15 mole) of aconitic acid triethyl ester are added in succession at the same temperature.
Finally, 120.93 g (1.2 moles) of N-methylmorpholine in 210 ml of tetrahydrofuran are added over 45 minutes. After 15 minutes the reaction mixture is poured, with efficient stirring, into 1500 ml of H~O, 200 g of sodium bicarbonate and 1400 ml of methylene chloride. The batch is stirred until the evolution of C02 has ceased. The resultant suspension is first filtered and the two pha~es of the filtrate are separated. The aqueous phase is extracted with two 300 ml portions of methylene chloride and the combined methylene chloride extracts are dried over sodium sulfate and concentrated by evaporation. ~nreacted constituents are distilled o~f from the resultant crude product (44.95 g; 95.4 %) under a high vacuum at 61UC, affording 31.38 g (66.6 ~) of ethoxymethyleneaconitic acid triethyl ester. ~H-NMR
spectrum (in CdCl3): 6.85 (lH singlet), 7.5 (lH singlet). The product is further processed direct.
31.38 g (0.1 mole) of ethoxymethyleneaconitic acid triethyl ester are heated in 314 ml of formic acid for 1 hour at 95C. The formic acid is then distilled off under a water pump vacuum. Distillation of the resldue under high v~cuum yields 10.00 g (62.4 %) o~ ~-pyrone-4,5-dicarboxylic acid diethyl ester (b.p. 82C/1.2 x 10 2 mbar). lH-NMR
spectrum (in CdC13): 6.40 (lH, singlet, 8.25 (lH singlet).
~g~2 Use Examples Example 2: Preparation of anthracene-9,10-quinone-2,3-dicarboxylic aciddiethyl ester With stirring, 45.79 g ~0.1908 mole) of ~-pyrone-4,5-dicarboxylic acid diethyl ester and 25.15 g (0.1590 mole) of naphthoquinone are refluxed in 150 ml of xylene for 17 hours. The hydroquinone initially formed ls unstable in air ln the reaction medium employed and oxidises sponta-neously to quinone.
The xylene is distilled off and the dlstillation residue is dissolved hot in 300 ml of methanol. The solution is cooled to 20VC and the crystalline crude product is flltered with suction, dissolved in 300 ml of chloroform and filtered over 100 g of silica gel, affording 20.73 g ~37 %) of anthracene-9,10-quinone-2,3-dicarboxylic acid diethyl ester of m.p. 153-155~C (recrystallisation from ethanol).
H-NMR spectrum (in CdCl3): 8.88 (singlet), ~.40 (multiplet), 7.73 (multiplet).
Example 3: Preparation of naphthacene-5,12-quinone-2,3-dicarboxylic acid diethyl ester In an autoclave, 15~91 g ~0.076 mole) of 1,4-anthraquinone and 18.42 g (0.076 mole) of ~-pyrone-4,5-dicarboxylic acid diethyl ester are heated in 34 ml of xylene for 24 hours to 160C. The xylene is then distilled off. The distillation residue is dissolved in chloroform and the solution is filtered over 1.2 g of silica gel (particle size:
0.040-0.063 mm) and the silica gel i9 rinsed with chloroform, affording 19.7 g of a crude dark brown substance which is sub~ected to subli-mation at 220C under a high vacuum. Yield: 6.3 g (30 %~ of naphtha-cene-5,12-quinone-2,3-dicarboxylic acid diethyl ester with a melting point of 208-209C. Mas3 spectrum: M+ = 402. The yield is quantitative with the recovery of unreacted a-pyrone-4,5-dicarboxylic acid diethyl e3ter.
1~9~
Example 4: Preparation of naphthalbne-1,4-quinone-6,7-dicarboxylic aclddiethyl ester With stirring, 2.4 g (0.01 mole) of a-pyrone-4,5-dicarboxylic acid diethyl ester and 5.4 g ~0.05 mole) of 1,4-benzoquinone are refluxed in 7 ml of 1,2-dichlorobenzene for 12 hours and the mixture i8 then allowed to stand for 5 hours at room temperature. The preclpitated black crystals are washed with dichlorobenzene and the combined dark dichlorobenzene solution is chromatographed over 36 g of silica gel (eluant: methylene chloride). The methylene chloride solution is evaporated to dryness in a rotary evaporator. Excess 1,4-benzoquinone also sublimes at a water bath temperature of 90C. Upon addition of 1 ml of ethyl ether, 1.1 g (36.4 %) of naphthalene-1,4-quinone-6,7-dicarboxylic acid diethyl ester (m.p. 59-62C) crystallises from the oily distillation residue. A further crop of crystals can be obtained from the mother liquors. lH-NMR spectrum (in CdCl3): 8.42 (singlet), 5.06 (singlet). Mass spectrum: M = 302.
Claims
What is claimed is:
1. A 2-oxo-2H-pyran-4,5-dicarboxylic acid diester of formula V
(V) , wherein R1 and R2 are each independently of the other an aliphatic hydrocarbon radical of 1 to 20 carbon atoms which are unsubstituted or substituted by cyano, halogen or C1-C12alkoxy.
2. An ester according to claim 1, wherein the radicals R1 and R2 are each independently linear or branched C1-C18alkyl, C3-C12cycloalkyl, C4-C24alkylcycloalkyl, C7-C15aralkyl or C8-C15alkaralkyl.
3. An ester according to claim 1, wherein the aliphatic hydrocarbon radicals R1 and R2 are each independently C1-C6alkyl.
4. An ester according to claim 1, wherein the aliphatic hydrocarbon radicals R1 and R2 are identical.
5. An ester according to claim 1, wherein the aliphatic hydrocarbon radicals R1 and R2 are each independently methyl or ethyl.
6. A process for the preparation of an ester of formula V according to claim 1, which comprises cyclising, an alkoxymethyleneaconitic acid triester of formula I
(I), wherein R1, R2, R3 and R4 are each independently aliphatic hydrocarbon radicals of 1 to 20 carbon atoms, which are unsubstituted or substi-tuted by cyano, halogen or C1-C12alkoxy in the presence of a strong anhydrous acid at elevated temperature, and isolating the resultant compound of formula V.
1. A 2-oxo-2H-pyran-4,5-dicarboxylic acid diester of formula V
(V) , wherein R1 and R2 are each independently of the other an aliphatic hydrocarbon radical of 1 to 20 carbon atoms which are unsubstituted or substituted by cyano, halogen or C1-C12alkoxy.
2. An ester according to claim 1, wherein the radicals R1 and R2 are each independently linear or branched C1-C18alkyl, C3-C12cycloalkyl, C4-C24alkylcycloalkyl, C7-C15aralkyl or C8-C15alkaralkyl.
3. An ester according to claim 1, wherein the aliphatic hydrocarbon radicals R1 and R2 are each independently C1-C6alkyl.
4. An ester according to claim 1, wherein the aliphatic hydrocarbon radicals R1 and R2 are identical.
5. An ester according to claim 1, wherein the aliphatic hydrocarbon radicals R1 and R2 are each independently methyl or ethyl.
6. A process for the preparation of an ester of formula V according to claim 1, which comprises cyclising, an alkoxymethyleneaconitic acid triester of formula I
(I), wherein R1, R2, R3 and R4 are each independently aliphatic hydrocarbon radicals of 1 to 20 carbon atoms, which are unsubstituted or substi-tuted by cyano, halogen or C1-C12alkoxy in the presence of a strong anhydrous acid at elevated temperature, and isolating the resultant compound of formula V.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1089/85-0 | 1985-03-11 | ||
| CH108985 | 1985-03-11 | ||
| CA000503589A CA1274536A (en) | 1985-03-11 | 1986-03-07 | Enol ethers and a process for their preparation and o-pyrones and a process for their preparation and the use thereof |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000503589A Division CA1274536A (en) | 1985-03-11 | 1986-03-07 | Enol ethers and a process for their preparation and o-pyrones and a process for their preparation and the use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1291142C true CA1291142C (en) | 1991-10-22 |
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ID=25670931
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000571476A Expired - Lifetime CA1291142C (en) | 1985-03-11 | 1988-07-07 | O-pyrones and a process for their preparation and the use thereof |
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| Country | Link |
|---|---|
| CA (1) | CA1291142C (en) |
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1988
- 1988-07-07 CA CA000571476A patent/CA1291142C/en not_active Expired - Lifetime
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