CA1274536A - Enol ethers and a process for their preparation and o-pyrones and a process for their preparation and the use thereof - Google Patents
Enol ethers and a process for their preparation and o-pyrones and a process for their preparation and the use thereofInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/34—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D309/36—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
- C07D309/38—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms one oxygen atom in position 2 or 4, e.g. pyrones
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
Enol ethers ant a process for thelr preparation 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 raticals, 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 ln the presence of strong anhydrous acids, in a manner which is known per se, to 2-oxo-2H-pyran-4,5-ticarboxylic acid diesters of formula V
(I) wherein R1, R2, R3 and R4 are each independently unsubstituted or substituted aliphatic hydrocarbon raticals, 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 ln the presence of strong anhydrous acids, in a manner which is known per se, to 2-oxo-2H-pyran-4,5-ticarboxylic acid diesters of formula V
Description
~274536 6-15288/+
Enol ethers and a process for their preparation - .
The present invention relates to alkoxymethyleneaconitic acid triesters, to a process for their preparation.
It is known that a number of aliphatic aldehydes and ketones react with CH 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 co~pounds (q.v. W. Lehnert, Tetrahedron Letters 54, 4723-4724 (1970), Tetrahedron 28, 663-666 (1972), Tetrahedron 29, 635-638 (1973), Tetrahedron 30, 301-305 (1974).
, ~ :
It is al90 known from N.P. Shusherina, Russian Chemical Reviews 43 (10), , ~ 1974, pp. 851-861, that e.g. methyl 2-oxo-2H-pyran-5-carboxylate can be !~; reactet as dlene component in Dlels-Alder reactions with different dienophile~. a-Pyrones having two e~ter groups in the 4-and 5-positions are not known. It is, however, desirable to provide these compounds, as Ç;~ the two functional groups permit their wide-ranging use as intermediates.
Accordingly, the invention relates to alkoxymethyleneaconitic acld triesters of formula I
ç ~ : ÇOOR~
;~ Rl ooC~ CR3 ( I ) o-R4 , ~
~ " '' ' . ~ '' ' ' ,' ~ . ' ' ' ' ' " ' ' ' ' ' ~X74536 wherein Rl, R2, R3 and R~ are each independently an sliphatic hydrocarbon radical of 1 to 20 carbon atoms, which are unsubstituted or substituted by cyano, halogen or C1-C1z-alkoxy.
R1, R2, R3 and R~ as hydrocarbon radicals each independently contain preferably 1 to 12, carbon atoms, and are each independently preferably unsubstituted or sub~tituted linear or branched alkyl, cycloalkyl, alkylcycloalkyl, aralkyl or alkaralkyl.
R1, R2, R3 snd R~ as alkyl sach independently contain preferably 1 to 12 and, most preferably, 1 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 R4 are each independently methyl or ethyl.
Rl, R2, R~ and R4 as cycloalkyl each independently contain from 3 to 12, preferably 3 to 8 and, most preferably, 4 to 6, ring carbon atom~.
Examples of cycloalkyl groups sre: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cyclo-dodceyl, with cyclopentyl or cyclohexyl being preferred.
Rl, R2, R3 and R~ as alkylcycloalkyl each independently contaln from 4 to 24 carbon atoms. ~-xamples are the above mentioned cycloaliphatic groups which are substituted by linear or branched alkyl, preferably by methyl, ethyl or propyl.
R~, R2, R3 and R4 as aralkyl and alkaralkyl each independently contain 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 oiety of aralkyl and alkaralkyl is preferably phenyl or naphthyl. E~amples of such radicals are benzyl, phenylethyl, 2-phenylpropyl, naphthylmethyl, methylbenzyl and ethyl-~ benzyl.
:' ~' ': ~
'." ~.., :'. , ~, . .: .
,, ~ ., .'' .,:, ,. : . . - :
~274S:~6 The aliphatic hydrocarbon radicals R~, R2, R3 and R~ may each indepen-dently be substituted by one or more, preferably by one to three, identical or different groups. Suitable substituents of R1 to R4 are those which do not react with TiCl4 under the reaction conditions.
Examples of such substituents are: cyano, halogen, in particular F, Cl, Br, preferably F and Cl, and alkoxy. Alkoxy substituents contain from 1 to 12, in particular from l 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 atom~.
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 R~ as haloalkyl each lndependently contain preferably from
Enol ethers and a process for their preparation - .
The present invention relates to alkoxymethyleneaconitic acid triesters, to a process for their preparation.
It is known that a number of aliphatic aldehydes and ketones react with CH 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 co~pounds (q.v. W. Lehnert, Tetrahedron Letters 54, 4723-4724 (1970), Tetrahedron 28, 663-666 (1972), Tetrahedron 29, 635-638 (1973), Tetrahedron 30, 301-305 (1974).
, ~ :
It is al90 known from N.P. Shusherina, Russian Chemical Reviews 43 (10), , ~ 1974, pp. 851-861, that e.g. methyl 2-oxo-2H-pyran-5-carboxylate can be !~; reactet as dlene component in Dlels-Alder reactions with different dienophile~. a-Pyrones having two e~ter groups in the 4-and 5-positions are not known. It is, however, desirable to provide these compounds, as Ç;~ the two functional groups permit their wide-ranging use as intermediates.
Accordingly, the invention relates to alkoxymethyleneaconitic acld triesters of formula I
ç ~ : ÇOOR~
;~ Rl ooC~ CR3 ( I ) o-R4 , ~
~ " '' ' . ~ '' ' ' ,' ~ . ' ' ' ' ' " ' ' ' ' ' ~X74536 wherein Rl, R2, R3 and R~ are each independently an sliphatic hydrocarbon radical of 1 to 20 carbon atoms, which are unsubstituted or substituted by cyano, halogen or C1-C1z-alkoxy.
R1, R2, R3 and R~ as hydrocarbon radicals each independently contain preferably 1 to 12, carbon atoms, and are each independently preferably unsubstituted or sub~tituted linear or branched alkyl, cycloalkyl, alkylcycloalkyl, aralkyl or alkaralkyl.
R1, R2, R3 snd R~ as alkyl sach independently contain preferably 1 to 12 and, most preferably, 1 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 R4 are each independently methyl or ethyl.
Rl, R2, R~ and R4 as cycloalkyl each independently contain from 3 to 12, preferably 3 to 8 and, most preferably, 4 to 6, ring carbon atom~.
Examples of cycloalkyl groups sre: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cyclo-dodceyl, with cyclopentyl or cyclohexyl being preferred.
Rl, R2, R3 and R~ as alkylcycloalkyl each independently contaln from 4 to 24 carbon atoms. ~-xamples are the above mentioned cycloaliphatic groups which are substituted by linear or branched alkyl, preferably by methyl, ethyl or propyl.
R~, R2, R3 and R4 as aralkyl and alkaralkyl each independently contain 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 oiety of aralkyl and alkaralkyl is preferably phenyl or naphthyl. E~amples of such radicals are benzyl, phenylethyl, 2-phenylpropyl, naphthylmethyl, methylbenzyl and ethyl-~ benzyl.
:' ~' ': ~
'." ~.., :'. , ~, . .: .
,, ~ ., .'' .,:, ,. : . . - :
~274S:~6 The aliphatic hydrocarbon radicals R~, R2, R3 and R~ may each indepen-dently be substituted by one or more, preferably by one to three, identical or different groups. Suitable substituents of R1 to R4 are those which do not react with TiCl4 under the reaction conditions.
Examples of such substituents are: cyano, halogen, in particular F, Cl, Br, preferably F and Cl, and alkoxy. Alkoxy substituents contain from 1 to 12, in particular from l 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 atom~.
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 R~ as haloalkyl each lndependently contain preferably from
2 to 6 carbon atoms. Examples are: 1-chloroeth-2-yl, 1-bromoeth-2-yl, 1-fluoroeth-2-yl, 2-chloroprop-2-yl, 1,1-dichloroeth-2-yl, 1,1-difluoro-eth-2-yl, 1,1,1-trichloroeth-2-yl, 1,1,1-trichloroprop-3-yl, I,l,l-tri-fluoroeth-2-yl, l,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 R~ are identical.
The compounds of thi~ invention can be prepsred by a novel process by reacting a formate with an aconitic acid trie8ter, under very mild reaction conditions, in simple manner and in high yield.
A further ob~ect of the present invention iB a process for the prepara-tion of alkoxymethyleneaconitic acid triesters of formula I by reacting carbonyl compounts with CH acidic bonts and an ester in the presence of TiCl4, a tertiary amine and a complexing ~olvent, which process comprises reacting, as carbonyl compound, an aconitic acid triester of formula II
ÇoOR2 C~ CoOR3 (II), Rl OOC-C~z~CH/
~,~
.
. ., - ~, ' .
: ' ' ' . : ' ' -.
_ 4 _ wherein Rl, R2, R3 and R4 are each independently unsubstituted or substituted aliphatic hydrocarbon radicals, and, as ester, a formate of formula III
H-C~ (III), 0-R~
wherein R4 independently has the same meaning as Rl, to give the enol ether of formula I.
Surprisingly, 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 -20 to +50C, in partlcular from 0 to +30C, and the reaction time may be several hours.
Some of the compounds of formula III are commercially available or they can be obtained by methods which are known per se by transesterification from the commercially available formates. The compounds of formula II are known and can be prepared e.g. by elimination of water from citrates.
., AD 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 5-fold excess.
In a preferred embodiment of the process, the allphatic hydrocarbon radicals R3 and R~ are each independently of the other C~-C6alkyl, preferably methyl or ethyl.
A partlcularly advantageous embodiment of the process is that wherein the radicals R~, R2, R3 and R~ are ideDtical, as a transesterification possible undar the indlcated 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) . ,7 wherein Rs, R6 and R7 are each independently branched or unbranched alkyl of preferably 1 to 20, most preferably 1 to 12, csrbon atoms, aralkyl or aryl of preferably 7 to 15 and 6 to lS carbon atoms respectlvely, or cycloalkyl of preferably 4 to 7 ring carbon atoms.
Aralkyl is preferably benzyl and sryl is preferably phenyl.
~urther suitable tertary amines are heteroaromatic amines or N-alkylated, preferably N-methylated, allphatic-heterocyclic amines. The hetero-aromatic amines preferably contain S or 6 ring members. The aliphatic-heterocyclic amines preferably contain 3 to 7, most preferably 5 to 7, ring members. They ~ay contain further hetero atoms, in particular N, 0 and S.
~, ~
Examples of such tertiary amlnes are: trimethylamine, triethylamine, methyl diethylaminel tri-n-propylamine, triisopropylamine, methyl diisoproyylamine, tri-n-butylamine, triisobutylamine, tri-tert-butyl-amine, trihexyla~ine, dimethyl cyclohexylamine, pyridine, quinoline, tiamines of the general formula (alkyl)2-N-(CH2)n-N~alkyl)2, where n ~ 2 to 6, N-al~ylpiperidine, N-alkylpyrrolidine, N-alkylmorpholine, N-alkyl-pyrazoline, N,N'-dlalkylpiperazine, wherein the alkyl moiety contains 1 to 4 carbon atoms ant is preferably methyl.
It is most preferred to use N-methylmorpholine as tertiary amlne.
An squimolar smount or an excess of tertiary amine ~ay be used, based on the a~conitic acid triester. The excess may be chosen such that the tertiary amine si~ultaneously acts as solvent. A 2- to 20-fold, prefer-ably a 4- to 12-fold, excess may suitably be used.
,s~
,, , ; ~ ., -............ , `- , ' , . - , : . - . . -~.~, - : ' ' : :: . . , ~I'Z7f~
An approximately equimolar amount or a ~light exce~ of TiCl4 can be used, based on the formate. It is preferred to use an equimolar amount.
It is advantageous to use at least 2 moles of complexing solvent per mole of TiCl4. 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 sre able to co-ordinate their hetero atoms with the titanium through free pairs of electrons. It is preferred to use ethers, in particular aliphatic ethers.
The following ethers are illustrative of those which may be suitably employed: diethyl ethers, di-n-propyl ether, diisopropyl ether, di-n-butyl ether, diisobutyl ether, di-tert-butyl ether, dihexyl ether, tetrahydrofuran, dioxane, glycol ethers of the general formula R8-o-(Ch2)n-O-R8, where n i9 2 to 6 and R8 is C1-C4alkyl, preferably methyl or ethyl, e.g. ethylene glycol dimethyl ether or ethylene glycol diethyl ether.
Further suitable ethers are e.g. polyalkylene glycol diethers which may correspond to the formula R8-o-(cnH2n-ot-x-R8~ wherein R8 is Cl-C4alkyl, preferably methyl or ethyl, n is 2 to 6, preferably 2 to 4, and x i8 2 to 4. Exemplary of such ethers are: diethylene glycol dimethyl ether, trlethylene glycol dimethyl ether, dipropylene glycol dimethyl ether and dibutylene glycol diethyl ether.
A preferred embodlment of the process of the invention comprises carrying out the reaction in the presence of an additional inert solvent, prefer-ably a polar aprotic solvent. Illustrative of such solvents are halogen-ated hydrocarbons such as methylene chloride, chloroform, carbon tetra-chloride, 1,2-dichloroethane, l,l,l-trichloroethane, 1,1,2,2-tetra-chloroethane, or substituted benzenes such as chlorobenzene, toluene or xylene.
,., f ' ' , ' ~ "' ' ' ' .
~Z7~
The compounds of formula I are useful polyfunctional intermediatea for the synthesis of organic compounds. They may be cyclised for example to novel ~-pyrone-4,5-dicarboxylic acid diesters of formula V
~ooR2 RI OOC~
i! ! (v \o~ ~
wherein R1 and R2 each independently of the other are aa defined for formula I.
Rl and R2 have the same preferred meanings as previously indicated hereinabove.
The compounds of formula V can be obtained by cyclising alkoxymethylene-aconitic acid triesters of formula I in a manner which i8 known per se.
The process comprises cyclising an alkoxymethyleneaconitic acid triester of formula I
cooR2 R~OOC~ /C~ ~CoOR3 (I), 0-R~
wherein R1, R2, R3 and R~ each independently have the meanings assigned to them above, in a manner known per se, in the presence of a atrong anhydrous acid at elevated temperature, and isolating the resultant compound of formula ~ in a manner known per se.
It is 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 preferably carried out in formic acid or acetic acid and without the addition of a solvent.
.
' -æ~6 The compound~ of formula V are useful polyfunctional intermediates for synthesising organlc compounds. They can be used e.g. as diene components in Diels-Alder reactions using different dienophiles. In such reactinns they 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 compound~.
The invention is illustrated in more detail by the following Examples.
F,xample 1: PreParation of ethoxYmethyleneaconitic acid triethyl ester With stirring, a solution of 113.14 g (0.6 mole) of titanium tetra-chloride in 150 ml of tetrachloromethane is added dropwi6e at 2-3C 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 H20, 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 snd the two pha~3es of the filtrate are separated. The aqueou~
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. Unreacted constituents are distillet off from the resultant crude product (44.95 g; 95.4 %) under a high vacuum at 61C, affording 31.38 g (66.6 %) of ethoxymethylenea.~onitic acid triethyl ester. lH-NMR spectrum (in CdC13): 6.85 (lH singlet~, 7.5 (lH
singlet). The product is further processed direct.
~se ~xamples:
. , Example 2: Preparation of ~-pyrone-4,5-dicarboxYlic acid diethylester 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 residue ,, ~
: . . . .
.
:-, . .. . . . . .
~7~5~6 under high vacuum yield~ 10.00 g (62.4 %) of ~-pyrone-4,5-dicarboxylic acid diethyl ester (b.p. 82C/1.2 x 10 mbar). 1H-NMR spectrum (iD
CdCl3): 6.40 (lH, ~inglet, 8.25 (lH singlet).
Example 3: Preparation of anthracene-9,10-quinone-2,3-dicarboxylic acid diethyl 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 ln 150 ml of xylene for 17 hours. The hydroquinone initially formed i5 un~table in air in the reaction medium employed and oxidi~e~ ~pontaneou~-ly to quinone.
The xylene is distilled off and the distillation residue i~ dissolved hot in 300 ml of methanol. The solution i~ cooled to 20C and the crystalline crude protuct i8 filtered with 6uction, dissolved in 300 ml of chloroform and flltered 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. 153-155C (recrystallisation from ethanol).
~H-NMR spectrum (ln CdC13): 8.88 (slnglet), 8.40 (multiplet), 7.73 (multiplet).
xample 4: Preparation of naphthacene-5,12-quinone-2,3-dicarboxylic acid ~ dlethy} ester f~ ~ In an autoclave, 15.97 g (0.076 mole) of 1,4-anthraquinone and 18.42 g (0.076 mole) of ~-pyrone-4,5-ticarboxylic acid diethyl ester are hested in 34 ml of xylene for 24 hours to 160C. The xylene is then distilled off. The distiIlation residue is dissolved in chloroform and the solution is~filteret over 1.2 g of silica gel (particle size: 0.040-0.063 mm) and fi~ the~sillcn~gel 18 rlnset with chloroform, affording 19.7 g of a crudedar~brown substance which is subJected to sublimation at 220C under a hlgh vacuum. Yielt: 6.3 g (30 %) of naphthacene-5,12-quinone-2,3-di-lf~ c-rboxy1ic acit diethyl ester with a melting point of 208-209C. Mass ;`kt ~
,-, ~ -, , . . . , . . .~ . .. . . . . .
. ,~,.. . .
... ~, ~ .. . . - , . . , . . .. ... . ~ .
,. . :
spectrum: M = 402. The yield is quantitative with the recovery of unreacted ~-pyrone-4,5-dicarboxylic acid diethyl ester.
Example 5: Preparation of naphthalene-1,4-quinone-6,7-dicarboxylic acid diethyl ester With stirring, 2.4 g (0.01 mole) of ~-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 is then allowed to stand for 5 hours at room temperature. The precipitated 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-~icarboxylic acid diethyl ester (m.p. 59-62C) crystalllses from the oily distillation residue. A
further crop of cryRtals can be obtained from the mother liquors. ~H-NMR
spectrum (in CdCl3): 8.42 (singlet), 5.06 (singlet). Mass spectrum:
M ~ 302.
, ~
, . . . .~
:
- , .
' .. . . . .. .
: , . , . . - - -. .
.. : . --, . ~ , - . .
. -
In a preferred embodiment of the enol ethers of formula I, the radicals Rl, R2, R3 and R~ are identical.
The compounds of thi~ invention can be prepsred by a novel process by reacting a formate with an aconitic acid trie8ter, under very mild reaction conditions, in simple manner and in high yield.
A further ob~ect of the present invention iB a process for the prepara-tion of alkoxymethyleneaconitic acid triesters of formula I by reacting carbonyl compounts with CH acidic bonts and an ester in the presence of TiCl4, a tertiary amine and a complexing ~olvent, which process comprises reacting, as carbonyl compound, an aconitic acid triester of formula II
ÇoOR2 C~ CoOR3 (II), Rl OOC-C~z~CH/
~,~
.
. ., - ~, ' .
: ' ' ' . : ' ' -.
_ 4 _ wherein Rl, R2, R3 and R4 are each independently unsubstituted or substituted aliphatic hydrocarbon radicals, and, as ester, a formate of formula III
H-C~ (III), 0-R~
wherein R4 independently has the same meaning as Rl, to give the enol ether of formula I.
Surprisingly, 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 -20 to +50C, in partlcular from 0 to +30C, and the reaction time may be several hours.
Some of the compounds of formula III are commercially available or they can be obtained by methods which are known per se by transesterification from the commercially available formates. The compounds of formula II are known and can be prepared e.g. by elimination of water from citrates.
., AD 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 5-fold excess.
In a preferred embodiment of the process, the allphatic hydrocarbon radicals R3 and R~ are each independently of the other C~-C6alkyl, preferably methyl or ethyl.
A partlcularly advantageous embodiment of the process is that wherein the radicals R~, R2, R3 and R~ are ideDtical, as a transesterification possible undar the indlcated 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) . ,7 wherein Rs, R6 and R7 are each independently branched or unbranched alkyl of preferably 1 to 20, most preferably 1 to 12, csrbon atoms, aralkyl or aryl of preferably 7 to 15 and 6 to lS carbon atoms respectlvely, or cycloalkyl of preferably 4 to 7 ring carbon atoms.
Aralkyl is preferably benzyl and sryl is preferably phenyl.
~urther suitable tertary amines are heteroaromatic amines or N-alkylated, preferably N-methylated, allphatic-heterocyclic amines. The hetero-aromatic amines preferably contain S or 6 ring members. The aliphatic-heterocyclic amines preferably contain 3 to 7, most preferably 5 to 7, ring members. They ~ay contain further hetero atoms, in particular N, 0 and S.
~, ~
Examples of such tertiary amlnes are: trimethylamine, triethylamine, methyl diethylaminel tri-n-propylamine, triisopropylamine, methyl diisoproyylamine, tri-n-butylamine, triisobutylamine, tri-tert-butyl-amine, trihexyla~ine, dimethyl cyclohexylamine, pyridine, quinoline, tiamines of the general formula (alkyl)2-N-(CH2)n-N~alkyl)2, where n ~ 2 to 6, N-al~ylpiperidine, N-alkylpyrrolidine, N-alkylmorpholine, N-alkyl-pyrazoline, N,N'-dlalkylpiperazine, wherein the alkyl moiety contains 1 to 4 carbon atoms ant is preferably methyl.
It is most preferred to use N-methylmorpholine as tertiary amlne.
An squimolar smount or an excess of tertiary amine ~ay be used, based on the a~conitic acid triester. The excess may be chosen such that the tertiary amine si~ultaneously acts as solvent. A 2- to 20-fold, prefer-ably a 4- to 12-fold, excess may suitably be used.
,s~
,, , ; ~ ., -............ , `- , ' , . - , : . - . . -~.~, - : ' ' : :: . . , ~I'Z7f~
An approximately equimolar amount or a ~light exce~ of TiCl4 can be used, based on the formate. It is preferred to use an equimolar amount.
It is advantageous to use at least 2 moles of complexing solvent per mole of TiCl4. 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 sre able to co-ordinate their hetero atoms with the titanium through free pairs of electrons. It is preferred to use ethers, in particular aliphatic ethers.
The following ethers are illustrative of those which may be suitably employed: diethyl ethers, di-n-propyl ether, diisopropyl ether, di-n-butyl ether, diisobutyl ether, di-tert-butyl ether, dihexyl ether, tetrahydrofuran, dioxane, glycol ethers of the general formula R8-o-(Ch2)n-O-R8, where n i9 2 to 6 and R8 is C1-C4alkyl, preferably methyl or ethyl, e.g. ethylene glycol dimethyl ether or ethylene glycol diethyl ether.
Further suitable ethers are e.g. polyalkylene glycol diethers which may correspond to the formula R8-o-(cnH2n-ot-x-R8~ wherein R8 is Cl-C4alkyl, preferably methyl or ethyl, n is 2 to 6, preferably 2 to 4, and x i8 2 to 4. Exemplary of such ethers are: diethylene glycol dimethyl ether, trlethylene glycol dimethyl ether, dipropylene glycol dimethyl ether and dibutylene glycol diethyl ether.
A preferred embodlment of the process of the invention comprises carrying out the reaction in the presence of an additional inert solvent, prefer-ably a polar aprotic solvent. Illustrative of such solvents are halogen-ated hydrocarbons such as methylene chloride, chloroform, carbon tetra-chloride, 1,2-dichloroethane, l,l,l-trichloroethane, 1,1,2,2-tetra-chloroethane, or substituted benzenes such as chlorobenzene, toluene or xylene.
,., f ' ' , ' ~ "' ' ' ' .
~Z7~
The compounds of formula I are useful polyfunctional intermediatea for the synthesis of organic compounds. They may be cyclised for example to novel ~-pyrone-4,5-dicarboxylic acid diesters of formula V
~ooR2 RI OOC~
i! ! (v \o~ ~
wherein R1 and R2 each independently of the other are aa defined for formula I.
Rl and R2 have the same preferred meanings as previously indicated hereinabove.
The compounds of formula V can be obtained by cyclising alkoxymethylene-aconitic acid triesters of formula I in a manner which i8 known per se.
The process comprises cyclising an alkoxymethyleneaconitic acid triester of formula I
cooR2 R~OOC~ /C~ ~CoOR3 (I), 0-R~
wherein R1, R2, R3 and R~ each independently have the meanings assigned to them above, in a manner known per se, in the presence of a atrong anhydrous acid at elevated temperature, and isolating the resultant compound of formula ~ in a manner known per se.
It is 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 preferably carried out in formic acid or acetic acid and without the addition of a solvent.
.
' -æ~6 The compound~ of formula V are useful polyfunctional intermediates for synthesising organlc compounds. They can be used e.g. as diene components in Diels-Alder reactions using different dienophiles. In such reactinns they 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 compound~.
The invention is illustrated in more detail by the following Examples.
F,xample 1: PreParation of ethoxYmethyleneaconitic acid triethyl ester With stirring, a solution of 113.14 g (0.6 mole) of titanium tetra-chloride in 150 ml of tetrachloromethane is added dropwi6e at 2-3C 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 H20, 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 snd the two pha~3es of the filtrate are separated. The aqueou~
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. Unreacted constituents are distillet off from the resultant crude product (44.95 g; 95.4 %) under a high vacuum at 61C, affording 31.38 g (66.6 %) of ethoxymethylenea.~onitic acid triethyl ester. lH-NMR spectrum (in CdC13): 6.85 (lH singlet~, 7.5 (lH
singlet). The product is further processed direct.
~se ~xamples:
. , Example 2: Preparation of ~-pyrone-4,5-dicarboxYlic acid diethylester 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 residue ,, ~
: . . . .
.
:-, . .. . . . . .
~7~5~6 under high vacuum yield~ 10.00 g (62.4 %) of ~-pyrone-4,5-dicarboxylic acid diethyl ester (b.p. 82C/1.2 x 10 mbar). 1H-NMR spectrum (iD
CdCl3): 6.40 (lH, ~inglet, 8.25 (lH singlet).
Example 3: Preparation of anthracene-9,10-quinone-2,3-dicarboxylic acid diethyl 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 ln 150 ml of xylene for 17 hours. The hydroquinone initially formed i5 un~table in air in the reaction medium employed and oxidi~e~ ~pontaneou~-ly to quinone.
The xylene is distilled off and the distillation residue i~ dissolved hot in 300 ml of methanol. The solution i~ cooled to 20C and the crystalline crude protuct i8 filtered with 6uction, dissolved in 300 ml of chloroform and flltered 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. 153-155C (recrystallisation from ethanol).
~H-NMR spectrum (ln CdC13): 8.88 (slnglet), 8.40 (multiplet), 7.73 (multiplet).
xample 4: Preparation of naphthacene-5,12-quinone-2,3-dicarboxylic acid ~ dlethy} ester f~ ~ In an autoclave, 15.97 g (0.076 mole) of 1,4-anthraquinone and 18.42 g (0.076 mole) of ~-pyrone-4,5-ticarboxylic acid diethyl ester are hested in 34 ml of xylene for 24 hours to 160C. The xylene is then distilled off. The distiIlation residue is dissolved in chloroform and the solution is~filteret over 1.2 g of silica gel (particle size: 0.040-0.063 mm) and fi~ the~sillcn~gel 18 rlnset with chloroform, affording 19.7 g of a crudedar~brown substance which is subJected to sublimation at 220C under a hlgh vacuum. Yielt: 6.3 g (30 %) of naphthacene-5,12-quinone-2,3-di-lf~ c-rboxy1ic acit diethyl ester with a melting point of 208-209C. Mass ;`kt ~
,-, ~ -, , . . . , . . .~ . .. . . . . .
. ,~,.. . .
... ~, ~ .. . . - , . . , . . .. ... . ~ .
,. . :
spectrum: M = 402. The yield is quantitative with the recovery of unreacted ~-pyrone-4,5-dicarboxylic acid diethyl ester.
Example 5: Preparation of naphthalene-1,4-quinone-6,7-dicarboxylic acid diethyl ester With stirring, 2.4 g (0.01 mole) of ~-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 is then allowed to stand for 5 hours at room temperature. The precipitated 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-~icarboxylic acid diethyl ester (m.p. 59-62C) crystalllses from the oily distillation residue. A
further crop of cryRtals can be obtained from the mother liquors. ~H-NMR
spectrum (in CdCl3): 8.42 (singlet), 5.06 (singlet). Mass spectrum:
M ~ 302.
, ~
, . . . .~
:
- , .
' .. . . . .. .
: , . , . . - - -. .
.. : . --, . ~ , - . .
. -
Claims (13)
1. An alkoxymethyleneaconitic acid triester of formula I
(I), wherein R1, R2, R3 and R4 are each independently an aliphatic hydrocarbon radical of 1 to 20 carbon atoms, which are unsubstituted or substituted by cyano, halogen or C1-C12-alkoxy.
(I), wherein R1, R2, R3 and R4 are each independently an aliphatic hydrocarbon radical of 1 to 20 carbon atoms, which are unsubstituted or substituted by cyano, halogen or C1-C12-alkoxy.
2. An ester according to claim 1, wherein the radicals R1, R2, R3 and R4 are each independently C1-C18alkyl, C3-C12cycloalkyl, C4-C24alkylcyclo-alkyl, C7-C15aralkyl or C8-C15alkaralkyl.
3. An ester according to claim 1, wherein the aliphatic hydrocarbon radicals R1, R2, R3 and R4 are each independently substituted by an alkoxy or cyano group or by one or more halogen atoms.
4. An ester according to claim 1, wherein the aliphatic hydrocarbon radicals R1, R2, R3 and R4 sre each independently C1-C6alkyl.
5. An ester according to claim 1, wherein the aliphatic hydrocarbon 5adicals R1, R2, R3 and R4 are identical.
6. An ester according to claim 1, wherein the aliphatic hydrocarbon radicals R1, R2, R3 and R4 are each independently methyl or ethyl.
7. A process for the preparation of an alkoxymethyleneaconitic acid triester of formula I according to claim 1 by reacting a carbonyl compound 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 aconitic acid triester of formula II
(II), wherein R1, R2 and R3 are each independently unsubstituted or substituted aliphatic hydrocarbon radicals, and, as ester, a formate of formula III
(III), wherein R4 independently has the same meaning as R1.
(II), wherein R1, R2 and R3 are each independently unsubstituted or substituted aliphatic hydrocarbon radicals, and, as ester, a formate of formula III
(III), wherein R4 independently has the same meaning as R1.
8. A process according to claim 7, wherein the reaction is carried out in the temperature range from -20° to +50°C.
9. A process according to claim 7, wherein the tertiary amine is is an amine of formula (IV) wherein R5, R6 and R7 are each independently branched or unbranched alkyl, cycloalkyl, aralkyl or aryl, or is a hetero-aromatic amine or an N-alkylated aliphatic heterocyclic amine.
10. A process according to claim 9, wherein the tertiary amine is N-methylmorpholine.
11. A process according to claim 7, wherein the complexing solvent is an ether,
12. A process according to claim 7, wherein an inert solvent is additionally employed in the reaction.
13. A process according to claim 7, wherein an equimolar amount of the formate of formula III or an excess thereof, based on the aconitic acid triester, is employed.
FO 7.3/DA/cw*/aeg*
FO 7.3/DA/cw*/aeg*
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000571476A CA1291142C (en) | 1985-03-11 | 1988-07-07 | O-pyrones and a process for their preparation and the use thereof |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1089/85-0 | 1985-03-11 | ||
| CH108985 | 1985-03-11 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000571476A Division CA1291142C (en) | 1985-03-11 | 1988-07-07 | O-pyrones and a process for their preparation and the use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1274536A true CA1274536A (en) | 1990-09-25 |
Family
ID=4202210
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000503589A Expired 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 |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0195743B1 (en) |
| JP (1) | JPS61212540A (en) |
| CA (1) | CA1274536A (en) |
| DE (1) | DE3673040D1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0344113A3 (en) * | 1988-05-27 | 1990-10-31 | Ciba-Geigy Ag | Substituted alpha-pyrones and naphthoquinones |
| DE58907546D1 (en) * | 1988-05-27 | 1994-06-01 | Ciba Geigy | Substituted naphthacen-5,12-diones and their use. |
| JP6044566B2 (en) * | 2014-03-04 | 2016-12-14 | 信越化学工業株式会社 | Positive resist material and pattern forming method using the same |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH662567A5 (en) * | 1984-03-23 | 1987-10-15 | Ciba Geigy Ag | 5,6,11,12-TETRATHIO- AND 5,6,11,12-TETRASELENOTETRACENES SUBSTITUTED IN 2-POSITION, METHOD FOR THEIR PRODUCTION AND THEIR USE. |
-
1986
- 1986-03-05 DE DE8686810114T patent/DE3673040D1/en not_active Expired - Lifetime
- 1986-03-05 EP EP19860810114 patent/EP0195743B1/en not_active Expired - Lifetime
- 1986-03-07 CA CA000503589A patent/CA1274536A/en not_active Expired
- 1986-03-11 JP JP5160186A patent/JPS61212540A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP0195743A3 (en) | 1988-05-04 |
| DE3673040D1 (en) | 1990-09-06 |
| JPS61212540A (en) | 1986-09-20 |
| EP0195743B1 (en) | 1990-08-01 |
| EP0195743A2 (en) | 1986-09-24 |
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