WO1991018861A1 - 2-(hydroxymethyl) acrylate derivatives and process for their preparation - Google Patents

2-(hydroxymethyl) acrylate derivatives and process for their preparation Download PDF

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Publication number
WO1991018861A1
WO1991018861A1 PCT/AU1991/000236 AU9100236W WO9118861A1 WO 1991018861 A1 WO1991018861 A1 WO 1991018861A1 AU 9100236 W AU9100236 W AU 9100236W WO 9118861 A1 WO9118861 A1 WO 9118861A1
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Prior art keywords
compound
acrylate
formula
reaction
hydroxymethyl
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PCT/AU1991/000236
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French (fr)
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Christopher Roy Strauss
Michael Neil Galbraith
Alan Francis Faux
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Commonwealth Scientific And Industrial Research Organisation
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Publication of WO1991018861A1 publication Critical patent/WO1991018861A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/15—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound oxygen atoms bound to the same unsaturated acyclic carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/39—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups
    • C07C205/42—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups having nitro groups or esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C07C205/43—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups having nitro groups or esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
    • C07C45/75—Reactions with formaldehyde
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/367—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms

Definitions

  • This invention is concerned with a process for the production of organic compounds and is particularly concerned with a process for the production of a l pha , be t a unsaturated compounds.
  • the invention is also concerned with novel organic compounds.
  • the former group allowed methyl acrylate [1] and an aqueous solution of formalin with a catalytic amount of diazabicyclo[2,2,2]octane (DABCO) to stir at room temperature for 10 days. After work-up and distillation they obtained [2] in 31% yield.
  • DABCO diazabicyclo[2,2,2]octane
  • the 6 latter group reported an isolated yield of 75% after shaking a similar reaction mixture for 48 hours at room temperature. Although their yields were at variance, both groups have shown that the reaction could proceed satisfactorily in aqueous medium with formaldehyde.
  • the present invention provides a process for the preparation of a compound of the general formula R 5 RCR 6 0H
  • Z represents an electron withdrawing group
  • R fi represents hydrogen, branched or straight-chained, substituted or unsubstituted C-._- fi alkyl, substituted or unsubstituted c 5 -c 1 2' cycloalkyl, aralkyl or alkaryl and
  • R in formulae I and III represents hydrogen, substituted or unsubstituted C ⁇ -Cg alkyl, lower alkenyl
  • (C ⁇ -Cg), alk-(C 1 -C 4 )aryl, aralkyl(C ⁇ C ⁇ or aryl, or R together with R, may form a cyclic ring and
  • R e in formulae I and II represents hydrogen
  • Z represents a member of the group consisting of
  • R. , R_, R_ , R., R-, and R R each independently represent hydrogen, branched or straight-chained, substituted or unsubstituted C-._-, violation alkyl, substituted or unsubstituted C--C-.., cycloalkyl, aralkyl or alkaryl. and R_ represents alkyl or aryl.
  • Representative compounds of formula II are: acrylonitrile, methyl acrylate, ethyl acrylate, iso-octyl acrylate, 2-ethylhexyl acrylate butyl acrylate, lauryl acrylate, phenyl acrylate; cyclohexylmethyl acrylate, cyclohexyl acrylate, cyclopentyl acrylate, phenylethyl acrylate, p-ethylphenyl acrylate, m-chlorophenyl acrylate, p-nitrophenyl acrylate, trichloromethyl acrylate, p-carboxymethylphenyl acrylate, p-methoxyphenyl acrylate, methyl vinyl ketone, isobutyl vinyl ketone, phenyl vinyl ketone, cyclohexyl vinyl ketone, p-chlorophenyl vinyl ketone, benzyl vinyl ketone,
  • Suitable carbonyl compounds of formula III are: formaldehyde, acetaldehyde, n-butyraldehyde, phenylacetaldehyde, benzaldehyde, octanal, crotonaldehyde, m-ethylphenylacetaldehyde, m-chloro- benzaldehyde, p-nitrophenylacetaldehyde,.
  • benzaldehyde p-methoxybenzaldehyde other substituted benzaldehydes such as salicyl aldehyde, vanillin and isovanillin, acetone, cyclohexanone, pentanone, methyl ethyl ketone, diethyl ketone, acetophenone furfural and benzophenone.
  • a further object of the present invention is to provide a more rapid continuous process for the production of compounds of formula I.
  • the present invention provides a process for the continuous preparation of a compound of formula I comprising:
  • reaction mixture to be rapidly heated to the desired temperature upon entering the reaction zone. Furthermore, the reaction mixture may be rapidly cooled upon leaving the reaction zone.
  • the reaction mixture may be recycled one or more times to increase the yield of the compound of formula I.
  • the reaction is carried out in the presence of an amine catalyst.
  • the catalyst is a tertiary amine catalyst.
  • An example of a suitable catalyst is diazabicyclo[2,2,2]octane (DABCO) .
  • At least one of the components in the reaction mixture should be capable of absorbing microwave radiation.
  • This may be, for example, the acrylic reactant, carbonyl reactant, catalyst, and/or solvent (if used) .
  • Control of the process may be effected by suitable selection of flow rate of the reaction mixture through the reaction zone, reaction temperature, pressure, frequency of microwave, power of microwave and/or residence time in the microwave zone.
  • reaction may be carried out in the microwave reactor described in co-pending International patent application No. PCT/AU89/00437 the disclosure of which is incorporated herein by reference.
  • the temperature of the mixture in the reaction zone is in the range 100-200°C.
  • the pressure at which the reaction is carried out may vary within a wide range and may be in the range 1 to 3000 or more atmospheres. Selection of these variables is determined by the reactivity of the reactants.
  • the present invention may result in greatly increased rates of reaction when compared to conventional processes.
  • the rate of reaction in the production of methyl-2-(hydroxymethyl) acrylate by the process of the present invention is of the order of 3000 times greater than the rate obtained in prior art processes.
  • a further advantage of the present invention is that it allows, for the first time, a successful Baylis-Hillman reaction on a beta substituted acrylic derivative such as t rans crotonaldehyde and crotononitrile.
  • the present invention provides novel compounds of formula I given above wherein Rr is other than hydrogen.
  • the present invention may also include a process for the continuous preparation of a compound of formula I comprising continuously providing a mixture of a compound of formula II and a compound of formula III to a heated reaction zone wherein the reaction mixture is rapidly heated and removing the reaction mixture from . the reaction zone.
  • a commercially available microwave oven of 700 watt output was fitted with a PTFE coil (3m x 6mm o.d. and 3mm i.d.), of volume 23.8 ml.
  • the coil was attached to a metering pump at the inlet end and passed into a condenser at the effluent end.
  • An in-line K-type thermocouple allowed monitoring of the temperature of the reaction mixture immediately after it exited the irradiation zone.
  • a pressure control valve allowed the column to be held under adjustable pressures ranging up to 15.5 bar, but pressures, which were monitored by a gauge, were usually kept below 12.4 bar for safety reasons. The modifications permitted the observation of the reaction mixture as it passed through the irradiation zone and were made in such a way as to prevent leakage of microwaves.
  • the formaldehyde solution used in the following examples may be prepared by conventional methods.
  • the formaldehyde may be conveniently prepared in the microwave reaction before hand, by acid catalysed hydrolysis of an aqueous slurry of paraformaldehyde, followed by neutralisation with base.
  • the mixture was heated over the temperature range 158-164°C at 9.3- 10.3 bar pressure and condensed to ⁇ 10°C immediately it had exited the irradiation zone.
  • the pH of the effluent was 5 and this was readjusted to 10 with further DABCO and then subjected to two further passes through the reactor, with adjustment of the pH to 10, before each pass.
  • Trans crotonaldehyde, freshly distilled before use (42.3g), an aqueous solution of 30% formaldehyde (100ml) and DABCO (2.3g) were stirred together at room temperature and passed through the microwave reactor at a flow rate of 15.5 ml/min.
  • the mixture was heated to 165°C at 90-100 p.s.i. pressure and the effluent collected in diethyl ether (100 ml) at 0°C.
  • the organic phase was separated and the aqueous phase saturated with NaCl and further extracted with ether (2 x 100 ml).
  • a stirred mixture of ethyl acrylate [13] (170 g, 1.7 mole), DABCO (21.1 g, 0.19 mole) and freshly prepared 25% aqueous formaldehyde solution (600 ml) at pH 10 was pumped through the continuous microwave reactor at a flow rate of 23.5 ml/min and at a flow rate of 23.5 ml/min and at a pressure of 600-800KPa.
  • the temperature of the effluent on the first pass was about 150°C.
  • the effluent was cooled immediately on exit from the microwave zone and the reaction mixture subjected to two further passes through the system, with re-adjustment of the pH to 10 before each additional pass.
  • the temperatures of the effluent for the second and third passes were 170°C and 175°C.
  • a mixture of crotononitrile [ll](33.5g; 0.5 mole), 25% aqueous formaldehye (120 ml) and DABCO was stirred vigorously and pumped through the continuous microwave reactor at a flow rate of 25 ml/min, and at a pressure of 1000-1250 KPa.
  • the temperature of the reaction mixture at the exit point of the microwave zone was 159-164°C.
  • the mixture was subjected to a second pass through the system (exit temp. 160-170°C) and after work up and extraction into CH 2 C1 2 , the product mixture was found by GC-MS to contain about 2% 2-(hydroxymethyl)but-2-enonitrile [12] .
  • n-butyl 2- (2-hydroxyi ⁇ opropyl )acrylate [171 .
  • a solution of n-butyl acrylate (9ml; 0.06 moles), acetone (28 ml; 0.38 moles) and DABCO (2.8g ; 0.025 moles) was heated in a sealed bomb at 120°C over several days. After 4.6 days the reaction mixture showed a 7% conversion of butyl acrylate to the product, which was assigned on the basis of GC-MS data.
  • the assigned product [17] had the following EIMS at
  • the mechanism 2'4, of the Baylis-Hillman reaction has been considered to involve Michael addition of the tertiary amine base (DABCO) onto the conjugated olefin to generate a stabilised carbanion, which adds in an aldol fashion to the carbonyl compound (formaldehyde), with the subsequent elimination of the base.
  • DABCO tertiary amine base
  • the most energetically favoured product thus could be expected to result.
  • the present invention in one form, provides a process whereby the Baylis-Hillman reaction can be carried out easily and continuously with a microwave reactor to form highly functionalised small molecules. Products were generated in times which were orders of magnitude less than those previously required, while yields were comparable. The strength of the system has been further demonstrated on molecules heretofore considered unreactive under Baylis-Hillman conditions.

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  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
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Abstract

A process for the preparation of a compound of general formula (I) which comprises reacting a compound of general formula (II) with a carbonyl compound of the general formula (III): RR6CO, wherein Z represents an electron withdrawing group and R6 represents hydrogen, branched or straight-chained, substituted or unsubstituted C1-18 alkyl, substituted or unsubstituted C5-C12 cycloalkyl, aralkyl or alkaryl and R in formulae (I and III) represents hydrogen, substituted or unsubstituted C1-C8 alkyl, lower alkenyl (C1-C8), alk-(C1-C4)aryl, aralkyl(C1-C4) or aryl, or R together with R6 may form a cyclic ring and R5 in formulae (I and II) represents hydrogen, C1-C18 alkyl, cycloalkyl, aralkyl, alkaryl, aryl or a heterocyclic ring such as a furyl ring, said reaction being carried out in the presence of microwave radiation.

Description

2-(HYDR0XY ETHYL) ACRYLATE DERIVATIVES AND PROCESS FOR THEIR PREPARATIO
Technical Field
This invention is concerned with a process for the production of organic compounds and is particularly concerned with a process for the production of a l pha , be t a unsaturated compounds. The invention is also concerned with novel organic compounds.
Background Art 1
US Patent No. 3,743,669 to Hillman e t a l discloses the reaction (hereinafter referred to as the Baylis-Hillman reaction) of a l pha , be ta , unsaturated esters, nitriles, amides or ketoneε with selected aldehydes under catalysis by tertiary amines at temperatures ranging from 0 -200 C to produce the corresponding 2-hydroxyalkyl derivatives. Reaction times ranging from hours to days, depending on the reactants, are required in the process taught in Hillman e t a l . Such long reaction times are obviously not conducive to commercial production.
Subsequently Hill and Isaacs 2 found that pressures. of
2-5 kbar enhanced the rate of reaction at room temperature considerably, although reaction times of up to 16 hours were still required. They also empirically derived an order of reactivity for the acrylic and aldehydic components as well as for the tertiary amine catalysts. They noted that a be t a substituent on the acrylic component, e.g. as is present in crotononitrile, prevented any reaction, even at pressures as high as 10 kbar, an observation consistent
3 with that of Perl utter and Teo , who also found that the reaction failed for fcefα-substituted acrylates. The synthetic utility of the Bayliε-Hillman reaction has been explored by several groups and much of that work has been the subject of a comprehensive review by Dreweε and Rooε . Mathias and coworkers as well as Fikentscher e t a I have both recently reported the preparation of methyl 2-(hydroxymethyl)acrylate [2] from [1] (for structural formulae, see Figures 1 and 2) by Baylis-Hillman methodology. The former group allowed methyl acrylate [1] and an aqueous solution of formalin with a catalytic amount of diazabicyclo[2,2,2]octane (DABCO) to stir at room temperature for 10 days. After work-up and distillation they obtained [2] in 31% yield. The 6 latter group reported an isolated yield of 75% after shaking a similar reaction mixture for 48 hours at room temperature. Although their yields were at variance, both groups have shown that the reaction could proceed satisfactorily in aqueous medium with formaldehyde.
However, the disadvantages of attempting to prepare reactive compounds batchwise, at ambient temperatures over lengthy periods, are obvious.
It is an object of the present invention to provide a process for the production of 2-hydroxyalkyl acrylic derivatives by the Baylis-Hillman reaction and the like which involves shorter reaction times and more moderate reaction conditions. Disclosure of Invention
Accordingly the present invention provides a process for the preparation of a compound of the general formula R5 RCR60H
I I HC = C - Z (I) which comprises reacting a compound of general formula
R5 H
I i HC = C - Z (II) with a carbonyl compound of general formula
RR6C0 (III)
wherein Z represents an electron withdrawing group and
Rfi represents hydrogen, branched or straight-chained, substituted or unsubstituted C-._-fi alkyl, substituted or unsubstituted c 5 -c 12' cycloalkyl, aralkyl or alkaryl and
R in formulae I and III represents hydrogen, substituted or unsubstituted Cη-Cg alkyl, lower alkenyl
(C^-Cg), alk-(C1-C4)aryl, aralkyl(C^C^ or aryl, or R together with R, may form a cyclic ring and
Re in formulae I and II represents hydrogen,
C.-C g alkyl, cycloalkyl, aralkyl, alkaryl, aryl or a heterocylic ring such as a furyl ring, said reaction being carried out in the presence of microwave radiation. Preferably, Z represents a member of the group consisting of
0 0 0 R7
I! II II / R3 I
-C-0R1 -C-R2, -C - N , -C=N-0Rg, -CN and S02Rg
\ R4 where R. , R_, R_ , R., R-, and RR each independently represent hydrogen, branched or straight-chained, substituted or unsubstituted C-._-,„ alkyl, substituted or unsubstituted C--C-.., cycloalkyl, aralkyl or alkaryl. and R_ represents alkyl or aryl.
Representative compounds of formula II are: acrylonitrile, methyl acrylate, ethyl acrylate, iso-octyl acrylate, 2-ethylhexyl acrylate butyl acrylate, lauryl acrylate, phenyl acrylate; cyclohexylmethyl acrylate, cyclohexyl acrylate, cyclopentyl acrylate, phenylethyl acrylate, p-ethylphenyl acrylate, m-chlorophenyl acrylate, p-nitrophenyl acrylate, trichloromethyl acrylate, p-carboxymethylphenyl acrylate, p-methoxyphenyl acrylate, methyl vinyl ketone, isobutyl vinyl ketone, phenyl vinyl ketone, cyclohexyl vinyl ketone, p-chlorophenyl vinyl ketone, benzyl vinyl ketone, crotonaldehyde, crotononitrile N,N-dimethyl acrylamide, N,N-dibutylacrylamide, N,N-dioctyl acrylamide, N,N-diphenyl acrylamide, N,N-dicyclohexyl acrylamide, 2 hydroxyethyl acrylate, hydroxy propylacrylate, and other like monomers.
Suitable carbonyl compounds of formula III are: formaldehyde, acetaldehyde, n-butyraldehyde, phenylacetaldehyde, benzaldehyde, octanal, crotonaldehyde, m-ethylphenylacetaldehyde, m-chloro- benzaldehyde, p-nitrophenylacetaldehyde,. m-carbomethoxy- benzaldehyde, p-methoxybenzaldehyde other substituted benzaldehydes such as salicyl aldehyde, vanillin and isovanillin, acetone, cyclohexanone, pentanone, methyl ethyl ketone, diethyl ketone, acetophenone furfural and benzophenone.
A further object of the present invention is to provide a more rapid continuous process for the production of compounds of formula I.
Accordingly in a further form the present invention provides a process for the continuous preparation of a compound of formula I comprising:
continuously providing a mixture of a compound of formula II and a carbonyl compound of formula III to a reaction zone;
irradiating said reaction zone with microwave radiation; and
removing the reaction mixture from the reaction zone.
The above process allows the reaction mixture to be rapidly heated to the desired temperature upon entering the reaction zone. Furthermore, the reaction mixture may be rapidly cooled upon leaving the reaction zone.
The reaction mixture may be recycled one or more times to increase the yield of the compound of formula I.
Preferably the reaction is carried out in the presence of an amine catalyst. More preferably the catalyst is a tertiary amine catalyst. An example of a suitable catalyst is diazabicyclo[2,2,2]octane (DABCO) .
At least one of the components in the reaction mixture should be capable of absorbing microwave radiation. This may be, for example, the acrylic reactant, carbonyl reactant, catalyst, and/or solvent (if used) .
Control of the process may be effected by suitable selection of flow rate of the reaction mixture through the reaction zone, reaction temperature, pressure, frequency of microwave, power of microwave and/or residence time in the microwave zone.
The reaction may be carried out in the microwave reactor described in co-pending International patent application No. PCT/AU89/00437 the disclosure of which is incorporated herein by reference.
Preferably the temperature of the mixture in the reaction zone is in the range 100-200°C. The pressure at which the reaction is carried out may vary within a wide range and may be in the range 1 to 3000 or more atmospheres. Selection of these variables is determined by the reactivity of the reactants.
As will be seen by reference to the Examples included hereinafter, the present invention may result in greatly increased rates of reaction when compared to conventional processes. For example, the rate of reaction in the production of methyl-2-(hydroxymethyl) acrylate by the process of the present invention is of the order of 3000 times greater than the rate obtained in prior art processes.
A further advantage of the present invention is that it allows, for the first time, a successful Baylis-Hillman reaction on a beta substituted acrylic derivative such as t rans crotonaldehyde and crotononitrile.
Accordingly in yet a further aspect, the present invention provides novel compounds of formula I given above wherein Rr is other than hydrogen.
The present invention may also include a process for the continuous preparation of a compound of formula I comprising continuously providing a mixture of a compound of formula II and a compound of formula III to a heated reaction zone wherein the reaction mixture is rapidly heated and removing the reaction mixture from . the reaction zone.
In order that the invention may be more readily understood the following non-limiting examples are given.
Modes for Carrying Out the Invention
Experimental
Continuous Microwave Reactor
A commercially available microwave oven of 700 watt output was fitted with a PTFE coil (3m x 6mm o.d. and 3mm i.d.), of volume 23.8 ml. The coil was attached to a metering pump at the inlet end and passed into a condenser at the effluent end. An in-line K-type thermocouple allowed monitoring of the temperature of the reaction mixture immediately after it exited the irradiation zone. A pressure control valve allowed the column to be held under adjustable pressures ranging up to 15.5 bar, but pressures, which were monitored by a gauge, were usually kept below 12.4 bar for safety reasons. The modifications permitted the observation of the reaction mixture as it passed through the irradiation zone and were made in such a way as to prevent leakage of microwaves.
Preparation of aqueous formaldehyde solution
The formaldehyde solution used in the following examples may be prepared by conventional methods. Advantageously the formaldehyde may be conveniently prepared in the microwave reaction before hand, by acid catalysed hydrolysis of an aqueous slurry of paraformaldehyde, followed by neutralisation with base.
Example 1
Preparat i on of me thy l 1- ihydr oxyme thy l , acry l a t e t2]
A mixture of methyl acrylate[l] (50g), freshly prepared aqueous formaldehyde solution (200 ml of 30%) at pH 7 and DABCO (7.0g) was stirred vigorously and pumped through the continous microwave reactor at. a flow rate of 15.5 ml/min. The mixture was heated over the temperature range 158-164°C at 9.3- 10.3 bar pressure and condensed to < 10°C immediately it had exited the irradiation zone. The pH of the effluent was 5 and this was readjusted to 10 with further DABCO and then subjected to two further passes through the reactor, with adjustment of the pH to 10, before each pass. The mixture was worked up by adjustment to pH 7, and extraction with diethyl ether to afford a crude oil (28 g) after evaporation. Finally, the pure product ( 20 g), b.p. 60-64°C/0.75 mm (cf lit.5 58-60°C/0.05 mm; lit.6 72-6°C / 0.3 mbar ) was isolated as a colourless oil in 29.7% yield. The product had the following spectral properties:
IR Spectrum (liquid film): 3400 (br. ), 1725, 1630 cm -1 ^Η nmr Spectrum; (90 MHz, CDC13): 6.20 (IH, br, vinylic proton), 5.80 (IH, br, vinylic proton), 4.24 (2H, s,CH2OH), 3.70 (3H, s,CH30), 3.63 (lH,br,0H) .
El MS at 70 eV: m/z (rel.int.): 116 [M+] (4), 115 (3), 99 (7), 87 (100), 85 (73), 84 (78), 83 (28), 57 (36), 56 (33), 55 (53).
Example 2
Prepara t i on of n-bυ t y l Z- i hydr oxyme t hy l , acry l a t e [4].
A mixture of n-butyl acrylate [3] (74.4 g), 30% formaldehyde solution at pH 7 (200 ml) and DABCO (7.0 g) was subjected to three passes through the microwave reactor, with flow rate 15.5 ml/min. , reaction temperature 170-180 C and pressure approximately 10.3 bar. The pH was adjusted to between 9 and 10 between passes, and the reaction mixture worked-up as for [2] as described above. The product [4], b.p. 86-88 C/1.9 mm Hg was obtained as a colourless oil (41g) in 45.2% isolated yield.
Analysis; Expect for CgH1403 : C 60.7%; H 8.9%; 0 30.3%.
Found C 60.6%; H 9.1%; 0 29.9%.
IR Spectrum (film): 3400 (br), 1715, 1633 cm-1. H nmr Spectrum (90 MHz, CDC1.,); 6.30 (IH, br. s, vinylic proton), 5.83 (IH, br. s, vinylic proton), 4.31 (2H,s,CH20H), 4.19 (2H,t,COOCH2) , 2.87 (lH,br, OH), 1.17-1.90 (4H, m, CH3-CH2-CH2-CH20), 0.93 (3K, t, CH3) .
Example 3
Prepara t i on of 2- t. hydr oxyme t hy l > acr y l on i t r i l e 18].
A mixture of acrylonitrile [7] (96g), 30% formaldehyde solution (300ml) and DABCO (9.7g) was twice passed through the irradiation zone of the microwave reactor at a flow rate of 15.5ml/min. Reaction temperature was 125-135°C at approximately 10.3 bar pressure. The mixture was neutralised with dilute sulphuric acid and extracted with diethyl ether (3 x 300ml). The solvent was dried and carefully evaporated to afford the crude product [8] (125.3 g; 84% yield), which was at least 90% pure by GC (on a S BP5 column, 25m in length; 50 C; for 1 min. , then programmed at 10 C/min to 200 C; He carrier gas flow rate, l.Oml/ in. Rt of product was 3.9 min.) and H nmr analysis. Distillation under reduced pressure allowed the product to be purified, b.p. 80°C/0.8 mm Hg
(cf lit. b. p. 84-6°C/0.3 mbar) but led to loss of material owing to dimerisation resulting in formation of di-2-cyanoallyl ether.
H nmr Spectrum of the product (90 MHz, CDC13 ) : 66.05 (2H,br, =CH2) , 4.17 (2H,br,CH20H) , 3.85 (lH,br,OH).
Example 4
Preparat i on of 3- ihydr oxymethy l )bυt -Z-en-2-one [61.
A mixture of methyl vinyl ketone [5] (41 g) , 30% formaldehyde solution (200 ml) and DABCO (7.0 g) was pumped through the PTFE coil at 15.5 ml/min. flow rate with no back pressure. The effluent, at 99-101 C, was passed into THF (150 ml) at 0 C. The aqueous phase was neutralised with 10% sulphuric acid and saturated with NaCl. The organic phase was separated and the aqueous extracted with further THF (2 x 100 ml). The pooled organic phase was dried (MgS04) and carefully evaporated to afford a crude residue (56g), which tended to polymerise on distillation under reduced pressure, but gave [6] as a colourless oil (10.0 g; 17% isolated yield), b. p. 62-5°C/0.8 mm Hg.
1H nmr Spectrum of 6 (90 MHz, CDC13): 66.08 (2H, m, =CH_), 4.25 (2H,br,CH„0H.) , 3.05 ■• ^
(lH,br,OH), 2.33 (3H, s, CH3) .
Example 5
Preparat i on of t rans-2- i hydr oxyme thy l ) bυ t -2-ena l tio].
Trans crotonaldehyde, freshly distilled before use (42.3g), an aqueous solution of 30% formaldehyde (100ml) and DABCO (2.3g) were stirred together at room temperature and passed through the microwave reactor at a flow rate of 15.5 ml/min. The mixture was heated to 165°C at 90-100 p.s.i. pressure and the effluent collected in diethyl ether (100 ml) at 0°C. The organic phase was separated and the aqueous phase saturated with NaCl and further extracted with ether (2 x 100 ml). The pooled organic phase was washed with H,0 (1 x 50 ml), dried with MgS04, concentrated in vacυo and the residue distilled under reduced pressure. The product was obtained as a colourless oil (7.8 g; 12.9% isolated yield), b.p. 79°C/2 mm Hg. 1H nmr Spectrum (250 MHz, CDC13): 9.38 (IH, s, CHO), 6.73 (IH, q,J = 7.1 Hz, =CH) , 4.37 (2H, s, CH20H), 2.80 (1, br, OH), 1.95 (3H, d J = 7.1 Hz, CH3) .
13C NMR Spectrum (63 MHz, CDC13) : 6195.5 (CHO), 152.1 (CH3CH=), 142.4 (=C(CH20H)CH0) , 55.1 (CH2OH), 14.8 (CH3). _!
IR Spectrum (film): 3400 (br), 1680, 1642 cm .
CI mass spectrum (CH4 reagent gas); m/z (rel.int) : 129 (M+29, 0.7), 111 [M+29-H20] (2), 101 [M+H ] (12), 83 [M-H20+H] (100).
Example 6
Preparat i on of Ethy l 2- shydroxyme thy l acry l a te [14].
A stirred mixture of ethyl acrylate [13] (170 g, 1.7 mole), DABCO (21.1 g, 0.19 mole) and freshly prepared 25% aqueous formaldehyde solution (600 ml) at pH 10 was pumped through the continuous microwave reactor at a flow rate of 23.5 ml/min and at a flow rate of 23.5 ml/min and at a pressure of 600-800KPa. The temperature of the effluent on the first pass was about 150°C. The effluent was cooled immediately on exit from the microwave zone and the reaction mixture subjected to two further passes through the system, with re-adjustment of the pH to 10 before each additional pass. The temperatures of the effluent for the second and third passes were 170°C and 175°C.
The mixture was extracted with ether (1 x 200 ml; 6 x 100 ml) and the organic extracts pooled, dried with MgSO., filtered and evaporated to dryness. The resulting pale yellow liquid (115 g) , was distilled under reduced pressure to give the product (69-9 g; 31.6% yield), most of which boiled in the range 62-70 °C/0.3 mm.
The product ethyl 2-(hydroxymethyl) acrylate [14 showed the following spectral characteristics: El Mass Spectrum at 70eV; m/z (rel. int.): 129 [M+-H ] (1), 101 [M+-Et] (43), 85 [M+-0Et ] (100), 84(53), 82(46), 55(76).
1 E nmr Spectrum (90 MHz; CDC13 : 6 1.28(t, 3H, CH3CH20), 4.0 (br. s, IH, OH), 4.20 (q, 2H, CH 3CH 20), 4.28 (s, 2H, CH20H) , 5.75 (br, IH, =CH) and 6.21 (br, IH, =CH) .
The above examples demonstrate the usefulness of the process of this invention using formaldehyde as the carbonyl compound. The following Examples demonstrate its usefulness for other carbonyl compounds. The reactions were performed using the method of Example 6 with appropriate adjustments.
Example 7
Preparation of 2- (hydroxymethyl )but-2-enonitr He [12 ].
A mixture of crotononitrile [ll](33.5g; 0.5 mole), 25% aqueous formaldehye (120 ml) and DABCO was stirred vigorously and pumped through the continuous microwave reactor at a flow rate of 25 ml/min, and at a pressure of 1000-1250 KPa. The temperature of the reaction mixture at the exit point of the microwave zone was 159-164°C. The mixture was subjected to a second pass through the system (exit temp. 160-170°C) and after work up and extraction into CH2C12, the product mixture was found by GC-MS to contain about 2% 2-(hydroxymethyl)but-2-enonitrile [12] .
This product showed the following EIMS at 70eV; m/z (rel. int.): 97[M+] (9), 96(8), 82(31), 79(14), 68(100), 55(23), 54(63), 52(98) 51(44), 49(65), 41(90)
Example 8
Preparat i on of n-bυty l 3-hydr oxy-2-methy l ene-3 - pheny l pr o i ona te [15].
Benzaldehyde, n-butylacrylate, and DABCO in the molar ratio of 1:1:0.1, were reacted at 120°C. After about 3 hours recycling, analysis by GC indicated a 23% conversion of the title product was achieved. A sample (250ml) of the reaction mixture was washed with dilute aqueous sulfuric acid to remove the DABCO and then extracted with diethyl ether (2 x 100 ml). The separated organic phase was dried with anhydrous magnesium sulfate and the ether removed by rotary evaporation. The resultant mixture was then distilled under reduced pressure to give the product (58g) bp 130 °C/0.4 mm.
This compound [15] had the following spectral properties:
El Mass Spectrum at 70eV, m/z (rel. int.): 234[M+] (14), 178(25), 177(42), 160(33), 159(42), 132(54), 115(30), 105(100), 79(50), 77(60).
H nmr (90MHz, CDC13): δ 0.88(t, 3H, CH3 ) , 1.0-1.7(m, 4H, CHjCHiCHs), 3.10(s, IH, CHOH) , 4.05(t, 2H, 0CH2), 5.50(8, IH, OH), 5.78(s, IH, =CH), 6.27(s, IH, =CH), 7.1-7.4(m, 5H, ArH) . Example 9
Prepara t i on of n-Bυ t y l Z -hydr oxy- 2-me t hy l ene - n-bu t anoat e [16] .
A mixture of acetaldehyde (49.6 g; 1.13 mole), n-butyl acrylate (32 g; 0.25 mole), DABCO (5.6 g; 0.05 mole) and water (69 ml) were reacted at 120°C. Analysis by GC indicated that the conversion of butyl acrylate to the product was 27% after the first pass. The reaction mixture was recycled for 1 hour.
A sample of the reaction mixture was then worked up by acidification to pH 6 with sulphuric acid, and extraction into ether. The organic phase was dried with anhydrous magnesium sulfate and the solvent evaporated. The residue was distilled under reduced pressure bp 70 °C/0.5 mm and the product [16] showed the following spectral properties:
El Mass Spectrum at 70eV, m/z (rel. int.): 172 [M+](l), 157(14), 116(10), 101(100), 99(54), 98(53), 97(31), 83(81), 81(28), 73(72), 71(38), 70(31), 57(40), 56(33), 55(85), 54(29), 53(34), 45(50), 43(92), 42(16), 41(99).
Η nmr (90MHz, CDC13): δ 1.0(t,3H,
CH3CH2CH2), 1.4(d, 3H, CH3CH0H) ,
1.17-1.90(m, 4H,
CH3CH2CH2CH2), 3.55(br. s, IH, OH), 4.26(t,
2H, C00CH2), 4.70(q, IH, CHOH), 5.85(ε, IH, =CH) and
6.20(s, IH, =CH).
Example 10
Preparation of n-butyl 2- (2-hydroxyiεopropyl )acrylate [171 . A solution of n-butyl acrylate (9ml; 0.06 moles), acetone (28 ml; 0.38 moles) and DABCO (2.8g; 0.025 moles) was heated in a sealed bomb at 120°C over several days. After 4.6 days the reaction mixture showed a 7% conversion of butyl acrylate to the product, which was assigned on the basis of GC-MS data. The assigned product [17] had the following EIMS at
70eV (m/z; rel. int.)
118866((MM+,, 11)),, 117711((MM+--MMee, 0.3), 113(M -OBu, 35) 112(34), 85(23), 84(25), 56(26), 43(100).
Results and Discussion
Because the microwave unit was fitted with a pressure control valve, it was possible to heat reaction mixtures to temperatures around 150 C and cool the effluent without loss of gaseous formaldehyde. Such a regime is difficult to achieve with conventional laboratory apparatus and could explain why previous workers ' using formaldehyde in Baylis-Hillman reactions did not heat their reaction mixtures.
The yields of hydroxymethyl derivatives obtained from methyl and butyl acrylate as well as acrylonitrile were 30%, 45% and 84% respectively. All reactions proceeded in minutes and in some cases, over-reaction may have occurred, highlighting the scope available for optimisation.
With the microwave reactor, compound [2] was prepared in virtually the same yield as that obtained batchwise
5 by Mathi s et a I , but at a production rate some 3200 times faster. Although Fikentscher and co-workers reported a yield which was 2.5 times higher than that obtained here for compound [2], the reaction rate was considerably longer (i.e. 640
7 times). It is also noteworthy that Isaacs and Hill disclose a batchwise preparation of compound [8], which was carried out on a 50 mmolar scale, at 5000 bar, over 1 hour, to achieve the product in 85% yield. Here, a comparable yield for compound [8] was obtained continuously, at a pressure of 10.3 bar and within a three minute residence time.
In addition to the rate enhancement discussed above, a further advantage of the process of the present invention is demonstrated by the successful Baylis-Hillman reaction achieved on two be tσ-substituted acrylic derivatives, t rans crotonaldehyde and crotononitrile, for the first time. With crotonaldehyde a single stereoiεomer was obtained. This product was assigned tr ans stereochemistry on the basis of the chemical shift of the aldehyde proton, at 9.38 ppm, in the H NMR spectrum. It has been shown in analogous systems that this proton signal resonance occurs in the range 9.3-9.5 for the trans isomer, but is considerably shifted downfield, to 10.0-10.1 ppm for their c is analogues. The mechanism 2'4, of the Baylis-Hillman reaction has been considered to involve Michael addition of the tertiary amine base (DABCO) onto the conjugated olefin to generate a stabilised carbanion, which adds in an aldol fashion to the carbonyl compound (formaldehyde), with the subsequent elimination of the base. The most energetically favoured product thus could be expected to result. Molecular orbital calculations carried out for both c is and trans isomers of [9] and
[10] indicated that the trans isomer was conformationally more stable than the c i s , in each case, by 0.80 and 0.85 kcal/mole, respectively, thus supporting the stereochemical assignment.
The products obtained by the reaction of methyl vinyl ketone and trans crotonaldehyde with formaldehyde, have novel functionalised isoprenoid skeletons and as such, could be utilised as the sythetic building blocks for larger molecules, including terpeneε. Although [6] and [10] were isolated in yields of only 10-20 %, the syntheses were rapid and involved inexpensive and readily available starting materials.
The present invention, in one form, provides a process whereby the Baylis-Hillman reaction can be carried out easily and continuously with a microwave reactor to form highly functionalised small molecules. Products were generated in times which were orders of magnitude less than those previously required, while yields were comparable. The strength of the system has been further demonstrated on molecules heretofore considered unreactive under Baylis-Hillman conditions.
Although the invention has been described in reference to particular embodiments it will be clear to the reader that modifications and variations of the specific examples described herein remain within the scope and spirit of the present invention.
REFERENCES
1. A.B. Baylis and M.E.D. Hillman,; Us Pa t en t No 3,743,669 .
2. J.S. Hill and N.S. Isaacs, Te trahedr on Le t t . 27, 5007 (1986).
3. P. Perlmutter and CC. Teo, Te trahedr on Let t . 25, 5951 (1984). 4. S.E. Drewes and G.H.P. Roos, Tetrahedron 44, 4653 (1988).
5. L.J. Mathias, S.H. Kusefoglu and A.O. Kress, Macro olecules 20, 2326 (1987).
6. R. Fikentscher, E. Hahn, A. Kud and A. Oftring, US Patent 4,654,432 (1987).
7. N.S. Isaacs and J. Hill European Patent Appl icat ion 0196708 (1986).

Claims

Claims
1. A process for the preparation of a compound of the general formula
Figure imgf000022_0001
I I
HC = C - Z (I) which comprises reacting a compound of general formula R5 H
I I HC = C - Z ' (II) with a carbonyl compound of general formula
Figure imgf000022_0002
wherein Z represents an electron withdrawing group and R_ represents hydrogen, branched or straight-chain, substituted or unsubstituted C-._1R alkyl, substituted or unsubstituted C -C12 cycloalkyl, aralkyl or alkaryl and R in formulae I and III represents hydrogen, substituted or unsubstituted C-CQ alkyl, lower alkenyl (C1-C8), alk-(C1-C4)aryl, aralkyl(C.-C4) or aryl, or R together with R, may form a cyclic ring and R-- in formulae I and II represents hydrogen, C-,-C-,R alkyl, cycloalkyl, aralkyl, alkaryl, aryl or a heterocylic ring such as a furyl ring, said reaction being carried out in the presence of microwave radiation.
2. A process according to claim 1 wherein ?, represents a member of the group consisting of
l8, -CN and -S02Rg
Figure imgf000023_0002
Figure imgf000023_0001
where R. , R», R_, R., R„ and R... each independently represent hydrogen, branched or straight-chained, substituted or unsubstituted C1_-.fi alkyl, substituted or unsubstituted C^-C.^ cycloalkyl, aralkyl or alkaryl. and Rn represents alkyl or aryl.
3. A process according to claim 1 wherein the compound of formula II is selected from acrylonitrile, methyl acrylate, ethyl acrylate, iso-octyl acrylate, 2-ethylhexyl acrylate butyl acrylate, lauryl acrylate, phenyl acrylate; cyclohexylmethyl acrylate, cyclohexyl acrylate, cyclopentyl acrylate, phenylethyl acrylate, p-ethylphenyl acrylate, m-chlorophenyl acrylate, p-nitrophenyl acrylate, trichloromethyl acrylate, p-carboxymethylphenyl acrylate, p-methoxyphenyl acrylate, methyl vinyl ketone, isobutyl vinyl ketone, phenyl vinyl ketone, cyclohexyl vinyl ketone, p-chlorophenyl vinyl ketone, benzyl vinyl ketone, crotonaldehyde, crotononitrile, N,N-dimethyl acrylamide, N,N-dibutylacrylamide, N,N-dioctyl acrylamide, N,N-diphenyl acrylamide N,N-dicyclohexyl acrylamide,
2-hydroxyethyl acrylate or hydroxypropyl acrylate
4. The process of claim 1 or claim 2 wherein the compound of formula III is a ketone.
5. The process of claim 3 wherein the ketone iε selected from acetone, cyclohexanone, pentanone, methyl ethyl ketone, diethyl ketone, acetophenone or benzophenone.
6. The process of claim 1 or claim 2 wherein the compound of formula III iε an aldehyde.
7. The process of claim 6 wherein the aldehyde iε selected from formaldehyde, acetaldehyde, n-butyraldehyde, phenylacetaldehyde, benzaldehyde, octanal, crotonaldehyde, m-ethylphenylacetaldehyde, m-chloro- benzaldehyde, p-nitrophenylacetaldehyde, m-carbomethoxy- benzaldehyde, p-methoxybenzaldehyde, salicyladehyde, vanillin, iso-vanillin and fufural .
8. The process of claim 7 wherein the aldehyde iε formaldehyde prepared by microwave reaction of acid catalysed hydrolysis of an aqueous slurry of paraformaldehyde.
5. The process of claim 1 or claim 2 for the continuous preparation of a compound of formula I, said process comprising:
continuously providing a mixture of a compound of formula II and a carbonyl compound of formula III to a reaction zone;
irradiating said reaction zone with microwave radiation; and
removing the reaction mixture from the reaction zone.
10. The process of claim 1 or claim 2 wherein the reaction is carried out in the presence of an amine catalyst.
11. The process of claim 10 wherein the catalyst iε a tertiary amine catalyst.
12. The process of claim 11 wherein the catalyst iε diazabicyclo[2,2,2]octane.
13. The process of claim 1 wherein the temperature of the reaction mixture is in the range 100-200°C
14. The process of claim 1 wherein the reaction is carried out a pressure in the range 1 to 3000 atmospheres.
15. The process of claim 9 wherein the reaction mixture produced by the process is recycled one or more times to the reaction zone and subjected to further microwave irradiation.
16. The process of claim 1 wherein the compound of formula I is methyl 2-(hydroxymethyl) acrylate.
17. The process of claim 1 wherein the compound of formula I is n-butyl- 2-(hydroxymethyl) acrylate.
18. The process of claim 1 wherein the compound of formula I is 2-(hydroxymethyl) acrylonitrile.
19. The process of claim 1 wherein the compound of formula I is 3-(hydroxymethyl) but-3-en-2-one.
20. The process of claim 1 wherein the compound of formula I is trans-2-(hydroxymethyl) but-2-enal.
21. The process of claim 1 wherein the compound of formula I is ethyl 2-(hydroxymethyl) acrylate.
22. The process of claim 1 wherein the compound of formula I is n-butyl 3-hydroxy-2-methylene-3-phenylpropionate.
23. The process of claim 1 wherein the compound of formula I is n-butyl 3-hydroxy-2-methylene-n-butanoate.
24. The process of claim 1 wherein the compound of formula I is 2-(hydroxymethyl) but-2-enonitrile.
25. The process of claim 1 wherein the compound of formula I is 2-(2-hydroxyisopropyl) acrylate.
26. A compound of the general formula:
Figure imgf000026_0001
HC = C - Z (I)
wherein Z represents a member of the group consisting of
Figure imgf000026_0002
-OR 8' -CN and S0 Δ„Roy
Figure imgf000026_0003
and R , R_, R3, R4, Rg, R„ and Rβ each independently represent hydrogen, branched or straight-chained, substituted or unsubstituted c. lg alkyl, substituted or unsubstituted Cc'C-i?. cycloalkyl, aralkyl or alkaryl and R in formulae I and III represents hydrogen, substituted or unsubstituted C1-Cg alkyl, lower alkenyl (C..-Cg), alk-(C1-C4)aryl, aralkyl(C-.-C.) or aryl, or R together with Rβ may form a cyclic ring and R5 in formulae I and II represents C-.-C1R alkyl, cycloalkyl, aralkyl, alkaryl, aryl or a heterocylic ring such as a furyl ring and Rq represents alkyl or aryl, provided that if z is CN, R,- iε other than methyl, ethyl or propyl.
27. The compound of claim 26 wherein the compound of formula I is 2-(hydroxymethyl) but-2-enal.
28. The compound of claim 26 wherein the compound of formula I is tranε-2-(hydroxymethyl) but-2-enal
29. The compound of claim 26 where the compound of formula I is 2- (hydroxymethyl)but-2-enonitrile.
30. A process for the continuous preparation of a compound of formula I (as hereinbefore defined) comprising continuously providing a mixture of a compound of formula II (as hereinbefore defined) and formaldehyde to a heated reaction zone whereby the reaction mixture is rapidly heated, and removing the reaction mixture from the reaction zone.
31. A process according to claim 28 wherein the reaction mixture is rapidly cooled upon removal from the reaction zone.
PCT/AU1991/000236 1990-06-01 1991-05-31 2-(hydroxymethyl) acrylate derivatives and process for their preparation WO1991018861A1 (en)

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