A method to form alkynols or acetylene alcoholates

Abstract

The present disclosure relates to the field of alternative methods to form alkynols and / or acetylene alcoholates. In a first aspect, the present disclosure concerns a method comprising the steps of i) providing a mixture comprising a solvent, 1,2-dibromoethane, a carbonyl compound and an alkali hydroxide, and ii) allowing the 1,2-dibromoethane, the carbonyl compound and the alkali hydroxide to react at a reaction temperature forming a reaction mixture, wherein the solvent comprises at least 85 wt% dimethyl sulfoxide.

Description

[0001] A method to form alkynols or acetylene alcoholates

[0002] Field of the invention

[0003] The present disclosure relates to the field of alternative methods to form alkynols and / or acetylene alcoholates.

[0004] Background of the invention

[0005] Alkynols and acetylene alcoholates are important compounds used for instance as reactants for a wide range of industrial chemical processes.

[0006] Conventionally, these compounds are produced by reacting acetylene with carbonyls. Furthermore, the reported procedures use a solvent saturated with acetylene. This is common regardless of the solvent and base used in the reaction of acetylene with carbonyls and is typically achieved by bubbling acetylene gas though the solutions or mixtures. Therefore, large to very large excesses of acetylene are utilized, and the yields reported are based on the carbonyl.

[0007] Due to the flammable and explosive nature of acetylene, there are precautions required when handling large excesses. In turn, these precautions increase the complexity of industrial production of alkynols and / or acetylene alcoholates.

[0008] Therefore, there are drawbacks accompanied with traditional methods to produce alkynols and acetylene alcoholate compounds.

[0009] Summary of the invention

[0010] The objective of the present disclosure is to overcome at least one drawback of the prior art and / or improve the methods for producing acetylene alcoholate and / or alkynol compounds.

[0011] In a first aspect, the present disclosure concerns a method comprising the steps of i) providing a mixture comprising a solvent, 1,2-dibromoethane, a carbonyl compound and an alkali hydroxide, and ii) allowing the 1,2-dibromoethane, the carbonyl compound and the alkali hydroxide to react at a reaction temperature forming a reaction mixture, wherein the solvent comprises at least 85 wt% dimethyl sulfoxide, and wherein the solvent comprises at least 1 wt% but less than 15 wt% alcohol.

[0012] In a second aspect, the present disclosure concerns a method comprising the steps of i) providing a mixture comprising a solvent, 1,2-dibromoethane, a carbonyl compound and an alkali hydroxide, and ii) allowing the 1,2-dibromoethane, the carbonyl compound and the alkali hydroxide to react at a reaction temperature forming a reaction mixture, wherein the solvent comprises at least 85 wt% dimethyl sulfoxide. Itemized embodiments

[0013] In one method according to the first aspect of the invention, the present disclosure concerns method comprising the steps of i) providing a mixture comprising a solvent, 1,2-dibromoethane, a carbonyl compound and an alkali hydroxide and ii) allowingthe 1,2-dibromoethane, the carbonyl compound and the alkali hydroxide to react at a reaction temperature forming a reaction mixture, wherein the solvent comprises at least 85 wt% dimethyl sulfoxide, wherein the solvent comprises at least 1 wt% but less than 15 wt% alcohol.

[0014] In one method according to the second aspect of the invention, the present disclosure concerns method comprising the steps of i) providing a mixture comprising a solvent, 1,2-dibromoethane, a carbonyl compound and an alkali hydroxide and ii) allowing the 1,2-dibromoethane, the carbonyl compound and the alkali hydroxide to react at a reaction temperature forming a reaction mixture, wherein the solvent comprises at least 85 wt% dimethyl sulfoxide.

[0015] In one method according to the invention, the present disclosure concerns a method wherein the reaction temperature is at least 15°C but wherein the reaction temperature is less than 30°C.

[0016] Advantageously, the reaction temperature is at least 16°C. More advantageously, the reaction temperature is at least 18°C. Advantageously the reaction temperature is less than 25°C. More advantageously the reaction temperature is less than 23°C.

[0017] In one method according to the invention, the present disclosure concerns a method wherein the carbonyl compound has the structure (1):

[0018] In one embodiment, R1 is selected from H or a C1-C12 alkyl group and R2 is selected from H, C1-C24 alkyl group, alkenyl group, aryl group, heteroaryl group, or a heterocyclic group. Advantageously R1 is selected from H or a C1-C5 alkyl group. More advantageously R1 is selected from H or a Cl alkyl group. Advantageously R2 is selected from H, C1-C24 alkyl, alkenyl group, phenyl, naphthyl, pyridinyl, indolyl, 2-furyl, 2-thienyl, 2-pyrrolidinyl, or a pyrrolyl group.

[0019] In one method according to the invention, the present disclosure concerns a method wherein the carbonyl compound has the structure (2):

[0020] In some embodiments, R3 is selected from a C1-C24 alkyl group, alkenyl group, or a heteroalkyl group, preferably wherein R3 is selected from a C2-C6 alkyl group, alkenyl group, or a heteroalkyl group.

[0021] In one method according to the invention, the alkali hydroxide is selected from potassium hydroxide, sodium hydroxide, lithium hydroxide or a combination thereof. Advantageously the alkali hydroxide is potassium hydroxide.

[0022] In one method according to the invention, the solvent comprises at least 87 wt% dimethyl sulfoxide, advantageously at least 88 wt% dimethyl sulfoxide, more advantageously at least 90 wt% dimethyl sulfoxide.

[0023] In one method according to the invention, the mixture comprises molecular sieves.

[0024] In one method according to the invention, the solvent comprises at least 1 wt% but less than 15 wt% alcohol. Preferably the alcohol is selected from methanol, ethanol or a mixture thereof.

[0025] In one method according to the invention, the present disclosure concerns a method wherein the molar ratio between 1,2-dibromoethane and the carbonyl compound is at least 0.1 but less than 2. Advantageously the molar ratio between 1,2-dibromoethane and the carbonyl compound is at least 0.3, more advantageously at least 0.6. Advantageously the molar ratio between 1,2-dibromoethane and the carbonyl compound less than 1.7, more advantageously less than 1.4.

[0026] In one method according to the invention, the molar ratio between the alkali hydroxide and 1,2- dibromoethane is at least 2 but less than 5. Advantageously the molar ratio between the alkali hydroxide and 1,2-dibromoethane is at least 2.5, more advantageously at least 3. Advantageously the molar ratio between the alkali hydroxide and 1,2-dibromoethane is less than 4.5, more advantageously less than 4.

[0027] In one method according to the invention, the concentration of 1,2-dibromoethane in the mixture is at least 0.07 M but less than 7 M. Advantageously the concentration of 1,2-dibromoethane in the mixture is at least 0.35 M, more advantageously at least 0.7 M. Advantageously the concentration of 1,2- dibromoethane in the mixture is less than 4 M, more advantageously less than 3 M. In one method according to the invention, the concentration of carbonyl compound in the mixture is at least 0.07 M but less than 7 M. Advantageously the concentration of carbonyl compound in the mixture is at least 0.35 M, more advantageously at least 0.7 M. Advantageously the concentration of carbonyl compound in the mixture is less than 4 M, more advantageously less than 3 M.

[0028] In one method according to the invention, the concentration of alkali hydroxide in the mixture is at least 1.4 M but less than 4 M. Advantageously the concentration of alkali hydroxide in the mixture is at least 2.1 M, more advantageously at least 2.8 M. Advantageously the concentration of alkali hydroxide in the mixture is less than 3.6 M, more advantageously less than 3.2 M.

[0029] In one method according to the invention, the present disclosure concerns a method wherein the method comprises the steps of iii) addition of a salt to the reaction mixture obtained in step ii) to form a neutralized reaction mixture and iv) filtration of the neutralized reaction mixture obtained in step iii) and collection of filtrate. Wherein the salt is selected from ammonium bromide, ammonium chloride, ammonium sulfate, ammonium nitrate or a combination thereof.

[0030] In one method according to the invention, the molar ratio of the salt is approximately:

[0031] Where nsaitdenotes the molar amount of the salt, nM0Hdenotes the molar amount of the alkali hydroxide, and 2- dibromoethane denotes the molar amount of 1,2-dibromoethane.

[0032] In one method according to the invention, the mixture in step i) is provided by mixing 1,2- dibromoethane, the carbonyl compound and dimethyl sulfoxide to form a premixture, and mixing the alkali hydroxide, dimethyl sulfoxide and alcohol to form a suspension. Wherein the premixture is added to the suspension to form the mixture in step i). Wherein the temperature is kept below 35°C during the addition of the premixture to the suspension. Advantageously the temperature is kept below 30°C, more advantageously below 25°C, even more advantageously below 20°C.

[0033] In one method according to the invention, the mixture in step i) is provided by mixing the alkali hydroxide and the solvent to form a suspension, wherein the 1,2-dibromoethane and the carbonyl compound are added to the suspension to form the mixture in step i), wherein the temperature is kept below 35°C during the addition of the 1,2-dibromoethane and the carbonyl compound to the suspension, preferably below 30°C, more preferably below 25°C, even more preferably below 20°C.

[0034] In one method according to the invention, the solvent comprises at least 3 wt% alcohol, advantageously at least 7 wt% alcohol, but wherein the solvent comprises less than 14 wt% alcohol, advantageously less than 12 wt% alcohol. Detailed description of the invention

[0035] The present patent disclosure relates to the field of methods for forming acetylene alcoholates and / or alkynols. The alkynol having the general structure according to: and the acetylene alcoholates having the general structure according to:

[0036] Where M denotes an alkali metal.

[0037] The invention relates to a method wherein acetylene alcoholates and / or alkynols can be formed with a high yield with respect to the reactants, as opposed to for instance using an excess of acetylene as a reactant. It will be apparent to those skilled in the art that many variations and modifications can be done within the scope of the invention as described in the specification and defined with reference to the claims below.

[0038] The method according to the present invention is based on a mixture comprising a solvent, 1,2- dibromoethane, a carbonyl compound and an alkali hydroxide. As will be apparent by those skilled in the art, the present method may be performed for a range of different carbonyls. Therefore, a range of different acetylene alcoholates and / or alkynols may be formed depending on the Rl, R2 and R3 groups in structure (3), (4), (5) and (6).

[0039] Additionally, as apparent to those skilled in the art, a subsequent isolation of the acetylene alcoholates and / or alkynols, formed by the method according to the present invention, may be performed by distillation, chromatography, extraction or analogous alternatives. A skilled person also understand that the choice of isolation technique is dependent on the nature of the formed acetylene alcoholates and / or alkynols.

[0040] In one method according to the first aspect of the invention, the present disclosure concerns a method comprising the steps of i) providing a mixture comprising a solvent, 1,2-dibromoethane, a carbonyl compound and an alkali hydroxide and ii) allowingthe 1,2-dibromoethane, the carbonyl compound and the alkali hydroxide to react at a reaction temperature forming a reaction mixture, wherein the solvent comprises at least 85 wt% dimethyl sulfoxide, wherein the solvent comprises at least 1 wt% but less than 15 wt% alcohol. This results in the formation of the acetylene alcoholate and / or alkynol.

[0041] In one method according to the second aspect of the invention, the present disclosure concerns method comprising the steps of i) providing a mixture comprising a solvent, 1,2-dibromoethane, a carbonyl compound and an alkali hydroxide and ii) allowing the 1,2-dibromoethane, the carbonyl compound and the alkali hydroxide to react at a reaction temperature forming a reaction mixture, wherein the solvent comprises at least 85 wt% dimethyl sulfoxide. A method according to the second aspect also results in the formation of the acetylene alcoholate and / or alkynol.

[0042] In one method according to the invention, the present disclosure concerns a method wherein the solvent comprises at least 85 wt% but less than 99 wt% dimethyl sulfoxide.

[0043] In one method according to the invention, the present disclosure concerns a method wherein the reaction temperature is at least 15°C but wherein the reaction temperature is less than 30°C.

[0044] Below and above this temperature range the yield of the acetylene alcoholate or alkynol is reduced. Without being bound by theory, this is believed to be a result of decomposition of intermediates leading to formation of by-products. In one method according to the invention, the reaction temperature is at least 16°C. More advantageously, the reaction temperature is at least 18°C. This further improves the yield of the acetylene alcoholate and / or alkynol.

[0045] Advantageously the reaction temperature is less than 25°C. More advantageously the reaction temperature is less than 23°C. This further improves the yield of the acetylene alcoholate and / or alkynol.

[0046] In one method according to the invention, the present disclosure concerns a method wherein the carbonyl compound has the structure according to (1).

[0047] In one method according to the invention, R1 is selected from H or a C1-C12 alkyl group and R2 is selected from H, C1-C24 alkyl group, alkenyl group, aryl group, heteroaryl group, or a heterocyclic group.

[0048] Carbonyl compounds according to this react with 1,2-dibromoethane to give high yield of the acetylene alcoholate and / or alkynol.

[0049] Advantageously R1 is selected from H or a C1-C5 alkyl group. More advantageously R1 is selected from H or a Cl alkyl group. These R1 groups further improve the yield of the acetylene alcoholate and / or alkynol.

[0050] Advantageously R2 is selected from H, C1-C24 alkyl, alkenyl group, phenyl, naphthyl, pyridinyl, indolyl, 2-furyl, 2-thienyl, 2-pyrrolidinyl, or a pyrrolyl group. These R2 groups further improve the yield of the acetylene alcoholate and / or alkynol.

[0051] In one method according to the invention, the present disclosure concerns a method wherein the carbonyl compound has the structure according to (2).

[0052] In one method according to the invention, R3 is selected from a C1-C24 alkyl group, alkenyl group, or a heteroalkyl group.

[0053] Carbonyl compounds according to this react with 1,2-dibromoethane to give high yield of the acetylene alcoholate and / or alkynol.

[0054] Advantageously R3 is selected from, a C2-C6 alkyl group, alkenyl group, or a heteroalkyl group. In one method according to the invention, the alkali hydroxide is selected from potassium hydroxide, sodium hydroxide, lithium hydroxide or a combination thereof.

[0055] These alkali hydroxides further improve the yield of the acetylene alcoholate and / or alkynol. Advantageously the alkali hydroxide is potassium hydroxide. This further improves the yield of the acetylene alcoholate and / or alkynol.

[0056] In one method according to the invention, the solvent comprises at least 87 wt% dimethyl sulfoxide. Dimethyl sulfoxide further improves the yield of the acetylene alcoholate and / or alkynol.

[0057] Advantageously the solvent comprises at least 88 wt% dimethylsulfoxide, more advantageously at least 90 wt%. this further improves the yield of the acetylene alcoholate and / or alkynol.

[0058] In one method according to the invention, the mixture comprises molecular sieves. This further improves the yield of the acetylene alcoholate and / or alkynol. Without being bound to theory, the molecular sieves remove water formed as a by-product which reduces the yield of the acetylene alcoholate and / or alkynol.

[0059] In one method according to the invention, the solvent comprises at least 1 wt% but less than 15 wt% alcohol. This further improves the yield of the acetylene alcoholate and / or alkynol.

[0060] In one method according to the invention, the alcohol is selected from methanol, ethanol or a mixture thereof. The solubility of the alkali hydroxide is further improved in these alcohols. This further improves the yield of the acetylene alcoholate and / or alkynol.

[0061] In one method according to the invention, the present disclosure concerns a method wherein the molar ratio between 1,2-dibromoethane and the carbonyl compound is at least 0.1 but less than 2. This further improves the yield of the acetylene alcoholate and / or alkynol with respect to the reactants. A molar ratio between 1,2-dibromoethane and the carbonyl compound below 0.1, result in excess 1,2- dibromoethane in the reaction mixture. A molar ratio between 1,2-dibromoethane and the carbonyl compound above 2 results in excess carbonyl in the mixture.

[0062] Advantageously the molar ratio between 1,2-dibromoethane and the carbonyl compound is at least 0.3, more advantageously at least 0.6. This further improves the yield of the acetylene alcoholate and / or alkynol with respect to the reactants.

[0063] Advantageously the molar ratio between 1,2-dibromoethane and the carbonyl compound less than 1.7, more advantageously less than 1.4. This further improves the yield of the acetylene alcoholate and / or alkynol with respect to the reactants.

[0064] In one method according to the invention, the molar ratio between the alkali hydroxide and 1,2- dibromoethane is at least 2 but less than 5. This further improves the yield of the acetylene alcoholate and / or alkynol. A molar ratio below 2 reduces the yield. A molar ratio above 5 results in complicated isolation of the acetylene alcoholate and / or alkynol. Advantageously the molar ratio between the alkali hydroxide and 1,2-dibromoethane is at least 2.5, more advantageously at least 3. This further improves the yield of the acetylene alcoholate and / or alkynol.

[0065] Advantageously the molar ratio between the alkali hydroxide and 1,2-dibromoethane is less than 4.5, more advantageously less than 4. This further improves the yield of the acetylene alcoholate and / or alkynol.

[0066] In one method according to the invention, the concentration of 1,2-dibromoethane in the mixture is at least 0.07 M but less than 7 M. This further improves the yield of the acetylene alcoholate and / or alkynol.

[0067] Advantageously the concentration of 1,2-dibromoethane in the mixture is at least 0.35 M, more advantageously at least 0.7 M. Advantageously the concentration of 1,2-dibromoethane in the mixture is less than 4 M, more advantageously less than 3 M. This further improves the yield of the acetylene alcoholate and / or alkynol.

[0068] In one method according to the invention, the concentration of carbonyl compound in the mixture is at least 0.07 M but less than 7 M. A concentration of carbonyl compound in the mixture below 0.07 M leads to a reduced concentration of the acetylene alcoholate and / or alkynol which complicates a subsequent rectification. A concentration above 7 M leads to significantly lower reaction rate.

[0069] Advantageously the concentration of carbonyl compound in the mixture is at least 0.35 M, more advantageously at least 0.7 M.

[0070] Advantageously the concentration of carbonyl compound in the mixture is less than 4 M, more advantageously less than 3 M. This further improves the reaction rate.

[0071] In one method according to the invention, the concentration of alkali hydroxide in the mixture is at least 1.4 M but less than 4 M. A concentration below 1.4 M reduces the yield. A concentration above 4 M leads to the solidification of the reaction mixture, resulting in a significantly lower reaction rate. Thus, a concentration of alkali hydroxide of at least 1.4 M but less than 4 M further improves the yield of the acetylene alcoholate and / or alkynol.

[0072] Advantageously the concentration of alkali hydroxide in the mixture is at least 2.1 M, more advantageously at least 2.8 M. This further improves the yield of the acetylene alcoholate and / or alkynol. Advantageously the concentration of alkali hydroxide in the mixture is less than 3.6 M, more advantageously less than 3.2 M. This further improves the yield of the acetylene alcoholate and / or alkynol. In one method according to the invention, the present disclosure concerns a method wherein the method comprises the steps of iii) addition of a salt to the reaction mixture obtained in step ii) to form a neutralized reaction mixture and iv) filtration of the neutralized reaction mixture obtained in step iii) and collection of filtrate. Wherein the salt is selected from ammonium bromide, ammonium chloride, ammonium sulfate, ammonium nitrate or a combination thereof. The addition of salt results improves the yield of the alkynol. Additionally, it improves the yield of a subsequent isolation. Without being bound by theory, this is believed to be a result of that the addition of salt neutralize the alkali hydroxide, increase the stability of the product during isolation, and prevents the reverse reaction of alkynol decomposition into acetylene and carbonyl.

[0073] In one method according to the invention, the molar ratio of the salt is approximately:

[0074] Where nsaitdenotes the molar amount of the salt, nM0Hdenotes the molar amount of the alkali hydroxide, and n^-dibromoethane denotes the molar amount of 1,2-dibromoethane.

[0075] This further improves the yield of the the alkynol.

[0076] In one method according to the invention, the mixture in step i) is provided by mixing 1,2- dibromoethane, the carbonyl compound and dimethyl sulfoxide to form a premixture, and mixing the alkali hydroxide, dimethyl sulfoxide and alcohol to form a suspension. Wherein the premixture is added to the suspension to form the mixture in step i). Wherein the temperature is kept below 35°C during the addition of the premixture to the suspension.

[0077] Keeping the temperature below 35°C during the addition of the premixture to the suspension further improves the yield of the acetylene alcoholate and / or alkynol. This reduces the formation of acetylene and / or vinylbromide. Advantageously the temperature is kept below 30°C, more advantageously below 25°C, even more advantageously below 20°C. This further improves the yield of the acetylene alcoholate and / or alkynol.

[0078] In one method according to the invention, the solvent comprises at least 3 wt% alcohol but less than 12 wt% alcohol. This further improves the yield of the acetylene alcoholate and / or alkynol. A solvent comprising at least 3 wt% alcohol further increases the solubility of the alkali hydroxide and further improves the yield of the acetylene alcoholate and / or alkynol. Advantageously the solvent comprises at least 7 wt% alcohol. Advantageously the solvent comprises less than 12 wt% alcohol. This further improves the yield of the acetylene alcoholate and / or alkynol. In one method according to the invention, the mixture in step i) is provided by initially mixing 1,2- dibromoethane, the carbonyl compound and dimethyl sulfoxide to form a premixture, and mixing the alkali hydroxide, dimethyl sulfoxide and alcohol to form a suspension, wherein the alkali hydroxide advantageously is potassium hydroxide and the alcohol advantageously is methanol. Subsequently, the premixture is added to the suspension to form the mixture in step i). Wherein the temperature is kept below 35°C during the addition of the premixture to the suspension. Advantageously, the temperature is kept below 30°C, more advantageously below 25°C during the addition of the premixture to the suspension. The mixture provided in step i) comprises a solvent, 1,2-dibromoethane, a carbonyl compound and an alkali hydroxide, wherein the solvent comprises at least 85 wt% but less than 99 wt% dimethyl sulfoxide, wherein the solvent comprises at least 1 wt% but less than 15 wt% alcohol. Thereafter, the 1,2-dibromoethane, the carbonyl compound and the alkali hydroxide are allowed to react at a reaction temperature forming a reaction mixture in step ii), wherein the reaction temperature is at least 15°C but less than 30°C, advantageously less than 25°C.

[0079] In one method according to the invention, the mixture in step i) is provided by initially mixing 1,2- dibromoethane, a carbonyl compound and dimethyl sulfoxide to form a premixture, and mixing potassium hydroxide, dimethyl sulfoxide and methanol to form a suspension. Subsequently, the premixture is added to the suspension to form the mixture in step i). Wherein the temperature is kept below 25°C during the addition of the premixture to the suspension. The mixture comprises a solvent, 1,2-dibromoethane, a carbonyl compound and potassium hydroxide, wherein the solvent comprises at least 85 wt% but less than 99 wt% dimethyl sulfoxide, and at least 1 wt% but less than 15 wt% methanol. Thereafter, the 1,2-dibromoethane, the carbonyl compound and the potassium hydroxide are allowed to react at a reaction temperature forming a reaction mixture, wherein the reaction temperature is at least 15°C but less than 25°C.

[0080] In one method according to the invention, the mixture in step i) is provided by initially mixing 1,2- dibromoethane, the carbonyl compound and dimethyl sulfoxide to form a premixture, and mixing the alkali hydroxide, dimethyl sulfoxide and alcohol to form a suspension, wherein the alkali hydroxide advantageously is potassium hydroxide and the alcohol advantageously is methanol. Subsequently, the premixture is added to the suspension to form the mixture in step i). Wherein the temperature is kept below 35°C during the addition of the premixture to the suspension. Advantageously, the temperature is kept below 30°C, more advantageously below 25°C during the addition of the premixture to the suspension. The mixture provided in step i) comprises a solvent, 1,2-dibromoethane, a carbonyl compound and an alkali hydroxide, wherein the solvent comprises at least 85 wt% but less than 99 wt% dimethyl sulfoxide, wherein the solvent comprises at least 1 wt% but less than 15 wt% alcohol. Thereafter, the 1,2-dibromoethane, the carbonyl compound and the alkali hydroxide are allowed to react at a reaction temperature forming a reaction mixture in step ii), wherein the reaction temperature is at least 15°C but less than 30°C, advantageously less than 25°C.

[0081] In one method according to the invention, the mixture in step i) is provided by initially mixing 1,2- dibromoethane, the carbonyl compound and dimethyl sulfoxide to form a premixture, and mixing the alkali hydroxide, dimethyl sulfoxide and alcohol to form a suspension, wherein the alkali hydroxide advantageously is potassium hydroxide and the alcohol advantageously is methanol. Subsequently, the premixture is added to the suspension to form the mixture in step i). Wherein the temperature is kept below 35°C during the addition of the premixture to the suspension. Advantageously, the temperature is kept below 30°C, more advantageously below 25°C during the addition of the premixture to the suspension. The mixture provided in step i) comprises a solvent, 1,2-dibromoethane, a carbonyl compound and an alkali hydroxide, wherein the solvent comprises at least 85 wt% but less than 99 wt% dimethyl sulfoxide. Advantageously the mixture comprises molecular sieves. Thereafter, the 1,2- dibromoethane, the carbonyl compound and the alkali hydroxide are allowed to react at a reaction temperature forming a reaction mixture in step ii), wherein the reaction temperature is at least 15°C but less than 30°C, advantageously less than 25°C. Thereafter, a salt is added to the reaction mixture obtained in step ii) to from a neutralized reaction mixture. Advantageously the salt is selected from ammonium bromide.

[0082] In one method according to the invention, the mixture in step i) is provided by initially mixing 1,2- dibromoethane, the carbonyl compound and dimethyl sulfoxide to form a premixture, and mixing the alkali hydroxide, dimethyl sulfoxide and alcohol to form a suspension, wherein the alkali hydroxide advantageously is potassium hydroxide and the alcohol advantageously is methanol. Wherein the carbonyl compound advantageously carbonyl compound has the structure according to (1). Wherein R1 is selected from H or a C1-C12 alkyl group and R2 is selected from H, C1-C24 alkyl group, aryl group, heteroaryl group, or a heterocyclic group.

[0083] Advantageously R1 is selected from H or a C1-C5 alkyl group. More advantageously R1 is selected from H or a Cl alkyl group.

[0084] Advantageously R2 is selected from H, C1-C24 alkyl, phenyl, naphthyl, pyridinyl, indolyl, 2-furyl, 2- thienyl, 2-pyrrolidinyl, or a pyrrolyl group.

[0085] Subsequently, the premixture is added to the suspension to form the mixture in step i). Wherein the temperature is kept below 35°C during the addition of the premixture to the suspension. Advantageously, the temperature is kept below 30°C, more advantageously below 25°C during the addition of the premixture to the suspension. The mixture provided in step i) comprises a solvent, 1,2- dibromoethane, a carbonyl compound and an alkali hydroxide, wherein the solvent comprises at least 85 wt% but less than 99 wt% dimethyl sulfoxide. Advantageously the mixture comprises molecular sieves. Thereafter, the 1,2-dibromoethane, the carbonyl compound and the alkali hydroxide are allowed to react at a reaction temperature forming a reaction mixture in step ii), wherein the reaction temperature is at least 15°C but less than 30°C, advantageously less than 25°C. Thereafter, a salt is added to the reaction mixture obtained in step ii) to from a neutralized reaction mixture. Advantageously the salt is selected from ammonium bromide.

[0086] In one method according to the invention, the method comprises i) proving a mixture comprising a solvent, 1,2-dibromoethane, a carbonyl compound and an alkali hydroxide. Wherein the solvent comprises at least 85 wt% but less than 1 wt% dimethyl sulfoxide, and at least 1 wt% but less than 15 wt% alcohol. Wherein the carbonyl compound advantageously carbonyl compound has the structure according to (1) or (2).

[0087] Wherein R1 is selected from H or a C1-C12 alkyl group and R2 is selected from H, C1-C24 alkyl group, aryl group, heteroaryl group, or a heterocyclic group.

[0088] Advantageously R1 is selected from H or a C1-C5 alkyl group. More advantageously R1 is selected from H or a Cl alkyl group.

[0089] Advantageously R2 is selected from H, C1-C24 alkyl, phenyl, naphthyl, pyridinyl, indolyl, 2-furyl, 2- thienyl, 2-pyrrolidinyl, or a pyrrolyl group.

[0090] Advantageously R3 is selected from a C1-C24 alkyl group, alkenyl group, or a heteroalkyl group, more advantageously R3 is selected from, a C2-C6 alkyl group, alkenyl group, or a heteroalkyl group.

[0091] A method comprising carbonyl compounds as defined above further increases the yield of the acetylene alcoholate and / or alkynol.

[0092] In one method according to the invention, the mixture in step i) is provided by mixing the alkali hydroxide and the solvent to form a suspension, wherein the 1,2-dibromoethane and the carbonyl compound are added to the suspension to form the mixture in step i), wherein the temperature is kept below 35°C during the addition of the 1,2-dibromoethane and the carbonyl compound to the suspension, preferably below 30°C, more preferably below 25°C, even more preferably below 20°C. A method according to this further increases the yield of the acetylene alcoholate and / or alkynol.

[0093] Advantageously, the mixture comprises molecular sieves. Subsequently, ii) the 1,2-dibromoethane, the carbonyl compound and the alkali hydroxide are allowed to react at a reaction temperature forming a reaction mixture, wherein the reaction temperature is at least 15°C but less than 30°C, advantageously less than 25°C. A person skilled in the art recognizes that using equimolar amounts of 1,2-dibromoethane and the carbonyl compound may be an advantage, although a wider range of the molar ratio is within the scope of the present invention.

[0094] The amount of salt is approximately:

[0095] Where nsaltdenotes the molar amount of the salt, nM0Hdenotes the molar amount of the alkali hydroxide, and denotes the molar amount of 1,2-dibromoethane. Although a person skilled in the art recognizes that a range of the molar ratio is within the scope of the present invention.

[0096] Although the present invention has been described with reference to specific methods, it will be apparent to those skilled in the art that many variations and modifications may be done within the scope of the invention as described in the specification and defined with reference to the claims below.

[0097] Examples

[0098] Example 1

[0099] A mixture of l,2-dibromoethane(1.39 mmol, 1 equivalent):acetone(1.39 mmol, 1 equivalent):dimethylsulfoxide (12:10:25 v:v; 120 pL + 100 pL + 250 pL = 0.48 mL;) was added slowly (25 pL / min) using a syringe pump to a suspension of potassium hydroxide (98%, 300 mg, 5.18 mmol, 4 equivalents) in 1.4 mL of dimethylsulfoxide and 0.1 mL of methanol containing 0.35 g of 4 A molecular sieves, while controlling the temperature to not exceed 20°C. After the addition, the reaction mixture was stirred at 20°C for another 4 hours, then it was neutralized with 272 mg (2.78 mmol, 2 equivalents) of ammonium bromide. The amount of generated acetylene alcohol was determined by GC-MS analysis. The yield was found to be 69%, i.e. 0.96 mmol was formed as compared to the 1.39 mmol of 1,2-dibromoethane and / or the 1.39 mmol of acetone added.

[0100] Example 2 (Reference Experiment)

[0101] A suspension of dimethyl sulfoxide (1000 pL), ethanol (100 pL), potassium hydroxide semi-hydrate (KOH-0.5H2O, 300 mg, 4.62 mmol, 3.3 equivalents), and 4 A molecular sieves (0.35 g) was stirred and cooled until it became viscous. Next, a mixture of 1,2-dibromoethane (120 pL, 1.39 mmol, 1 equivalent) and acetone (100 pL, 1.39 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while maintaining the temperature below 20°C.

[0102] Afterward, the reaction was neutralized with ammonium chloride (97 mg, 1.81 mmol, 1.3 equivalents). The resulting 2-methyl-3-butyn-2-ol was quantified using GC-MS analysis, which revealed a yield of 71%. This corresponds to 0.99 mmol of 2-methyl-3-butyn-2-ol, based on the initial 1.39 mmol of 1,2- dibromoethane and / or acetone added.

[0103] Example 3 (NaOH as alkali hydroxide)

[0104] A suspension of dimethyl sulfoxide (1000 pL), ethanol (100 pL), sodium hydroxide (NaOH, 207 mg, 4.62 mmol, 3.3 equivalents), and 4 A molecular sieves (0.35 g) was stirred and cooled until it became viscous.

[0105] Subsequently, a mixture of 1,2-dibromoethane (120 pL, 1.39 mmol, 1 equivalent) and acetone (100 pL, 1.39 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while maintaining the temperature below 20°C.

[0106] After completion, the reaction was neutralized with ammonium chloride (97 mg, 1.81 mmol, 1.3 equivalents). The resulting 2-methyl-3-butyn-2-ol was quantified using GC-MS analysis, which revealed a yield of 2%.

[0107] Example 4 (Without molecular sieves)

[0108] A suspension of dimethyl sulfoxide (1000 pL), ethanol (100 pL), and potassium hydroxide semi-hydrate ( KOH-0.5H2O, 300 mg, 4.62 mmol, 3.3 equivalents) was stirred and cooled until it became viscous.

[0109] Next, a mixture of 1,2-dibromoethane (120 pL, 1.39 mmol, 1 equivalent) and acetone (100 pL, 1.39 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while maintaining the temperature below 20°C.

[0110] Afterward, the reaction was neutralized with ammonium chloride (97 mg, 1.81 mmol, 1.3 equivalents). The resulting 2-methyl-3-butyn-2-ol was quantified using GC-MS analysis, which revealed a yield of 38%. Example 5 (Water instead of alcohol)

[0111] A suspension of dimethyl sulfoxide (1000 pL), water (100 pL), and potassium hydroxide semi-hydrate (KOH-0.5H2O, 300 mg, 4.62 mmol, 3.3 equivalents) was stirred and cooled until it became viscous.

[0112] Next, a mixture of 1,2-dibromoethane (120 pL, 1.39 mmol, 1 equivalent) and acetone (100 pL, 1.39 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while maintaining the temperature below 20°C.

[0113] Afterward, the reaction was neutralized with ammonium chloride (97 mg, 1.81 mmol, 1.3 equivalents). The resulting 2-methyl-3-butyn-2-ol was quantified using GC-MS analysis, which revealed a yield of 20%.

[0114] Example 6 (Without alcohol)

[0115] A suspension of dimethyl sulfoxide (1000 pL) and potassium hydroxide semi-hydrate (KOH-0.5H2O, 300 mg, 4.62 mmol, 3.3 equivalents) was stirred and cooled until it became viscous.

[0116] Next, a mixture of 1,2-dibromoethane (120 pL, 1.39 mmol, 1 equivalent) and acetone (100 pL, 1.39 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while maintaining the temperature below 20°C.

[0117] Afterward, the reaction was neutralized with ammonium chloride (97 mg, 1.81 mmol, 1.3 equivalents). The resulting 2-methyl-3-butyn-2-ol was quantified using GC-MS analysis, which revealed a yield of 49%.

[0118] Example 7 (Methanol as alcohol)

[0119] A suspension of dimethyl sulfoxide (1000 pL), methanol (100 pL), and potassium hydroxide semihydrate (KOH-0.5H2O, 300 mg, 4.62 mmol, 3.3 equivalents) was stirred and cooled until it became viscous.

[0120] Next, a mixture of 1,2-dibromoethane (120 pL, 1.39 mmol, 1 equivalent) and acetone (100 pL, 1.39 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while maintaining the temperature below 20°C. Afterward, the reaction was neutralized with ammonium chloride (97 mg, 1.81 mmol, 1.3 equivalents). The resulting 2-methyl-3-butyn-2-ol was quantified using GC-MS analysis, which revealed a yield of 65%.

[0121] Example 8 (50 % Methanol)

[0122] A suspension of dimethyl sulfoxide (500 pL), methanol (500 pL), and potassium hydroxide semi-hydrate ( KOH-0.5H2O, 300 mg, 4.62 mmol, 3.3 equivalents) was stirred and cooled to 10°C.

[0123] Subsequently, a mixture of 1,2-dibromoethane (120 pL, 1.39 mmol, 1 equivalent) and acetone (100 pL, 1.39 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while maintaining the temperature below 20°C.

[0124] After completion, the reaction was neutralized with ammonium chloride (97 mg, 1.81 mmol, 1.3 equivalents). The resulting 2-methyl-3-butyn-2-ol was quantified using GC-MS analysis, which revealed a yield of 2%.

[0125] Example 9 (Elevated temperature 40 °C)

[0126] A mixture of 1,2-dibromoethane (120 pL, 1.39 mmol, 1 equivalent) and acetone (100 pL, 1.39 mmol, 1 equivalent) was added to a suspension of dimethyl sulfoxide (1000 pL), ethanol (100 pL), potassium hydroxide semi-hydrate (KOH-0.5H2O, 300 mg, 4.62 mmol, 3.3 equivalents), and 4 A molecular sieves (0.35 g).

[0127] The reaction mixture was stirred for 4 hours at 40 °C.

[0128] After completion, the reaction was neutralized with ammonium chloride (97 mg, 1.81 mmol, 1.3 equivalents). The resulting 2-methyl-3-butyn-2-ol was quantified using GC-MS analysis, which revealed a yield of 32%.

[0129] Example 10 (Lower molar ratio between alkali hydroxide and 1,2-dibromoethane)

[0130] A suspension of dimethyl sulfoxide (1000 pL), ethanol (100 pL), and potassium hydroxide semi-hydrate ( KOH-0.5H2O, 200 mg, 3.08 mmol, 2.2 equivalents) was stirred and cooled until it became viscous. Next, a mixture of 1,2-dibromoethane (120 pL, 1.39 mmol, 1 equivalent) and acetone (100 pL, 1.39 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while maintaining the temperature below 20°C.

[0131] Afterward, the reaction was neutralized with ammonium chloride (97 mg, 1.81 mmol, 1.3 equivalents). The resulting 2-methyl-3-butyn-2-ol was quantified using GC-MS analysis, which revealed a yield of 2%.

[0132] Example 11 (Formaldehyde as carbonyl compound)

[0133] A suspension of dimethyl sulfoxide (1000 pL), ethanol (100 pL), potassium hydroxide semi-hydrate (KOH-0.5H2O, 200 mg, 3.08 mmol, 2.2 equivalents), and 37% formaldehyde aqueous solution (112 pL, 1.39 mmol, 1 equivalent) was stirred and cooled until it became viscous.

[0134] Subsequently, 1,2-dibromoethane (120 pL, 1.39 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while maintaining the temperature below 20°C.

[0135] Afterward, the reaction was neutralized with ammonium chloride (97 mg, 1.81 mmol, 1.3 equivalents). The resulting propargyl alcohol was quantified using GC-MS analysis, which revealed a yield of 26%.

[0136] Example 12 (Isolation of 2-methyl-3-butyn-2-ol)

[0137] A suspension of dimethyl sulfoxide (10 mL), ethanol (1 mL), potassium hydroxide semi-hydrate (KOH-0.5H2O, 3 g, 46 mmol, 3.3 equivalents), and 4 A molecular sieves (3.5 g) was stirred and cooled until it became viscous.

[0138] Next, a mixture of 1,2-dibromoethane (1.2 mL, 14 mmol, 1 equivalent) and acetone (1.0 mL, 14 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while keeping the temperature below 20°C.

[0139] After completion, the reaction was neutralized with ammonium chloride (1 g, 18 mmol, 1.3 equivalents). Fractional distillation of the resulting mixture produced 0.66 g of 2-methyl-3-butyn-2-ol (56% yield).

[0140] Example 13 (2-Methylpropanal as carbonyl compound (aldehyde), Isolation of product) A suspension of dimethyl sulfoxide (10 mL), ethanol (1 mL), potassium hydroxide semi-hydrate (KOH-0.5H2O, 3 g, 46 mmol, 3.3 equivalents), and 4 A molecular sieves (3.5 g) was stirred and cooled until it became viscous.

[0141] Next, a mixture of 1,2-dibromoethane (1.2 mL, 14 mmol, 1 equivalent) and 2-methylpropanal (1.3 mL, 14 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while keeping the temperature below 20°C.

[0142] After completion, the reaction mixture was poured into a solution of ammonium chloride (1 g, 18 mmol, 1.3 equivalents) in 40 mL of water and extracted with diethyl ether (3 x 15 mL). The combined organic extracts were dried over magnesium sulfate. The residue obtained after solvent removal was distilled under reduced pressure, yielding 0.65 g of 4-methyl-l-pentyn-3-ol (48% yield).

[0143] Example 14 (2-Methylbutyral as carbonyl compound (aldehyde), Isolation of product)

[0144] A suspension of dimethyl sulfoxide (10 mL), ethanol (1 mL), potassium hydroxide semi-hydrate (KOH-0.5H2O, 3 g, 46 mmol, 3.3 equivalents), and 4 A molecular sieves (3.5 g) was stirred and cooled until it became viscous.

[0145] Next, a mixture of 1,2-dibromoethane (1.2 mL, 14 mmol, 1 equivalent) and 2-methylbutyral (1.5 mL, 14 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while keeping the temperature below 20°C.

[0146] After completion, the reaction mixture was poured into a solution of ammonium chloride (1 g, 18 mmol, 1.3 equivalents) in 40 mL of water and extracted with diethyl ether (3 x 15 mL). The combined organic extracts were dried over magnesium sulfate. The residue obtained after solvent removal was distilled under reduced pressure, yielding 0.91 g of 4-methyl-l-hexyn-3-ol (58% yield).

[0147] Example 15 (Cyclohexanone as carbonyl compound, Isolation of product)

[0148] A suspension of dimethyl sulfoxide (10 mL), ethanol (1 mL), potassium hydroxide semi-hydrate (KOH-0.5H2O, 3 g, 46 mmol, 3.3 equivalents), and 4 A molecular sieves (3.5 g) was stirred and cooled until it became viscous. Subsequently, a mixture of 1,2-dibromoethane (1.2 mL, 14 mmol, 1 equivalent) and cyclohexanone (1.5 mL, 14 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while keeping the temperature below 20°C.

[0149] After completion, the reaction mixture was poured into a solution of ammonium chloride (1 g, 18 mmol, 1.3 equivalents) in 40 mL of water and extracted with diethyl ether (3 x 15 mL). The combined organic extracts were dried over magnesium sulfate. The residue obtained after solvent removal was distilled under reduced pressure, yielding 1.18 g of 2-cyclohexyl-3-butyn-2-ol (68% yield).

[0150] Example 16 (4-Methyl-2-pentanone as carbonyl compound, Isolation of product)

[0151] A suspension of dimethyl sulfoxide (10 mL), ethanol (1 mL), potassium hydroxide semi-hydrate (KOH-0.5H2O, 3 g, 46 mmol, 3.3 equivalents), and 4 A molecular sieves (3.5 g) was stirred and cooled until it became viscous.

[0152] Subsequently, a mixture of 1,2-dibromoethane (1.2 mL, 14 mmol, 1 equivalent) and 4-methyl-2- pentanone (1.8 mL, 14 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while keeping the temperature below 20°C.

[0153] After completion, the reaction mixture was poured into a solution of ammonium chloride (1 g, 18 mmol, 1.3 equivalents) in 40 mL of water and extracted with diethyl ether (3 x 15 mL). The combined organic extracts were dried over magnesium sulfate. The residue obtained after solvent removal was distilled under reduced pressure, yielding 1.05 g of 3,5-dimethyl-l-hexyn-3-ol (60% yield).

[0154] Example 17 (6-Methyl-5-hepten-2-one as carbonyl compound (long-chain ketone), Isolation of product)

[0155] A suspension of dimethyl sulfoxide (10 mL), ethanol (1 mL), potassium hydroxide semi-hydrate (KOH-0.5H2O, 3 g, 46 mmol, 3.3 equivalents), and 4 A molecular sieves (3.5 g) was stirred and cooled until it became viscous.

[0156] Subsequently, a mixture of 1,2-dibromoethane (1.2 mL, 14 mmol, 1 equivalent) and 6-methyl-5-hepten- 2-one (2.1 mL, 14 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while keeping the temperature below 20°C. After completion, the reaction mixture was poured into a solution of ammonium chloride (1 g, 18 mmol, 1.3 equivalents) in 40 mL of water and extracted with diethyl ether (3 x 15 mL). The combined organic extracts were dried over magnesium sulfate. The residue obtained after solvent removal was distilled under reduced pressure, yielding 0.99 g of dehydrolinalool (47% yield).

[0157] Example 18 (Geranyl acetone as carbonyl compound (long-chain ketone), Isolation of product)

[0158] A suspension of dimethyl sulfoxide (10 mL), ethanol (1 mL), potassium hydroxide semi-hydrate (KOH-0.5H2O, 3 g, 46 mmol, 3.3 equivalents), and 4 A molecular sieves (3.5 g) was stirred and cooled until it became viscous.

[0159] Subsequently, a mixture of 1,2-dibromoethane (1.2 mL, 14 mmol, 1 equivalent) and geranyl acetone (3.1 mL, 14 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while keeping the temperature below 20°C.

[0160] After completion, the reaction mixture was poured into a solution of ammonium chloride (1 g, 18 mmol, 1.3 equivalents) in 40 mL of water and extracted with diethyl ether (3 x 15 mL). The combined organic extracts were dried over magnesium sulfate. The residue obtained after solvent removal was purified by column chromatography (silica, hexane), yielding 1.60 g of dehydronerolidol (52% yield).

[0161] Example 19 (Acetophenone as carbonyl compound (aromatic ketone), Isolation)

[0162] A suspension of dimethyl sulfoxide (10 mL), ethanol (1 mL), potassium hydroxide semi-hydrate (KOH-0.5H2O, 3 g, 46 mmol, 3.3 equivalents), and 4 A molecular sieves (3.5 g) was stirred and cooled until it became viscous.

[0163] Subsequently, a mixture of 1,2-dibromoethane (1.2 mL, 14 mmol, 1 equivalent) and acetophenone (1.6 mL, 14 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while keeping the temperature below 20°C.

[0164] After completion, the reaction mixture was poured into a solution of ammonium chloride (1 g, 18 mmol, 1.3 equivalents) in 40 mL of water and extracted with diethyl ether (3 x 15 mL). The combined organic extracts were dried over magnesium sulfate. The residue obtained after solvent removal was purified by column chromatography (silica, hexane), yielding 0.69 g of 2-phenyl-3-butyn-2-ol (34% yield). Example 20 (4-Acetyl-pyridine as carbonyl compound (hetaryl ketone), Isolation)

[0165] A suspension of dimethyl sulfoxide (10 mL), ethanol (1 mL), potassium hydroxide semi-hydrate (KOH-0.5H2O, 3 g, 46 mmol, 3.3 equivalents), and 4 A molecular sieves (3.5 g) was stirred and cooled until it became viscous.

[0166] Subsequently, a mixture of 1,2-dibromoethane (1.2 mL, 14 mmol, 1 equivalent) and 4-acetyl-pyridine (1.6 mL, 14 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while keeping the temperature below 20°C.

[0167] After completion, the reaction mixture was poured into a solution of ammonium chloride (1 g, 18 mmol, 1.3 equivalents) in 40 mL of water and extracted with diethyl ether (3 x 15 mL). The combined organic extracts were dried over magnesium sulfate. The residue obtained after solvent removal was purified by column chromatography (silica, hexane), yielding 0.25 g of 2-(pyridin-4-yl)-3-butyn-2-ol (12% yield).

[0168] Example 21 (2-Acetylthiophene as carbonyl compound (hetaryl ketone), Isolation)

[0169] A suspension of dimethyl sulfoxide (10 mL), ethanol (1 mL), potassium hydroxide semi-hydrate (KOH-0.5H2O, 3 g, 46 mmol, 3.3 equivalents), and 4 A molecular sieves (3.5 g) was stirred and cooled until it became viscous.

[0170] Subsequently, a mixture of 1,2-dibromoethane (1.2 mL, 14 mmol, 1 equivalent) and 2-acetylthiophene (1.5 mL, 14 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while keeping the temperature below 20°C.

[0171] After completion, the reaction mixture was poured into a solution of ammonium chloride (1 g, 18 mmol, 1.3 equivalents) in 40 mL of water and extracted with diethyl ether (3 x 15 mL). The combined organic extracts were dried over magnesium sulfate. The residue obtained after solvent removal was purified by column chromatography (silica, hexane), yielding 0.08 g of 2-(thiophen-2-yl)-3-butyn-2-ol (4% yield).

[0172] Example 22 (2-Acetylfuran as carbonyl compound (hetaryl ketone), Isolation) A suspension of dimethyl sulfoxide (10 mL), ethanol (1 mL), potassium hydroxide semi-hydrate (KOH-0.5H2O, 3 g, 46 mmol, 3.3 equivalents), and 4 A molecular sieves (3.5 g) was stirred and cooled until it became viscous.

[0173] Subsequently, a mixture of 1,2-dibromoethane (1.2 mL, 14 mmol, 1 equivalent) and 2-acetylfuran (1.5 mL, 14 mmol, 1 equivalent) was added to the suspension. The reaction mixture was stirred for 4 hours while keeping the temperature below 20°C.

[0174] After completion, the reaction mixture was poured into a solution of ammonium chloride (1 g, 18 mmol, 1.3 equivalents) in 40 mL of water and extracted with diethyl ether (3 x 15 mL). The combined organic extracts were dried over magnesium sulfate. The residue obtained after solvent removal was purified by column chromatography (silica, hexane), yielding 0.23 g of 2-(furan-2-yl)-3-butyn-2-ol (12% yield).

[0175] Example 23 (Continuous flow reaction)

[0176] A fixed-bed reactor equipped with endcaps and porous metal frits (length 25 mm, inner diameter 25 mm) was filled with a mixture of potassium semi-hydrate (6 g, 92 mmol, 3.3 equivalents) and 4 A molecular sieves (7 g).

[0177] A reaction mixture consisting of dimethyl sulfoxide (20 mL), ethanol (2 mL), acetone (2 mL, 28 mmol, 1 equivalent), and 1,2-dibromoethane (2.4 mL, 28 mmol, 1 equivalent) was delivered into the reactor using a syringe pump at a flow rate of 5 mL / hour, with a residence time of 80 minutes. The reactor temperature was maintained below 20°C throughout.

[0178] GC-MS analysis of the outgoing solution revealed a 64% yield of 2-methyl-3-butyn-2-ol.

[0179] Summary of results

[0180] Results for the examples are summarized in Table 1.

[0181] Table 1. Summary of results from examples.

[0182] *lsolated yield as described in corresponding example.

Claims

Claims1. A method for forming alkynols and / or acetylene alcoholates comprising the steps of: i) providing a mixture comprising a solvent, 1,2-dibromoethane, a carbonyl compound and an alkali hydroxide, wherein the solvent comprises at least 85 wt% dimethyl sulfoxide, ii) allowing the 1,2-dibromoethane, the carbonyl compound and the alkali hydroxide to react at a reaction temperature forming a reaction mixture comprising alkynols and / or acetylene alcoholates.

2. A method according to claim 1, wherein the reaction temperature is at least 15°C, preferably at least 16°C, more preferably at least 18°C but wherein the reaction temperature is less than 30°C, preferably less than 25°C, more preferably less than 23°C.

3. A method according to any of claims 1-2, wherein the carbonyl compound has the structure (1) or (2):wherein R1 is selected from H or a C1-C12 alkyl group, preferably selected from H or a C1-C5 alkyl group, more preferably selected from H or a Cl alkyl group; and wherein R2 is selected from H, C1-C24 alkyl group, alkenyl group, aryl group, heteroaryl group, or a heterocyclic group, preferably selected from H, C1-C24 alkyl, phenyl, naphthyl, pyridinyl, indolyl, 2-furyl, 2- thienyl, 2-pyrrolidinyl, or a pyrrolyl group wherein R3 is selected from a C1-C24 alkyl group, alkenyl group, or a heteroalkyl group, preferably wherein R3 is selected from a C2-C6 alkyl group, alkenyl group, or a heteroalkyl group.

4. A method according to any one of claims 1-3, wherein the alkali hydroxide is selected from potassium hydroxide, sodium hydroxide, lithium hydroxide or a combination thereof, preferably wherein the alkali hydroxide is potassium hydroxide.

5. A method according to any of claims 1-4, wherein the solvent comprises at least 87 wt% dimethyl sulfoxide, preferably at least 88 wt% dimethylsulfoxide, more preferably at least 90 wt% dimethylsulfoxide.

6. A method according to any of claims 1-5, wherein the mixture comprises molecular sieves.

7. A method according to any of claims 1-6, wherein the solvent comprises at least 1 wt% but less than 15 wt% alcohol, preferably wherein the alcohol is selected from methanol, ethanol or a mixture thereof.

8. A method according to any of claims 1-7, wherein the molar ratio between 1,2- dibromoethane and the carbonyl compound is at least 0.1, preferably at least 0.3, more preferably at least 0.6 but wherein the molar ratio between 1,2-dibromoethane and the carbonyl compound less than 2, preferably less than 1.7, more preferably less than 1.4.

9. A method according to any one of claims 1-8, wherein the molar ratio between the alkali hydroxide and 1,2-dibromoethane is at least 2, preferably at least 2.5, more preferably at least 3 but wherein the molar ratio between alkali hydroxide and 1,2-dibromoethane is less than 5, preferably less than 4.5, more preferably less than 4.

10. A method according to any of claims 1-9, wherein the concentration of 1,2-dibromoethane in the mixture is at least 0.07 M, preferably at least 0.35 M, more preferably at least 0.7 M but wherein the concentration of 1,2-dibromoethane in the mixture is less than 7 M, preferably less than 4 M, more preferably less than 3 M.

11. A method according to any of claims 1-10, wherein the concentration of carbonyl compound in the mixture is at least 0.07 M, preferably at least 0.35 M, more preferably at least 0.7 M but wherein the concentration of carbonyl compound in the mixture is less than 7 M, preferably less than 4 M, more preferably less than 3 M.

12. A method according to any one of claims 1-11, wherein the concentration of alkali hydroxide in the mixture is at least 1.4 M, preferably at least 2.1 M, more preferably at least 2.8 M, but wherein the concentration of alkali hydroxide in the mixture is less than 4 M, preferably less than 3.6 M, more preferably less than 3.2 M.

13. A method according to any one of claims 1-12, wherein the method comprises the steps of: iii) addition of a salt to the reaction mixture obtained in step ii) to form a neutralized reaction mixture, wherein the salt is selected from ammonium bromide, ammonium chloride, ammonium sulfate, ammonium nitrate or a combination thereof, and iv) filtration of the neutralized reaction mixture obtained in step iii) and collection of filtrate.

14. A method according to any one of claims 1-13, wherein the mixture in step i) is provided by mixing the alkali hydroxide and the solvent to form a suspension, wherein the 1,2- dibromoethane and the carbonyl compound are added to the suspension to form the mixture in step i), wherein the temperature is kept below 35°C during the addition of the 1,2- dibromoethane and the carbonyl compound to the suspension, preferably below 30°C, more preferably below 25°C, even more preferably below 20°C.

15. A method according to any one of claims 1-14, wherein the solvent comprises at least 3 wt% alcohol, preferably at least 7 wt% alcohol, but wherein the solvent comprises less than 14 wt% alcohol, preferably less than 12 wt% alcohol.

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