WO2015112096A1

WO2015112096A1 - Condensation of aldehyde

Info

Publication number: WO2015112096A1
Application number: PCT/SG2015/050009
Authority: WO
Inventors: Ting LU; Liuqun Gu; Yugen Zhang
Original assignee: Agency For Science, Technology And Research
Priority date: 2014-01-23
Filing date: 2015-01-23
Publication date: 2015-07-30

Abstract

The present disclosure relates to a process for producing hydroxyketone by condensation of one or more 5 aldehydes in the presence of a thiazolium salt of Formula I as defined herein, and a base.

Description

Condensation of Aldehyde

Technical Field

The present invention generally relates to a process for producing hydroxyketone from aldehyde.

Background

The development of processes for the production of bio-based commodity chemicals has been of industrial interest. Utilizing renewable bio-chemicals as a source for further transformation and production is highly desirable. It is not only desirable from an environmental perspective as biochemical transformations usually comprise carbon neutral cycles and biodegradable materials; but also because of its economical benefit.

Bioethanol is currently produced from biomass in a large amount (105 billion litres in 2011) and is mainly used as biofuel. It holds considerable potential as a versatile building block for the chemical industry. The use of bioethanol for the production of value-added chemicals is economically viable and may lead to a decrease in overall CO₂ emission. Processes for the conversion of ethanol to bulk chemicals are known. However, most of the successfully accessible products from bioethanol are lower carbon C2 chemicals or related products such as ethylene, acetaldehyde, acetic acid, ethylacetate and hydrogen. Industrial processes for the production of C4 chemicals are known, such as for butadiene and 1-butanol. However, these processes suffer from low selectivity and efficiency that erode a significant part of their economic value.

These disadvantages may be attributed to the fact that ethanol is a difficult substrate for dehydrogenation and condensation into higher carbon products, such as C4 chemicals. The major challenge for the conversion of ethanol to C4 chemicals is ensuring selective condensation or coupling of C2 to C4. For example, a base-catalyzed aldol condensation of acetaldehyde is difficult to control and easily leads to mixtures of oligomeric and polymeric side products. iV-heterocyclic carbene (NHC) catalyzed acetoin condensation reactions provide another possibility for the conversion of C2 to C4. However, known processes for such condensation reactions are complicated and require multiple steps. These processes are also known to possess low selectivity, poor tolerancy to impurities, low reaction efficiency and require costly precatalysts .

There is therefore a need to provide a process for conversion of lower carbon products to higher carbon products that overcome, or at least ameliorate, one or more of the disadvantages described above.

Summary

According to a first aspect of the present disclosure, there is provided a process for producing hydroxyketone by condensation of one or more aldehydes in the presence of a thiazolium salt and a base,

wherein said thiazolium salt is of formula I :

Formula 5

wherein

R¹ represents -alkylaryl, -alkylheteroaryl , alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl or heterocyclyl ;

R², R³ and R⁴ independently represent hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl or heterocyclyl; wherein each said R¹, R², R³ and R⁴ group is optionally substituted by one or more substituents; and

X^~ represents an anion.

Advantageously, the disclosed process may be highly selective with high yields and minimal side products.

The disclosed process may require only a small amount of thiazolium salt as a precatalyst, thus leading to cost efficiency. Advantageously, the thiazolium salt may be highly tolerant to impurities such as water. Therefore, the disclosed process may not require specific pretreatment for reactors and reagents, further contributing to cost savings and a minimally complicated process.

The disclosed process may further not require the use of multiple and overly complicated steps.

The thiazolium salt and/or base may be reused for subsequent reactions thereby advantageously leading to cost efficiency and convenience.

In a second aspect, there is provided a process for obtaining acetoin, comprising the steps of:

a) obtaining acetaldehyde from ethanol; and

b) producing acetoin by self-condensation of acetaldehyde in the presence of a disclosed thiazolium salt and a base.

In a third aspect, there is provided a hydroxyketone produced by the disclosed process.

In a fourth aspect, there is provided a thiazolium salt of the following formula:

wherein X is an anion and n represents an integer from 1 to 100,000. Definitions

The following words and terms used herein shall have the meaning indicated.

As used herein, the term "aliphatic" refers to an organic compound or radical characterized by a straight chain or branched chain structure, or closed ring structure, any of which may contain saturated carbon bonds, and optionally, one or more unconjugated carbon- carbon unsaturated bonds, such as a carbon-carbon double bond. The aliphatic groups may have from 1 to 10 carbon atoms, e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 carbon atoms.

As used herein, the term "alkyl" includes within its meaning monovalent ("alkyl") and divalent ("alkylene") straight chain or branched chain saturated aliphatic groups having from 1 to 12 carbon atoms, eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms. For example, the term alkyl includes, but is not limited to, methyl, ethyl, 1-propyl, isopropyl, 1-butyl, 2-butyl, isobutyl, tert- butyl, amyl, 1, 2-dimethylpropyl, 1 , 1-dimethylpropyl , pentyl, isopentyl, hexyl, 4-methylpentyl , 1-methylpentyl, 2-methylpentyl , 3-methylpentyl , 2, 2-dimethylbutyl, 3,3- dimethylbutyl, 1 , 2-dimethylbutyl , 1 , 3-dimethylbutyl ,

1 , 2 , 2-trimethylpropyl , 1 , 1 , 2-trimethylpropyl, 2- ethylpentyl, 3-ethylpentyl, heptyl, 1-methylhexyl, 2,2- dimethylpentyl , 3, 3-dimethylpentyl, 4 , 4-dimethylpentyl , 1 , 2-dimethylpentyl , 1 , 3-dimethylpentyl , 1_?4- dimethylpentyl , 1 , 2 , 3-trimethylbutyl , 1,1,2- trimethylbutyl , 1 , 1 , 3-trimethylbutyl, 5-methylheptyl, 1- methylheptyl , octyl, nonyl, decyl, undecyl, dodecyl and the like. Alkyl groups may be optionally substituted.

As used herein, the term "alkenyl" refers to divalent straight chain or branched chain unsaturated aliphatic groups containing at least one carbon-carbon double bond and having from 2 to 12 carbon atoms, eg, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms carbon atoms. For example, the term alkenyl includes, but is not limited to, ethenyl, propenyl, butenyl, 1-butenyl, 2-butenyl, 2- methylpropenyl , 1-pentenyl, 2-pentenyl, 2-methylbut-l- enyl, 3-methylbut-l-enyl , 2-methylbut-2-enyl , 1-hexenyl, 2-hexenyl, 3-hexenyl, 2 , 2-dimethyl-2-butenyl , 2-methyl-2- hexenyl, 3-methyl-l-pentenyl, 1 , 5-hexadienyl and the like. Alkenyl groups may be optionally substituted.

As used herein, the term "alkynyl" refers to trivalent straight chain or branched chain unsaturated aliphatic groups containing at least one carbon-carbon triple bond and having from 2 to 12 carbon atoms, eg, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms carbon atoms. For example, the term alkynyl includes, but is not limited to, ethynyl, propynyl, 1-butynyl, 2-butynyl, 1- pentynyl, 2-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 3- methyl-l-pentynyl, and the like, alkynyl groups may be optionally substituted.

The term "aryl", or variants such as "aromatic group" or "arylene" as used herein refers to monovalent ("aryl") and divalent ("arylene") single, polynuclear, conjugated and fused residues of aromatic hydrocarbons having from 6 to 10 carbon atoms. Such groups include, for example, phenyl, biphenyl, naphthyl, phenanthrenyl, and the like. Aryl groups may be optionally substituted. The term "cycloalkyl" as used herein refers to a non- aromatic mono- or multicyclic ring system comprising about 3 to about 10 carbon atoms. The cycloalkyl can be optionally substituted with one or more "ring system substituents " which may be the same or different, and are as defined herein. Non-limiting examples of suitable monocyclic cycloalkyls include cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl and the like. Non-limiting examples of suitable multicyclic cycloalkyls include decalinyl, norbornyl, adamantyl and the like. Further non- limiting exam les of cycloalkyl include the following:

As used herein, the term "solid base" refers to a dried or granular compound that yields a basic solution when dissolved in a solvent.

As used herein, the term "inorganic base" includes within its meaning alkaline and alkaline earth metal bases. Non-limiting examples include alkaline and alkaline earth metal alkoxides, alkaline and alkaline earth metal acetates, alkaline and alkaline earth metal carbonates, alkaline and alkaline earth metal bicarbonates, alkaline and alkaline earth metal hydroxides, alkaline and alkaline earth metal oxides, alkaline and alkaline earth metal phosphates, and alkaline and alkaline earth metal hydrogen phosphates or mixtures thereof. Non-limiting examples include sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, magnesium hydroxide, barium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, lithium carbonate, calcium carbonate, magnesium carbonate, barium carbonate, sodium bicarbonate, potassium bicarbonate, sodium methoxide, potassium methoxide, sodium tertiary butoxide, potassium tertiary butoxide, or mixtures thereof.

As used herein, the term "organic base" refers to a non-metallic and basic organic species. The organic base may contain an amino group, a pyridinyl group, a derivative of a carboxylic acid, or mixtures thereof. Non- limiting examples include pyridine, alkyl amine, morpholine, imidazole, benzimidazole, triethylamine, benzyldiethylamine, dimethylethyl amine, imidazole, salts of carboxylic acids, or mixtures thereof.

The term "heteroaryl" as used herein refers to an aromatic monocyclic or multicyclic ring system comprising about 5 to about 14 ring atoms in which one or more of the ring atoms is an element other than carbon, for example nitrogen, oxygen or sulfur, alone or in combination. "Heteroaryl" may also include a heteroaryl as defined above fused to an aryl as defined above. Non- limiting examples of suitable heteroaryls include pyridyl, pyrazinyl, furanyl, thienyl, pyrimidinyl, pyridone (including N-substituted pyridones), isoxazolyl, isothiazolyl , oxazolyl, thiazolyl, pyrazolyl, furazanyl, pyrrolyl, pyrazolyl, triazolyl, 1 , 2 , 4-thiadiazolyl, pyrazinyl, pyridazinyl, quinoxalinyl , phthalazinyl, oxindolyl, imidazo[l , 2-a] pyridinyl, imidazo[2,l - b]thiazolyl, benzofurazanyl, indolyl, azaindolyl, benzimidazolyl, benzothienyl, quinolinyl, imidazolyl, thienopyridyl, quinazolinyl , thienopyrimidyl , pyrrolopyridyl , imidazopyridyl, isoquinolinyl , benzoazaindolyl, 1 , 2, 4-triazinyl, benzothiazolyl and the like. The term "heteroaryl" also refers to partially saturated heteroaryl moieties such as, for example, tetrahydroisoquinolyl , tetrahydroquinolyl and the like. Heteroaryl groups may be optionally substituted.

The term "heterocycle " as used herein refers to a group comprising a covalently closed ring herein at least one atom forming the ring is a carbon atom and at least one atom forming the ring is a heteroatom. Heterocyclic rings may be formed by 3, 4, 5, 6, 7, 8, 9, or more than 9 atoms, any of which may be saturated, partially unsaturated, or aromatic. Any number of those atoms may be heteroatoms (i.e., a heterocyclic ring may comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, or more than 9 heteroatoms) . Herein, whenever the number of carbon atoms in a heterocycle is indicated (e.g., C1-C6 heterocycle), at least one other atom (the heteroatom) must be present in the ring. Designations such as "C1-C6 heterocycle" refer only to the number of carbon atoms in the ring and do not refer to the total number of atoms in the ring. It is understood that the heterocylic ring will have additional heteroatoms in the ring. In heterocycles comprising two or more heteroatoms, those two or more heteroatoms may be the same or different from one another. Heterocycles may be optionally substituted. Binding to a heterocycle can be at a heteroatom or via a carbon atom. Examples of heterocycles include heterocycloalkyls (where the ring contains fully saturated bonds) and heterocycloalkenyls (where the ring contains one or more unsaturated bonds) such as, but are not limited to the following:

wherein D, E, F, and G independently represent a heteroatom. Each of D, E, F, and G may be the same or different from one another.

The term "optionally substituted" as used herein means the group to which this term refers may be unsubstituted, or may be substituted with one or more groups other than hydrogen provided that the indicated atom' s normal valency is not exceeded, and that the substitution results in a stable compound. Such groups may be, for example, halogen, hydroxy,, oxo, cyano, nitro, alkyl, alkoxy, haloalkyl, ha1oa1 koxy , ary1 -4 -a1koxy, a1ky11hio , hydroxyaIky1 , alkoxyalkyl, cycloalkyl, cycloalkylalkoxy, alkanoyl, alkoxycarbonyl , alkylsulfonyl, alkylsul fonyloxy, a1ky1su1 fony1a1ky1 , ary1su1 fony1 , ary1su1 fony1oxy, ary1 su1fony1a1ky1 , a1ky1 su1fona .ido, a1 ky1a ido , alkylsulfonamidoalkyl , alkylamidoalkyl , arylsulfonamido, arylcarboxamido, arylsulfonamidoaIky1 , ary1carboxamidoalky1 , aroy1 , aroy1 -4-a1ky1 , aryla1kanoy1 , acyl, aryl, arylalkyl, alkylaminoalkyl , a group RR^yN-, R^xOCO(CH₂)_m, R^xCON(R^y) (CH₂)_m, R^xR^YNCO ( CH₂ ) _m, R^xR^YNS0₂ ( CH₂ ) _m or R^xS0₂NR^y (CH₂) m (where each of R^x and R^y is independently selected from hydrogen or alkyl , or where appropriate RR^y forms part of carbocylic or heterocyclic ring and m is 0, 1 , 2, 3 or 4), a group R^xR^YN(CH₂)_p- or R^xR^y ( CH₂ ) _P0- (wherein p is 1 , 2, 3 or 4); wherein when the substituent is R^xR^yN(CH₂)_p- or R^xR^y (CH₂) _pO, R^x with at least one CH₂ of the (CH₂)_D portion of the group may also form a carbocyclyl or heterocyclvi group and R^y may be hydrogen, alkyl.

The term "substituted" as used herein means the group to which this term refers is substituted with one or more groups other than hydrogen provided that the indicated atom' s normal valency is not exceeded, and that the substitution results in a stable compound. Such groups may be, for example, halogen, hydroxy, oxo, cyano, nitro, alkyl, alkoxy, haloalkyl, haloalkoxy, arylalkoxy, a1ky11hio, hydroxya1ky1 , alkoxya1ky1 , cyc1oa1ky1 , cycloalkylalkoxy, alkanoyl, alkoxycarbonyl, alkylsulfonyl, alkylsulfonyloxy, alkylsulfony1a1ky1 , ary1 su1fony1 , arylsulfonyloxy, arylsulfonylalkyl, alkylsulfonamido, alkylamido, alkylsulfonamidoalkyl, alkylamidoalkyl, arylsu1 fonamido, arylcarboxamido, arylsul fonamidoalky1 , arylcarboxamidoalkyl, aroyl, aroyl-4-alkyl, arylalkanoyl , acyl, aryl, arylalkyl, alkylaminoalkyl, a group R^xR^yN—, R^xOCO (CH₂);„, R^xCON(R^y) (CH₂)_ra, R^xR^yNCO ( CH₂ ) _n;, R^xR^yNS0₂ ( CH₂ ) _n, or R^xS0₂NR^y (CH₂)_m (where each of R^x and R^y is independently selected from hydrogen or alkyl , or where appropriate RR^y forms part of carbocylic or heterocyclic ring and m is 0, 1 , 2, 3 or 4), a group R^xR^yN(CH₂)_p- or R^xR^yN (CH₂) _pO- (wherein p is 1 , 2, 3 or 4); wherein when the substituent is R^xR^yN(CH₂)_p- or R^XR^YN (CH₂) _pO, R^x ith at least one CH₂ of the (CH₂) _o portion of the group may also form a carbocyclyl or heterocyclyl group and R^y may be hydrogen, alkyl. Such groups may also be, for example, halogen, hydroxy, cyano, oxo, oxide, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy-, hydroxyalkyl-, heteroalkyl, cyanoalkyl-, alkoxy, optionally substituted aryl, optionally substituted -O-aryl, optionally substituted -O-alkyl-aryl, optionally substituted heteroaryl, optionally substituted arylalkyl-, optionally substituted arylalkoxy, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl-, optionally substituted -0- heterocycloalkyl, -N(R⁵)₂, -alkyl-N (R⁵) ₂, -NC(0)R⁵, -C(0)R⁵, -C0₂R⁵, -S0₂R⁵, -S0₂N(R⁵)₂ and a polymer radical, wherein said optionally substituted moieties are optionally substituted with one or more substituents selected from the group consisting of alkyl, halogen, haloalkyl, hydroxyl, -CN, -N(R⁵)₂, -H₂P0₄, -H₃P₂0₇.

As used herein, any partial structure in square brackets and referred to with index n represents a repeating unit. As used herein, n may be an integer between 1 to 100,000, 100 to 100,000, 500 to 100,000, 1000 to 100, 000, 2000 to 100,000, 3000 to 100,000 , 4000 to

100 , 000, 5000 to 100, 000, 6000 to 100, , 000, 7000 to

100 , 000, 8000 to 100, ( D00, 9000 to 100,000, 10,000 to

100 , 000, 11, 000 to 100, 000, 12, 000 to 100, 000, 13,000 to

100 , 000, 14, 000 to 100, 000, 15, 000 to 100, 000, 16,000 to

100 , 000, 17, 000 to 100, 000, 18,000 to 100, 000, 19,000 to

100 , 000, 20, 000 to 100, 000, 21,000 to 100, 000, 22,000 to

100 , 000, 23, 000 to 100, 000, 24,000 to 100, 000, 25,000 to

100 , 000, 26, 000 to 100, 000, 27,000 to 100, 000, 28,000 to

100 , 000, 29, 000 to 100, 000, 30, 000 to 100, 000, 31,000 to

100 , 000, 32, 000 to 100, 000, 33, 000 to 100, 000, 34,000 to

100 , 000, 35, 000 to 100, 000, 36,000 to 100, 000, 37,000 to 100, 000, 38, 000 to 100 , 000, 39, 000 to 100, 000, 40, 000 to

100, 000, 41, 000 to 100 , 000, 42, 000 to 100, 000, 43, 000 to

100, 000, 44, 000 to 100 , 000, 45, 000 to 100, 000, 46, 000 to

100, 000, 47, 000 to 100 , 000, 48, 000 to 100, 000, 49, 000 to

100, 000, 50, 000 to 100 , 000, 51, 000 to 100, 000, 52, 000 to

100, 000, 53, 000 to 100 , 000, 54, 000 to 100, 000, 55, 000 to

100, 000, 56, 000 to 100 , 000, 57, 000 to 100, 000, 58, 000 to

100, 000, 59, 000 to 100 , 000, 60, 000 to 100, 000, 61, 000 to

100, 000, 62, 000 to 100 , 000, 63, 000 to 100, 000, 64, 000 to

100, 000, 65, 000 to 100 , 000, 66, 000 to 100, 000, 67, 000 to

100, 000, 68, 000 to 100 , 000, 69, 000 to 100, 000, 70, 000 to

100, 000, 71, 000 to 100 , 000, 72, 000 to 100, 000, 73, 000 to

100, 000, 74, 000 to 100 , 000, 75, 000 to 100, 000, 76, 000 to

100, 000, 77, 000 to 100 , 000, 78, 000 to 100, 000, 79, 000 to

100, 000, 80, 000 to 100 , 000, 81, 000 to 100, 000, 82, 000 to

100, 000, 83, 000 to 100 , 000, 84, 000 to 100, 000, 85, 000 to

100, 000, 86, 000 to 100 , 000, 87, 000 to 100, 000, 88, 000 to

100, 000, 89, 000 to 100 , 000, 90, 000 to 100, 000, 91, 000 to

100, 000, 92, 000 to 100 , 000, 93, 000 to 100, 000, 94, 000 to

100, 000, 95, 000 to 100 , 000, 96, 000 to 100, 000, 97, 000 to

100, 000, 98,000 to 100, 000 r - 99,000 to 100,000, 1 to

99,000, 1 to 98, 000, 1 to 97 , 000 r 1 to 96, 000, 1 to

95, 000, 1 to 94, 000, 1 to 93 , 000 r 1 to 92, 000, 1 to

91, 000, 1 to 90, 000, 1 to 89 , 000 r 1 to 88, 000, 1 to

87,000, 1 to 86,000, 1 to 85 , 000 r 1 to 84, 000, 1 to

83, 000, 1 to 82, 000, 1 to 81 , 000 r 1 to 80, 000, 1 to

79,000, 1 to 78,000, 1 to 77 , 000 r 1 to 76, 000, 1 to

75, 000, 1 to 74,000, 1 to 73 , 000 r 1 to 72, 000, 1 to

71,000, 1 to 70,000, 1 to 69 , 000 r 1 to 68, 000, 1 to

67, 000, 1 to 66,000, 1 to 65 , 000 r 1 to 64, 000, 1 to

63, 000, 1 to 62, 000, 1 to 61 , 000 r 1 to 60, 000, 1 to

59,000, 1 to 58, 000, 1 to 57 , 000 r 1 to 56, 000, 1 to

55, 000, 1 to 54, 000, 1 to 53 , 000 r 1 to 52, 000, 1 to

51, 000, 1 to 50, 000, 1 to 49 , 000 r 1 to 48, 000, 1 to 47,000, 1 to 46, 000, 1 to 45 , 000, 1 to 44,000, 1 to

43, 000, 1 to 42, 000, 1 to 41, 000, 1 to 40, 000, 1 to

39,000, 1 to 38, 000, 1 to 37, 000, 1 to 36, 000, 1 to

35, 000, 1 to 34, 000, 1 to 33, 000, 1 to 32, 000, 1 to

31, 000, 1 to 30, 000, 1 to 29, 000, 1 to 28, 000, 1 to

27,000, 1 to 26,000, 1 to 25, 000, 1 to 24, 000, 1 to

23, 000, 1 to 27,000, 1 to 21, 000, 1 to 20, 000, 1 to

19,000, 1 to 18,000, 1 to 17, 000, 1 to 16, 000, 1 to

15, 000, 1 to 14,000, 1 to 13, 000, 1 to 12, 000, 1 to

11,000, 1 to 10,000, 1 to 9, 000, 1 to 8, 000, 1 to 7, 000 , 1 to 6,000, 1 to 5,000, 1 to 4, 000 , 1 to 3,000 , 1 to 2,000,

1 to 1, ooc 1, i to 500, 1 to 100, or n may be 1, 100 , 500,

1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000,

10,000, 11, 000, 12, 000, 13,000, 14, 000, 15,000, 16,000,

17,000, 18, 000, 19, 000, 20,000, 21, 000, 22,000, 23, 000,

24,000, 25, 000, 26, 000, 27,000, 28, 000, 29,000, 30, 000,

31, 000, 32, 000, 33, 000, 34,000, 35, 000, 36,000, 37, 000,

38, 000, 39, 000, 40, 000, 41,000, 42, 000, 43, 000, 44,000,

45, 000, 46, 000, 47, 000, 48,000, 49, 000, 50, 000, 51, 000,

52, 000, 53, 000, 54, 000, 55, 000, 56, 000, 57, 000, 58, 000,

59,000, 60, 000, 61, 000, 62, 000, 63, 000, 64, 000, 65, 000,

66,000, 67, 000, 68, 000, 69,000, 70, 000, 71,000, 72, 000,

73, 000, 74, 000, 75, 000, 76,000, 77, 000, 78,000, 79,000,

80,000, 81, 000, 82, 000, 83,000, 84, 000, 85, 000, 86,000,

87,000, 88, 000, 89, 000, 90,000, 91, 000, 92, 000, 93, 000,

94, 000, 95 ,000 96,000 97,000, 98,000, 99, 000, or

100, 000 •

As used herrein, the term "metal catalyst" i .nc.lud.es, for example , el'emental powders, εsalts, and organometallic compounds of a metal . Exempla;cy meta.1 cata1y 'sts are transition eta 1 catalysts. The term "t ransitioin metal" describes, for example, any meta 1 in Groups III through

VII of the periodic table, for example, elements 21 through 30 (scandium through zinc) , 39 through 48 (yttrium through cadmium) , 57 through 80 (lanthanum through mercury) , and 89 through 103 (actinium through la rencium) . Useful metallic catalysts include, for example, copper, iron, gold, silver, cobalt, ruthenium, rhodium, palladium, iridium, platinum, osmium, nickel and zinc catalysts. Useful transition metals include, for example, copper (I) and copper (II) .

Any carbon or heteroatom with unsatisfied valences in the text, schemes, examples, structural formulae, and any Tables herein is assumed to have the hydrogen atom or atoms to satisfy the valences.

The word "substantially" does not exclude "completely" e.g. a composition which is "substantially free" from Y may be completely free from Y. Where necessary, the word "substantially" may be omitted from the definition of the invention.

Unless specified otherwise, the terms "comprising" and "comprise", and grammatical variants thereof, are intended to represent "open" or "inclusive" language such that they include recited elements but also permit inclusion of additional, unrecited elements.

As used herein, the term "about", in the context of concentrations of components of the formulations, typically means +/- 5% of the stated value, more typically +/- 4% of the stated value, more typically +/- 3% of the stated value, more typically, +/- 2% of the stated value, even more typically +/- 1% of the stated value, and even more typically +/- 0.5% of the stated value.

Throughout this disclosure, certain embodiments may be disclosed in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosed ranges. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

Certain embodiments may also be described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the disclosure. This includes the generic description of the embodiments with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.

Detailed Disclosure of Embodiments

Exemplary, non-limiting embodiments of the disclosed process will now be disclosed.

According to the present disclosure, there is provided a process for producing hydroxyketone by condensation of one or more aldehydes in the presence of a thiazolium salt and a base.

The thiazolium salt may be a precatalyst. The thiazolium salt may be a compound comprising a thiazolium moiety. The thiazolium salt may be of formula I:

wherein R¹ represents -alkylaryl, -alkylheteroaryl , alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl or heterocyclyl ;

R², R³ and R⁴ independently represent hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl or heterocyclyl ;

wherein each said R¹, R², R³ and R⁴ group is optionally substituted by one or more substituents; and

X^~ represents an anion.

R¹ may be an alkyl, alkenyl, or alkynyl selected from C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl such as methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, butenyl, pentenyl, hexenyl, ethynyl, propynyl, butynyl, pentynyl, or hexynyl . R¹ may be optionally substituted with one or more substituents.

R¹ may be -alkylheteroaryl selected from - alkylpyridyl , -alkylpyrazinyl, -alkylfuranyl, - alkylthienyl , -alkylpyrimidinyl , -alkylpyridone (including N-substituted pyridones) , -alkylisoxazolyl, - alkylisothiazolyl, -alkyloxazolyl, -alkylthiazolyl, - alkylpyrazolyl , -alkylfurazanyl, -alkylpyrrolyl , - alkylpyrazolyl , -alkyltriazolyl , -alkyl-1 , 2 , 4- thiadiazolyl , -alkylpyrazinyl, -alkylpyridazinyl- substituted quinoxalinyl, -alkylphthalazinyl, - alkyloxindolyl , -alkylimidazo [1, 2-a] pyridinyl, imidazo [ 2 , 1-b] thiazolyl , -alkylbenzofurazanyl , - alkylindolyl , -alkylazaindolyl, -alkylbenzimidazolyl, benzothienyl , -alkylquinolinyl , -alkylimidazolyl, - alkylthienopyridyl , -alkylquinazolinyl , - alkylthienopyrimidyl, -alkylpyrrolopyridyl , - alkylimidazopyridyl, -alkylisoquinolinyl, - alkylbenzoazaindolyl, -alkyl-1 , 2 , 4-triazinyl or - alkylbenzothiazolyl . R¹ may be optionally substituted with one or more substituents .

The alkyl group of said -alkylheteroaryl may be selected from Ci-C₆ alkyl such as methyl, ethyl, propyl, butyl, pentyl, or hexyl .

The heteroaryl group of said -alkylheteroaryl may be substituted by one or more substituents. Said substituents may be selected from the group independently selected from the group consisting of halogen, hydroxy, cyano, oxo, oxide, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy-, hydroxyalkyl-, heteroalkyl, cyanoalkyl-, alkoxy, optionally substituted aryl, optionally substituted -0- aryl, optionally substituted -O-alkyl-aryl, optionally substituted heteroaryl, optionally substituted arylalkyl-, optionally substituted arylalkoxy, optionally substituted heterocycloalkyl , optionally substituted heterocycloalkylalkyl-, optionally substituted -0- heterocycloalkyl, -N(R⁵)₂, -alkyl-N (R⁵) ₂, -NC(0)R⁵, -C(0)R⁵, -C0₂R⁵, -S0₂R⁵, -S0₂N (R⁵) ₂ and a polymer radical,

wherein said optionally substituted moieties are optionally substituted with one or more substituents selected from the group consisting of alkyl, halogen, haloalkyl, hydroxyl, -CN, -N(R⁵)₂, -H₂P0₄, and -H₃P₂0₇; wherein R⁵ represents hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl or heterocyclyl .

R¹ may be heteroaryl selected from pyridyl, pyrazinyl, furanyl, thienyl, pyrimidinyl, pyridone (including N- substituted pyridones), isoxazolyl, isothiazolyl , oxazolyl, thiazolyl, pyrazolyl, furazanyl, pyrrolyl, pyrazolyl, triazolyl, 1 , 2 , 4-thiadiazolyl , pyrazinyl, pyridazinylsubstituted quinoxalinyl , phthalazinyl, oxindolyl, imidazo [ 1, 2-a] pyridinyl, imidazo[2,l- b] thiazolyl, benzofurazanyl, indolyl, azaindolyl, benzimidazolyl, benzothienyl, quinolinyl, imidazolyl, thienopyridyl, quinazolinyl , thienopyrimidyl , pyrrolopyridyl , imidazopyridyl, isoquinolinyl , benzoazaindolyl, 1 , 2 , 4-triazinyl or benzothiazolyl . R¹ may be optionally substituted with one or more substituents .

R¹ may be -alkylaryl selected from -alkylphenyl, - alkylbiphenyl, -alkylnaphthyl, or -alkylphenanthrenyl . R¹ may be optionally substituted with one or more substituents .

The aryl group of said -alkylheteroaryl may be substituted by one or more substituents. Said substituents may be selected from the group independently selected from the group consisting of halogen, hydroxy, cyano, oxo, oxide, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy-, hydroxyalkyl-, heteroalkyl, cyanoalkyl-, alkoxy, optionally substituted aryl, optionally substituted -0- aryl, optionally substituted -O-alkyl-aryl, optionally substituted heteroaryl, optionally substituted arylalkyl-, optionally substituted arylalkoxy, optionally substituted heterocycloalkyl , optionally substituted heterocycloalkylalkyl-, optionally substituted -0- heterocycloalkyl, -N(R⁵)₂, -alkyl-N (R⁵) ₂, -NC(0)R⁵, -C(0)R⁵, -C0₂R⁵, -S0₂R⁵, -S0₂N (R⁵) ₂ and a polymer radical,

wherein said optionally substituted moieties are optionally substituted with one or more substituents selected from the group consisting of alkyl, halogen, haloalkyl, hydroxyl, -CN, -N(R⁵)₂, -H₂P0₄, and -H₃P₂0₇; wherein R⁵ represents hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl or heterocyclyl . R¹ may be aryl selected from phenyl, biphenyl, naphthyl, or phenanthrenyl . R¹ may be optionally substituted with one or more substituents .

R may be an alkyl, alkenyl, or alkynyl selected from Ci-C₆ alkyl, C₂-C₆ alkenyl, or C₂-C₆ alkynyl such as methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, butenyl, pentenyl, hexenyl, ethynyl, propynyl, butynyl, pentynyl, or hexynyl .

R" may be heteroaryl selected from pyridyl, pyrazinyl, furanyl, thienyl, pyrimidinyl, pyridone (including N- substituted pyridones), isoxazolyl, isothiazolyl , oxazolyl, thiazolyl, pyrazolyl, furazanyl, pyrrolyl, pyrazolyl, triazolyl, 1 , 2 , 4-thiadiazolyl , pyrazinyl, pyridazinylsubstituted quinoxalinyl , phthalazinyl, oxindolyl, imidazo [ 1, 2-a] pyridinyl, imidazo[2,l- b] thiazolyl, benzofurazanyl, indolyl, azaindolyl, benzimidazolyl, benzothienyl, quinolinyl, imidazolyl, thienopyridyl, quinazolinyl , thienopyrimidyl , pyrrolopyridyl , imidazopyridyl, isoquinolinyl , benzoazaindolyl, 1, 2, 4-triazinyl or benzothiazolyl .

R may be aryl selected from phenyl, biphenyl, naphthyl, or phenanthrenyl.

R² may be substituted with one or more substituents selected from the group consisting of halogen, hydroxy, cyano, oxo, oxide, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy-, hydroxyalkyl-, heteroalkyl, cyanoalkyl-, alkoxy, optionally substituted aryl, optionally substituted -O-aryl, optionally substituted -O-alkyl-aryl, optionally substituted heteroaryl, optionally substituted arylalkyl-, optionally substituted arylalkoxy, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl-, optionally substituted -0- heterocycloalkyl, -N(R⁵)₂, -alkyl-N (R⁵) ₂, -NC(0)R⁵, -C(0)R⁵, -C0₂R⁵, -S0₂R⁵, -S0₂N (R⁵) ₂ and a polymer radical, wherein said optionally substituted moieties are optionally substituted with one or more substituents selected from the group consisting of alkyl, halogen, haloalkyl, hydroxyl, -CN, -N(R⁵)₂, -H₂P0₄, and -H₃P₂0₇; wherein R⁵ represents hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl or heterocyclyl .

R^J may be an alkyl, alkenyl, or alkynyl selected from Ci-C₆ alkyl, C₂-C₆ alkenyl, or C₂-C₆ alkynyl such as methyl, ethyl, propyl, butyl, pentyl, hexyl, ethenyl, propenyl, butenyl, pentenyl, hexenyl, ethynyl, propynyl, butynyl, pentynyl, or hexynyl .

R^J may be heteroaryl selected from pyridyl, pyrazinyl, furanyl, thienyl, pyrimidinyl, pyridone (including N- substituted pyridones), isoxazolyl, isothiazolyl , oxazolyl, thiazolyl, pyrazolyl, furazanyl, pyrrolyl, pyrazolyl, triazolyl, 1 , 2 , 4-thiadiazolyl , pyrazinyl, pyridazinylsubstituted quinoxalinyl , phthalazinyl, oxindolyl, imidazo [ 1, 2-a] pyridinyl, imidazo[2,l- b] thiazolyl, benzofurazanyl, indolyl, azaindolyl, benzimidazolyl, benzothienyl, quinolinyl, imidazolyl, thienopyridyl, quinazolinyl , thienopyrimidyl , pyrrolopyridyl , imidazopyridyl, isoquinolinyl , benzoazaindolyl, 1, 2, 4-triazinyl or benzothiazolyl .

R^J may be aryl selected from phenyl, biphenyl, naphthyl, or phenanthrenyl .

R^J may be substituted with one or more substituents selected from the group consisting of halogen, hydroxy, cyano, oxo, oxide, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy-, hydroxyalkyl-, heteroalkyl, cyanoalkyl-, alkoxy, optionally substituted aryl, optionally substituted -O-aryl, optionally substituted -O-alkyl-aryl, optionally substituted heteroaryl, optionally substituted arylalkyl-, optionally substituted arylalkoxy, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl-, optionally substituted -0- heterocycloalkyl, -N(R⁵)₂, -alkyl-N (R⁵) ₂, -NC(0)R⁵, -C(0)R⁵, -C0₂R⁵, -S0₂R⁵, -S0₂N (R⁵) ₂ and a polymer radical,

X^~ represents an anion. The anion may be hydroxide, halide (i.e. fluoride, chloride, bromide or iodide), sulfate, nitrite or nitrate ions.

In one embodiment, the thiazolium salt may be of formula I :

FctraoSa I

wherein

R¹ represents -alkylaryl or -alkylheteroaryl;

R² represents alkyl;

R³ represents alkyl; and

R⁴ represents hydrogen,

wherein each said R¹, R², R³ and R⁴ group is optionally substituted by one or more substituents;

and X^~ is as defined herein.

In another embodiment, the thiazolium salt may be of formula I :

Formula I

wherein R¹ represents -alkylaryl optionally substituted with a polymer radical, or -alkylheteroaryl substituted with one or more alkyl or -N(R⁵)₂;

R² represents alkyl;

R³ represents alkyl independently substituted with hydroxyl or -H₃P₂0₇;

R⁴ represents hydrogen; and

R⁵ represents hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl or heterocyclyl .

In another embodiment, the thiazolium salt may be of formula I :

wherein R¹ represents -methylphenyl optionally substituted with a polymer radical, or -methylpyrimidine substituted with one or more methyl or -NH₂;

R² represents methyl;

R³ represents ethyl independently substituted with hydroxyl or -H₃P₂0₇; and

R⁴ represents hydrogen.

The thiazolium salt may be selected from the group consisting of:

wherein X^~ represents an anion as defined above; and n represents an integer as defined herein.

In one embodiment, the disclosed thiazoium salt maylected from the roup consisting of:

wherein n is as defined herein.

The base may be an organic or inorganic base.

The inorganic base may be an alkaline and alkaline earth metal alkoxide, alkaline and alkaline earth metal acetate, alkaline and alkaline earth metal carbonate, alkaline and alkaline earth metal bicarbonate, alkaline and alkaline earth metal hydroxide, alkaline and alkaline earth metal oxide, alkaline and alkaline earth metal phosphate, and alkaline and alkaline earth metal hydrogen phosphate, or mixtures thereof. The inorganic base may be lithium acetate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, magnesium hydroxide, barium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, lithium carbonate, calcium carbonate, magnesium carbonate, barium carbonate, sodium bicarbonate, potassium bicarbonate, sodium methoxide, potassium methoxide, sodium tertiary butoxide, potassium tertiary butoxide, or mixtures thereof.

The inorganic base may be selected from the group consisting of LiOMe, NaOMe, KOMe, LiOEt, NaOEt, KOEt, LiOAc, NaOAc, KOAc, Li₂C0₃, Na₂C0₃, K₂C0₃, CaC0₃, MgC0₃, BaC0₃, LiOH, NaOH, KOH, Ca (OH) ₂, Mg(OH)₂, Ba (OH) ₂ and mixtures thereof.

The inorganic base may be selected from the group consisting of Na₂C0₃, K₂C0₃, KOAc, NaOH, and mixtures thereof . The organic base may contain an amino group, a pyridinyl group, a derivative of a carboxylic acid, or mixtures thereof. The organic base may be pyridine, alkyl amine, morpholine, imidazole, benzimidazole, triethylamine, benzyldiethylamine, dimethylethyl amine, imidazole, salts of carboxylic acids, or mixtures thereof. The organic base may be selected from the group consisting of SB1, SB2, SB3, SB4 and SB5 :

SSB1 $82 SB3 SS4 SBS

1 Ion exchanger II, Merck, product No: 104768

² Ion exchanger III, Merck, product No: 104767 n represents an integer from 100 to 100,000.

The base may be used in its solid form, for example as a solid base. Advantageously, the solid base may be reused or recycled for subsequent reactions thereby leading to cost efficiency and convenience. The solid base may be selected from the group consisting of SB1, SB2, SB3, SB4 and SB5 as defined herein.

The solid base may be used together with a drying reagent, for example, a molecular sieve. The molecular sieve may be a crystalline metal aluminosilicate or molecular sieve Sigma-Aldrich-208604, 4A MS.

The disclosed process may also be performed in the absence of a drying reagent.

The present disclosure provides a process for producing hydroxyketone by condensation of one or more aldehydes in the presence of a thiazolium salt and an inorganic base.

Advantageously, the use of an inorganic base in the disclosed process may lead to high yields of optionally substituted hydroxyketone, for example, yields equal or greater than 85%, 90%, 95%, or 98%. Advantageously and surprisingly, the use of an inorganic base instead of an organic base may surprisingly lead to superior yields.

The present disclosure provides a process for producing hydroxyketone by condensation of one or more aldehydes in the presence of a thiazolium salt and a base selected from the group consisting of alkaline and alkaline earth metal acetates, alkaline and alkaline earth metal carbonates, alkaline and alkaline earth metal bicarbonates , alkaline and alkaline earth metal hydroxides, alkaline and alkaline earth metal oxides, alkaline and alkaline earth metal phosphates, and alkaline and alkaline earth metal hydrogen phosphates, SB1, SB2, SB3, SB4 and SB5 as defined herein, and mixtures thereof.

Advantageously, the disclosed process may be highly selective with high yields and minimal side products. The disclosed process may advantageously not require the use of multiple and overly complicated steps.

The thiazolium salt may be present at a concentration of about 0.010 rnol% to about 1.5 mol% . The thiazolium. salt may be present at a concentration of about 0.040 mol% to about 1.5 mol%, about 0.080 mol% to about 1.5 mol%, about 0,1 mol% to about 1.5 mol%, about 0.3 mol% to about 1.5 mol%, about 0.5 mol% to about 1.5 mol%, about 0.8 mol% to about 1.5 mol%, about 1.0 mol% to about 1.5 mol%, about 1.2 mol% to about 1.5 mol%, or about 0.010 mol%, about or about 0.040 mol%, or about 0.045 mol%, or about 0.080 mol%, or about 0.1 mol%, or about 0.3 mol%, or about 0.5 mol%, or about 0.8 rnol%, or about 1.0 mol%, or about 1.2 mol%, or about 1.5 mol% .

The disclosed thiazoium precatalyst may be a polymer- supported precatalyst. The polymer-supported thiazolium precatalyst may be a polystyrene-supported thiazolium precatal st. The polymer-supported thiazolium precatalyst

wherein X a anio and n is as defined herein

Ad antageously, the disclosed thiazolium precatalysts may be able to tolerate the presence of impurities in the reaction mixture, such as water or alchol. Therefore, the disclosed process may not require specific pretreatment for reactors and reagents, further contributing to cost savings and a minimally complicated process. The use; of the disclosed precatalysts in the disclosed process may further advantageously lead to high yields and high efficiency .

Advantageously, the disclosed process may require the use of only a small amount of thiazolium salt as a precatalyst, further contributing to cost-savings and an economical process.

The disclosed thiazolium precatalysts may further be recycled and reused for subsequent reaction thereby leading to cost-savings and an economical process.

The aldehyde may be a carbonyl compound. The aldehyde may be of formula II:

wherein R⁶ represents alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl or heterocyclyl,

wherein R⁶ is optionally substituted by one or more substituents . The aldehyde may be acetaldehyde and formaldehyde. The hydroxyketone may be any ketone comprising one o hydroxy groups. The hydroxyketone may be of formul

Fsfmuk HI

wherein

R⁷ and R⁹ independently represent hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl and heterocyclyl; and

R⁸ represents alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl and heterocyclyl,

wherein each said R⁷, R⁸ and R⁹ group is optionally substituted by one or more substituents .

The hydroketone may be an alpha-hydroxyketone or beta-hydroxyketone . The hydroxyketone may be of formula Ilia:

wherein R⁷ and R⁹ independently represent hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl and heterocyclyl ,

wherein each said R⁷ and R⁹ group is optionally substituted by one or more substituents. The hydroxyketone may be acetoin. In one embodiment of the disclosed process, a hydroxyketone of formula Ilia is produced by condensation of one or more aldehydes of formula II in the presence of a thiazolium salt of formula I, and a base:

Formul ;

Fo«K¾ Ola wherein

R¹ represents -alkylaryl optionally substituted with a polymer radical or -alkylheteroaryl substituted with one or more alkyl or -N(R⁵)₂;

R², R⁶, R⁷ and R⁸ independently represent alkyl;

R³ represents alkyl substituted with hydroxyl or - H₃P₂0₇;

R⁴ represents hydrogen;

R⁵ represents hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl or heterocyclyl; and the base is selected from the group consisting of Na₂CC>3, K₂CO₃, KOAc, NaOH, SB1, SB2, SB3, SB4, SB5, and mixtures thereo :

wherein n is as disclosed herein.

In another embodiment of the disclosed process, acetoin is produced by condensation of acetaldehyde in the presence of a thiazolium salt of formula I, and a base:

Formula I

wherein

R¹ represents -alkylaryl optionally substituted with a polymer radical or -alkylheteroaryl substituted with one or more alkyl or -N(R⁵)₂; R² represents alkyl;

R³ represents alkyl substituted with hydroxyl or -H3P2O7;

R⁴ represents hydrogen;

R⁵ represents hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl or heterocyclyl ; and

the base is selected from the group consisting of Na₂C0₃, K₂C0₃, KOAc, NaOH, SB1, SB2, SB3, SB4, SB5, and mixtures thereof:

wherein n is as disclosed herein.

The disclosed process may comprise the self- condensation of aldehyde to hydroxyketone.

The disclosed process may be conducted at a temperature between about 40 °C to about 200 °C. The temperature may be conducted at a temperature between about 40 °C to about 190 °C, about 40 °C to about 180 °C, about 40 °C to about 170 °C, about 40 °C to about 160 °C, about 40 °C to about 150 °C, about 40 °C to about 140 °C, about 40 °C to about 130 °C, about 40 °C to about 120 °C, about 40 °C to about 110 °C, about 40 °C to about 100 °C, about 40 °C to about 80 °C, about 40 °C to about 60 °C, about 50 °C to about 200 °C, about 60 °C to about 200 °C, about 70 °C to about 200 °C, about 80 °C to about 200 °C, about 90 °C to about 200 °C, about 100 °C to about 200 °C, about 110 °C to about 200 °C, about 120 °C to about 200 °C, about 130 °C to about 200 °C, about 140 °C to about 200 °C, about 150 °C to about 200 °C, about 160 °C to about 200 °C, about 170 °C to about 200 °C, about 180 °C to about 200 °C, about 190 °C to about 200 °C, about 70 °C to about 130 °C, about 80 °C to about 130 °C, about 90 °C to about 130 °C, about 100 °C to about 130 °C, about 110 °C to about 130 °C, about 120 °C to about 130 °C, about 70 °C to about 120 °C, about 70 °C to about 110 °C, about 70 °C to about 100 °C, about 70 °C to about 90 °C, about 70 °C to about 80 °C, about 80 °C to about 120 °C, or at a temperature of about 40 °C, about 50 °C, about 60 °C, about 70 °C, about 80 °C, about 90 °C, about 100 °C, about 110 °C, about 120 °C, about 130 °C, about 140 °C, about 150 °C, about 160 °C, about 170 °C, about 180 °C, about 190 °C, or about 200 °C.

The disclosed process may be conducted for a period of about 50 minutes to about 24 hours. The disclosed process may be conducted for a period of about 50 minutes to about 480 minutes, about 60 minutes to about 480 minutes, about 80 minutes to about 480 minutes, about 100 minutes to about 480 minutes, about 120 minutes to about 480 minutes, about 140 minutes to about 480 minutes, about 160 minutes to about 480 minutes, about 180 minutes to about 480 minutes, about 200 minutes to about 480 minutes, about 220 minutes to about 480 minutes, about 240 minutes to about 480 minutes, about 260 minutes to about 480 minutes, about 280 minutes to about 480 minutes, about 300 minutes to about 480 minutes, about 320 minutes to about 480 minutes, about 340 minutes to about 480 minutes, about 360 minutes to about 480 minutes, about 380 minutes to about 480 minutes, about 400 minutes to about 480 minutes, about 420 minutes to about 480 minutes, about 440 minutes to about 480 minutes, about 460 minutes to about 480 minutes, about 50 minutes to about 460 minutes, about 50 minutes to about 440 minutes, about 50 minutes to about 420 minutes, about 50 minutes to about 400 minutes, about 50 minutes to about 380 minutes, about 50 minutes to about 360 minutes, about 50 minutes to about 340 minutes, about 50 minutes to about 320 minutes, about 50 minutes to about 300 minutes, about 50 minutes to about 280 minutes, about 50 minutes to about 260 minutes, about 50 minutes to about 240 minutes, about 50 minutes to about 220 minutes, about 50 minutes to about 200 minutes, about 50 minutes to about 180 minutes, about 50 minutes to about 160 minutes, about 50 minutes to about 140 minutes, about 50 minutes to about 120 minutes, about 50 minutes to about 100 minutes, about 50 minutes to about 80 minutes, about 50 minutes to about 60 minutes, about 50 minutes to about 460 minutes.

The disclosed process may be conducted for a period in a range of about 50 minutes to about 24 hours, about 50 minutes to about 22 hours, about 50 minutes to about 20 hours, about 50 minutes to about 18 hours, about 50 minutes to about 16 hours, about 50 minutes to about 14 hours, about 50 minutes to about 12 hours, about 50 minutes to about 10 hours, about 50 minutes to about 8 hours, about 50 minutes to about 6 hours, about 50 minutes to about 4 hours, about 50 minutes to about 2 hours, about 1 hour to about 24 hours, about 2 hours to about 24 hours, about 4 hours to about 24 hours, about 6 hours to about 24 hours, about 8 hours to about 24 hours, about 10 hours to about 24 hours, about 12 hours to about 24 hours, about 14 hours to about 24 hours, about 16 hours to about 24 hours, about 18 hours to about 24 hours, about 20 hours to about 24 hours, about 22 hours to about 24 hours, or about 50 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, about 12 hours, about 13 hours, about 14 hours, about 15 hours, about 16 hours, about 17 hours, about 18 hours, about 19 hours, about 20 hours, about 21 hours, about 22 hours, about 23 hours or about 24 hours.

The disclosed process may further comprise the step of obtaining the aldehyde from an alcohol. The alcohol may be a Ci to C6 alcohol, for example, methanol, ethanol, propanol, butanol, pentanol, hexanol .

The present disclosure provides a process for obtaining acetoin, comprising the steps of:

a) obtaining acetaldehyde from ethanol; and

The disclosed process may be conducted at a temperature between about 80 °C to about 120 °C, or at about 80 °C, about 85 °C, about 90 °C, about 95 °C, about 100 °C, about 105 °C, about 110 °C, about 115 °C or about 120 °C.

The disclosed process may be conducted for a period in the range of about 50 minutes to about 480 minutes, about 400 minutes to about 480 minutes, about 420 minutes to about 480 minutes, about 440 minutes to about 480 minutes, about 460 minutes to about 480 minutes, about 50 minutes to about 460 minutes, about 50 minutes to about 440 minutes, about 50 minutes to about 420 minutes, about 50 minutes to about 400 minutes, about 50 minutes to about 380 minutes, about 50 minutes to about 360 minutes, about 50 minutes to about 340 minutes, about 50 minutes to about 320 minutes, about 50 minutes to about 300 minutes, about 50 minutes to about 280 minutes, about 50 minutes to about 260 minutes, about 50 minutes to about 240 minutes, about 50 minutes to about 220 minutes, about 50 minutes to about 200 minutes, about 50 minutes to about 180 minutes, about 50 minutes to about 160 minutes, about 50 minutes to about 140 minutes, about 50 minutes to about 120 minutes, about 50 minutes to about 100 minutes, about 50 minutes to about 80 minutes, about 50 minutes to about 60 minutes, about 50 minutes to about 460 minutes.

The disclosed process may require about 0.040 mol%, about 0.045 mol%, about 0.1 mol%, about 0.3 mol%, about 0.5 mol%, or about 1.0 mol% of the disclosed thiazolium salt.

a) obtaining acetaldehyde from ethanol; and b) producing acetoin by self-condensation of acetaldehyde in the presence of about 0.040 mol% to about 1.0 mol% thiazolium salt and a base,

wherein the thiazolium salt is selected from the group consisting of:

1.1 the base is selected from the group consisting of Na₂C0₃, K₂C0₃, KOAc, NaOH, SB1, SB2, SB3, SB4, SB5, and mixtures th reof :

wherein n represents an integer 100 to 100,000, and wherein the process is conducted at a temperature between about 80 °C and 120 °C for a time period between about 50 minutes to about 4 hours.

Advantageously, the reaction systems comprising the precatalysts 1, 2, 9, 10 and 11 together with a base selected from the group consisting of Na₂CC>3, K₂CO₃, KOAc, NaOH, SB1, SB2, SB3, SB4, and SB5 may be tolerant to impurities such as water and ethanol . Therefore, the disclosed process may not require specific pretreatment for reactors and reagents, further contributing to cost savings and a minimally complicated process.

Advantageously, precatalysts 1, 2, 9, 10 and 11 may be reused for subsequent reactions thereby advantageously leading to cost efficiency and convenience.

The use of the precatalysts 1, 2, 9, 10 and 11 together with a base selected from the group consisting of Na₂C0₃, K₂C0₃, KOAc, NaOH, SB1, SB2, SB3, SB4, and SB5 at a temperature between about 80 °C and 120 °C for a time period between about 50 minutes to about 4 hours in the disclosed process may advantageously lead to high yields of hydroxyketone, for example yields equal or greater than 85%, 90%, 95%, or 98%.

The use of the precatalysts 1, 2, 9, 10 and 11 together with a base selected from the group consisting of Na₂C0₃, K₂CO₃, KOAc, NaOH, SB1, SB2, SB3, SB4, and SB5 at a temperature between about 80 °C and 120 °C for a time period between about 50 minutes to about 4 hours in the disclosed process may advantageously lead to minimal side products and not require the use of multiple and overly complicated steps.

Solid bases SB1, SB2, SB3, SB4, and SB5 may be reused or recycled in the disclosed process for subsequent reactions thereby leading to cost efficiency and convenience.

The acetoin may further be converted to a vinyl ketone or diol .

The base may be as defined herein.

The disclosed process may be useful in converting a lower alcohol to higher carbon chemicals. For example, the disclosed process may be useful in converting ethanol to C4 bulk chemicals, such as 2, 3-butadiol, methylethylketone, methylvinylketone and butenes.

Scheme 1. Ethanol upgrading to C4 bulk chemicals via acetoin condensation

The disclosed hydroxyketone may be a a stable and flexible intermediate that can be converted to many C4 bulk chemicals, such as 2,3-butadiol and methylvinylketone (MVK) . The h droxyketone ma be acetoin.

O

MEK byterse

9S 94% Scheme 2. Transformations from acetoin to other C4 industrial chemicals

The present disclosure also provides for hydroxyketone obtained by a disclosed process.

The present disclosure also provides for a thiazolium salt of the following formula:

wherein X and n are as defined herein.

Examples

Non-limiting examples of the invention and a comparative example will be further described in greater detail by reference to specific Examples, which should not be construed as in any way limiting the scope of the invention . Experimental

Materials

SB1, Poly ( 4-vinylpyridine ) , Sigma-Alrich, product No: 547697-100G; SB2, Ion exchanger II, Merck, product No: 104768; SB3, Ion exchanger III, Merck, product No: 104767; SB4, Silica bond diethylamine, SiliCycle, product No: R76530B; SB5, Poly (acrylic acid sodium salt), Sigma- Alrich, product No: 447013-100G; Molecular sieve from Sigma-Aldrich-208604, 4A MS.

General procedure for acetoin formation via condensation of acetaldehyde

To a 4 mL thick wall glass tube with stirring bar was added precatalyst, base, and acetaldehyde. The tube was then sealed. After the reaction mixture was stirred at the indicated temperature and time, the mixture was cooled to room temperature and part of it was transferred to a NMR tube for ¹R NMR analysis. The Spectrum is consisent with the analytical standard purchased (Sigma-Aldrich) .

1H NMR (400 MHz, CDC1₃) δ 4.58 (br, 1H) , 4.23 (q, J = 7.2 Hz, 1H) , 2.20 (s, 3H), 1.32 (d, J = 7.2 Hz, 3H) . ynthesis of polystyrene supported thiazolium salt 11

To a dried two-necked round flask with a condensor was added (chloromethyl) polystyrene (1.8 g, 9.9 rranol) , anhydrous acetonitrile (30 mL) , dioxane (30 mL) and 4- methyl-5-thiazoleethanol (2.85 mL, 3 equiv.) . The mixture was refluxed for 2 days. Filtration was performed to remove unreacted 4-methyl-5-thiazoleethanol and solvents. The solid was then washed with acetonitrile (10 mL) , dioxane (10 mL) and ethanol (10 mL) . After it was dried in vacuum, the precatalyst 11 was ready for use (3.036g, loading of precatalyst : 2.84 mmol/g) .

General procedure for recycle experiments

To a 4 mL thick wall dry glass tube with stirring bar was added precatalyst, base, and acetaldehyde . The tube was then sealed. After the reaction mixture was stirred at the indicated temperature and time, the mixture was cooled to room temperature and kept standing for 2 hours. Part of it was then transferred to a NMR tube for ¹H NMR analysis and the rest was decanted to another tube using a dropper, with the solid mixture at the bottom. Another 2 mL acetaldehyde was added into the tube and it was sealed immediately for a second run.

General procedure for conversion of 2,3-diol to butene

In a 8 ml flame dried heavy-wall sealed tube with stirring bar was charged with 2 , 3-butanediol (70 mg, 0.78 mmol) and CH₃Re0₃ (MTO) (10 mg, 0.04 mmol) . Under an argon atmosphere, 3-octanol (5 ml) was added. The reaction was conducted for 1 hour at 180 °C. After cooling to room temperature, an internal standard (mesitylene (20 \i^~L, 0.14 mmol) ) was added to the reaction mixture for a ¹H NMR measurement. A mixture of trans/cis butene was obtained in a 94% combined yield.

¹H NMR (400 MHz, CDC1₃) δ 5.33-5.40 (m, 1H) , 1.50-1.53 (m, 3H) .

Procedures for conversion MVK to MEK

In a 10 ml reaction flask with stirring bar was added methylvinylketone (MVK) (85 μΐ, ~ 1 mmol) and 10% Pd/C (53 mg, 0.05 mmol) in CH₂CI₂ (3 ml) was added. The reaction was stirred under ¾ (~ 1.1 atm) , which was charged with a balloon. After 1 hour, ¹H NMR measurement indicated a full conversion of MVK into methylethylketone (MEK) .

¹H NMR (400 MHz, CDCI₃) δ 2.40 (q, J = 7.2 Hz, 2H) , 2.13 (s, 3H) , 1.04 (t, J = 7.2 Hz, 3H) .

Example 1: Results of various precatalysts in acetoin formation via self-condensation of acetaldehyde

2

K, - R.. 4

Various precatalysts were screened in acetoin condensation reactions in neat acetaldehyde in the presence of sodium carbonate or potassium carbonate (Table 1).

Surprisingly, the production of acetoin was not observed with most of screened precatalysts probably due to poor solubility of precatalysts and inorganic bases. The precatalysts ( 5a-5d and 6a, b) with imidazolium skeleton were generally inert for the reaction (entries 6-11, Table 1), while the triazolium precatalyst 8 was too reactive so that very poor selectivity was observed (entry 13, Table 1) . The imidazolinelium precatalyst 3a showed promising results with 17% acetoin yield (entry 3, Table 1) . However, under higher temperature, the selectivity suffered (entry 18, Table 1) . No better result was achieved in further screening of other precatalysts ( 3a, 3b, 4 and 7 ) with the imidazolinelium skeleton (entries 3-5 and 12, Table 1). Surprisingly, the thiazolium precatalysts of the present invention (1, 2, 9 and 10) proved to be more suitable for the acetaldehyde self-condensation reaction. Excellent yields could be obtained in a clean manner by elevating the temperature to 80 °C (50 min to 4h) with 1 mol% precatalyst 1, or 2 or 10 (entries 1, 2 and 14-18, Table 1) .

Table 1

Reaction conditions: A mixture of precatalyst (0.035 mmol) , Na_∑C0₃ (0.05 mmol) and 2 mL acetaldehyde (35.5 mmol) were stirred in a sealed tube at the room temperature for 16h. ^b K₂CO₃ (0.035 mmol ) was used. ^c Reaction was run for 2 days. ^d Some complex by-products were observed. ^e Reaction was run at 80 °C for 4 hours. ^f Reaction was run at 80 °C for 50 mins in the presence of K₂CO₃ (0.035 mmol ) . ⁹ Reaction was run at 60 °C for 4 hours. Example 2 : Base screening for catalyzed acetoin reaction

Although there are reported works in which acetoin could be achieved in yield of up to 68% with 5 mol% precatalyst 1 and 30 mol% Et₃ in absolute ethanol, our control experiment results indicated that lower loading of precatalyst 1 and Et3 (or other organic base such as DBU) (both in 1 mol%) led to poor efficiency, in which only less than 50% acetoin was obtained, together with other side products (entries 1 and 2, Table 2) . However, it was found that the inorganic bases including K₂CO₃, Na₂CC>3, KOAc and NaOH advantageously and surprisingly worked well for this reaction (entries 3-5, Table 2) . Similar phenomenon was also observed in the reaction with precatalyst 2. As shown in Table 2, the use of organic bases such as DBU, DIPEA and triethylamine gave no desired product besides some side products (entries 6-8, Table 2) .

Table 2

a Reaction conditions: A mixture of precatalyst (0.035 mmol) , base (0.035 mmol) and 2 mL acetaldehyde (35.5 mmol) was stirred in a sealed dried tube at indicated temperatures . ^b Complex by-products were observed. ^c No product was detected.

Example 3 : Water and ethanol tolerances of precatalyst

In the process of upgrading bioethanol to C4 chemicals, ethanol was first dehydrogenated/oxidized to acetaldehyde . Thus, ethanol and water residues are inevitable in the acetaldehyde feedstock. The tolerance to ethanol and water was measured in acetoin reaction with precatalyst 1 and 2. As shown in Table 3, with precatalyst 1, the existence of ethanol (up to 13 wt%) had little influence on the reaction (entries 1-3, Table 3) . Precatalyst 2 could tolerate up to 2.5 wt% of ethanol impurity without compromising on the reactivity (entries 4- 6, Table 3) . Both catalystic systems were not sensitive toward moisture. Advantageously, the reactions could be set up without specific pretreatments for reactors and reagents. For precatalyst 2, there was almost no influence on the reaction with no more than 3 wt% of water in the system (entries 7-8, Table 3) . The good tolerancy of precatalysts 1 and 2 make them very suitable for an ethanol upgrading process.

Table 3

Entri Precatal Base Ethan Wate Temp Time Yield es yst (mol%) ol r (°C) (min (%)

(mol%) (wt%) (wt% s)

)

3 1 (1) NaOH (1) 13 - 80 50 95

4 2 (1) Na₂C0₃ 80 120 62

(1.3)

5 2 (1) Na₂C0₃ 2 80 120 57

(1.3)

6 2 (1) Na₂C0₃ 5 80 120 36

(1.3)

7 2 (1) Na₂C0₃ 100 240 92

(1.3)

8 2 (1) Na₂C0₃ 3 100 240 86

(1.3)

9 2 (1) Na₂C0₃ 11 100 240 60

(1.3)

Reaction conditions: A mixture of precatalyst (0.035 mmol) , sodium carbonate (or potassium carbonate) (0.035 mmol or 0.045 mmol), ethanol (0.1 mL to 0.3 mL) and 2 mL acetaldehyde (35.5 mmol) was stirred in a sealed tube (without pre-drying) at different temperature .

Example 4 : Effect of temperature and precatalyst loading

In order to minimize the cost for potential industrial application, further optimization by elevating reaction temperature and decreasing the loading of the three best precatalysts 1, 2 and 10 were investigated. It was found that in larger scale (20 mL) , the reaction was completed at 80 °C in 4 hours yielding 97% acetoin with 1 mol% precatalyst 2 loaded, and almost no side product was obsereved (entry 1, Table 4) . Higher temperature could accelerate the reaction albeit with more impurities (entry 2, Table 4) . Comparable yield could also be achieved with precatalyst 10 in the presence of much less base (entry 4, Table 4) . However, for both precatalyst 2 and 10, more than 0.5 mol% loading was used to push the reaction to completion as well as to suppress the competitive pathways

(entries 2, 3 and 5, Table 4) . On the other hand, much higher TON could be achieved for precatalyst 1. In a larger scale test (34g and 78g) , with 0.1 mol% or 0.045 mol% precatalyst 1/sodium hydroxide, acetoin yields up to 98%

(TON 980) and 85% (TON 1888) were achieved respectively.

Table 4

Entry Precatalyst Base Scale Temp Time Yield TON

(mol%) (mol%) mL <°C) (h) (%)

9 1(0.045) ^c NaOH 100 120 15 85 1888

(0.06)

a Reaction conditions : A mixture of precatalyst, sodium carbonate (or potassium carbonate) , and acetaldehyde was stirred in a sealed dry tube at different temperature . ^b'By^¬ products were detected. ^c The reactors were used without drying.

Example 5: Acetoin formation with solid catalyst or solid bases

SB1 SB2 S£B SB SB5 Polystyrene supported thiazolium precatalyst 11 was prepared for the purpose of catalyst seperation and recycling. Several solid bases were applied for this acetoin formation reaction (Scheme 2, Table 6) . Precatalyst 1 with solid bases SB1, SB2 and SB3 did not give promising results even under dry conditions, but gave excellent results (> 95% acetoin yield) when dry reagent (MS) was used in the systems, probably due to the high water content in the commercial solid bases. Interestingly, precatalyst 1 with weak solid bases SB4 and SB5 gave excellent acetoin yield (98%) without any dry reagent. The catalyst could be recycled together with solid bases although there is some deactivation observed for the recycled catalysts (entries 4-8, Table 5) . The activity of solid precatalyst 11 is relatively lower than precatalyst 1 (entries 9-14, Table 5) . Table 5

Reaction condition: A mixture of precatalyst (0.035 mmol) , base and 2 mL acetaldehyde (35.5 mmol) was stirred in a sealed tube at indicated temperatures . ^a 200 mg of ion exchanger resin was used in the presence of 300 mg of 4A MS. ^b Scale up to 8 mL acetaldehyde . ^c'By-products were detected.

Example 6 : Acetaldehyde from ethanol

Precatalysts 1 and 2 were tested with fresh acetaldehyde from ethanol by oxidation. A CuO/SiC>2 (SBA-16) catalyst was used for ethanol oxidization in a fix bed reaction system. Acetaldehyde (4 g scale, 83% of acetaldehyde with unreacted ethanol as major impurity) was collected and used as feedstock for the acetoin condensation reaction. Surprisingly, 99% of acetoin yield was achieved with 1 mol% of precatalyst 1 in the presence of dry K₂C0₃. A similar result was observed when applying 1 mol% precatalyst 2 in the presence of unpretreated Na₂CC>3, leading to a 95% conversion of as-prepared acetaldehyde exclusively to acetoin. This result demonstrated that the disclosed thiazolium precatalysts are suitable for an ethanol to C4 chemical upgrading process.

Acetoin is a stable and flexible intermediate that can be converted to many C4 bulk chemicals, such as 2,3- butadiol and methylvinylketone (MVK) . Herein, the transformations of 2,3-butadiol to butene via deoxydehydration (DODH) and methylvinylketone (MVK) to methylethylketone (MEK) via hydrogenation reaction with Pd/C as catalyst were also demonstrated (Scheme 2) . Excellent yields for both transformations were achieved.

Scheme 2 Applications

The disclosed process may be highly selective with high yields and minimal side products.

The disclosed process may require the use of only a small amount of thiazolium salt as a precatalyst, thus leading to a cost efficient process. The thiazolium salt may be advantageously highly tolerant to impurities such as water. Therefore, the disclosed process may not require specific pretreatment for reactors and reagents, further contributing to cost savings and a minimally complicated process .

The disclosed process may only require a small amount of thiazolium salt precatalyst which may also be recycled thereby leading to cost efficiency and convenience..

The disclosed process may not require the use of multiple and overly complicated steps.

It will be apparent that various other modifications and adaptations of the invention will be apparent to the person skilled in the art after reading the foregoing disclosure without departing from the spirit and scope of the invention and it is intended that all such modifications and adaptations come within the scope of the appended claims.

Claims

A process for producing hydroxyketone condensation of one or more aldehydes in presence of a thiazolium salt and a base,

wherein said thiazolium salt is of formula

wherein

R¹ represents -alkylaryl, -alkylheteroaryl, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl or heterocyclyl;

R², R³ and R⁴ independently represent hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl or heterocyclyl;

X^~ represents an anion. 2. A process according to claim 1, wherein each R¹,

R², R³ and R⁴ group is unsubstituted or substituted with one or more substituents, which may be the same or different, each independently selected from the group consisting of halogen, hydroxy, cyano, oxo, oxide, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy-, hydroxyalkyl-, heteroalkyl, cyanoalkyl-, alkoxy, optionally substituted aryl, optionally substituted -O-aryl, optionally substituted -O-alkyl-aryl, optionally substituted heteroaryl, optionally substituted arylalkyl-, optionally substituted arylalkoxy, optionally substituted heterocycloalkyl , optionally substituted heterocycloalkylalkyl-, optionally substituted -O-heterocycloalkyl, -N(R⁵)₂, -alkyl- N(R⁵)₂, -NC(0)R⁵, -C(0)R⁵, -C0₂R⁵, -S0₂R⁵, -S0₂N(R⁵)₂ and a polymer radical,

wherein said optionally substituted moieties are optionally substituted with one or more substituents selected from the group consisting of alkyl, halogen, haloalkyl, hydroxyl, -CN, -N(R⁵)₂, -H₂P0₄, -H₃P₂0₇; and

R⁵ represents hydrogen, alkyl, alkenyl, alkynyl, arbocyclyl, aryl, heteroaryl or heterocyclyl .

The process according to any one of the preceding claims, wherein:

R¹ represents -alkylaryl or -alkylheteroaryl;

R² represents alkyl;

R³ represents alkyl; and

R⁴ represents hydrogen,

wherein each said R¹, R², R³ and R⁴ group is optionally substituted by one or more substituents .

The process according to any one of the preceding claims, wherein:

R¹ represents -alkylaryl optionally substituted with a polymer radical, or -alkylheteroaryl substituted with one or more alkyl or -N(R⁵)₂; R² represents alkyl;

R³ represents alkyl independently substituted with hydroxyl or -H₃P₂C>7;

R⁴ represents hydrogen; and R represents hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl or heterocyclyl .

5. The process according to any one of the preceding claims, wherein the thiazolium salt is selected from the group consisting of:

wherein n represents an integer between 1 to 100, 000.

6. The process according to any one of the preceding claims, wherein the base is an inorganic base.

7. The process according to claim 6, wherein the inorganic base is selected from the group consisting of alkaline and alkaline earth metal alkoxides, alkaline and alkaline earth metal acetates, alkaline and alkaline earth metal carbonates, alkaline and alkaline earth metal bicarbonates , alkaline and alkaline earth metal hydroxides, alkaline and alkaline earth metal oxides, alkaline and alkaline earth metal phosphates, alkaline and alkaline earth metal hydrogen phosphates, and mixtures thereof. 8. The process according to any one of claims 6 or 7, wherein the inorganic base is selected from the group consisting of LiOMe, NaOMe, KOMe, LiOEt, NaOEt, KOEt, LiO-tBu, NaO-tBu, KO-tBu, LiOAc, NaOAc, KOAc, Li₂C0₃, Na₂C0₃, K₂C0₃, CaC0₃, MgC0₃, BaC0₃, LiOH, NaOH, KOH, Ca (OH) ₂, Mg (OH) ₂, Ba (OH) ₂ and mixtures thereof .

9. The process according to claim 8, wherein the inorganic base is selected from the group consisting of Na₂C0₃, K₂C0₃, KOAc, NaOH, and mixtures thereof.

10. The process according to any one of claims 1 to 5, wherein the base is an organic base.

11. The process according to claim 10, wherein the organic base is selected from the group consisting of SB1, SB2, SB3, SB4, SB5, and mixtures thereof:

wherein n represents 100 to 100,000

12. The process according to any one

preceding claims, wherein the aldehyde formula II :

wherein R⁶ is optionally substituted by one or more substituents .

13. The process according to according to any one of the preceding claims, wherein the aldehyde is selected from the group consisting of acetaldehyde and formaldehyde.

14. The process according to according to any one of the preceding claims, wherein the hydroxyketone is of formula III:

wherein

R⁸ represents alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl and heterocyclyl, wherein each said R⁷, R⁸ and R⁹ group is optionally substituted by one or more substituents . 15. The process according to any one of the preceding claims, wherein the hydroxyketone is selected from the group consisting of alpha- hydroxyketone or beta-hydroxyketone . 16. The process according to according to any one of the preceding claims, wherein the hydroxyketone is of formula Ilia:

wherein R⁷ and R⁹ independently represent hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heteroaryl and heterocyclyl,

wherein each said R⁷ and R⁹ group is optionally substituted by one or more substituents. 17. The process according to any one of the preceding claims, wherein the hydroxyketone is acetoin .

18. The process according to claim 1, wherein a hydroxyketone of formula Ilia is produced by condensation of one or more aldehydes of formula II in the presence of a thiazolium salt of formula I, and a base:

Formul ;

wherein

R¹ represents -alkylaryl optionally substituted with a polymer radical or -alkylheteroaryl substituted with one or more alkyl or -N(R⁵)₂; R², R⁶, R⁷ and R⁸ independently represent alkyl; R³ represents alkyl substituted with hydroxyl or -H3P2O7;

R⁴ represents hydrogen;

the base is selected from the group consisting of Na₂C0₃, K₂CO₃, KOAc, NaOH, SB1, SB2, SB3, SB4, SB5, and mixtures thereof:

wherein n represents an integer from 100 to 100, 000.

19. The process according to claim 18, wherein acetoin is produced by condensation of acetaldehyde in the presence of a thiazolium salt of formula I, and a base:

wherein

R³ represents alkyl substituted with hydroxyl or -H3P2O7;

R⁴ represents hydrogen;

wherein n represents an integer from 100 to 100, 000. 20. The process according to any one of claims 2 to

19, wherein the polymer radical is selected from the group consisting of a polystyrene radical.

21. The process according to any one of claims 18 to 20, wherein the thiazolium salt is selected from the group consisting of:

22. The process according to any one of the preceding claims, wherein the hydroxyketone is formed by self-condensation of the aldehyde.

23. The process according to any one of the preceding claims, which is conducted at a temperature between 40 °C to 200 °C.

24. The process according to any one of the preceding claims, which is conducted for a period between 50 minutes to 24 hours.

25. The process according to any one of the preceding claims, wherein the thiazolium salt is present at a concentration of between 0.01 mol% to 1.5 mol%.

26. The process according to any one of the preceding claims, comprising the step of obtaining the aldehyde from an alcohol. 27. The process according to claim 26, wherein the aldehyde is obtained by oxidizing the alcohol in the presence of a metal catalyst.

28. A process for obtaining acetoin, comprising the steps of:

c) obtaining acetaldehyde from ethanol; and

d) producing acetoin by self-condensation of acetaldehyde in the presence of a thiazolium salt as defined in any one of claims 1 to 5 and a base.

The process according to claim 28, further comprising the step of converting acetoin to a vinyl ketone or diol.

30. The process according to any one of claims 28 to 29, wherein the base is as defined in any one of claims 6 to 11.

31. Hydroxyketone obtained by the process according to any one of the preceding claims.

32. A thiazolium salt of the following formula:

wherein X is an anion and n represents an integer from 1 to 100,000.