阅读说明：本技术 一氧化氮作为不饱和化合物的顺式/反式异构化催化剂 (Nitric oxide as a catalyst for cis/trans isomerization of unsaturated compounds ) 是由 雷奈·托拜厄斯·史德姆勒 纳丁·格雷纳 安吉拉·维尔德曼 于 2013-12-18 设计创作，主要内容包括：本发明涉及一氧化氮作为不饱和化合物的顺式/反式异构化催化剂,使不饱和化合物A顺式/反式异构化的方法,所述化合物A选自由不饱和酮、不饱和缩酮、不饱和醛、不饱和缩醛、不饱和羧酸、不饱和羧酸酯和不饱和羧酸酰胺组成的组。已观察到：所述异构化非常有效且快速。(The present invention relates to a process for cis/trans isomerization of an unsaturated compound a selected from the group consisting of an unsaturated ketone, an unsaturated ketal, an unsaturated aldehyde, an unsaturated acetal, an unsaturated carboxylic acid ester and an unsaturated carboxylic acid amide, with nitric oxide as a cis/trans isomerization catalyst for the unsaturated compound. It has been observed that: the isomerization is very efficient and fast.)

1. A process for cis/trans isomerization of an unsaturated compound a selected from the group consisting of unsaturated ketones, unsaturated ketals, unsaturated aldehydes, unsaturated acetals, unsaturated carboxylic acids, unsaturated carboxylic acid esters, unsaturated carboxylic acid amides and unsaturated alcohols, said process comprising the steps of:

a) Providing a cis or trans isomer of unsaturated compound a;

b) Adding nitric oxide to the cis or trans isomer of the unsaturated compound a of step a);

c) Heating the mixture of nitric oxide and the cis-or trans-isomer of the unsaturated compound a to a temperature between 10 ℃ and the boiling point of the unsaturated compound a, in particular between 20 ℃ and the boiling point of the unsaturated compound a;

Thereby producing a mixture of cis/trans isomers of the unsaturated compound a;

Characterized in that the unsaturated compound A has at least one prochiral carbon-carbon double bond and no conjugated carbon-carbon double bond.

2. a method according to claim 1, characterized in that: the unsaturated compound A is unsaturated ketone or unsaturated ketal or unsaturated aldehyde or unsaturated acetal or unsaturated alcohol.

3. Method according to any of the preceding claims, characterized in that: introducing the nitric oxide to the unsaturated compound A at atmospheric pressure or at most 1MPa overpressure.

4. A method according to claim 3, characterized in that: said overpressure is equal to 10 to 300 kPa.

5. method according to any of the preceding claims, characterized in that: the nitric oxide is added in step b) as a gas mixture with at least one other gas, preferably with an inert gas, most preferably with nitrogen.

6. The method according to claim 5, characterized in that: the amount of said nitric oxide in said gas mixture is in the range of 10-60 wt.%.

7. Method according to any of the preceding claims, characterized in that: the unsaturated compound A has the formula (I) or (II) or (IID) or (IIE)

wherein Q represents H or CH₃M and p represent, independently of one another, a value from 0 to 3 with the proviso that: the sum of m and p is 0 to 3;

Wherein the wavy line represents a carbon-carbon bond that is linked to an adjacent carbon-carbon double bond such that said carbon-carbon double bond is either in the Z-configuration or in the E-configuration, wherein the substructures in formulae (I) and (II) and (IID) and (IIE) represented by s1 and s2 may be in any order;

and wherein the formulae (I) and (II) and (IID) and (IIE) have the dotted line thereinThe double bond of (a) represents a single carbon-carbon bond or a double carbon-carbon bond;

And whereinRepresenting the stereocenter.

8. A process for producing a specific cis-isomer and a specific trans-isomer of an unsaturated compound A, respectively, from a mixture of cis-and trans-isomers of the unsaturated compound A, the unsaturated compound A being selected from the group consisting of an unsaturated ketone, an unsaturated ketal, an unsaturated aldehyde, an unsaturated acetal, an unsaturated carboxylic acid ester, an unsaturated carboxylic acid amide and an unsaturated alcohol, the process comprising the steps of

i) Providing a mixture of cis-isomer and trans-isomer of the unsaturated compound A, wherein the weight of the cis-isomer is W_{Cis form}And the weight of the trans isomer is W_{Trans form}；

ii) addition of nitric oxide

iii) heating the mixture to a temperature T_iso1the temperature is the isomer I_lbpThe boiling point of, the isomer I_lbphaving the lowest boiling point of the cis/trans isomer mixture of step i);

iv) distilling off the isomer I_lbpAnd collecting said isomer I_lbp；

v) cis/trans isomerization in the presence of said nitric oxide added in step ii) has a higher degree of isomerization than said isomer I_lbpHigher boiling isomer I_hbp；

Wherein step ii) may occur before, during or after steps iii) and/or iv); and wherein, after step v), steps ii), iii), iv) and v) are subsequently repeated

And wherein, if isomer I is collected_lbpIs the cis isomer of the unsaturated compound A, all of the collected isomers I_lbpIs higher than W_{Cis form}；

Or

If isomer I is collected_lbpIs the trans isomer of the unsaturated compound A, all of the collected isomers I_lbpIs higher than the total weight of W_{Trans form}；

And wherein the weight W_{Cis form}And weight W_{Trans form}Respectively 0 g to 10 tons with the proviso that W_{Cis form}And W_{Trans form}is greater than 70/30 or less than 30/70, with the proviso that W_{Cis form}And W_{Trans form}Both are not 0 grams;

Characterized in that the unsaturated compound A has at least one prochiral carbon-carbon double bond and no conjugated carbon-carbon double bond.

9. the method of claim 8, wherein: the collected isomer I_lbpThe weight of the isomer is higher than W_{Cis form}And W_{Trans form}80% by weight of the sum, preferably higher than W_{Cis form}And W_{Trans form}90% by weight of the sum.

10. A process for producing a specific cis-isomer and a specific trans-isomer of an unsaturated compound A, respectively, from a mixture of cis-and trans-isomers of the unsaturated compound A, the unsaturated compound A being selected from the group consisting of an unsaturated ketone, an unsaturated ketal, an unsaturated aldehyde, an unsaturated acetal, an unsaturated carboxylic acid ester, an unsaturated carboxylic acid amide and an unsaturated alcohol, the process comprising the steps of

a) Providing a mixture of cis-isomer and trans-isomer of the unsaturated compound A, wherein the weight of the cis-isomer is W_{Cis form}And the weight of the trans isomer is W_{Trans form}；

b) Adding nitric oxide

c) Heating the mixture to a temperature T_iso1The temperature is the isomer I_lbpThe boiling point of, the isomer I_lbpHaving the lowest boiling point of the cis/trans isomer mixture of step a);

d) Distilling off the isomer I_lbp

e) Isolation of the particular isomer I from the residue of step d)_hbpThe isomer I_hbpHaving a ratio to said isomer I_lbpHigher boiling point and collecting said isomer I_hbp；

f) Cis/trans isomerisation of the isomer I in the presence of the nitric oxide added in step b)_lbpAnd the remainder of step e) (if present after step e));

Wherein step b) may occur before, during or after steps c) and/or f); and wherein, after said step f), said steps b), c), d), e) and f) are subsequently repeated

And wherein, if isomer I is collected_hbpIs the cis isomer of the unsaturated compound A, the collected isomer I_hbpIs higher than W_{Cis form}；

Or

If isomer I is collected_hbpIs the trans isomer of the unsaturated compound A, the collected isomer I_hbpIs higher thanW_{Trans form}；

And wherein the weight W_{cis form}And the weight W_{Trans form}Respectively 0 g to 10 tons with the proviso that W_{Cis form}And W_{Trans form}Is greater than 70/30 or less than 30/70, with the proviso that W_{Cis form}And W_{Trans form}both are not 0 grams;

Characterized in that the unsaturated compound A has at least one prochiral carbon-carbon double bond and no conjugated carbon-carbon double bond.

11. A method according to any one of claims 8-10, characterized in that: introducing nitric oxide into the unsaturated compound A at atmospheric pressure or at most 1MPa overpressure.

12. A composition comprising:

-nitric oxide, and

Unsaturated compounds A of the formula (I) or (II) or (IID) or (IIE)

Wherein Q represents H or CH₃M and p represent, independently of one another, a value from 0 to 3 with the proviso that: the sum of m and p is 0 to 3,

Wherein the wavy line represents a carbon-carbon bond that is linked to an adjacent carbon-carbon double bond such that the carbon-carbon double bond is either in the Z-configuration or in the E-configuration, wherein the substructures in the formulae (I) and (II) and (IID) and (IIE) represented by s1 and s2 may be in any order;

And wherein said formulae (I) and (II) and (IID) and (IIE) have a dotted line thereinThe double bond of (a) represents a single carbon-carbon bond or a double carbon-carbon bond;

And whereinIn the representation of a solidA core;

Characterized in that the unsaturated compound A has at least one prochiral carbon-carbon double bond and no conjugated carbon-carbon double bond.

13. A ketal or acetal selected from the group consisting of 2- (4, 8-dimethylnon-3, 7-dien-1-yl) -2,5, 5-trimethyl-1, 3-dioxane, 2, 6-dimethyl-10, 10-bis (2,2, 2-trifluoroethoxy) undec-2, 6-diene, 2- (4, 8-dimethylnon-3-en-1-yl) -2,5, 5-trimethyl-1, 3-dioxane, 6, 10-dimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) undec-5-ene, 2,5, 5-trimethyl-2- (4,8, 12-trimethyltridec-3-en-1-yl) -1, 3-dioxane, (R) -2,5, 5-trimethyl-2- (4,8, 12-trimethyltridec-3-en-1-yl) -1, 3-dioxane, 6,10, 14-tri-methyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadec-5-ene, (R) -6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadec-5-ene, 2,5, 5-trimethyl-2- (4,8, 12-trimethyltridec-3, 7, 11-trien-1-yl) -1, 3-dioxane, 2,6, 10-trimethyl-14, 14-bis (2,2, 2-trifluoroethoxy) pentadecan-2, 6, 10-triene, 2,5, 5-trimethyl-2- (4,8, 12-trimethyltridec-3, 7-dien-1-yl) -1, 3-dioxane, 6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadecan-5, 9-diene, 2- (2, 6-dimethylhept-1-en-1-yl) -5, 5-dimethyl-1, 3-dioxane, 3, 7-dimethyl-1, 1-bis (2,2, 2-trifluoroethoxy) oct-2-ene, 3, 7-dimethyl-1, 1-bis (2,2, 2-trifluoroethoxy) oct-2, 6-diene, 2, 6-dimethyl-8, 8-bis (2,2, 2-trifluoroethoxy) oct-2-ene, (R) -2, 6-dimethyl-8, 8-bis (2,2, 2-trifluoroethoxy) oct-2-ene, 2- (4, 8-dimethylnon-1, 3, 7-trien-1-yl) -2,5, 5-trimethyl-1, 3-dioxane, 2, 6-dimethyl-10, 10-bis (2,2, 2-trifluoroethoxy) undec-2, 6, 8-triene, 2, 5-dimethyl-2- (4,8, 12-trimethyltridec-3-en-1-yl) -1, 3-dioxane, (R) -2, 5-dimethyl-2- (4,8, 12-trimethyltridec-3-en-1-yl) -1, 3-dioxane, 6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadec-5-ene and (R) -6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadec-5-ene and all their possible E/Z isomers.

14. Use of nitric oxide as a catalyst for the cis/trans isomerization of an unsaturated compound a selected from the group consisting of unsaturated ketones, unsaturated ketals, unsaturated aldehydes, unsaturated acetals, unsaturated carboxylic acids, unsaturated carboxylic acid esters and unsaturated carboxylic acid amides.

Technical Field

The present invention relates to cis/trans isomerization of unsaturated compounds.

Background

The unsaturated compound has a carbon-carbon double bond. These compounds exist in either the cis or trans configuration. In particular, unsaturated compounds having a functional group containing C ═ O are technically very important and have different properties, depending on which double bond isomer (cis or trans) is present in the corresponding compound. These compounds are of particular importance for the fields of perfumery, pharmaceutical compositions and the synthesis of vitamins, in particular vitamin K1 and tocopherol. Isomers differ in particular in terms of odor and in terms of their behavior towards asymmetric addition to the individual carbon-carbon double bonds.

It is known that carbon-carbon double bonds can be isomerized. EP 0858986 a1 discloses a process for the isomerization of vitamin a compounds having a multiconjugated carbon-carbon double bond (-C ═ C —) system by means of nitric oxide. However, it is known that: compounds with isolated (non-conjugated) double bonds behave, in particular reactivity, significantly differently than compounds with multiple conjugated carbon-carbon double bonds.

disclosure of Invention

Therefore, the problems to be solved by the present invention are: an isomerization method and an isomerization catalyst which are very effective for a compound selected from the group consisting of an unsaturated ketone, an unsaturated ketal, an unsaturated aldehyde, an unsaturated acetal, an unsaturated carboxylic acid ester, an unsaturated carboxylic acid amide and an unsaturated alcohol are provided, respectively.

Surprisingly, it has been found that: the problems can be solved by the methods according to claims 1 and 10 and by the compositions according to claim 12. It has been found that: nitric oxide is particularly suitable for isomerising the above compounds. It is very effective in isomerizing the carbon-carbon double bonds of these compounds. Thanks to the process of the invention it is possible to convert substantially all undesired isomers into the desired isomer. This is possible not only in the case of the pure isomers but also in the case of mixtures.

Other aspects of the invention are the subject of other independent claims. Particularly preferred embodiments are the subject of the dependent claims.

Detailed Description

In a first aspect, the present invention relates to a process for the cis/trans isomerization of an unsaturated compound a selected from the group consisting of unsaturated ketones, unsaturated ketals, unsaturated aldehydes, unsaturated acetals, unsaturated carboxylic acids, unsaturated carboxylic acid esters, unsaturated carboxylic acid amides and unsaturated alcohols, said process comprising the steps of:

a) Providing a cis or trans isomer of unsaturated compound a;

b) Adding nitric oxide to the cis or trans isomer of the unsaturated compound a of step a);

c) heating a mixture of nitric oxide and a cis-or trans-isomer of an unsaturated compound a to a temperature between 10 ℃ and the boiling point of the unsaturated compound a, in particular between 20 ℃ and the boiling point of the unsaturated compound a;

Thereby producing a mixture of cis/trans isomers of the unsaturated compound a.

in the context of substituents, fragments (moieties) or groups, the term "independently of each other" in this document means: the same designated substituents, fragments or groups may occur simultaneously in different meanings in the same molecule.

“C_x-yAn-alkyl "group is an alkyl group containing x to y carbon atoms, i.e., for example, C_1-3-an alkyl group is an alkyl group comprising 1 to 3 carbon atoms. The alkyl group may be linear or branched. For example, -CH (CH)₃)-CH₂-CH₃Is considered to be C₄-an alkyl group.

“C_x-yAn-alkylene "group is an alkylene group containing from x to y carbon atoms, i.e., for example, C₂-C₆Alkylene groups are alkyl groups containing from 2 to 6 carbon atoms. The alkylene group may be linear or branched. For example, -CH (CH)₃)-CH₂The radical is considered to be C₃-an alkylene group.

"phenolic alcohol" is expressed in this document: an alcohol having a hydroxyl group directly bonded to an aromatic group.

The term "stereocenter" as used in this document is an atom bearing groups in which exchange of any two of these groups results in the production of stereoisomers. Stereoisomers are isomeric molecules having the same molecular formula and bonded atomic order (makeup), but whose atoms are not spatially oriented in three dimensions.

The configuration at the stereocenter is defined as R or S. The R/S-concepts and rules for determining the absolute configuration in stereochemistry are known to the person skilled in the art.

In this document, a carbon-carbon double bond is defined as "prochiral" if the addition of a hydrogen molecule to the carbon-carbon double bond results in the formation of a stereogenic carbon center.

Cis/trans isomers are configurational isomers having different orientations at the double bond. In this document, the term "cis" is used equivalently to "Z" and vice versa; the term "trans" is used equivalently to "E" and vice versa. Thus, for example, the term "cis/trans isomerization catalyst" is equivalent to the term "E/Z isomerization catalyst".

The term "cis/trans isomerization catalyst" is a catalyst capable of isomerizing a cis isomer (Z-isomer) to a cis/trans isomer mixture (E/Z isomer mixture) or a trans isomer (E isomer) to a cis/trans isomer mixture (E/Z isomer mixture).

The terms "E/Z", "cis/trans" and "R/S" refer to mixtures of E and Z, cis and trans, and R and S, respectively.

The term "isomerization" (isometrization or isometrize) should be understood throughout the document as being limited to cis/trans isomerization.

An "equilibrium cis/trans ratio" is the ratio of a particular pair of cis and trans isomers obtained as a result of subjecting the cis or trans isomer to isomerization for an extended period of time using the method of the present invention (i.e., until no further change in cis/trans ratio is observed over time). Each pair of cis/trans isomers has a different equilibrium cis/trans ratio.

An "unbalanced cis/trans ratio" is any cis/trans isomer ratio that is different from an "balanced cis/trans ratio".

"unsaturated" compounds, unsaturated ketones, ketals, aldehydes, acetals, carboxylic acids, unsaturated carboxylic esters, unsaturated carboxylic amides or unsaturated alcohols are defined asOf olefinsKetones, aldehydes, ketals, aldehydes, acetals, carboxylic acids, unsaturated carboxylic acid esters, unsaturated carboxylic acid amides or unsaturated alcohols which are unsaturated (i.e. have at least one carbon-carbon double bond in their chemical structure), but which have no multi-conjugated carbon-carbon double bonds (i.e. more than two conjugated carbon-carbon double bonds), and preferably have at least one prochiral carbon-carbon double bond. Preferably, the "unsaturated" compound has no conjugated carbon-carbon double bonds.

In this document, if the same symbol label or group label is found in several formulae, the definitions made for said group or symbol in the context of one particular formula also apply to the other formulae comprising said same label.

In this document, any individual dashed line represents the bond through which a substituent is bound to the rest of the molecule.

In this document, bold is indicated by, for example, A or I_IbpOr I_hbpIn this document only for improving readability and for identification.

Unsaturated Compound A

The unsaturated compound a is selected from the group consisting of unsaturated ketones, unsaturated ketals, unsaturated aldehydes, unsaturated acetals, unsaturated carboxylic acids, unsaturated carboxylic acid esters, unsaturated carboxylic acid amides and unsaturated alcohols, having at least one carbon-carbon double bond in its chemical structure and preferably at least one prochiral carbon-carbon double bond.

It may have more than 1 prochiral carbon-carbon double bond and/or 1 or more non-prochiral carbon-carbon double bonds.

Preferably, the unsaturated compound A has the formula (I-0A) or (I-0B) or (I-0C) or (I-0D) or (I-0E) or (I-0F)

Wherein R' represents a linear or alicyclic hydrocarbon group optionally containing additional carbon-carbon double bonds, however in the case of formula (I-0B) or (I-0D) or (I-0F) no conjugated double bonds, in the case of formula (I-0A) or (I-0C) or (I-0E) at most one conjugated double bond; q' represents a group selected from the group consisting of

Wherein R is⁰Represents C₁-C₄-an alkyl group, in particular representing a methyl group;

Q¹And Q²Represents C₁-C₁₀Alkyl radicals or halogenated C₁-C₁₀An alkyl group; c₁-C₄Alkyl radicals or together forming C₂-C₆Alkylene radical or C₆-C₈A cycloalkylene group;

R' represents C₁-C₄-an alkyl group, in particular representing a methyl or ethyl group; and is

R' represents H or C₁-C₄-an alkyl group, in particular representing a methyl or ethyl group;

And wherein the wavy line represents a carbon-carbon bond that is linked to an adjacent carbon-carbon double bond such that said carbon-carbon double bond is either in the Z-configuration or in the E-configuration;

And wherein said formula (I-0B) or (I-0D) or (I-0F) has a dotted lineThe double bond of (a) represents a single carbon-carbon bond or a double carbon-carbon bond.

In one embodiment, formula (I-0A) or (I-0C) has a group R 'of the formula'

And which is preferably a methyl ketone or a ketal thereof, preferably alpha-ionone, beta-ionone, gamma-ionone; alpha-iso-ionone, beta-iso-ionone, gamma-iso-ionone; alpha-n-methyl ionone, beta-n-methyl ionone or gamma-n-methyl ionone; or a ketal thereof.

Preferably, the unsaturated compound a is an unsaturated ketone or unsaturated ketal or unsaturated aldehyde or unsaturated acetal or unsaturated alcohol.

In a preferred embodiment, the unsaturated compound a is an unsaturated ketone or a ketal thereof or an unsaturated aldehyde or an acetal thereof and has a carbon-carbon double bond in the γ, δ position relative to the carbonyl group.

In another preferred embodiment, the unsaturated compound a is an unsaturated ketone or a ketal thereof or an unsaturated aldehyde or an acetal thereof and has a carbon-carbon double bond in the α, β position relative to the carbonyl group.

In yet another preferred embodiment, the unsaturated compound a is an unsaturated ketone or a ketal thereof or an unsaturated aldehyde or an acetal thereof and has a carbon-carbon double bond in the α, β position relative to the carbonyl group and a carbon-carbon double bond in the γ, δ position relative to the carbonyl group, but no carbon-carbon double bond in the e, ζ position relative to the carbonyl group.

Strongly preferred unsaturated compounds A are of the formula (I) or (II) or (IID) or (IIE)

wherein Q represents H or CH₃M and p represent, independently of one another, a value from 0 to 3 with the proviso that: the sum of m and p is 0 to 3;

Wherein the wavy line represents a carbon-carbon bond that is linked to an adjacent carbon-carbon double bond such that said carbon-carbon double bond is either in the Z-configuration or in the E-configuration, wherein the substructures in formulae (I) and (II) and (IID) and (IIE) represented by s1 and s2 may be in any order;

And wherein the formulae (I) and (II) and (IID) and (IIE) have the dotted line thereinThe double bond of (a) represents a single carbon-carbon bond or a double carbon-carbon bond;

And whereinRepresenting the stereocenter.

The sum of m and p is preferably 0 to 2, in particular 0 or 1.

Thus, the unsaturated compounds of the formula (I) or (II) or (IID) or (IIE) can be used as sole substances or in useA labeled stereocenter or a mixture of different stereoisomers with different orientations at the double bond of the wavy bond. Preferably, however, the unsaturated compound a of formula (I) or (II) is a separate substance having a specific configuration at the stereocenter and at the double bond. Preferably, the configuration of the stereocenter is the R configuration. If p.gtoreq.2, preferablyAll the different stereocenters of the label are in the same configuration, i.e.: all S configurations or all R configurations, preferably all in R configuration.

Particularly suitable unsaturated compounds are of formula (II). Most preferably, the unsaturated ketone or unsaturated aldehyde is selected from the group consisting of 3, 7-dimethyloct-2, 6-dienal, 3, 7-dimethyloct-2-enal, 6, 10-dimethylundec-3, 5, 9-trien-2-one, 6, 10-dimethylundec-5, 9-dien-2-one, 6, 10-dimethylundec-5-en-2-one, 6, 10-dimethylundec-3, 5-dien-2-one, (R) -6, 10-dimethylundec-3-en-2-one, 6,10, 14-trimethylpentadeca-5, 9, 13-trien-2-one, 6,10, 14-trimethylpentadeca-5, 9-dien-2-one, 6,10, 14-trimethylpentadeca-5-en-2-one and (R) -6,10, 14-trimethylpentadeca-5-en-2-one and all their possible E/Z-isomers.

most preferably, the unsaturated ketone or unsaturated aldehyde is a ketone.

Furthermore, very suitable compounds of the formula (IID) or (IIE) are geraniol, nerol and farnesol.

acetal/ketal

Furthermore, preferably, the unsaturated compound a is a ketal or acetal of an unsaturated ketone or unsaturated aldehyde, in particular an acetal or ketal of the formula (I) or (II).

The person skilled in the art knows per se that ketals are formed from ketones or acetals are formed from aldehydes.

The ketal of an unsaturated ketone can preferably be formed from the above-described unsaturated ketone and an alcohol. Acetals of unsaturated aldehydes may be formed from the above-mentioned unsaturated aldehydes and alcohols.

Known to those skilled in the art: alternative routes to the synthesis of acetals or ketals exist. In principle, ketals and acetals can also be formed by treating ketones or aldehydes with ortho esters or by trans-ketalization (transketalization) reactions, as disclosed, for example, in Tetrahedron Letters 1997,38(45),7867-7870 or in Lorette and Howard in j.org.chem.1960,25,521-525, both of which are incorporated herein by reference in their entirety.

Preferably, a ketal or acetal is formed from the above-described unsaturated ketone or unsaturated aldehyde and alcohol.

In principle, the alcohol used for ketal or acetal formation can be any alcohol, i.e.: the alcohol may contain 1 or more hydroxyl groups. The alcohol may be a phenolic alcohol or an aliphatic or cycloaliphatic alcohol. Preferably, however, the alcohol has one hydroxyl group (═ monoalcohol) or two hydroxyl groups (═ diol).

If the alcohol has one hydroxyl group, the alcohol is preferably an alcohol having 1 to 12 carbon atoms. Specifically, the alcohol having one hydroxyl group is selected from the group consisting of: methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-methyl-1-propanol, 2-butanol, pentan-1-ol, 3-methylbutan-1-ol, 2-dimethylpropan-1-ol, pentan-3-ol, pentan-2-ol, 3-methylbutan-2-ol, 2-methylbutan-1-ol, hexan-2-ol, hexan-3-ol, 2-methyl-1-pentanol3-methyl-1-pentanol, 4-methyl-1-pentanol, 3-methyl-2-pentanol, 4-methyl-2-pentanol, 2-methyl-3-pentanol, 2-dimethyl-1-butanol, 2, 3-dimethyl-1-butanol, 3-dimethyl-2-butanol, 2-ethyl-1-butanol, and heptanol, octanol and halogenated C_1-C₈All structural isomers of alkyl alcohols, in particular 2,2, 2-trifluoroethanol. Particularly suitable are primary or secondary alcohols. Preferably, primary alcohols are used as alcohols having one hydroxyl group. Specifically, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol or 2,2, 2-trifluoroethanol, preferably methanol, ethanol, 1-propanol, 1-butanol or 2,2, 2-trifluoroethanol is used as the alcohol having one hydroxyl group.

In another embodiment, the alcohol is a diol. Preferably, the diol is selected from the group consisting of: ethane-1, 2-diol, propane-1, 3-diol, butane-1, 4-diol, butane-1, 3-diol, butane-1, 2-diol, butane-2, 3-diol, 2-methylpropane-1, 2-diol, 2-methylpropane-1, 3-diol, 2-dimethylpropane-1, 3-diol, 1, 2-dimethylpropane-1, 3-diol, 3-methylpentane-2, 4-diol and 2- (hydroxymethyl) cyclohexanol, benzene-1, 2-diol and cyclohexane-1, 2-diol. The preferred stereoisomer of the two cyclohexane-1, 2-diols is the same formula (syn-) -cyclohexane-1, 2-diol (═ cis-cyclohexane-1, 2-diol).

In one embodiment, 2 hydroxyl groups are bonded to 2 adjacent carbon atoms, and thus these diols are vicinal diols. The vicinal diols form 5-membered rings in the ketal or acetal.

Particularly suitable are vicinal diols selected from the group consisting of ethane-1, 2-diol, propane-1, 2-diol, butane-2, 3-diol, 2-methylpropane-1, 2-diol, benzene-1, 2-diol and cyclohexane-1, 2-diol of the same formula, in particular ethane-1, 2-diol.

Other particularly suitable are diols in which the hydroxyl groups are separated by 3 carbon atoms, thus forming a very stable 6-membered ring in the ketal or acetal. Particularly suitable diols of this type are propane-1, 3-diol, butane-1, 3-diol, 2-methylpropane-1, 3-diol, 2-methylbutane-1, 3-diol, 2-dimethylpropane-1, 3-diol, 1, 2-dimethylpropane-1, 3-diol, 3-methylpentane-2, 4-diol and 2- (hydroxymethyl) cyclohexanol.

Preferably, primary alcohols are used as diols.

Reaction conditions and stoichiometry for acetal or ketal formation are known to those skilled in the art. In particular, acetals or ketals are formed under the influence of acids.

Preferred ketals of unsaturated ketones or preferred acetals of unsaturated aldehydes are of the formula (XI) or (XII)

The radicals and symbols in formulae (XI) and (XII) have the same meanings as defined previously in this document in relation to formulae (I) and (II).

Q¹And Q²Alone or together represent C₁-C₁₀Alkyl radicals or halogenated C₁-C₁₀An alkyl group;

Or together form C₂-C₆Alkylene radical or C₆-C₈A cycloalkylene group.

In particular, Q¹and Q²represents

Linear type C₁-C₁₀Linear C of alkyl radicals or fluoro₁-C₁₀Alkyl radical, preferably linear C₁-C₄Alkyl radicals or-CH₂CF₃radical (I)

Or a group of the formula

Wherein Q is³、Q⁴、Q⁵And Q⁶Independently of one another, a hydrogen atom or a methyl or ethyl group.

Preferably, the ketal or acetal of formula (XI) or (XII) is (E) -2- (4, 8-dimethylnon-3, 7-dien-1-yl) -2,5, 5-trimethyl-1, 3-dioxane, (E) -2, 6-dimethyl-10, 10-bis (2,2, 2-trifluoroethoxy) undec-2, 6-diene, (E) -2- (4, 8-dimethylnon-3-en-1-yl) -2,5, 5-trimethyl-1, 3-dioxane, (E) -6, 10-dimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) undec-5-ene, (E) -2,5, 5-trimethyl-2- (4,8, 12-trimethyltridec-3-en-1-yl) -1, 3-dioxane, (R, E) -2,5, 5-trimethyl-2- (4,8, 12-trimethyltridec-3-en-1-yl) -1, 3-dioxane, (E) -6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadec-5-ene, (R, E) -6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadec-5-ene, (Z) -2- (4, 8-dimethylnon-3, 7-dien-1-yl) -2,5, 5-trimethyl-1, 3-dioxane, (Z) -2, 6-dimethyl-10, 10-bis (2,2, 2-trifluoroethoxy) undec-2, 6-diene, (Z) -2- (4, 8-dimethylnon-3-en-1-yl) -2,5, 5-trimethyl-1, 3-dioxane, (Z) -6, 10-dimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) undec-5-ene, (Z) -2,5, 5-trimethyl-2- (4,8, 12-trimethyltridec-3-en-1-yl) -1, 3-dioxane, (R, Z) -2,5, 5-trimethyl-2- (4,8, 12-trimethyltridec-3-en-1-yl) -1, 3-dioxane, 2,5, 5-trimethyl-2- ((3E,7E) -4,8, 12-trimethyltridec-3, 7, 11-trien-1-yl) -1, 3-dioxane, (6E,10E) -2,6, 10-trimethyl-14, 14-bis (2,2, 2-trifluoroethoxy) pentadeca-2, 6, 10-triene, 2,5, 5-trimethyl-2- ((3E,7E) -4,8, 12-trimethyltridec-3, 7-dien-1-yl) -1, 3-dioxane, (5E,9E) -6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadecane-5, 9-diene, 2,5, 5-trimethyl-2- ((3Z,7E) -4,8, 12-trimethyltridec-3, 7, 11-trien-1-yl) -1, 3-dioxane, 2,5, 5-trimethyl-2- ((3E,7Z) -4,8, 12-trimethyltridec-3, 7, 11-trien-1-yl) -1, 3-dioxane, 2,5, 5-trimethyl-2- ((3Z,7Z) -4,8, 12-trimethyltridec-3, 7, 11-trien-1-yl) -1, 3-dioxane, (6Z,10E) -2,6, 10-trimethyl-14, 14-bis (2,2, 2-trifluoroethoxy) pentadecane-2, 6, 10-triene, (6E,10Z) -2,6, 10-trimethyl-14, 14-bis (2,2, 2-trifluoroethoxy) pentadecane-2, 6, 10-triene, (6Z,10Z) -2,6, 10-trimethyl-14, 14-bis (2,2, 2-trifluoroethoxy) pentadecane-2, 6, 10-triene, 2,5, 5-trimethyl-2- ((3Z,7E) -4,8, 12-trimethyltridec-3, 7-dien-1-yl) -1, 3-dioxane, 2,5, 5-trimethyl-2- ((3E,7Z) -4,8, 12-trimethyltridec-3, 7-dien-1-yl) -1, 3-dioxane, 2,5, 5-trimethyl-2- ((3Z,7Z) -4,8, 12-trimethyltridec-3, 7-dien-1-yl) -1, 3-dioxane, (5Z,9E) -6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadecane-5, 9-diene, (5E,9Z) -6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadeca-5, 9-diene, (5Z,9Z) -6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadeca-5, 9-diene, (E) -2- (2, 6-dimethylhept-1-en-1-yl) -5, 5-dimethyl-1, 3-dioxane, (E) -3, 7-dimethyl-1, 1-bis (2,2, 2-trifluoroethoxy) oct-2-ene, (E) -3, 7-dimethyl-1, 1-bis (2,2, 2-trifluoroethoxy) oct-2, 6-diene, (Z) -2- (2, 6-dimethylhept-1-en-1-yl) -5, 5-dimethyl-1, 3-dioxane, (Z) -3, 7-dimethyl-1, 1-bis (2,2, 2-trifluoroethoxy) oct-2-ene, (Z) -3, 7-dimethyl-1, 1-bis (2,2, 2-trifluoroethoxy) oct-2, 6-diene, 2, 6-dimethyl-8, 8-bis (2,2, 2-trifluoroethoxy) oct-2-ene, (R) -2, 6-dimethyl-8, 8-bis (2,2, 2-trifluoroethoxy) oct-2-ene, 2- ((1Z,3E) -4, 8-dimethylnon-1, 3, 7-trien-1-yl) -2,5, 5-trimethyl-1, 3-dioxane, 2- ((1E,3Z) -4, 8-dimethylnon-1, 3, 7-trien-1-yl) -2,5, 5-trimethyl-1, 3-dioxane, 2- ((1Z,3Z) -4, 8-dimethylnon-1, 3, 7-trien-1-yl) -2,5, 5-trimethyl-1, 3-dioxane, (6Z,8E) -2, 6-dimethyl-10, 10-bis (2,2, 2-trifluoroethoxy) undec-2, 6, 8-triene, (6E,8Z) -2, 6-dimethyl-10, 10-bis (2,2, 2-trifluoroethoxy) undec-2, 6, 8-triene, (6Z,8Z) -2, 6-dimethyl-10, 10-bis (2,2, 2-trifluoroethoxy) undec-2, 6, 8-triene, (Z) -2, 5-dimethyl-2- (4,8, 12-trimethyltridec-3-en-1-yl) -1, 3-dioxane, (R, Z) -2, 5-dimethyl-2- (4,8, 12-trimethyltridec-3-en-1-yl) -1, 3-dioxane, (Z) -6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadec-5-ene and (R, Z) -6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadec-5-ene.

In step a), the cis-or trans-isomer of unsaturated compound a is provided.

In one embodiment, only one single stereoisomer of compound a is provided. The single stereoisomer of compound a may be the result of a stereotactic synthesis or separation process of stereoisomers.

in another embodiment, the cis or trans isomer of unsaturated compound a is provided as a mixture of cis and trans isomers in a non-equilibrium cis/trans ratio. Typically, the non-equilibrium cis/trans ratio is greater than 70/30, preferably greater than 80/20, more preferably greater than 90/10 or less than 30/70, preferably less than 20/80, more preferably less than 10/90.

Nitric oxide

In step b), adding nitric oxide to the cis or trans isomer of the unsaturated compound a of step a);

Nitric oxide is a cis/trans isomerization catalyst that isomerizes carbon-carbon double bonds.

Preferably, the introduction of nitric oxide into the unsaturated compound a is carried out at atmospheric pressure or at an overpressure of at most 1 MPa.

More preferably, the nitric oxide is introduced into the unsaturated compound a at atmospheric pressure or at an overpressure of at most 1 MPa.

Nitric oxide may be added in step b) as a gas mixture with at least one other gas, preferably with an inert gas, most preferably with nitrogen.

Preferably, the amount of nitric oxide in the gas mixture is in the range of 10-60 wt.%.

The nitric oxide can be applied from a gas cylinder or can be prepared on site, e.g. from NaNO as described in the experimental part₂、FeSO₄And sulfuric acid preparation.

Isomerization of

In step c), the mixture of nitric oxide and the cis-or trans-isomer of unsaturated compound a is heated to a temperature between 20 ℃ and the boiling point of the unsaturated compound a, in particular between 50 ℃ and the boiling point of the unsaturated compound a. In this document, "the boiling point of unsaturated compound a" is defined as the boiling point of the lowest boiling cis or trans isomer formed by the process.

Under the action of nitric oxide and temperature, cis-isomer and/or trans-isomer of unsaturated compound A are isomerized. The ratio of cis and trans isomers formed by isomerization gradually tends towards (convert) equilibrium over time, e.g. an equilibrium cis/trans ratio. The equilibrium cis/trans ratio is a specific value which is different for each unsaturated compound a.

Isomerization of the cis or trans isomer of the unsaturated compound a is of great interest, since one of the isomers is very often the isomer of interest. The cis and trans isomers mostly have different properties. For example, the interesting core properties (e.g. odor or reactivity in a particular chemical reaction) of the cis isomer are significantly different compared to the trans isomer. In the case of citral, the trans-isomer geranial (═ E) -3, 7-dimethyloctan-2, 6-dienal) has a strong lemon odor, while the cis-isomer neral (═ Z) -3, 7-dimethyloctan-2, 6-dienal) has a less strong lemon odor but is sweeter. On the other hand, if the unsaturated compound a has a prochiral carbon-carbon double bond, derivatization of this prochiral carbon-carbon double bond may lead to the formation of chiral compounds of a particular stereoisomeric configuration. For example, asymmetric hydrogenation of the unsaturated compound A leads to the formation of stereocenters of the R or S configuration.

isomerization offers the only possibility to convert at least part of the undesired isomer into the desired isomer (═ isomer of interest). By carrying out the isomerization and separation process in an optimal manner, it is even possible to achieve: starting from the undesired isomer or a mixture of desired and undesired cis/trans isomers, substantially all undesired isomers can be converted to the desired isomer. Further details regarding the possibilities will be given later in this document.

The above-described process for cis/trans isomerization of unsaturated compound a results in a mixture of cis/trans isomers of unsaturated compound a.

The desired isomer can be isolated from the mixture. Because the cis and trans isomers have different boiling points, the separation method that is favored is distillation. To minimize thermal degradation of the isomers, distillation under reduced pressure and by means of a distillation column is suggested. However, the boiling points are very often very similar, and nevertheless, by using specific distillation techniques and equipment, the desired isomer can be separated or at least enriched.

Since the lowest boiling isomer is not always the isomer of interest, there is a need in principle for two different processes of interest as described below.

If the lowest boiling isomer is the isomer of interest, in a further aspect the present invention relates to a process for the production of a specific cis-isomer and a specific trans-isomer of an unsaturated compound A, respectively, from a mixture of cis-and trans-isomers of an unsaturated compound A, said unsaturated compound A being selected from the group consisting of an unsaturated ketone, an unsaturated ketal, an unsaturated aldehyde, an unsaturated acetal, an unsaturated carboxylic acid ester, an unsaturated carboxylic acid amide and an unsaturated alcohol, said process comprising the following step i) providing a mixture of cis-and trans-isomers of an unsaturated compound A, wherein the weight of the cis-isomer is W_{Cis form}And the weight of the trans isomer is W_{Trans form}；

ii) addition of nitric oxide

iii) heating the mixture to a temperature T_iso1The temperature is the isomer I_lbpThe boiling point of, the isomer I_lbpHaving the lowest boiling point of the cis/trans isomer mixture of step i);

iv) distillation of isomer I_lbpAnd collecting isomer I_lbp；

v) cis/trans isomerization in the presence of said nitric oxide added in step ii) to form isomer I_lbpHigher boiling isomer I_hbp；

Wherein step ii) may occur before, during or after steps iii) and/or iv); and wherein, after step v), steps ii), iii), iv) and v) are subsequently repeated

And wherein, if isomer I is collected_lbpIs the cis isomer of the unsaturated compound A, all collected isomers I_lbpIs higher than W_{Cis form}；

Or

If isomer I is collected_lbpIs the trans isomer of the unsaturated compound A, all collected isomers I_lbpIs higher than W_{Trans form}；

And wherein the weight W_{Cis form}And weight W_{Trans form}Are each 0 gTo 10 tons with the proviso that W_{Cis form}And W_{Trans form}Is greater than 70/30 or less than 30/70, with the proviso that W_{Cis form}And W_{Trans form}Both of which are not 0 grams.

in this process, in step i) a mixture of cis-isomer and trans-isomer of the unsaturated compound A is provided, wherein the weight of cis-isomer is W_{Cis form}And the weight of the trans isomer is W_{Trans form}. Because of the weight of the cis isomer W_{Cis form}Or weight W of trans isomer_{Trans form}In the range of 0 g to 10 tons, with the proviso that W_{Cis form}And W_{Trans form}Both are not 0 grams, so the "mixture" in this context also applies to the individual stereoisomers, not just to the true isomeric mixtures.

In a preferred embodiment, the weight W_{Cis form}And weight W_{Trans form}Neither is 0 g, so that both cis and trans isomers of the unsaturated compound a are actually present in the mixture provided in step i).

In this process, the isomer of interest (i.e., the desired isomer) is isomer I_lbpThe isomer I_lbpIs the isomer having the lowest boiling point of the cis/trans isomer mixture provided in step i).

In step iv), the isomer I is separated and collected by distillation_lbp。

In order to optimize the purity, the distillation is carried out by using specific distillation techniques, ensuring that the impurities resulting from the other isomers are as low as possible. In particular, it is also achieved: only a portion of the desired isomer (i.e., the purest fraction) was collected in the distillation, while the remainder remained in the distillation flask.

In order to optimize the yield of the desired isomer, in step v), in the presence of nitric oxide (added in step ii)), it has the specific isomer I_lbpHigher boiling isomer I_hbpis isomerized by cis/trans.

Even in the preferred case, in step iv) only part of the isomer I_lbpIs distilled and collectedThe distillation residue still contains isomer I_lbp. In this case, the distillation residue is subjected to cis/trans isomerization in step v).

Isomerizing isomer I continuously or batchwise in the presence of nitric oxide_hbpAnd/or distilling the residue. Since the distillation residue is enriched in the undesired isomer to achieve a non-equilibrium cis/trans ratio by removing the desired product, the system was adjusted according to le chatelier's principle and explored to achieve an equilibrium cis/trans ratio by promoting the conversion (i.e., isomerization) of the undesired isomer to the desired isomer using the cis/trans isomerization catalyst nitric oxide. By subsequently repeating steps iii), iv) and v) after step v), an increase in yield is ensured. Desired isomer I_lbpThe overall yield of (a) is strongly dependent on the number of repetitions and/or the separation efficiency by distillation.

This process results in the net (net) conversion of the undesired isomer to the desired isomer, in other words this means: when in the initial mixture of cis and trans isomers of unsaturated compound A provided in step a), the cis isomer has a weight W_{Cis form}And the trans isomer has a weight W_{Trans form}When the temperature of the water is higher than the set temperature,

If isomer I is collected_lbpIs cis isomer of the unsaturated compound A, the collected isomer I_lbpIs higher than W_{Cis form}；

Or

if isomer I is collected_lbpis a trans isomer of the unsaturated compound A, the collected isomer I_lbpIs higher than W_{Trans form}。

As mentioned above, in principle, substantially all of the undesired isomer can be converted into the desired isomer.

Thus, preferably, isomer I is collected_lbpThe weight of the isomer is higher than W_{cis form}And W_{Trans form}80% by weight of the sum, preferably higher than W_{Cis form}And W_{Trans form}90% by weight of the sum.

If the higher boiling isomer is the isomer of interest, in another aspect, the present invention relates to a process for producing a specific cis-isomer and a specific trans-isomer of an unsaturated compound A, respectively, from a mixture of cis-and trans-isomers of the unsaturated compound A, said unsaturated compound A being selected from the group consisting of an unsaturated ketone, an unsaturated ketal, an unsaturated aldehyde, an unsaturated acetal, an unsaturated carboxylic acid ester, an unsaturated carboxylic acid amide and an unsaturated alcohol, said process comprising the steps of

a) Providing a mixture of cis-isomer and trans-isomer of unsaturated compound A, wherein the weight of cis-isomer is W_{Cis form}And the weight of the trans isomer is W_{Trans form}；

b) Adding nitric oxide

c) Heating the mixture to a temperature T_iso1The temperature is the isomer I_lbpThe boiling point of, the isomer I_lbpHaving the lowest boiling point of the cis/trans isomer mixture of step a);

d) Isomer I is distilled off_lbp

e) Isolation of the particular isomer I from the residue of step d)_hbpthe isomer I_hbpHaving the specific isomer I_lbpHigher boiling point and collecting said isomer I_hbp；

f) Cis/trans isomerization of isomer I in the presence of nitric oxide added in step b)_lbpAnd the remainder of step e) (if present after step e));

wherein step b) may occur before, during or after steps c) and/or f); and wherein, after step f), steps b), c), d), e) and f) are subsequently repeated

And wherein, if isomer I is collected_hbpIs cis isomer of the unsaturated compound A, the collected isomer I_hbpIs higher than W_{Cis form}；

Or

If isomer I is collected_hbpIs a trans isomer of the unsaturated compound A, the collected isomer I_hbpIs higher than W_{Trans form}；

And wherein the weight W_{Cis form}And weight W_{Trans form}Respectively 0 g to 10 tons with the proviso that W_{Cis form}And W_{Trans form}is greater than 70/30 or less than 30/70, with the proviso that W_{Cis form}And W_{Trans form}Both of which are not 0 grams.

In the process, in step a) a mixture of cis-isomer and trans-isomer of unsaturated compound A is provided, wherein the weight of cis-isomer is W_{cis form}and the weight of the trans isomer is W_{Trans form}. Because of the weight of the cis isomer W_{Cis form}Or weight W of trans isomer_{Trans form}In the range of 0 g to 10 tons, with the proviso that W_{Cis form}And W_{Trans form}Both are not 0 grams, so the "mixture" in this context also applies to the individual stereoisomers, not just to the true isomeric mixtures.

In a preferred embodiment, the weight W_{Cis form}And weight W_{Trans form}Neither is 0 g, so that both cis and trans isomers of the unsaturated compound a are actually present in the mixture provided in step a).

In this process, the isomer of interest (i.e., the desired isomer) is isomer I_hbpThe isomer I_hbphaving the specific isomer I_lbpHigher boiling point, the isomer I_lbpIs the isomer having the lowest boiling point of the cis/trans isomer mixture provided in step a).

In step d), the lowest-boiling isomer I is distilled off_lbp。

Isolation of the particular isomer I from the distillation residue of step d)_hbpAnd collected in step e), the isomer I_hbphaving the specific isomer I_lbpThe higher the boiling point of the water,

The particular isomer I is preferably carried out by a particular distillation technique_hbpE.g. using side take-off points (side take-off points) in a rectification column and finally further rectifying the material collected at said side take-off points, e.g. EP 2269998 a2 (in particular)Techniques and devices disclosed in fig. 1 and 3), the entire contents of which are incorporated herein by reference.

In order to optimize isomer I_hbpBy carrying out the distillation in steps d) and e) using specific distillation techniques, it is ensured that as few impurities as possible are produced due to the other isomers. In particular, it is also achieved: only a portion of the desired isomer I was collected in the distillate_hbp(i.e., the purest fraction), while the other fractions are separated from the remainder remaining in the distillation flask and the lowest boiling isomer I distilled off in step d)_lbpAnd (6) merging.

In step f), isomerizing the isomer I in the presence of the nitric oxide added in step b)_lbpAnd the remainder of step e) (if present after step e)).

Even in the preferred case, in step e) only part of the isomer I_hbpIs distilled and collected, the distillation residue still comprising isomer I_hbp。

Isomerizing isomer I continuously or batchwise in the presence of nitric oxide_lbpAnd the remainder of step e). Since the distillation residue is enriched in the undesired isomer to achieve a non-equilibrium cis/trans ratio by removing the desired product, the system was adjusted according to le chatelier's principle and explored to achieve an equilibrium cis/trans ratio by promoting the conversion (i.e., isomerization) of the undesired isomer to the desired isomer using the cis/trans isomerization catalyst nitric oxide. By subsequently repeating steps c), d), e) and f) after step f), an increase in yield is ensured. Desired isomer I_hbpThe overall yield of (a) is strongly dependent on the number of repetitions and/or the separation efficiency by distillation.

This process results in the net (net) conversion of the undesired isomer to the desired isomer, in other words this means: when the first mixture of cis and trans isomers of the saturated compound A provided in step a), the cis isomer has a weight W_{Cis form}And the trans isomer has a weight W_{Trans form}When the temperature of the water is higher than the set temperature,

If isomer I is collected_hbpIs thatCis-isomer of unsaturated Compound A, collected isomer I_hbpIs higher than W_{Cis form}；

Or

If isomer I is collected_hbpIs a trans isomer of the unsaturated compound A, the collected isomer I_hbpIs higher than W_{Trans form}；

As mentioned above, in principle, substantially all of the undesired isomer can be converted into the desired isomer.

Thus, preferably, isomer I is collected_hbpThe weight of the isomer is higher than W_{Cis form}And W_{Trans form}80% by weight of the sum, preferably higher than W_{Cis form}And W_{Trans form}90% by weight of the sum.

in both methods for producing the specific cis-isomer and the specific trans-isomer of the unsaturated compound a, respectively, discussed in the previous paragraph, it is preferred to introduce nitric oxide to the unsaturated compound a at atmospheric pressure or at most 1MPa overpressure.

In another aspect, the present invention relates to a composition comprising

-nitric oxide, and

unsaturated compounds A of formula (I) or (II) or (IID) or (IIE).

In this document, nitric oxide and unsaturated compounds a of formula (I) or (II) or (IID) or (IIE) as well as their ratios and their preferred embodiments have been discussed in detail previously.

In another aspect, the invention relates to a ketal or acetal selected from the group consisting of 2- (4, 8-dimethylnon-3, 7-dien-1-yl) -2,5, 5-trimethyl-1, 3-dioxane, 2, 6-dimethyl-10, 10-bis (2,2, 2-trifluoroethoxy) undec-2, 6-diene, 2- (4, 8-dimethylnon-3-en-1-yl) -2,5, 5-trimethyl-1, 3-dioxane, 6, 10-dimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) undec-5-ene, 2,5, 5-trimethyl-2- (4,8, 12-trimethyltridec-3-en-1-yl) -1, 3-dioxane, (R) -2,5, 5-trimethyl-2- (4,8, 12-trimethyltridec-3-en-1-yl) -1, 3-dioxane, 6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadec-5-ene, (R) -6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadec-5-ene, 2,5, 5-trimethyl-2- (4,8, 12-trimethyltridec-3, 7, 11-trien-1-yl) -1, 3-dioxane, 2,6, 10-trimethyl-14, 14-bis (2,2, 2-trifluoroethoxy) pentadecan-2, 6, 10-triene, 2,5, 5-trimethyl-2- (4,8, 12-trimethyltridec-3, 7-dien-1-yl) -1, 3-dioxane, 6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadecan-5, 9-diene, 2- (2, 6-dimethylhept-1-en-1-yl) -5, 5-dimethyl-1, 3-dioxane, 3, 7-dimethyl-1, 1-bis (2,2, 2-trifluoroethoxy) oct-2-ene, 3, 7-dimethyl-1, 1-bis (2,2, 2-trifluoroethoxy) oct-2, 6-diene, 2, 6-dimethyl-8, 8-bis (2,2, 2-trifluoroethoxy) oct-2-ene, (R) -2, 6-dimethyl-8, 8-bis (2,2, 2-trifluoroethoxy) oct-2-ene, 2- (4, 8-dimethylnon-1, 3, 7-trien-1-yl) -2,5, 5-trimethyl-1, 3-dioxane, 2, 6-dimethyl-10, 10-bis (2,2, 2-trifluoroethoxy) undec-2, 6, 8-triene, 2, 5-dimethyl-2- (4,8, 12-trimethyltridec-3-en-1-yl) -1, 3-dioxane, (R) -2, 5-dimethyl-2- (4,8, 12-trimethyltridec-3-en-1-yl) -1, 3-dioxane, 6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadec-5-ene and (R) -6,10, 14-trimethyl-2, 2-bis (2,2, 2-trifluoroethoxy) pentadec-5-ene and all their possible E/Z isomers.

These ketals and acetals are particularly suitable for being isomerized according to the process of the invention.

Finally, in another aspect, the present invention relates to the use of nitric oxide as a catalyst for the cis/trans isomerization of an unsaturated compound a selected from the group consisting of unsaturated ketones, unsaturated ketals, unsaturated aldehydes, unsaturated acetals, unsaturated carboxylic acids, unsaturated carboxylic acid esters and unsaturated carboxylic acid amides. In this document, the use has been discussed in detail previously.

Examples

The invention is further illustrated by the following experiments.

Production of NO and isomerization experiments

Nitric oxide has been produced as shown in figure 1. Under argon, 5.86g of aqueous sulfuric acid (20%) (12.0mmol) are carefully added dropwise with stirring over 10 minutes to a flask containing the cakeThere was 0.86g NaNO₂(12.1mmol) and 3.12g FeSO₄.7H₂A solution of O (11.2mmol) in water (5 mL). Calculated sulfuric acid and NaNO₂And FeSO₄To yield 250mL NO gas (43 mol%). A constant flow of nitric oxide was established and the flask containing the unsaturated compound A to be isomerized (25.6mmol) was bubbled (bubbleinto) over 10 minutes under stirring. The nitric oxide leaving the reaction flask was diluted with air and washed with NaOH solution. Thereafter, the solution was stirred at room temperature for the indicated time.

In a first series of experiments, the isomer of 6, 10-dimethylundec-5, 9-dien-2-one has been isolated by distillation. The E-isomer had been separated with a content of 99.5% of (E) -6, 10-dimethylundec-5, 9-dien-2-one (determined by GC) and the Z-isomer had been separated in a concentrated fraction with a content of 76.5% of (Z) -6, 10-dimethylundec-5, 9-dien-2-one and 21.4% of (E) -6, 10-dimethylundec-5, 9-dien-2-one (total of 99.5% of isomers, determined by GC).

The material is then isomerized by NO as described above. After a certain reaction time, the amounts of the E and Z isomers were determined periodically by GC.

Figure 2) shows the results of these isomerization experiments. The x-axis represents the reaction time and the y-axis represents the percentage of the measured isomer and the median E-isomer in the sample (E/(E + Z)). For example, an E/(E + Z) value of 80% represents an E/Z ratio of 80: 20.

Fig. 2) shows: the equilibrium cis/trans ratio of 6, 10-dimethylundec-5, 9-dien-2-one is between 60 and 65% E/(E + Z).

In a second series of experiments, the isomer of 6, 10-dimethylundec-5-en-2-one has been isolated by distillation. The E-isomer had been separated with a content of 95.5% of (E) -6, 10-dimethylundec-5-en-2-one (determined by GC) and the Z-isomer had been separated in a concentrated fraction with a content of 74.3% of (Z) -6, 10-dimethylundec-5-en-2-one and a content of 24.8% of (E) -6, 10-dimethylundec-5-en-2-one (99.2% of isomers in total, determined by GC).

these species are then isomerized by NO as described above. After a certain reaction time, the amount of each isomer was periodically determined by GC.

Figure 3) shows the results of these isomerization experiments. The x-axis represents the isomerization time and the y-axis represents the percentage of the measured isomer and the middle E-isomer in the sample (E/(E + Z)). For example, an E/(E + Z) value of 80% represents an E/Z ratio of 80: 20. The experiment shows that: NO is a very effective isomerization catalyst. In the isomerization of the E isomer, as many points as in the isomerization of the Z isomer have not been measured, giving the impression that the E isomer will be isomerized slower (see dashed line), however, only due to linear interpolation between the two points. Fig. 3) also illustrates: the equilibrium cis/trans ratio of 6, 10-dimethylundec-5-en-2-one is about 65% E/(E + Z).

In a third series of experiments, the isomers of 3,7, 11-trimethyl-1, 6, 10-dodecatrien-3-ol have been isolated by distillation. The E-isomer had been isolated with a content of 99.5% of (E) -3,7, 11-trimethyl-1, 6, 10-dodecatrien-3-ol (determined by GC) and the Z-isomer with a content of 99.7% of (Z) -3,7, 11-trimethyl-1, 6, 10-dodecatrien-3-ol (determined by GC).

The material is then isomerized by NO as described above. After a certain reaction time, the amount of each isomer was periodically determined by GC.

Figure 4) shows the results of these isomerization experiments. The x-axis represents the isomerization time and the y-axis represents the percentage of the measured isomer and the middle E-isomer in the sample (E/(E + Z)). For example, an E/(E + Z) value of 80% represents an E/Z ratio of 80: 20. The experiment shows that: NO is a fast isomerization catalyst. Fig. 4) also illustrates: the equilibrium cis/trans ratio of 3,7, 11-trimethyl-1, 6, 10-dodecatrien-3-ol is between 52 and 82% E/(E + Z).

In a fourth series of experiments, the isomers of 6,10, 14-trimethylpentadeca-5, 9, 13-trien-2-one have been isolated by distillation. The EE-isomer has been isolated with a content of 99.5% of (5E,9E) -6,10, 14-trimethylpentadeca-5, 9, 13-trien-2-one, a content of 0% of (5Z,9Z) -6,10, 14-trimethylpentadeca-5, 9, 13-trien-2-one and a content of the sum of 0.5% of (5E,9Z) -and (5Z,9E) -6,10, 14-trimethylpentadeca-5, 9, 13-trien-2-one (98.4% in total of 6,10, 14-trimethylpentadeca-5, 9, 13-trien-2-one, measured by GC).

The material is then isomerized by NO as described above. After a certain reaction time, the amount of each isomer was periodically determined by GC.

The results of these isomerization experiments are shown in FIGS. 5a) -c). The x-axis represents the isomerization time and the y-axis in FIG. 5a) represents the weight ratio of EE/(ZZ + EZ + ZE + EE). The y-axis in FIG. 5b) represents the weight ratio (EZ + ZE)/(ZZ + EZ + ZE + EE). The y-axis in FIG. 5c) represents the weight ratio ZZ/(ZZ + EZ + ZE + EE). Fig. 5a) -c) show: all isomers were isomerized to provide: an isomer ratio of about 50% EE/(ZZ + EZ + ZE + EE), about 45% (EZ + ZE)/(ZZ + EZ + ZE + EE) and about 15% ZZ/(ZZ + EZ + ZE + EE).

In a fifth series of experiments, the isomers of 6,10, 14-trimethylpentadeca-5, 9-dien-2-one have been isolated by distillation. The mixture of EZ-and ZE-isomers had been separated with a content of the sum of 93.3% of (5E,9Z) -and (5Z,9E) -6,10, 14-trimethylpentadeca-5, 9-dien-2-one, a content of 3.0% of (5E,9E) -6,10, 14-trimethylpentadeca-5, 9-dien-2-one and a content of 1.0% of (5Z,9Z) -6,10, 14-trimethylpentadeca-5, 9-dien-2-one (total of 97.3% of 6,10, 14-trimethylpentadeca-5, 9-dien-2-one, measured by GC).

The material is then isomerized by NO as described above. After a certain reaction time, the amount of each isomer was periodically determined by GC.

The results of these isomerization experiments are shown in FIGS. 6a) -c). The x-axis represents the isomerization time and the y-axis in FIG. 6a) represents the weight ratio of EE/(ZZ + EZ + ZE + EE). The y-axis in FIG. 6b) represents the weight ratio (EZ + ZE)/(ZZ + EZ + ZE + EE). The y-axis in FIG. 6c) represents the weight ratio ZZ/(ZZ + EZ + ZE + EE). Fig. 6a) -c) show: all isomers were isomerized with an equilibrium close to about 15% ZZ/(ZZ + EZ + ZE + EE), about 45% (EZ + ZE)/(ZZ + EZ + ZE + EE) and about 40% EE/(ZZ + EZ + ZE + EE).