DD287712A5 - METHOD FOR THE PRODUCTION OF ALPHA, BETA-UNSATURATED CARBONYL COMPOUNDS - Google Patents

Abstract

The invention relates to a process for the preparation of a, b-ungesaettigten carbonyl compounds by aldol condensation of aldehydes, ketones or an aldehyde with a ketone. According to the invention, the reaction is carried out in the presence of alkyl titanates in a neutral medium with or without a solvent. The target products can be used as important intermediates for organic syntheses, in particular for the production of pharmaceuticals, pesticides, fragrances, flavors and dyes. {A, b-unsubstituted carbonyl compound; aldol condensation; Aldehyde-aldehyde implementation; Ketone ketone implementation; Aldehyde-ketone implementation; ; Alkyl titanate; Intermediate for organic syntheses; ; Fragrance and flavoring; Dye}

Description

Field of application of the invention

The invention relates to an access roads for the preparation of α, β-unsaturated carbonyl compounds by Aldokondensation of aldehydes, ketones, or an aldehyde with a ketone, α, β-unsaturated carbonyl compounds are important intermediates in organic synthesis, in particular for the production of medicaments, crop protection agents, perfume and flavorings as well as dyes.

Characteristic of the known state of the art

Aldol condensation is one of the most widely used methods for the formation of carbon-carbon bonds in organic chemistry. The reaction is carried out in protic solvent. As basic catalysts, alkali and alkaline earth hydroxides, hydroxide, potassium carbonate, potassium cyanide, disodium hydrogen phosphate, borax, sodium acetate, sodium sulfite and soap solutions have been proven. Acid catalysts such as hydrochloric acid and phosphoric acid also effect aldolization (HO House, Modern Synthetic Methods, 2nd Edition, Benjamin, New York, 1972, Chapter 10, AT Nielsen, WJ Holubien, Organic Reactions 16 (1968), 1). For aldol condensation of formaldehyde with acetaldehyde and higher homologues in the gas phase at temperatures between 200 and 36O ⁰ C zinc, bismuth and chromium oxides are used as catalysts. Aldol condensations are very advantageously carried out using basic ion exchangers. Under these conditions, gums are strongly suppressed (MJ Astle, JA Zaslowsky, Ind. Eng. Chem. 44 (1952), 2869). More recently, various metal derivatives of onolisierton

Carbonyl compounds for stereoselective Aldolreaktlonen used. The metals used are tin, silicon, boron and aluminum. Tltan (IV) chloride has also been successfully used (T. Mukaiyama, Angew Chem 89 (1977), 858; Angew Chem. Int. Ed. Engl. 16 (1978), 817 and Organic Reactions 28 [1982], 203 ). All these reactions carried out in the liquid phase have in common that α, β-unsaturated carbonyl compounds are obtained only in acidic or basic medium. This is disadvantageous since undesirable secondary reactions, such as discoloration, gumming and decomposition, are observed especially in the case of sensitive aldehydes and ketones under acidic or basic conditions, which lead to considerable yield reductions.

Object of the invention

The object of the invention is to produce α, β-unsaturated carbonyl compounds from aldehydes and / or ketones under neutral conditions, in which way the secondary reactions caused by acidic or basic catalysts should be avoided so as to increase the yields and the work-up - and reduce cleaning costs.

Explanation of the essence of the invention

The object of the invention is to find a condensing agent which allows to carry out an aldol condensation of carbonyl compounds under neutral conditions and if possible using catalytic amounts. This object is achieved by reacting α, β-unsaturated carbonyl compounds of the general formula 1 in which R ¹ , R ² , R ³ and R ^{4 are} hydrogen, unbranched or branched, saturated or unsaturated alkyl or cycloalkyl radicals, substituted or unsubstituted heterocyclic mean or aromatic radicals, and wherein R 'with R ² and R ³ with R ⁴ may be connected by bridges, by aldol condensation of carbonyl compounds of the general formula 2, wherein R * and R ¹ have the abovementioned meanings, with carbonyl compounds of the general formula 3 in which R ³ and R ^{4 have} the abovementioned meanings, according to the invention with titanates of the general formula 4 in which R ^{5 is} an unbranched or branched alkyl radical having 1 to 20 carbon atoms or an unsubstituted or substituted phenyl radical, reacted with or without solvent.

The carbonyl compounds of the general formula 2 and 3 can according to the invention be identical or nonidentical aldehydes, aldehyde and ketone or identical and nonidentical ketones. The reaction can be carried out in solvents such as hexane, benzene, toluene or decalin but also without solvents. Depending on the reactivity of the carbonyl compounds, the reaction is carried out in the temperature range from 0 to 200 ° C. Particularly suitable condensing agents are tetraisopropyl, tetra-n-propyl, tetra-n-butyl and tetra-tert-butyl titanate. The titanates do not have to be used in stoichiometric amounts; they are also effective when catalytic amounts are used.

To obtain the erfindungsgomäß prepared ι α, β-unsaturated carbonyl compounds, the approaches are mixed with water and freed by filtration of titanium (IV) oxide. The α, β-unsaturated carbonyl compounds are extracted from the filtrate and purified by distillation, crystallization or chromatography. Due to the neutral reaction both in the reaction and in the workup, the α, β-unsaturated carbonyl compounds of general formula 1 are obtained in good yield.

AutfOhrungtbeltplete example 1

2- {n-pentyl) non-2-en-1-al (1, R ¹ = nC ₆ H ₁₃ , R ² = H, R '= nC ₆ H ", R ⁴ = H)

A solution of n-heptanal (5.7 g, 50 mmol) in absciutem hexane (50ml) at 2O ⁰ C with tetra-isopropyl titanate (20ml, 77 mmol)

staggered and allowed to stand at this temperature for 2 h. Then diethyl ether (100 ml) and water (30 ml) are added.

The resulting suspension is filtered through soy sand. After separation and drying of the organic phase is the Solvent removed in vacuo and the residue purified by distillation. Yield: 4.6 g (88%); Bp 155 ° C / 15Torr.

¹ H-NMR (CDCl ₃ ): 0.81 ppm (6H, 2 t, J 6Hz, 2CH ₃ ), 6.36 ppm (1 H, t, J 7Hz, olefinic proton) ¹³ C-NMR (CDCl ₃ ): 13.74, 22.30, 23.80, 28.25, 28.50, 28.73, 28, 86, 31, 43, 31, 63, 63, 73, 154, 48 and 194.87 ppm.

MS (e / z, e.i.): 210 (M, 92%), 169 (60%).

Example 2

2- (n-pentyl) -3-phenylprop-2-enal (1, R ¹ = C ₄ H ₆ , R ² = H, R ³ = nC ₆ H ", R ⁴ = H)

A solution of heptanal (5.7g, 50mmol) in absolute toluene (20ml) and a solution of tetra-isopropyl titanate (7.1ml,

25 mmol) in the same solvent (20 ml) are added dropwise simultaneously over 2 h to a boiling solution of benzaldehyde (53 g, 500 mmol) in toluene (100 ml). After cooling, it is stirred with diethyl ether (200 ml) and water (50 ml). The resulting suspension is nitrated over sea sand. After separation and drying of the organic phase is the

Solvent removed in vacuo and the residue purified by distillation. Yield: 5.7 g (56%); Cp 174 to 175 "C / 20Torr.

'H-NMrt (CDCl ₃ ): 0.81 ppm (3' I, t, J 6Hz, CH ₃ ), 7.20 to 7.90 ppm (5 aromatic and 1 olefinic proton).

MS (e / z, e.i.): 202 (M, 2.5%), 160 (3%), 130 (4.5%).

Example 3

i-phenyloct-i-en-3-one (1, R ¹ = C ₆ H ₆ , R ² = H, R ³ = H, R * = nC ₆ H ")

A solution of benzaldehyde (5.3g, 50mmol), heptan-2-one (5.7g, 60mmol) and tetra-t-butyl titanate (17g, 50mmol) in

absolute toluene (50 mmol) is heated to boiling under argon for 4 h. After cooling, diethyl ether (100 ml) and water (30 ml) are added. The resulting suspension is filtered over sea sand. After separation and drying of the organic phase, the solvent is removed in vacuo and the residue is purified by distillation.

Yield: 7.0 g (71%); Bp 140 to 150 ^e C / 5 χ 10 " ³ Torr (Kugelrohr).

¹ H-NMR (CDCl ₃ ): 0.92 ppm (3H, t, J 6Hz, CH ₃ ), 6.68 ppm (2H, d, J 6Hz, olefinic protons), 7.20 to 7.60 ppm (5H, m , aromatic protons).

MS (o / z, e.i.): 202 (M, 7%), 173 (3%), 159 (4.5%), 131 (100%).

Example 4

2-cyclopentylidene-cyclopentan-1-one (1, R'-R '= (CHj) ₄ , R ³ -R ⁴ = (CH ₂ ) ₃ )

A mixture of cyclopentanone (22g), tetra-isopropyl titanate (5ml, 18mmol) and absolute toluene (50ml) becomes Siodon for 2 hours

heated. After cooling, diethyl ether (100 ml) and water (50 ml) are added. The resulting suspension is over

Sea sand filtered. After separation and drying of the organic phase, the solvent is removed in vacuo and the Residue by distillation goreinigt. Yield: 9a (46%); Bp 95 ° C / 5 χ 10 " ³ torr.

MS (e / z, c.i): 151 (M + 1.100%), 83 (20%).

Example 5

2- (n-pentyl) -3-phenylprop-2-enal (1, R ¹ = C ₆ H ₆ , R ² = H, R ³ = nC ₆ Hti, R ⁴ = H)

Heptanal (0.69ml, 5mmol) becomes inngsam to a boiling solution of benzaldehyde (5.3g, 50mmol) and tetra-t-butyl titanate

(0.085 ml, 0.25 mmol) was added dropwise. The mixture is heated to boiling for a further 4 h. After cooling, it is washed with diethyl ether (20 ml) and

Water (5ml) and worked up as described in Example 2.

Yield: 0.61 g (60%).

Example β

2- (n-pentylidene) cyclopentan-1-one (1, R ¹ = nC «H ,, R ¹ = H, R ³ -R ⁴ = (CHj) ₃ )

Pentanal (2.6g, 25mmol) and tetra-t-butyl titanate (5ml, 16.8mmol) are added to a solution of cyclopentanone (21g,

250 mmol) in absolute toluene. The mixture is heated to boiling for 2 h. After cooling, diethyl ether (100 ml) and water (30 ml) are added. The resulting suspension is filtered through sea sand. After separation and drying of the organic phase, the solvent is removed in vacuo and the residue is purified by distillation.

Yield: 2.8g! 74%); Bp. 130 ° C / 20 Torr (Kugelrohr).

¹ H-NMR (CDCl ₃ ): 0.33 ppm (3H, m, CH ₃ ), 2.52 (10H, m, 5CH,), 6.60 ppm (1H, t, J 7Hz, olefinic proton).

¹³ C-NMR (CDCl ₃ ): 13,85,25,31,26,77,29,39,30,62,38,56,135,96,137,30,206,63.

MS (m / z, e.i.): 152 (M, 32%), 123 (55%), 97 (75%), 55 (100%).

-C = C-C-R

R '

H ₂ CC

R ³

Ti (ORj

Claims (10)

1. A process for the preparation of α, β-unsaturated carbonyl compounds of the general formula 1, in which R ¹ , R ² , R ³ and R ^{4 are} hydrogen, unbranched or branched, saturated or unsaturated alkyl or .Cycloalkylreste, substituted or unsubstituted heterocyclic or mean aromatic radicals and where R ¹ with R ² and R with R ⁴ may be connected by bridges ^3, by Aldokondensation of Carbonylveroindungen of the general formula 2 in which R ¹ and R ² have the abovementioned meanings, with carboxyl compounds of the general formula 3, in which R ³ and R ^{4 have} the abovementioned meanings, characterized in that the said carbonyl compounds in the presence of titanates of the general formula 4 in which R ^{5 is} an unbranched or branched alkyl radical having 1 to 20 carbon atoms or an unsubstituted or substituted phenyl radical, be reacted with or without solvent. 2. The method according to claim 1, characterized in that one uses as carbonyl compounds of the general formula 2 and 3 identical aldehydes. 3. The method according to claim 1, characterized in that 2 and 3 non-identical aldehydes are used as carbonyl compounds of the general formulas. 4. The method according to claim 1, characterized in that is used as the carbonyl compound of the general formula 2 is an aldehyde and carbonyl compound of the general formula 3, a ketone. 5. The method according to claim 1, characterized in that 2 and 3 identical ketones are used as carbonyl compounds of the general formulas. 6. The method according to claim 1, characterized in that the non-identical ketones used as carbonyl compounds of the general formulas 2 and 3. 7. The method according to claim 1 to 6, characterized in that preferably tetra-isopropyl, tetra-n-propyl, tetra-n-butyl or tetra-tert-butyl titanate are used for the condensation reaction. 8. Verfahien according to claim 1 to 7, characterized in that the titanates of the general formula 4 are used only in catalytic amounts. 9. The method according to claim 1 to 8, characterized in that one carries out the reaction in hexane, benzene, toluene or decalin. 10, Process according to Claims 1 to 9, characterized in that the reaction is carried out in a temperature range from 0 to 200 ^° C. For this 1 page formulas