CS209012B1 - Process for the production of new 4-pentenal enamines - Google Patents

Abstract

Enamines of 4-pentenal of the general formula I, 7 N-CH=CH-CH2-CH«CH2 (I) i R2 ! in which R1 and R2 denote the same or different alkyls with 3 to 5 carbon atoms, or R1 and R? together denote a pentamethylene chain or the residue: —CH2CH2OCH2CH2, are intermediates in the production of pharmaceuticals. They can be prepared by condensing 4-pentenal of the formula Π CH2=CH-CH2-CH2-CHO (II) with an organic base of the general formula III, R1—NH—R2 (III) i in which R1 and R2 denote the same or different alkyls ee ■ 3 to 5 carbon atoms, or R1 and R2 together denote a pentamethylene chain or the residue -CH2CH2OCH2CH2-, in the presence of a dehydrating agent in the temperature range from -15 to +30 °C, and by cleavage of the reaction mixture by heating to boiling under appropriately reduced pressure.

Description

The invention relates to a process for the production of new enamines of 4-pentenal of the general formula I, > N-CH=CH-CH ₂ -CH=CH ₂ (I) · r ^2/ in which R ¹ and R ² denote the same or different alkyls with 3 to 5 carbon atoms, or R ¹ and R ² together denote a pentamethylene chain or the residue -CH ₂ CH ₂ OCH ₂ CH ₂ The compounds of the general formula I, not yet described, represent intermediates in the production of drugs. They are produced by the process according to the invention, the essence of which is that 4-pentenal of the formula II

CH ₂ =CH-CH ₂ -CH ₂ -CH=O (II) condenses in the presence of a water-removing agent* with an organic base of the general formula ΠΙ,

R ¹ - NH - R ² (III), i í ' I in which R ¹ and 2 ² mean the same as in formula I, in the temperature range from -15 °C to + 30 °C, preferably at 0 °C, after which the obtained mixture is subjected to a cleavage reaction by heating to boiling under reduced pressure of 1.25 to ; 3.60 kPa.

A number of substances can be used as dehydrating agents, e.g. alkaline earth metal oxides, but preferably alkali metal carbonates or molecular sieves.

In the actual implementation of the process according to the invention, an excess, but very preferably a stoichiometric amount (i.e. two equivalents) of an organic base of the general formula III is used for the reaction.

Enamines of the general formula I can be prepared ! alternatively by heating 4-pentenal of the formula ^{II to} boiling with a minimum stoichiometric amount of an organic base of the general formula III. Compared to the method according to the invention, this method is less general and can only be used with bases of the general formula ΙΠ in which R ¹ or R ² is a branched alkyl.

The following examples merely illustrate but do not limit the generality of the method according to the invention.

Example 1

To a mixture of 255 g (3 mol) of piperidine (III, R ¹ + R ² = CH ₂ (CH ₂ ) ₃ CH ₂ ) and 125 g of potassium carbonate is added dropwise over 45 minutes with stirring and cooling with ice 126.3 g (1.5 mol) of 4-pentenal (II). The reaction mixture is stirred for a further 3 h under cooling and left to stand for 14 h at room temperature. The liquid phase is separated:

! and the solid portion is washed on a frit with 4x 100 ml of toluene. The combined organic phases are concentrated on a rotary vacuum evaporator and the residue is distilled on a 30 cm long injection column in a nitrogen atmosphere. A fraction with a boiling point of 83 to 85 °C/1250 Pa is collected. i 181.4 g of 1-(1,4-pentadienyl)piperidine (I, R ¹ + R ² = CH ₂ (CH ₂ ) ₃ CH ₂ ) is obtained, which corresponds to 80.1% of theory.

Example 2 [To a stirred mixture of 84 g (1 mol) of 4-pentenal (II) and 25 g of molecular sieve, 230 g (2 mol) of propylisobutylamine (III, R ¹ = CH ₃ CH ₂ CH ₂ , R ² = (CH ₃ ) ₂ CHCH ₂ ) are added dropwise while cooling to 5 °C and the mixture is allowed to warm to room temperature while stirring.

The liquid phase is separated and the molecular sieve is washed with 2 x 100 ml chloroform. The combined liquid phases are concentrated in vacuo on an evaporator and the residue is distilled on a 26 cm long injection column in a reduced vacuum of a water pump. 119.1 g (65.8%) of N-isobutyl-N-propyl-(1,4-pentadienyl-yl)amine (I, R ¹ = CH ₃ CH ₂ CH ₂ , R ² = (CH ₃ ) ₂ CHCH ₂ ), which has a boiling point of 107 to

110.5 °C at 3.6 kPa. »

Example 3

To a stirred mixture of 78.5 g (0.5 mol) of dipentylamine [(ΠΙ), R ¹ = R ² = CH ₃ (CH ₂ ) ₃ CH ₂ ) and potassium carbonate at 0 °C was added 21 g (0.25 mol) of 4-pentenal (II) over a period of 30 min. The mixture was stirred without cooling for a further 4 h and then left to stand for 24 h at room temperature. The liquid product was separated and the solid was washed with 100 ml of benzene in three portions. The liquid phases were combined and the benzene was evaporated under reduced pressure. The residue was then distilled in vacuo using a water pump. 37.9 g of N,N-dipentyl(1,4-pentadien-1-yl)amine (I, R ¹ = R ² : — CH ₃ (CH ₂ ) ₃ CH ₂ ) are obtained, which corresponds to 68.1% of theory. The boiling point is in the range of 96.5 to 99.5 °C at 1350 Pa.

Example 4

To a solution of 10.73 g (75 mmol) of isobutylpentylamine (ΠΙ, R ¹ = (CH3)2CHCH2, R ² = CH3(CH ₂ ) ₃ CH ₂ ) in 50 ml of benzene was added 6.3 g (75 mmol) of 4-pentenal (II) and the mixture was heated under a water separator to boiling for 7 h. The reaction mixture was concentrated on a rotary vacuum evaporator. The residue was distilled under water pump vacuum to obtain 13.4 g of N-isobutyl-N-pentyl-(1,4-pentadien-1-yl)amine (I, R ¹ = (CH3)2CHCH2, R ² = CH3(CH ₂ ) ₃ CH ₂ ), which corresponds to 85.3% of theory.

[ The substance boils at 91 to 94 °C/1450 Pa.

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of the novel 4-pentenal enamines of the formula I, R ^{2 <} N-CH = CH-CH, -CH = CH, (I) wherein R ¹ and R ² denote the same or different C 3 -C 5 alkyls or R ¹ and R ² together denote a pentamethylene chain or the radical -CH ₂ CH ₂ OCH ₂ CH ₂ - characterized in that the 4-pentenal of formula II is present CH ₂ = CH-CH ₂ -CH ₂ -CH = O (II) condenses in the presence of a water scavenger, with an organic base of formula III, R ¹ -NH-R ² (III) 209 012 wherein R ¹ and R ^{2 are the} same as in formula I, at temperatures from -15 to +30 ° C, preferably at 0 ° C, after which the resulting mixture is cleaved by heating to boiling under reduced pressure 1.25 to 3.60 kPa.