GB2162180A

GB2162180A - Pyridone derivatives

Info

Publication number: GB2162180A
Application number: GB08518531A
Authority: GB
Inventors: Hans-Georg Schmidt
Original assignee: Dynamit Nobel AG
Current assignee: Dynamit Nobel AG
Priority date: 1984-07-24
Filing date: 1985-07-23
Publication date: 1986-01-29
Also published as: JPS6137770A; GB8518531D0; GB2162180B; DE3427146A1; FR2568250A1

Abstract

Pyridone derivatives of formula (I> <IMAGE> wherein R is hydrogen, or optionally substituted alkyl or aryl are useful as intermediates for cyclopropane carboxylic acid derivatives. The pyridones can be prepared by reacting a dihydro- alpha -pyrone, or a pentanoic acid (ester), with an amine or ammonia.

Description

SPECIFICATION Pyridone derivatives This invention relates to new pyridone derivatives and to the preparation of these compounds.

According to one aspect of this invention, there are provided pyridone derivatives having the general formula (I)

in which Ri stands for hydrogen or optionally substituted straight-chained or branched alkyl residues or aryl residues.

The alkyl residues can be of any desired chain length. They can also possess up to 18 C-atoms, more preferably from 1 to 8 C-atoms. The alkyl residues can also be substituted, substituents preferably being aryl residues, for example phenyl, which can optionally be substituted by alkyl groups or halogen, or carboxylic acid residues. Preferably the substituents are arranged in the a-position to the nitrogen atom or terminally, although other substitution arrangements react in like manner.

It is furthermore possible that four different substituents be provided on one carbon atom of the alkyl chain so that this carbon atom is an optically active centre. The term optically active centre includes also structures with dissymetry such as for example atropisomerism. Such optically active compounds are the preferred compounds. They are suitable for the production of cis-caronaldehyde lactones which serve as intermediates for especially effective insecticides.

An aryl residue R' is preferably phenyl or naphthyl. These residues can also be nuclearly substituted by halogen or by C1 to C4 alkyl residues.

The production of the compounds of this invention takes place according to the second aspect of this invention by reacting either 3,4-dihydro-4,4-dimethyl-pyrones or 5-oxo-pentanoic acid derivatives with compounds of the formula H2NRX, in which Ri has the above-indicated meaning.

In addition to using ammonia, monoalkylamines, preferably with up to 18 C-atoms which can optionally also be substituted can be used as compounds of formula H2NR. Preferred substituents are the phenyl group or a carboxylic acid residue. The phenyl group can be substituted by alkyl or halogen (e.g.

chlorine or bromine). If an amine is employed which contains an asymmetric carbon atom, i.e. an optically active form of the amine is be employed, then an optically active pyridone is obtained. An arylamine of formula H2NRa may also be used.

The reaction proceeds more rapidly in the presence of acids as catalysts. Preferred catalysts are aromatic sulphonic acids, such as for example p-toluene sulphonic acids, or the water-free metal halides known in the narrower sense as Lewis acids, such as AlCI3, FeCI3, BF3. However phosphoric acids such as for example H3PO4 may also be employed as catalysts. The addition of a catalyst is however not essential.

If the indicated oc-pyrones are employed as starting materials, the reaction already proceeds at ambient temperature. Warming increases the rate of reaction; Therefore, the reaction mixture can be heated to temperatures up to 250"C.

The dihydro-o-pyrones, which are employed as starting materials, correspond to the formula

They can be produced for example according to the process described in DE-A-29 52 068.

The reaction between the (x-pyrone and the amine proceeds in the desired direction with any desired ratios of reaction partners to one another. Preferably however the a-pyrnne is employed in excess, with the excess being able to amount to up to 100 mol%. After the completion of the reaction, the excess pyrone can easily be separated off from the desired pyridone by distillation and be recovered.

If 5-oxo-pentanoic acid derivatives are employed as starting materials for the production of the new pyridones, these correspond to the formula

in which R2 stands for hydrogen or for alkyl residues with 1 to 8 C-atoms. In this case, the reaction temperature is preferably from 80 to 250"C and the reaction partners are preferably in a stoichiometric ratio to one another. The same catalysts as aforesaid are preferably used.

The new pyridones are predominantly high boiling compounds. They can therefore be easily purified by distillation off of the starting materials and any by-products which may be present. The reaction can therefore in general be carried out in the absence of solvents.

It is however also possible to carry out the reaction for the production of the new compounds in the presence of solvents; this is especially recommended if the new compounds are crystalline or the amine to be employed is not a liquid. Suitable compounds for use as solvents are chiefly those compounds in which the water being produced in the reaction is not soluble and which can be removed from the reaction vessel in the form of an azeotropic mixture with the solvent. Examples of suitable solvents are aliphatic ethers, aromatic, optionally nuclearly chlorinated hydrocarbons or straight-chained or branched alkanes. There may be named as possible representatives of this group of substances, dimethyl ether, benzene, toluene, xylene, chlorobenzene, hexane and isooctane.

The new pyridones of this are valuable intermediate products for the production of insecticides and pharmaceuticals. For this purpose, they can be reacted with halogen or alkali alcoholate in an alcohol to form 3-azabicyclo [3.1.0.]-hexane derivatives of the formula

which are analogous to the known cyclopropane carboxylic acid ester acetals, which are starting materials for the production of insecticides with pyrethroid structure.

The following Examples illustrate this invention: Example 1 A mixture of 117 g of aniline, 316 g of 4,4-dimethyl-3,4-dihydro-a-pyrone and 0.5 g of p4oluene sulphonic acid was warmed for 18 hours at 80"C. Then the reaction mixture was distilled in vacuo. 112 g of unreacted 4,4-dimethyl-3,4-dihydro-a-pyrone passed over at 40 to 500C (0.1 Torr). The N-phenyl-4,4-dimethyl- 3,4dihydro-a-pyridone reaction product distilled at 120 to 1250C (0.1 Torr) following on after an intermediate fraction. Yield 193 g (80.16%).

NMR-spectrum (90 MHz, CDCI3): 3(ppm) = 1.14 (6 H); 2.52 (2 H); 5.10, 6.14 (2 H); 7.16 -7.40 (5 H).

Example 2 A mixture of 2.4 g of aniline and 4 g 3,3-dimethyl-5-oxo-pentanoic acid was heated in the presence of 1 mg of p-tolune sulphonic acid to 1200C. The toluene distilling off was led through a H2O separator which was filled with a molecular sieve and then was led back to the reactor. After 18 hours reaction time, the material present in the reaction vessel was worked up as in Example 1. 1 g of N-phenyl-4,4-dimethyl-3,4 dihydro-ol-pyridone was obtained.

Example 3 A mixture of 11.8 g of aniline and 20 g of 3,3-dimethyl-5-oxo-pentanoic acid methyl ester was heated in the presence of 1 mg of p-toluene sulphonic acid at 90do. After a reaction time of 18 hours, working up was carried out in an analogous manner to Example 1. 8.2 g of N-phenyl-4,4-dimethyI-3,4-dihydro-a-pyr done were obtained.

Example 4 4 g of gaseous NH3 were introduced into a mixture of 76 g of 4,4-dimethyl-3,4-dihydro-a-pyrone, 0.5 g of p-toluene sulphonic acid and 155 g of toluene. Then stirring took place at ambient temperature for 24 hours and the reaction mixture was then worked up distillatively. 22.1 g of 4,4-dimethyl-3,4-dihydro- apyridone passed over at 118 to 125"CII Torr and after cooling to ambient temperature became crystalline (melting point: 55 to 56 C).

NMR-spectrum (90 MHz, CDCI3): ô (ppm): 1.08 (6 H); 2.31 (2 H); 4.91 (1 H); 5.99 (1 H); 8.84 (1 H) Example 5 A mixture of 463 g of d (+)-a-phenylethylamine, 964 g of 4,4-dimethyl-3,4-dihydro-a-pyrone and 0.5 g p-toluenesulphonic acid was heated at 80"C for 12 hours. Then working up took place distillatively. After a first running, the N-(a-phenylethyl)-4,4-dimethyl-3,4-dihydro-- pyridone passed over at 1500C/l Torr.

(Yield 760 g).

NMR-spectrum (90 MHZ, CDCI3): b (ppm): 1.01 (3 H); 1.04 (3 H); 1.51 (3 H): 6.01 (1 H); 2.40 (2 H); 4.93 u. 5.75 (2 H); 7.27 (5 H).

Specific rotation: a2g - -3.6.

Claims

1. Pyridones having the general formula

2. A pyridone according to claim 1, in which the residue RI contains at least one optically actively acting centre.

3. A pyridone as claimed in claim 1, wherein RI is alkyl containing up to 18 C-atoms or aryl which is optionally substituted by alkyl, halogen or carboxyl.

4. N-phenyl-4,4-dimethyl-3,4-dihydro-a-pyridone.

5. 4,4-dimethyl-3,4-dihydro-o-pyridone.

6. N-(oe-phenylethyl )-4,4-d imethyl-3,4-d ihydro-o-pyridone.

7. A process for the preparation of a pyridone as claimed in any preceding claim wherein a dihydro-a- pyrone of the formula

is reacted with an amine of the formula

in which R' has the meaning indicated in claim 1.

8. A process for the preparation of a pyridone as claimed in any one of claims 1 to 6, wherein a 5oxo-pentanoic acid derivatives of the formula

in which R2 stands for hydrogen or an alkyl residue with 1 to 8 C-atoms is reacted with an amine of the general formula Ill.

in which R1 has the meaning given in claim 1.

9. A process as claimed in claim 7 or 8, which is carried out in the presence of a catalyst which is an aromatic sulphonic acid, a phosphoric acid or a Lewis acid.

10. A process as claimed in claim 7, 8 or 9, which is carried out at a temperature in the range from ambient temperature to 250"C.

11. A process for the preparation of a pyridone having the general formula given in claim 1, substantially as described in any one of the foregoing Examples.