JPH0347276B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates generally to the field of pyridine chemistry, and more particularly to certain pyridine derivatives that have shown particular utility as catalysts in acylation and alkylation and related reactions.

There is ample documentation on the effects of catalysts. The ability of these substances to change the rate of chemical reactions without themselves being consumed and without their own chemical equivalence changing is highly appreciated in both laboratory and commercial applications. Beneficial. In pyridine chemistry, pyridine itself is known to act as a parent compound for a large group of congeners and other derivatives, and as a catalyst and solvent for certain types of reactions. However, reaction times are often long and associated with low yields. A typical example of these is an "acylation type" reaction. As used herein, this means
It refers not only to what is traditionally called acylation, in which an acyl group is incorporated into an organic molecule by substitution, but also, for example, formylation, carbamoylation,
phosphorylation, arylsulfonylation, lactonization,
It is also understood to mean recognized related reactions such as cyanylation, esterification, etc. Also representative are "alkylation-type" reactions, which as used herein are defined as alkylation in the classical sense of introducing an alkyl group into an organic compound by substitution or addition, as well as alkylation, such as It is understood to mean recognized related reactions such as alkylsilylation, tritylation, etc.

For these acylation- and alkylation-type reactions, as for other reactions in general, there is a continuing search for more effective chemically active catalysts. In this study, 4-dimethylaminopyridine was found to effectively catalyze acylation and alkylation as well as several similar reactions [G. Höffle, W. Schüttekritz and H. Forbrytsgen, Angew .Chem.Int.Ed.
Engl., 17 , 569 (1978)]. 4-dimethylaminopyridine is reported to be about ¹⁰⁴ times more active than pyridine itself, previously used as a catalyst and solvent as described above. Regarding specific reactions, for example, it is difficult to acylate tertiary alcohols smoothly and in high yields due to steric hindrance, as is well known. However, treatment of linalool with acetic anhydride and 4-dimethylaminopyridine in triethylamine reportedly yields 80% yield of linalyl acetate after 14 hours at 24°C. The sterically hindered phenol mesitol (more precisely identified as 2,,4,6-trimethylphenol) is also smoothly acylated in high yield with acetic anhydride in the presence of 4-dimethylaminopyridine. [G. Höfle and W. Schüttekrich, Synthesis,
619 (1972)].

The versatility and capabilities of 4-dimethylaminopyridine as a catalyst are best illustrated by considering its use in processes of particular commercial importance. For example, 4-dimethylaminopyridine can be used to form polyurethanes from p-toluene-diisocyanate and glycols (UK Patent Nos. 990635 and 990633) and polyepoxides (UK Patent No. 1201756) and polyamides (UK Patent No. 1207673). It is stated that it promotes It is reported in German Patent No. 2155152 that the production of ampicillin by treating 6-isocyanatopenicillinate with D-N-benzyloxycarbonyl-2-phenylglycine is also catalyzed by 4-dimethylaminopyridine. has been done. Commercial production has also been reported for phosphorothioate esters with insecticidal and acaricidal activity of pyridine, pyrazine (Belgium Patent No. 832047) and pyrimidine (UK Patent No. 2011415).

Despite these advantages experienced with 4-dimethylaminopyridine as a catalyst, disadvantages have also been observed regarding its use. One drawback is that this compound is a solid. This poses problems both for laboratory use and for industrial applications, particularly where the method of adding solids to batch or continuous reactions can be difficult. This compound may therefore be used in conjunction with a co-solvent in order to alleviate at least some of this problem. However, it is often difficult to separate the desired product from the catalyst in its stimulating state, especially if it is basic. Furthermore, recovery of the 4-dimethylaminopyridine catalyst itself often proves to be extremely difficult under such conditions. These difficulties would not be observed with liquid catalysts that are as effective as 4-dimethylaminopyridine in reactions such as the examples above. The inventors were not aware of such catalysts prior to the present invention. Although pyridine is indeed a liquid, it is much less active as a catalyst, as mentioned above.

One aspect of the present invention is the following formula: A catalyst for an acylation or alkylation reaction consisting of liquid 4-(4'-methylpiperidino)pyridine having the structure and the compound.

The above compound is a liquid and is a good catalyst, far superior to pyridine and at least comparable to 4-dimethylaminopyridine, without the disadvantages observed with these compounds, in reactions of the acylation type and alkylation type. Show ability. Preliminary tests have given us confidence that the compositions of the invention can be further used as catalysts and possibly in other applications as well. Furthermore, the inventors expect that future testing will identify other liquid compositions that belong to this family and may prove to have similar advantages in catalytic and other applications. ing.

The compounds of the invention are in liquid form, isolated and
It has been identified as having a boiling point of 163°C at a pressure of 5.5mmHg.

In terms of utility, the 4-(4'-methylpiperidino)pyridine of the present invention is itself far superior to pyridine as a catalyst in acylation- and alkylation-type reactions, with at least 4-
It was proven to be comparable to dimethylaminopyridine. A quantitative comparison of the catalytic abilities of the compounds of the present invention and 4-dimethylaminopyridine was carried out using the method described by Connors and Albert, J.Pharm.Science, 62, 845 (1973). For example, under standard conditions, the acylation of isopropanol with acetic anhydride progresses to 92% after 5 minutes at 40°C in the presence of 4-dimethylaminopyridine and 88% in the presence of 4-(4'-methylpiperidino)pyridine. It was %.
As a second example, the acylation of t-butanol, a sterically hindered alcohol, is performed using acetic anhydride.
During 2 hours at 69°C, 38% completion was achieved using 4-dimethylaminopyridine as catalyst. This can be compared to 37% acylation using the 4-(4'-methylpiperidino)pyridine of the present invention under the same conditions. As a third example, 4 of the present invention
- by tritylation (more fully termed triphenylmethylation) of benzyl alcohol using a (4'-methylpiperidino)pyridine catalyst,
The product was obtained in 89% yield after standing overnight at room temperature under nitrogen.

In each reaction tested to date, the catalyst of the present invention has worked effectively and no problems have arisen due to the use of co-solvents or other additives, or due to re-isolation and recovery of the catalyst after completion of the reaction. .
From the above results, the 4-(4'-methylpiperidino)pyridine of the present invention can act as a catalyst similarly well in other acylation-type and alkylation-type reactions as previously described in this specification. It is reasonable to expect that there will be.

To facilitate a better understanding of the description herein and the nature and scope of the invention,
The following detailed examples are given of methods for preparing (4'-methylpiperidino)pyridine and its subsequent use as a catalyst in alkylation-type and alkylation-type reactions.

Example 4 - 31.5 parts of cyanopyridine, 25 parts of water, 44 parts of concentrated hydrochloric acid
1 part and 21 parts of 2-vinylpyridine were added. The resulting mixture was heated to 60°C for 6 hours, cooled to 30°C, at which point 36.5 parts of 4-methylpiperidine were added. The mixture was then stirred at 30°C for 2 hours, at which point 200 parts of 40% sodium hydroxide was added,
The mixture was boiled under reflux for a further 2 hours. The solution is then cooled, the organic layer separated and distilled to give 5.5
4-(4'-
35 parts of methylpiperidino)pyridine were obtained.

Then 13.6 g (0.1 mol) of 2,4,6-trimethylphenol in 100 ml of methylene chloride and 4
-(4'-methylpiperidino)pyridine 8.5g (0.05
2,4,6-trimethylphenyl acetate was prepared by slowly adding 15 g (0.15 mol) of acetic anhydride to a solution of 2,4,6-trimethylphenyl acetate. After the reaction mixture was allowed to stand for 2 hours, diethyl ether was added and the ether solution was washed with dilute hydrochloric acid and then with saturated sodium bicarbonate solution. The extract was dried (MgSO ₄ ), the solvent was removed, and the residue was distilled to 0.5 mm
15.5 g (87%) of 2,4,6-trimethylphenyl acetate having a boiling point of 64 DEG C. in Hg was obtained. 4-
The (4'-methylpiperidino)pyridine catalyst was recovered in dilute hydrochloric acid and reisolated by standard neutralization, extraction and distillation procedures.

The production of triphenyl methyl benzyl ether also requires 11 g of benzyl alcohol in methylene chloride.
(0.01 mol), triphenylmethyl chloride 33.4 g
(0.12 mol) and 4-(4'-methylpiperidino)
This was done by standing a mixture of 1 g (0.006 mol) of pyridine at room temperature under nitrogen overnight. The reaction mixture was evaporated to near dryness the next day and the residue was crystallized from ethanol to yield 31 g (89%) of triphenylmethylbenzyl ether, melting point 95°C. The 4-(4'-methylpiperidino)pyridine catalyst remained unchanged and was re-isolated by standard neutralization, extraction and distillation procedures.

Claims (1)

[Claims] Primary formula: 4-(4'-methylpiperidino)pyridine represented by Quadratic formula: An acylation or alkylation reaction method characterized by using 4-(4'-methylpiperidino)pyridine represented by as a liquid reaction catalyst. 3. The method according to claim 2, further comprising the step of recovering the catalyst after the reaction. 4. Claim 2 or 3, wherein the reaction is an acylation reaction.
Method described. 5. The method according to claim 2 or 3, wherein the reaction is an alkylation reaction. 6. Process according to claim 2 or 3, wherein the use of the catalyst is carried out in the absence of co-solvents.