CS269409B1

CS269409B1 - Method of alpha-dialkylaminoacrylic acid's esters preparation

Info

Publication number: CS269409B1
Application number: CS886124A
Authority: CS
Inventors: Zdenek Ing Drsc Arnold
Original assignee: Zdenek Ing Drsc Arnold
Priority date: 1988-09-14
Filing date: 1988-09-14
Publication date: 1990-04-11
Also published as: CS612488A1

Abstract

Je popisován obecný způsob přípravy esterů kyselinyíá -dialkylaminoakrylové obecného vzorce CHo=C.C00R * I η o kde R je primární, sekundární nebo terciární alkyl nebo aralkyl s jedni* až devíti uhlíky a kupiny Ri a R2 jsou bua stejné nebo různé, a to alkyly neb aralkyly s jedním až devíti uhlíky nebo spolu tvoří péti až sedmičlenný kruh, který obsahuje atom dusíku nebo atom dusíku a kyslíku, Popisovaný způsob vychází z esterů kyseliny pyrohro.znové, které se převádějí na žádané produkty reakcí a činidlem, získaným z odpovídajícího aminu a anorganického halogenidu, a to tak. aby reakční smée neobsahovala volný amin. Produkty jsou potenciálními léčivy, insekticidy, komplexačními činidly a jiné. Kromě nesporného technického významu se mohou uplatnit i v oblasti teoretické.A general method of preparation is described dialkylaminoacrylic acid esters general formula CHo = C.C00R * I η o where R is primary, secondary or tertiary alkyl or aralkyl having one to nine the carbons and coupons of R 1 and R 2 are either the same or different, namely alkyl or aralkyl with one to nine carbons or together forming a circle of up to seven, which contains a nitrogen atom or a nitrogen atom; Oxygen, The process is based on esters pyruvic acid, which are converted the desired products by reaction and reagent, obtained from the corresponding amine a of an inorganic halide. that the reaction mixture did not contain free amine. Products are potential drugs, insecticides, complexing agents and others. Except undeniable technical significance can also apply in the theoretical field.

Description

EN 269 409 B1 1

The present invention provides a general process for the preparation of esters of dialkylaminoacrylic acid. Dyalkylaminoacrylates of the general formula

wherein H is primary, secondary or tertiary alkyl or aralkyl of up to nine carbons;

carbons or together form a fifth to seven membered ring containing a nitrogen or nitrogen atom and oxygen, have not been studied at all, although their structural elements -enamine aggregation together with the ester function do so. compounds are very attractive organic synthase intermediates. these substances are also remarkable from a theoretical point of view. A unique derivative of this group, methyl piperidinoacrylate, was prepared in connection with the study tsv. of captodative olefins, i.e. olefins carrying an electron donor and electrakoeptorous group at the same carbon double bond atom. Said compound was isolated in low yield (5 to 10 µg) as one of the products of the reaction between methyl-chlorocrylate and piperidine (8 Mignani, Z. Jaun, R. Merenyi and HQ Viehe, J. Riga and J. Verbist). , Tetrahedron Lett, 25, 1571-1574 (1984)) The lack of suitable methods for their preparation has hindered deeper study of these compounds.

The availability of dialkylaminoacrylates is solved by the present invention, a process for preparing esters

at a temperature in the range of + 20 to -30 ° C, at least a stoichiometric amount of chloride selected from the group consisting of aluminum, arsenic, titanium and tin, is added to the reaction mixture, followed by addition of an ester of pyruvic acid of the formula CH 2 CO COOK, where H has the same meaning as above and the product is in an insulating manner.

The general method for the synthesis of dialkylaminoacrylates described in this invention is based on esters of pyruvic acid. In the course of the process described, the CH-JCO of the starting ester must be converted to enamine. As is known, pyruvic acid esters (purvates) undergo extremely easily both hydrolysis and a number of other nucleophilic reactions including condensation. Thus, the condition for their conversion to the desired esters is the mild reaction conditions, and in particular the absence of free amine, which could convert the ester function to amide. This requirement eliminates the use of most of the eaminase-friendly methods. The present invention has been based on the teachings of While and Weingarten, J. Org. Chem. The authors have found that many ketones, including steroids hindered, can be converted to enamines by reaction with amines in the presence of some inorganic chlorides, mostly tri- and tetra-chlorides, of which TiCl 4 - TiCl 4 is the best. For conversion

ropes - it was necessary to modify the reaction arrangement and its conditions, in particular to prevent the pyruvate ethyl and the free amine. This was achieved by initially adding to the solution of the corresponding amine in an inert solvent an amount of chlorine to keep the chloride in a slight stoichiometric excess. The basic stoichiometric process is further exemplified by two examples, the first of which relates to the use of tetrachloride, the second to trichloride: 2 CH 3 CO 2 COOR + 6 (CH 3) 2 NH + TiCl + = 2 CH 2 = C. (ch3) 2 2 C8 269 409 B1 3 CH 3 CO.COOB + 9 (GH-pgMH + 2 AsCl-j = 3 CH 2 = C.COOB + 6 (CH-j) 2NHHCl + As 2 O 3 to (CH 3) 2

For this method, the number of inorganic tri- and tetrahalides, and the elements belonging to IIIA, IV and VA groups of the periodic table can be used, the quality and yield of the product being dependent on the nature of the halide used. For example, TiCl 2, which is recommended (vis Vhite and Veingarten) as the most effective halide for enamine synthesis, gives a poorer result to pyruvate than, for example, AsCl 3, which is a mere reactive halide. This can be explained by the aforementioned high sensitivity of pyruvates to the cross-linking agents. This sensitivity requires such careful reaction, in particular tempering, preferably in the range of +15 to -30 ° C.

The described reaction can be carried out essentially in any inert solvent, for example saturated or aromatic hydrocarbon, chlorinated solvents, etc. Dry ether can be used with great advantages, especially in cases; when it is productive. Product isolation is simple in all cases. The by-products of the amines together with the oxides are aspirated and the product isolated by rectification or crystallization. The invention is further illustrated by the following examples, which do not limit it in any way. Example 1 Methyl methyl dimethylaminoacrylate

To a 2 L three-necked flask equipped with a stirrer, scoopers and thermometer was added a solution of 67.6 g (1 mol) of dimethylamine in 600 mL of dry ether. With stirring and external cooling, a solution of 60.4 g (28 ml, 1/3-mol) of arsenic chloride AsCl 3 in 200 ml of ether was run at -20 ° C for about 30 minutes. The reaction mixture was stirred for an additional 30 minutes, then a solution of 51.05 g (0.5 mol) of pyruvic acid methyl ester in about 100 ml of ether was added dropwise at -20 ° C over about 20 minutes. Stirring without cooling until the temperature reached room temperature and left for the next day. The precipitate was filtered off with suction, washed with 3x100 ml of dry ether, the solution obtained was filtered through a small silica gel column and the ether was distilled off through a column under a very slight vacuum. The product is isolated by rectification; 53.6 g (83% -dimethylaminoacrylate methyl, boiling point 40-51.5 ° C / 9 Torr. XH NMB (ODCl-j): 5, β5β (1 Η); 4.43β (1 H); 78s (3H); 2.63s (6H) Example 2 «(-Molyolinoacrylate Methyl)

In the same apparatus as in Example 1, a solution of 19 g (0.1 mol) of TiCl 4 in solution was added dropwise to a solution of 52.3 g (0.6 mol) of morpholine in 250 ml of a mixture of cyclohexane-benzene (1: 1) at -25 ° C. 60 ml cyclohexane. After stirring for 30 min, a solution of 20.4 g (0.2 mol) of pyruvic acid methyl ester in 60 ml of benzene was added dropwise at -25 ° C. Stirring without cooling for 4 hours, left for the next day. The precipitate was filtered off with suction, washed well with benzene / cyclohexane and filtered through a pad of silica gel. The solvents were stripped off in vacuo. 20.8 g of residue were obtained, which crystallized upon cooling. The yield of methyl p-morpholinoacrylate was 60.8%. The substance can be crystallized at low temperatures (-30 ° C) from ether, mp 46-49 ° C. NMB (CDCl3): 5.26s (1H); 4.63s (1H); 3.79s (3H); 2.98-3.92m (4H); 2.82-3.0m (4H). EXAMPLE 3 Methyl morpholinoacrylate was prepared according to procedure 2a, except that SnCl4 (26 g, 0.1 mol) was used instead of TiCl2. The product was zinc in 68% yield.

Claims

EXAMPLE 4 The methyl c-morpholinoacrylate was prepared according to the procedure of Example 1a, except that an equivalent amount of AlCl3 was used instead of ZeCl2. Yield 70%. EXAMPLE 5 Methyl tert-amino-acrylate was prepared by the same procedure as in Example 1a, except that morioline (130.7 g, 1.5 mol) was taken up in place of dimethylamine. The crystalline product was obtained in 92% yield. EXAMPLE 6 Methyl-2-piperidinoacrylate The procedure of Example 1 was followed except that piperin was used as amine and was operated at +20 ° C. 75% of the desired product was obtained, m.p. 57 ° C / 0.5 Torr. XH NMH (CDCl3): 5.11a (1 1) {4.5β (1 H) {3.78s (3H) j 3.0 - 2.7m (4H) 1.8-1.4m (6H). EXAMPLE 7 Methyl-3-pyrrolidinoacrylate The procedure was as in Example 1 except that pyrrolidine was introduced as the amine. The elution fraction was isolated from 59 to 61 ° C / 1 Torr. in 10% yield. 1H NMR (CDCl3): 4.73s (1H)} 4.16a (1H); 3.78a (3H); 3.3 - 2.98m

(2H); 2.0-1.74m (2H). EXAMPLE 8 c-Dimethylaminoacrylate t-butylnithe In a manner similar to Example 1, the desired product was obtained in a yield of 75%. B.v. 72.5-74.5 ° C / 11 Torr. 1 H NMR (CDCl 3): 4.87a (1H); 4.45a (1H); 2.62s (6H); 1.55a (9H). Example 9 < tb > < tb > < tb > < tb > < tb > ______________________________________ < tb > The product was obtained in a yield of 55%. · Esters of Z-dialkylaminoacrylic acid provide a wide variety of organic syntheses. They may be subjected to a number of electrophilic substitution reactions typical of enamines (acylation, reaction with carbonyl compounds, etc.) as well as for captodative. olefins (see S. Mignani et al., supra). Notable possibilities are provided by the cycloaddition reaction region, α1 already within the reactions of the Diels-Alder type or 22 + 2j cycloaddition reaction to form compounds with a four-membered, i.e., cyclobutane ring. Many of the products reported by the reaction are potential drugs, inectioids, complexing agents, etc. In addition to their undeniable technical significance, they can also be applied in the theoretical field. OBJECT OF THE INVENTION Process for the preparation of esters of dialkylaminoacrylic acid of the general formula CH = C.COOH1 1 2 CS 269 409 B1 wherein B is primary, secondary or tertiary alkyl or aralkyl of up to nine carbon atoms and E and R are both standing or different, namely alkyl or aralkyl and up to nine carbon atoms, or together form a five to seven membered ring containing a nitrogen atom or nitrogen and oxygen, characterized in that the amine of general formula B 1 R 4 NH, wherein R 1 and B have the same As above, dissolved in an inert solvent, at least 20 ° C to -30 ° C, at least stoichiometric amounts of the chloride of the selected group including aluminum, arsenic, titanium and tin are added, followed by addition of the pyruvic acid ester of the formula. CH 2 CO.COOR wherein B is the same as above and the product is isolated in a conventional manner. &