Method of pinner reaction course and ending tracing during imidate synthesis

CS 272135 Bl

The invention relates to a process for monitoring the course and completion of the Pinnar reaction in the synthesis of imidates of the formula I.

NH. HC1¹ — ^{0 R}2 where R_x means CH₃-,C₂H₅-,C₆H₅-, R₃0₂C-CH₂-, and denote R₂, R₃ methyl, ethyl.

The Pinner synthesis of imidates is performed by reacting the appropriate nitrile with an anhydrous alcohol, in an anhydrous medium in the presence of anhydrous hydrogen chloride, by the procedures summarized with appropriate reference in Chem. Roar. 61,179 (1961), in the work of R. Roger and Douglas G. Nelson: The Chemistry of Imidates and the like. The reaction is generally carried out at 0 DEG C. in the presence of a suitable anhydrous solvent, for example chloroform, ether, nitrobenzene, dioxane, benzene, said solvents serving as diluent and at the same time protecting the imidate itself from atmospheric moisture and subsequent reactions. A slight excess, usually 1.1 mol of HCl per 1 mol of nitrile, is used in the hydrogen chloride gas. Lower molar ratios of HCl to nitrile (^ 1) cause a low conversion of the starting nitrile to the imidate, the yield of the isolated imidates deteriorating significantly. Molar ratios of HCl higher than 1.15 mol / mol of nitrile, on the other hand, worsen the conditions of crystallization and separation of imidates - the products are often in a gel-like, poorly filterable form. Monitoring of the time course of saturation of the reaction mixture with hydrogen chloride and completion of saturation at the desired optimal molar ratio is usually performed by discontinuous analysis of samples taken during the reaction or most often by weighing the reaction mixture, including the apparatus itself. Methods of control with sampling are difficult, · lengthy, do not allow continuous monitoring of the entire course of the reaction, and thus possible automatic control of the process. Weighing the reaction mixture, for example using electromechanical balances, offers some possibilities for continuous monitoring of the reaction, automated process control, but the disparity between the weight of hydrogen chloride consumed and the weight of the reaction mixture with the weight of the apparatus does not guarantee the required accuracy of the hydrogen chloride feed. CH1 / nitrite ratio.

A simple method and apparatus has now been found for monitoring the progress and termination of the Pinner reaction. The essence of the method is to monitor the course and completion of the Pinner reaction of acetonitrile, alcohol and anhydrous hydrogen chloride in toluene to the desired imidate according to the invention, that a conductometric determination is used. Preferably, a conductometric sensor is placed in the reaction mixture and the course of the hydrogen chloride saturation is recorded in graphical form on a recorder. The actual saturation of the HCl reaction mixture is terminated when the curve shows a permanent monotonic decrease after reaching the conductivity maximum, which is usually 10 to 20 minutes after reaching the conductivity maximum at an almost constant reaction temperature.

The invention overcomes the above-mentioned drawbacks of the prior art methods, thus creating the preconditions for a possible automatic process control on an operational scale. The invention preferably complements the process according to MS. Author's Certificate No. 268 639 «Process for the preparation of methyl iminoacetate hydrochloride. The quality of the conductometric indication of the end of the reaction is not affected by the possible return of the mother toluene filtrates to the next operation.

The invention is illustrated by the following non-limiting examples, and by the figures which show the conductivity as a function of time and thus the course of saturation of the reaction mixture with hydrogen chloride and are evidence of the actual method of carrying out, indicating and terminating the Pinner reaction.

Example 1

To a pre-weighed glass reactor equipped with an external cooling bath, a thermometer, a high-speed stirrer, a conductometric sensor (C_R= 0.621 cm^-1) with a reflux condenser, a nitrogen inlet above the surface and an anhydrous HCl inlet under a stirrer, 82 g (2 mol

CS 272135 B1 ly) acetonitrile /. then 70.48 g of anhydrous methanol and 160 ml of toluene. The resulting batch is cooled to 0 ° C with stirring and the function of the conductometer and linear recorder is checked. A constant flow of anhydrous HCl (0.68 g / min) is then set, a recorder is started and about 80/2 g (2.2 mol) of HCl are introduced into the reaction mixture over 2 to 2.5 hours. The temperature of the reaction mixture is maintained at 5 to 7 ° C with an accuracy of -2 ° C during the saturation and a graphical record of the course of the reaction on a recorder is observed. As soon as the maximum conductivity is reached under otherwise constant conditions (temperature, HCl flow) and the further course of the curve has a decreasing tendency, the supply of hydrogen chloride is closed within 10 to 15 minutes (see Fig. No. 1-curve A, Δ = 13/3 min.) and a control analysis of the mixture (by sampling and determination of HCl) and / or a weighing of the reaction mixture or apparatus is performed. In this way, it was found that 77 g of HCl (2.13 mol) was absorbed in the reaction mixture, which was in good relation to the desired molar ratio of HCl / nitrile, i.e. 1 <HCl / nitrile 1,1 1.15.

Further procedure and work-up of the reaction mixture was similar to that in MS. Author's Certificate No. 268 639: Process for the preparation of methyl aminoacetate hydrochloride (0.Kalab et al.) and 190 g of dry product, i.e. 86.7% of theory for acetonitrile, were obtained according to the above procedure.

Example 2

82 g of acetonitrile were introduced into the reactor according to Example 1,¹ then 70.48 g of anhydrous methanol, 132 ml of the mother toluene filtrate from Example 1 and 28 ml of fresh toluene. after reaching the maximum conductivity (see Fig.l-curve Β / δ 18.5 min.). By the control methods described above, it was found that 86 g of HCl / i.e. 2.36 mol and 1/18 mol of HCl / mol of nitrile, respectively, were absorbed in the reaction mixture. In order to obtain the optimum molar ratio of HCl / nitrile, a further 5/76 g of acetonitrile (0.14 mol) and 4.55 g of methanol (0.142 mol) were introduced into the reaction mixture and the reaction mixture was worked up as in Example 1. 218.7 g of dry product were thus obtained, i.e. 93.3% of theory.

Example 3

410 g of acetonitrile (10 mol), 352.4 g (11 mol) of anhydrous methanol and 686/54 (800 ml) of toluene were introduced into a 2/5 l glass reactor equipped according to Example 1. The hydrogen chloride flow was adjusted to 2/366 g HCl / min. and the further procedure, the conductometric sensor and the actual method of monitoring the progress of the reaction were similar to Example 1. The HCl supply was stopped 20 minutes after reaching the maximum conductivity (see Fig. No. 2 δ ^ = 20 min). The control revealed 396 g of absorbed HCl (theory 401 g), 1 i.e. 1.09 mol HCl / mol nitrile.

By the same procedure as in the previous Example 1, 953 g of dry product were obtained, i.e. 87% of theory.