CS243669B1 - 2-nitro-1,3-propanediole's alkaline salt bromination method - Google Patents

Abstract

The essence is that it is brominated use mixed halogen brouchlor or bromination of the alkali salt is performed first 2-nitro-1,3-propanediol by equimolar amount bromine and is further brominated secondary bromine released from the formed alkali metal bromide subsequent with chlorine. Alkali salt of 2-nitro-1 3-Propanediol is brominated in suspension in the medium an anhydrous solvent that is under reaction conditions inert to the reactants and reaction products and in which the alkali metal chloride is not dissolved and vice versa dissolve under cold or after of heat 2-bromo-2-nitro-1,3-propanediol. Then the insoluble chloride is separated from a soluble product. Optionally, bromination alkaline salts of 2-nitro-1,3-propanediol carried out in solution in an organic solvent mixture or solvents and water and the product is isolated. 2-bromo-2-nitro-1,3-propanediol is high effective antimicrobial agent and uses as a preservative for cosmetic products and Household Chemistry.

Description

(54) a bromination method of the alkali salt of 2-nitro-1,3-propanediol

The principle consists in using a mixed halogen brouchlor for bromination or first bromination of the alkali salt

Of 2-nitro-1,3-propanediol with an equimolar amount of elemental bromine and further brominated with secondary bromine released from the formed alkali metal bromide by subsequent treatment with chlorine. Alkaline salt of 2-nitro-1,

3-Propanediol is brominated in suspension in an anhydrous solvent medium which is inert under the reaction conditions to the reactants and reaction products and in which the alkali metal chloride does not dissolve and, conversely, dissolves cold or hot 2-bromo-2-nitro-1 3-propanediol. The insoluble chloride is then separated from the soluble product. Optionally, bromination of the alkali salt of 2-nitro-1,3-propanediol is carried out in solution in a mixture of an organic solvent or solvents and water and the product isolated.

2-Bromo-2-nitro-1,3-propanediol is a highly potent antimicrobial and is used as a preservative in cosmetics and household chemicals.

The present invention relates to a process for the bromination of an alkali salt of 2-nitro-1,3-propanediol into 2-bromo-2-nitro-1,3-propanediol.

2-Bromo-2-nitro-1,3-propanediol is a highly potent antimicrobial that is used as a preservative in cosmetic and home chemistry products.

The production of 2-bromo-2-nitro-1,3-propanediol is basically always based on the alkali salt of 2-nitro-1,3-propanediol, most often the sodium salt, prepared by the alkali catalysed addition of nitromethane to formaldehyde (Schmldt Ε., Wilkendorf R. : Berichte £, 389 (1919); Darzens O .: Compt. Rend.2i> 5,942 (1947), which is brominated with elemental bromine according to the scheme: HCH ₂ -CNa (NO ₂ ) -CH ₂ OH + Br ₂ = HOCH 8 -BrNC (4) -CH ₂ OH + NaBr

The bromination was initially carried out in diethyl ether (Schmidt Ε., Wilkendorf R .: Berichte, 389 (1919)), later carbon disulfide or carbon tetrachloride was used as reaction medium (Trippet S., Walker DM: J. Chem. Soc. 1960, 2976).

In all cases, the solvent used was either unsuitable for industrial purposes due to a high degree of flammability (diethyl ester or carbon disulfide) or did not allow simple and effective separation of the alkali metal bromide from the product (carbon tetrachloride).

Bromination carried out in a two-phase water-1,2-dichloroethane system in the presence of excess calcium chloride (Wessedorf R .: Ger. Offen. 1,804.068 (1970)) allowed a more efficient separation of the bromide, which remained largely together with calcium chloride in solution, but practically the salted product contained an unacceptably high proportion of inorganic salts which could only be removed by repeated crystallization from water at the expense of large losses in product yield.

Moreover, the waste solution of sodium bromide and calcium chloride is difficult to dispose of and constitutes a significant barrier in industrial scale. Improvement has been achieved by conducting bromination with halogenated hydrocarbons (e.g. chloroform, dichloromethane or 1,2-dichloromethane) or saturated alkyl carboxylic acid esters (e.g. ethyl acetate) or methyl ether.

This process allows for the effective separation of the inorganic salt from the organic product directly in the reaction mixture, but, as with all processes used hitherto, it has the disadvantage of requiring two equivalents of hardly available bromine, the equivalent being consumed to form waste alkali metal bromide.

The latter disadvantages substantially reduce the bromination process of the alkali salt of 2-nitro-1,3-propanediol according to the invention, which consists in using brominated halogenated bromine or bromination of the alkali salt of 2-nitro-3- propendiol with an equimolar amount of elemental bromine and brominated secondary to the resulting alkali metal bromide by subsequent treatment with chlorine, wherein the alkali salt of 2-nitro-1,3-propanediol is suspended in an anhydrous solvent medium inert to the reagents under reaction conditions. in which the alkali metal chloride does not dissolve and, on the other hand, dissolves cold or hot 2-bromo-2-nitro-1,3-propanediol, then the insoluble chloride is separated from the soluble product, optionally by bromination of the alkali salt 2 -nitro-1,3-propanediol is carried out in solution in an organic solvent mixture; or solvent and water and the product isolated.

The bromochlorine solution is prepared in a solvent medium by reacting equimolar amounts of bromine and chlorine in advance, or the brominating agent is prepared in situ by bromination with elemental bromine while introducing chlorine into the reaction mixture.

The solvent, the cold-dissolving 2-bromo-2-nitro-3-propanediol and the non-solvent of the alkali metal chloride, is an alkyl ester of a saturated carboxylic acid of formula

O

R-O -? - R, (I.) wherein R is alkyl of 1 to 3 carbon atoms in the chain and R is hydrogen or alkyl α, and 2 carbon atoms in the chain (for example, ethyl acetate or methyl acetate).

The cold 2-bromo-2-nitro-1,3-propanediol solvent and the limited alkali metal chloride solvent is an aliphatic saturated alcohol having 1 to 3 carbon atoms in the chain (e.g., methanol or ethyl alcohol).

The hot, solvent-dissolving 2-bromo-2-nitro-1,3-propanediol and non-solvent alkali metal chloride is a halogenated hydrocarbon having 1 and 2 carbon atoms and 1 to 3 halogen atoms (chloroform or 1,2-dichloroethane or dichloromethane).

Alternatively, the solvent is an aliphatic saturated C1-C3 alcohol mixed with water in a ratio of 1 wt. alcohol by volume 0.3 to 3 wt. parts of water (methanol or ethanol mixed with water).

The corresponding alkali metal chloride is formed as a by-product. Qromchlor is readily prepared by reacting equimolar amounts of bromine and chlorine in a suitable solvent, where, depending on the type of solvent and other reaction conditions, in particular the procedure for dosing both halogens, it is believed to exist as a chemical individual or in situ directly in the reaction mixture. .: Preparative Reactions in Organic Chemistry, Czechoslovak Academy of Sciences, Prague 1955, Volume II, page 172; Mills JF, Schneider JA; Ind. Eng. Chem. Prod. Res. Develop., Vol. 12, No. 3, 1973).

As the solvent forming the reaction medium, it is preferable to use a halogenated hydrocarbon in which the alkali metal chloride formed does not dissolve and, conversely, 2-bromo-2-nitro-1,3-propanediol, preferably chloroform or 1,2-dichloroethane, dissolves cold or hot. or more preferably an alkyl ester (number of carbons in the chain of 1 to 3), a saturated carboxylic acid (number of carbons in the chain of 1 to 3), most preferably ethyl acetate.

The use of said solvents allows separation of the excreted inorganic salt from the dissolved product by filtration. Using water-dilute alcohols as the reaction medium (Harakawa M .: Japanese Patent 57-2242 (1982)), it is possible to separate undesired inorganic salts only when the final product crystallizes at the cost of greater losses.

The main advantage of the method of bromination of the alkali salt of 2-nitro-1,3-propanediol according to the invention is, besides the substantially higher reactivity of the brominating agent (Burger K., Qeuzer F., Schulek E .: Talanta X, 97 (1960)) Compared with the prior art, since the entire amount of the reaction is consumed for bromination of the organic molecule, and an alkali metal chloride is produced as a by-product, which can be disposed of or used on an industrial scale.

When halogenated hydrocarbons or alkyl esters of saturated carboxylic acids or aliphatic saturated alcohols, in which the alkali metal chloride by-product is insoluble or only slightly soluble, there is also the possibility of its easy and effective separation from the desired product.

The bromination can be effected by first treating the bromine with bromine Gram to one mole of the 2-nitro-1,3-propanediol alkali salt and completing the reaction by introducing the chlorine Gram in the reaction mixture, whereby bromine released by oxidation of the alkali metal bromide or a solution of bromochlor in an appropriate reaction solvent may be prepared beforehand by introducing an equimolar amount of chlorine gas to the present bromine in the solvent, preferably with cooling to about 0 ° C. Advantageously, the reaction may be carried out by continuously adding, in portions with cooling, a suspension of the alkali salt of 2-nitro-1,3-propanediol in the solvent, and simultaneously introducing chlorine into the reaction mixture.

The bromination procedure according to the invention is illustrated by the following examples:

Example 1

120 g of dry 2-nitro-1,3-propanediol sodium salt (0.84 mol) are ground in 500 ml of chloroform so that the particle diameter does not exceed 1 mm. The suspension was gradually added at -10 to +5 ° C to a solution of 67.4 g (0.42 mol) of bromine in 75 ml of chloroform.

30 g of chlorine (0.42 mol) are then introduced into the reaction mixture, while cooling to this temperature and stirring, for about 30 minutes, and the reaction mixture is then stirred at a temperature of up to 5 ° C for 1 hour.

A suspension of 8 g of activated carbon in 50 ml of chloroform is added to the reaction mixture, the mixture is heated to boiling and the precipitated sodium chloride is rapidly filtered off with activated charcoal. After cooling, a first crop of product (about 80 g) crystallized from the filtrate, after concentration of the mother liquor a second crop of about 43 g was obtained.

The total yield of 2-bromo-2-nitro-1,3-propanediol is 123 g (73% of the theoretical yield per sodium salt of 2-nitro-1,3-propanediol).

Example 2

37.1 g of sodium hydroxide (0.93 mol) are dissolved in 495 g of dry methanol and, after cooling to about 25 DEG C., 55.7 g of paraformaldehyde (1.85 mol) are dissolved. The solution is cooled to 0 to -10 ° C and 51.5 g of nitromethane (0.84 mol) are gradually added at this temperature.

After stirring at this temperature for 1 hour, the precipitated 2-nitro-1,3-propanediol sodium salt is thoroughly centrifuged or aspirated and used immediately for the next reaction. Mix thoroughly in 450 g of dry 1,2-dichloroethane such that the diameter of the suspension particles does not exceed 1 mm.

The suspension was then gradually added at -10 to +5 ° C to a solution of 67.4 g of bromine (0.42 mol) and 30 g of chlorine (0.42 mol) in 250 ml of 1,2-dichloroethane and the white suspension of the reaction mixture stirring at the same temperature for 1 hour.

The precipitated sodium chloride is filtered off and the solvent is distilled off under reduced pressure at a maximum of 45 ° C. 160 g of crude product are obtained which, after crystallization from water, yields 136 g (i.e. 80% of the theoretical yield on nitromethane) of 2-bromo-2-nitro-1,3-propanediol containing 99.5% of active ingredient.

Example 3

The sodium salt of 2-nitro-1,3-propanediol is prepared in the batch and by the procedure described in Example 2. After drying or centrifuging, the dried product is thoroughly mixed in 450 g of dry ethyl acetate so that the particle diameter of the suspension does not exceed 1 mm. The suspension is then gradually added at -10 to +5 ° C to a solution of 67.4 g (0.42 mol) of bromine in 250 g of dry ethyl acetate while stirring and introducing chlorine into the reaction mixture.

The rate of addition of the sodium salt suspension and the rate of chlorine introduction are controlled so that the reaction is complete within 30 to 45 minutes. The end of the reaction is indicated by consumption of 30 g of chlorine (0.42 mol) and decolourisation of the reaction mixture.

After stirring for 1 hour, the precipitated sodium chloride is filtered off and the solvent is distilled off under reduced pressure at a maximum of 45 ° C. 168 g of crude product are obtained, which, after recrystallization from water, yields 140 g (i.e. 83% of the theoretical yield on nitromethane) of 2-bromo-2-nitro-1,3-propanediol containing min. 99% of active substance.

Example 4

40 g (1 mol) of sodium hydroxide are dissolved in 250 ml of methanol and, after cooling to about 25 DEG C., 170.5 g (2.1 mol) of 37% formaldehyde are added to the solution. The solution is cooled to -10 to +5 ° C and 61 g (1 mol) of nitromethane is gradually added while maintaining the temperature in this interval.

The reaction mixture was stirred for an additional 1 hour and then 80 g (0.5 mol) of bromine was added dropwise at this temperature. After all the bromine has been added, 35.5 g (0.5 mol) of chlorine is introduced into the reaction mixture with stirring and maintaining the temperature in the above interval.

The reaction mixture finally has a yellow-orange to reddish color and a slightly acidic reaction. After stirring for two hours, the precipitated sodium chloride is filtered off, and the filtrate is distilled off under reduced pressure at a temperature of max. 45 ° C and partly water and the distillation residue, weighing approximately 300 g, are cooled to about 5 ° C.

Crystalline 2-bromo-2-nitro-1,3-propanediol is precipitated with stirring in an amount of 120 g (60% of the theoretical yield for the nitromethane used) with a purity of min. 98.5%. Treatment of the mother liquor with 5-fold extraction with an equal volume of ethyl acetate and concentration of the combined extracts in vacuo gave an additional crop which, after recrystallization with ethyl acetate-chloroform (1.2), gave about 24 g of product with min. content of 98.5% active ingredient. The total yield of 2-bromo-2-nitro-1,3-propanediol is 134 g, i.e. 73% of the theoretical yield for the nitromethane used.

Example 5

In a procedure similar to that of Example 4, instead of 250 ml of methanol, 50 ml of water and 200 ml of ethanol were used, and instead of 40 g (1 mol) of sodium hydroxide, 56.1 g (1 mol) of potassium hydroxide was used. 126 g (i.e. about 63% of the theoretical yield per nitromethane) of 2-bromo-2-nitro-1,3-propanediol are obtained in a purity of min. 98.5%.

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of 2-bromo-2-nitro-1,3-propanediol in an anhydrous solvent-inert solvent and reaction product medium in which the insoluble alkali metal salt formed is a soluble preparation, optionally in an organic solvent or solvents, and water, characterized in that the bromination is carried out at -20 to 25 ° C with an equimolar amount of bromine either in the form of a mixed bromochloro halogen prepared by reaction of equimolar amounts of bromine and chlorine, optionally in situ during bromination with elemental bromine with chlorine introduction; bromine and bromine secondly released from the formed alkali metal bromide by subsequent treatment with chlorine, then the product is isolated.