CS229101B1 - Process for preparing 2.bromo-2-nitro, 1,1-propanediol - Google Patents

Abstract

The invention relates to a method for preparing 2-bromo-2-nitro-1,3-propadiol, which is a preservative in cosmetic and household chemical products. Existing production processes are technologically demanding. This advantage is eliminated by the method according to the invention, which consists in using an anhydrous medium of an industrially common reaction solvent for the bromination of the isolated alkaline salt of 2-nitro-1,3-propadiol, in which only the product dissolves when cold or after heating, and the bromide is easily separated in a solid state and practically pure with the possibility of further use.

Description

The present invention relates to a process for the preparation of 2-bromo-2-nitro-1,3-propadiol. This substance is used as a preservative in cosmetics and household chemicals.

2-Bromo-2-nitro-1,3-propanediol is one of the new generation of antimicrobials and is used in a number of applications alone or in synergistic combinations with other active substances. Its advantage is balanced efficacy on G + and G- bacteria and favorable low toxicity, it does not irritate the skin and mucous membranes and does not have sensitizing effects.

The essence of the preparation of 2-bromo-2-nitro-1,3-propanediol is almost always in the first stage of the addition of nitromethane to formaldehyde to give 2-nitro-1,3-propanediol which is immediately treated with an alkali metal or alkaline earth metal hydroxide or alkaline metal hydroxide. of the alcoholate into the corresponding salt, most often sodium. In the second step, the 2-nitro-1,3-propanediol salt is brominated to 2-bromo-2-nitro-1,3-propanediol. At the end of the last century, the preparation of 2-bromo-2-nitro-1,3-propanediol by reaction of sodium salt of 2-nitro-1,3-propanediol with bromine in diethyl ether was described (Schmidt E., Wilkendorf R .: Berichte 52. 389) (1919)), and later also carbon monoxide or carbon tetrachloride (Trippett S., Walker DM: J. Chem. Soc. 1960 «2976), either the solvent being unsuitable for industrial scale (fire hazard diethyl ether or carbon disulphide) or not simple and effective separation of the bromide from the product (carbon tetrachloride). If the bromination was later carried out in a two-phase water-1,2-dichloroethane system in the presence of excess calcium chloride (Wessendorf Rt Ger. Offen. 1,804 * 068 (1970)),

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229 101

Although bromide, unlike the product, was largely in solution together with calcium chloride, it was difficult to dispose of industrially and the practically salted product contained too much inorganic salts that could only be removed by repeated crystallization from water. Crystallization of 2-bromo-2-nitro-1,3-propanediol from industrial scale water is technologically demanding, since the product forms very solid crystalline layers on the walls of the apparatus and stirrer, which are difficult to remove and process.

The improved preparation process of the present invention eliminates these difficulties. The essence is that the solid alkali salt of 2-nitro-1,3-propanediol collects in the form of a suspension in an anhydrous reaction solvent medium which is inert to the reactants and reaction products under the conditions and in which the alkali bromide does not dissolve. metal, and vice versa, dissolve in the cold or hot 2-bromo-2-nitro-1,2-propanediol, which is obtained after the solvent has been distilled off in the solid state, optionally recrystallized. It is preferred that the cold-dissolving reaction solvent is a saturated carboxylic acid 2-bromo-2-nitro-1,3-propanediol alkyl ester or ethyl acetate or methyl acetate. The 2-bromo-2-nitro-1,3-propanediol reaction solvent is then preferably a halogenated hydrocarbon having 1 or 2 carbon atoms and having 1 to 3 halogen atoms or chloroform or 1,2-dichloroethane or dichloromethane. Preferably, 2-bromo-2-n-tro-1,3-propanediol is recrystallized by cooling a warm, saturated aqueous solution of 2-bromo-2-nitro-1,3-propanediol with stirring in a coolant medium which is under the given conditions, an inert organic liquid, immiscible with water and non-dissolving 2-bromo-2'-nitro-1,3-propanediol. The auxiliary medium is preferably an aromatic hydrocarbon having 1 benzene core and 1 to 3 methyl groups on the core or without methyl groups on the core, for example benzene, toluene or xylene, or a halogenated hydrocarbon having 1 or 2 carbon atoms and 2 to 6 halogen atoms, for example carbon tetrachloride, trichlorethylene or tetrachlorethylene.

As the reaction solvent for bromination, either is used

- 3 229 101 a halogenated hydrocarbon in which 2-bromo-2-nitro-1,3-propanediol is dissolved hot, preferably chloroform or 1,2-dichloroethane, or more preferably an alkyl ester (number of carbons in the chain of 1 to 3), saturated carboxylic acids (number of carbons 1 to 3), preferably ethyl acetate, in which the product dissolves easily even when cold. Using a halogenated hydrocarbon, the bromide is filtered off hot, and either cooling the saturated filtrate yields a major portion of the crude product and concentrating the residue after concentrating the filtrate, or concentrating the filtrate directly after concentrating the bromide to obtain the entire crude product yield at once. However, due to the relatively low solubility of 2-bromo-2-nitro-1,3-propanediol in halogenated hydrocarbons, it is necessary to work at about 2-3 times greater dilution of the reaction mixture than in the case of esters in order to avoid product loss. In particular, the use of the above-mentioned esters, in which the product dissolves very well even in the cold, appears to be more advantageous and the dilution of the reaction mixture is determined by virtually only the stirrability of the 2-nitro-1,3-propanediol salt suspension. After filtration of the bromide from the cold reaction mixture, the solvent is distilled directly from the filtrate under reduced pressure (the product is thermolabile) and the crude product is freed from colored impurities as in the case of halogenated hydrocarbons by recrystallization from water using activated carbon. The yields of the crude product without recrystallization reached 92 to 96% of theory on bromine with an active compound content of 96 to 100%, the yield of crystallization from water being about 88% of the feed. For crystallization from water, for example, some aromatic hydrocarbons (benzene, toluene, xylene, etc.) or, more preferably, some halogenated hydrocarbons, such as carbon tetrachloride, may be used as an auxiliary coolant, which must be inert, immiscible with water and a non-solvent product. trichlorethylene, perchlorethylene and the like

As the source of the alkali salt of 2-nitro-1,3-propanediol has been used previously described (Sohmidt E., Wilkendorf R .: Berichte 52. 389 (1919))? (Darzens G .: Compt. Rend. 225 (1947)) an alkali catalysed addition of nitromethane to formaldehyde, which is released from paraformaldehyde directly in the reaction medium of an alkali metal methanol or alkali metal methoxide in excess of methanol.

Example 1. _{22g 101}

120.7 g of sodium (5.25 mol) are dissolved in 3,750 ml of anhydrous methanol and, after cooling to about 25 DEG C., 330.0 g of paraformaldehyde (11.0 mol) are dissolved. The solution is cooled to 0 to -10 ° C and at this temperature 305.2 g of naithromethane (5.0 mol) are gradually added. The white suspension is stirred at the same temperature for 1 hour and then thoroughly centrifuged or aspirated. Dried under reduced pressure at about 30 ° C to constant weight to yield the sodium salt of 2 _T nitro-1,3-propanediol (crystallizes with two molecules of methanol) is 984.0 g, i.e. 95% for nitromethane, the content of active substance is 99.5% (polarographically).

721 g of dry sodium salt of 2-nitro-1,3-propanediol (3.48 mol), ground up to a particle diameter of not more than 1 mm, are well mixed in 3000 ml of chloroform. The suspension was then gradually added at -10 to +5 ° C to a solution of 548 g of bromine (3.43 mol) in 600 ml of chloroform, and the reaction mixture was then allowed to heat for 1 hour at the same temperature. A suspension of 50 g of activated carbon in 300 ml of chloroform is then added, the entire contents are heated to reflux and the sodium bromide and activated charcoal are rapidly filtered off. From the filtrate, after cooling, the first crop of crude product, i.e. after drying 390 g, crystallizes, after concentration of the mother liquor, 200 g, i.e. a total of 86% of theoretical yield on bromine, containing 98.7% active ingredient and 0.7%. of inorganically bound bromine.

Due to the content of inorganically bound bromine (sodium bromide) and especially the reddish coloration, it is advisable to carry out recrystallization from water: 4 g of activated carbon are suspended in 225 ml of distilled water and the mixture is heated to 70 ° 0. 500 g of 2-bromo-2-nitro-1,3-propanediol are added in one portion and the temperature is raised to 65 DEG C. by dissolution. After dissolution, the mixture is filtered while hot in 500 ml of well stirred carbon tetrachloride pre-cooled to -5 to 5.

-10 [deg.] C. and with stirring and giving the filtrate, the elevated temperature is sucked off at the same temperature for 1 hour and dried at max. 45 [deg.] 0 440 g of white 2-bromo-2-nitro-1 / crystallization, containing 99.5% of bound bromine.

cooling until it is brought to Θ to -5 ° C. After mixing, the product is thoroughly centrifuged or constant weight. I-Propanediol is obtained, i.e. 88% yield of active ingredient and 0.2% inorganic

Example 2

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1.10 kg of sodium hydroxide (27.5 mol) are dissolved in 18.7 l of dry methanol and, after cooling to about 25 DEG C., 1.66 kg of paraformaldehyde (55.3 mol) are dissolved. The solution was cooled to 0-10 ° C and 1.53 kg of nitromethane (25.1 mol) was gradually added at this temperature. After stirring at the same temperature for 1 hour, the white suspension of sodium 2-nitro-1,3-propanediol is thoroughly centrifuged or aspirated and used immediately. Mix thoroughly in 15% O 1 dry ethyl acetate so 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 3.73 kg of bromine (23.3 mol) in 7.3 L of dry ethyl acetate, and the white suspension of the reaction mixture was stirred at the same temperature for 1 hour. The sodium bromide is filtered off and the solvent is distilled off under reduced pressure at max. 45 ° C. There are obtained 4 »40 kg of crude product, i.e. 94.5% of the theoretical yield on bromine, containing 99.3% of active ingredient and 0.6% of inorganically bound bromine. The orange-colored crude product is recrystallized from water:

1.98 L of distilled water was suspended in 35 g of activated carbon and heated to 70 ° C. 4.40 kg of 2-bromo-2-nitro-1,3-propanediol are added in one portion and the temperature dropped to 65 ° C by dissolution. After dissolution, the mixture is filtered while hot into 4.4 L of well stirred trichlorethylene precooled to -5 to -10 ° C and allowed to crystallize with stirring and cooling until the temperature is lowered to 0 to -5 ° C by adding the filtrate. After stirring for 1 hour at the same temperature, the product is thoroughly centrifuged or aspirated and dried at max. 45 ° C to constant weight. 3.87 kg of white 2-bromo-2-nitro-1,3-propanediol are obtained, i.e. 88% crystallization yield, containing 99.8% active ingredient and 0.1% inorganically bound bromine.

When carrying out the crystallization of the crude product from water on an industrial scale, it is advantageous to dissolve the crude product residue without prior separation, ie by adding water and activated carbon directly to the evaporator in the distillation apparatus.

Claims (8)

SUBJECT OF THE INVENTION 229 101 Process for the preparation of 2-bromo-2-nitro-1,3-propanediol by bromination of the alkali salt of 2-nitro-1,3-propanediol characterized in that the solid alkali salt of 2-nitro-1,3-propanediol is brominated in the form of a suspension in the presence of an anhydrous reaction solvent inert to the reactants and reaction products under the conditions and in which the alkali metal bromide does not dissolve and, on the contrary, dissolves in the cold or hot 2-bromo-2-nitro-4,3-propanediol; which is obtained after distillation of the solvent in the solid state, optionally recrystallized. 2. Method of claim 1, wherein the reaction solvent for dissolving cold 2-bromo-2-nitro-1,3-propanediol is an alkyl ester of a saturated carboxylic acid of formula I, R ⁰ "0-CR ₁ (I) wherein R is alkyl of 1 to 3 carbon atoms in the chain and R 1 is hydrogen or alkyl of 1 to 2 carbon atoms in the chain. 3. A process according to claim 1 or 2, wherein the reaction solvent is ethyl acetate or methyl acetate. 4. The process of claim 1, wherein the hot-dissolving reaction solvent of 2-bromo-2-nitro-1,3-propanediol is a halogenated hydrocarbon having 1 or 2 carbon atoms and 1 to 3 halogen atoms. 5. A process according to claim 1 or 2 or 3 or 4 wherein the reaction solvent is chloroform or 4,2-dichloroethane or dichloromethane. 6. The process of item 1 a or 2 a or 3 a or 4 a or 5, characterized in that the 2-bromo-2-nitro-1,3-propanediol is reacted by cooling the hot saturated aqueous solution of 2-bromo7. 229 101 Of 2-nitro-1,3-propanediol with stirring in a coolant medium which is an inert, water-immiscible organic liquid under the conditions and insoluble 2-bromo-2-nitro-1,3-propanediol. 7. A process according to claim 1, or 2 and 3 or or 4 and or 5 or 6, wherein the cooling medium is an aromatic hydrocarbon having 1 benzene core and 1 to 3 methyl groups on the core or without methyl groups. such as benzene, toluene or xylene. 8. A process according to claim 1 or 2 or 3 and or 4 and or 5 and or 6 or 7, characterized in that the auxiliary cooling medium is a halogenated hydrocarbon having 1 or 2 carbon atoms and 2 to 6 halogen atoms, for example carbon tetrachloride. , trichloroethylene or tetrachlorethylene.