Preparation method of bromoacetic anhydride

Abstract

The invention relates to a preparation method of bromoacetic anhydride. The preparation method comprises the following steps: adding a certain amount of organic solvent into a reaction kettle; a certain amount of bromoacetic acid is added, the weight ratio of the organic solvent to the bromoacetic acid is (3-5): 1, a certain amount of acetic anhydride is added, and the ratio of the acetic anhydride to the bromoacetic acid is (1-3): 1; then adding a certain amount of solid acid catalyst resin, wherein the addition amount of the resin is 2-5% of the weight of the bromoacetic acid; the reaction temperature is controlled by the addition of the solvent, and the solvent after reaction can be recycled and reused without loss; due to the addition of the solid acid resin catalyst, the formation of mixed anhydride is effectively inhibited, and the generation of the target product bromoacetic anhydride is promoted; after the reaction is finished, the effective separation of the resin can be realized through precipitation without filtration; the target product can be obtained by distillation after the reaction, so that the operation steps are reduced, and the time is saved; the process is low in raw material cost, simple to operate, high in product quality and easy for industrial production.

Description

Technical Field

[0001] The invention relates to a method for preparing an organic compound, in particular to a method for preparing bromoacetic anhydride by catalysis of a strongly acidic solid acid resin. Background Art

[0002] Bromoacetic anhydride is an important fine chemical raw material and pharmaceutical intermediate. Bromoacetic anhydride and its derivatives are widely used in the pharmaceutical, fragrance, pesticide and other industries. For example, it is used to prepare neuropeptide Y analogs for breast cancer diagnosis, raw materials for preparing N-bromoacetyl-β-glycinamide, and fluorescent biosensors for anti-galectin-3. At present, the price of bromoacetic anhydride on the market is expensive, which limits its application. Therefore, the development of high-quality bromoacetic anhydride is of great significance.

[0003] At present, the preparation methods of bromoacetic anhydride mainly include the following:

[0004] 1. In a dichloromethane solution, bromoacetic acid is dehydrated under the action of N,N'-diisopropylcarbodiimide to obtain the target product. N,N'-diisopropylurea is removed by suction filtration, and the filtrate is concentrated to obtain the target product.

[0005] 2. In dichloromethane solution, bromoacetic acid and DCC react to dehydrate, filter, and concentrate the filtrate to obtain the target product.

[0006] 3. Add bromoacetic acid to acetic anhydride, heat to reflux, and then distill under reduced pressure to obtain the target product.

[0007] 4. In dichloromethane, react with bis(2-oxo-3-oxazolidinyl)phosphinoyl chloride to obtain the target product.

[0008] 5. In the toluene solution, bromoacetyl bromide and sodium bromoacetate are reacted, filtered, the filter cake is washed with a non-protonic solvent and then filtered, the filtrate is combined to obtain a bromoacetic anhydride solution, and the target product is obtained after concentration.

[0009] Method 1 and method 2 differ only in the dehydrating agent, and both post-treatments require filtration to remove the generated urea. Bromoacetic anhydride products are very easy to absorb water. During the filtration process, bromoacetic anhydride easily absorbs water and turns into bromoacetic acid, which reduces the product content and causes the product quality to fail to meet the standards. Method 3 has a high operating temperature, and the target product forms more mixed anhydride, and the product yield is very low. Method 4 uses ether extraction and separation, which is highly dangerous. Method 5 has a high raw material cost and is difficult to achieve the goal of industrial production.

[0010] The current process has problems such as low yield, complex treatment, high environmental requirements, and high raw material costs. Therefore, it is of great significance to develop a method with simple operation and high yield. Summary of the invention

[0011] In view of the deficiencies in the prior art, the present invention provides a method for preparing bromoacetic anhydride. The method comprises the following steps: adding a certain amount of bromoacetic acid and acetic anhydride into an organic solvent, and then adding a certain amount of solid acid resin, mixing, and heating the mixture to a reflux state to obtain a target product, thereby improving the product yield and product quality.

[0012] The present invention is achieved through the following technical solutions:

[0013] A method for preparing bromoacetic anhydride comprises the following steps:

[0014] (1) Add a certain amount of organic solvent into the reaction kettle;

[0015] (2) adding a certain amount of bromoacetic acid, the weight ratio of the organic solvent to the bromoacetic acid is 3-5:1,

[0016] (3) then adding a certain amount of acetic anhydride, the ratio of acetic anhydride to bromoacetic acid being 1-3:1;

[0017] (4) then adding a certain amount of solid acid catalyst resin, the amount of resin added is 2%-5% by weight of bromoacetic acid, preferably 3%;

[0018] (5) The reaction temperature is 100-110°C, the reaction time is 3-8h, preferably 5h, the boiling point is lower than 100°C, and the reaction temperature is reflux temperature.

[0019] Wherein, the organic solvent is a mixture of one or more of benzene, xylene and dichlorobenzene.

[0020] Wherein, the solid acid catalyst resin adopts commercially available T-62MPDRY.

[0021] The solid acid catalyst resin is first soaked in methanol for 5 hours, then filtered, and the solid is dried under reduced pressure. The treated solid acid resin catalyst can be used for the reaction. Through methanol soaking, moisture and other impurities in the resin can be removed, which plays an activation role. If not treated, the moisture will consume acetic anhydride and the active center will be reduced.

[0022] The beneficial effects of the present invention are:

[0023] (1) The reaction temperature is controlled by the addition of solvent, and the solvent can be recycled after the reaction without loss;

[0024] (2) The addition of the solid acid resin catalyst effectively inhibits the formation of mixed anhydride and promotes the formation of the target product bromoacetic anhydride;

[0025] (3) After the reaction is completed, the resin can be effectively separated by precipitation without filtering;

[0026] (4) The target product can be obtained by distillation after the reaction, which reduces the operation steps and saves time;

[0027] (5) The process has low raw material cost, simple operation, high product quality, and is easy to industrialize. DETAILED DESCRIPTION

[0028] The preferred embodiments of the present invention are described in detail below so that the advantages and features of the present invention can be more easily understood by those skilled in the art, thereby making a clearer and more definite definition of the protection scope of the present invention.

[0029] Preparation before implementation:

[0030] The commercially available solid acid catalyst resin is soaked in methanol for 5 hours, then filtered, and the solid is dried under reduced pressure. The treated solid acid resin catalyst can be used for the reaction.

[0031] Embodiment 1:

[0032] 139g of bromoacetic acid, 102g of acetic anhydride and 2.78g of solid acid catalyst resin were added to 417g of toluene and heated under reflux for 3h. The upper layer of liquid was transferred to the distillation tower, and the resin was left in the reactor to continue the next batch of reactions. The reaction liquid was pumped to the distillation tower for distillation to obtain 103.9g of product with a yield of 80%.

[0033] Embodiment 2:

[0034] 139g of bromoacetic acid, 306g of acetic anhydride and 6.95g of solid acid resin were added to 695g of toluene and heated under reflux for 8h. The upper layer of liquid was transferred to the distillation tower, and the resin was left in the reactor to continue the next batch of reactions. The reaction liquid was pumped to the distillation tower for distillation to obtain 116.6g of product with a yield of 90%.

[0035] Embodiment three:

[0036] 139g of bromoacetic acid, 204g of acetic anhydride and 4.87g of solid acid resin were added to 556g of toluene and heated under reflux for 5.5h. The upper layer of liquid was transferred to the distillation tower, and the resin was left in the reactor to continue the next batch of reactions. The reaction liquid was pumped to the distillation tower for distillation to obtain 123.4g of product with a yield of 95%.

[0037] Embodiment 4:

[0038] 139g of bromoacetic acid and 102g of acetic anhydride, 2.78g of solid acid catalyst resin (not pre-soaked in methanol) were added to 417g of toluene, and heated to reflux for 3h. The upper layer of liquid was transferred to the distillation tower, and the resin was left in the reactor to continue the next batch of reactions. The reaction liquid was pumped to the distillation tower for distillation to obtain 64.9g of product with a yield of 50%.

[0039] Comparative Example:

[0040] 139 g of bromoacetic acid and 102 g of acetic anhydride were added to 417 g of toluene, heated under reflux for 3 h, cooled, transferred to a distillation tower for distillation, and 51.9 g of product was obtained with a yield of 40%.

[0041] Comparative analysis:

[0042] In the prior art, no resin catalyst is added. During the reaction of the product, acetic anhydride absorbs water and becomes acetic acid. The generated acetic acid and bromoacetic acid form a mixed anhydride under the dehydration effect of acetic anhydride. The substance is an impurity, and the reaction to generate the mixed anhydride is not selective. The addition of the resin in the present invention significantly inhibits the generation of the mixed anhydride, promotes the reaction in the positive direction, and generates the target product bromoacetic anhydride.

[0043] The above-mentioned embodiments only express several implementation methods of the present invention, and the description is relatively specific and detailed, but it cannot be understood as limiting the scope of the invention patent. It should be pointed out that for ordinary technicians in this field, several modifications and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention.

Claims

1. A method for preparing bromoacetic anhydride, characterized in that: The steps include: (1) Add a certain amount of organic solvent into the reaction kettle; (2) adding a certain amount of bromoacetic acid, the weight ratio of the organic solvent to the bromoacetic acid is 3-5:1, (3) then adding a certain amount of acetic anhydride, the ratio of acetic anhydride to bromoacetic acid being 1-3:1; (4) then adding a certain amount of solid acid catalyst resin, the amount of resin added is 2%-5% of the weight of bromoacetic acid; (5) The reaction temperature is 100-110°C and the reaction time is 3-8h.

2. The method for preparing bromoacetic anhydride according to claim 1, wherein: The organic solvent is a mixture of one or more of benzene, xylene and dichlorobenzene.

3. The method for preparing bromoacetic anhydride according to claim 1, characterized in that: The solid acid catalyst resin is T-62MPDRY.

4. The method for preparing bromoacetic anhydride according to claim 1 or 3, characterized in that: The solid acid catalyst resin is first soaked in methanol for 5 hours, then filtered, and the solid is dried under reduced pressure. The treated solid acid resin catalyst can be used for the reaction.