CN116102436A - A new process for preparing serinol - Google Patents

Abstract

The invention relates to a new process for synthesizing serinol by using 2-nitro-1,3-propanediol sodium salt as a raw material under catalytic hydrogenation conditions. By adding ionic liquid to the reaction, the decomposition of 2-nitro-1,3-propanediol sodium salt is reduced, and the yield of serinol is greatly improved. The process does not need to change the original equipment, produces almost no by-products, and is more economical and environmentally friendly.

Description

A new process for preparing serinol

technical field

The invention belongs to the field of medicine and chemical industry, and relates to a technique for increasing the yield of serinol in a catalytic hydrogenation reaction.

Background technique

Iopamidol is a non-ionic water-soluble contrast agent commonly used in radiology department, mainly used in neurointervention, coronary angiography, enhanced CT scan and angiography. Its main advantages are low toxicity, less allergic reactions, little impact on liver and kidney functions, and less likely to cause contrast nephropathy. Therefore, the market demand for iopamidol is very large and is increasing year by year. One of the synthetic raw materials of iopamidol is serinol, i.e. 2-amino-1,3-propanediol, reducing the production cost of serinol will help to reduce the production cost of iopamidol, so the development of economical and environmentally friendly silk A new process for the preparation of amino alcohol has great economic and social benefits.

Wherein, the molecular formula of iopamidol is:

Wherein, the molecular formula of serinol is:

After searching, it was found (DE2742981, US4448999, US6509504, US4221740) that a common method for preparing serinol is: nitromethane and paraformaldehyde under the action of caustic soda to generate 2-nitro-1,3-propanediol sodium salt , the latter is reduced to serinol by catalytic hydrogenation, and finally obtained by distillation under reduced pressure.

The method is simple to operate, and the raw materials used are cheap and easy to obtain. However, in the above method, the yield of serinol prepared by catalytic hydrogenation of 2-nitro-1,3-propanediol sodium salt is not high and unstable, mainly because a large amount of by-products are produced in this step reaction. In order to increase the yield of serinol, new processes that can reduce the formation of by-products must continue to be developed. In order to determine the way of by-products, first use carbon nuclear magnetic resonance spectroscopy to analyze the structure of a large number of high-boiling substances remaining in the still, and compare it with the standard spectrum of the presumed substance, and determine that it is trishydroxymethylaminomethane, that is, 2-amino -2-Hydroxymethyl-1,3-propanediol (Figure 1). According to the structure of this by-product, it is inferred that its production route is: (1) 2-nitro-1,3-propanediol sodium salt I is decomposed into 2-nitroethanol sodium salt II and formaldehyde (Russian chemical Bulletin, 2009,58( 10), 2063-2069; 2011, 60(8), 1703-1711); (2) Further addition reaction between formaldehyde and 2-nitro-1,3-propanediol sodium salt I to generate trimethylolnitromethane III; (3) Trimethylolnitromethane III is reduced to by-product trishydroxymethylaminomethane IV under catalytic hydrogenation conditions, resulting in a low yield of serinol. The yield of each batch of serinol was unstable due to the different degrees of decomposition of the sodium salt of 2-nitro-1,3-propanediol.

Wherein, the reaction formula that described trishydroxymethylaminomethane produces is:

Contents of the invention

The purpose of the present invention is to provide a new process for preparing serinol which is more economical and environment-friendly without changing the existing equipment.

In order to achieve the above object, the new technology adopted in the present invention is to add ionic liquid to the catalytic hydrogenation reaction of 2-nitro-1,3-propanediol sodium salt to reduce the decomposition rate of 2-nitro-1,3-propanediol sodium salt , thus greatly increasing the yield of serinol without changing the existing equipment. The technical scheme adopted by the present invention is specifically as follows.

A preparation method of serinol, using methanol as a solvent, under the action of caustic soda, addition reaction of nitromethane and paraformaldehyde occurs, the obtained addition product is hydrogenated and reduced to serinol, and finally purified by high vacuum distillation, specifically Proceed as follows:

Step 1: Preparation of 2-nitro-1,3-propanediol sodium salt

Add nitromethane, paraformaldehyde, and caustic soda solution to methanol in sequence, control the reaction temperature at 25°C-30°C, and filter to obtain 2-nitro-1,3-propanediol sodium salt filter cake.

Step 2: Prepare Serinol

To methanol, sequentially add the 2-nitro-1,3-propanediol sodium salt filter cake, ammonium chloride, ionic liquid and palladium/carbon prepared in step 1, and pass in hydrogen, and the reaction temperature is 15°C-20°C, The reaction time was 48 hours, and the catalyst was filtered out to obtain a serinol solution.

Wherein, the addition amount of the ionic liquid is 0.5%-10% of the mass of the 2-nitro-1,3-propanediol sodium salt filter cake, preferably 3%-10%, more preferably 6%.

Step 3: Purification by high vacuum distillation

The methanol solution of serinol obtained in step 2 is first evaporated to remove methanol and then serinol in a high vacuum state.

By adopting the technology for synthesizing serinol by catalytic hydrogenation of the present invention, the yield of the obtained serinol is high and stable, the existing equipment is not changed, and the production cost is reduced.

4. Specific implementation

Example 1

Step 1: Preparation of 2-nitro-1,3-propanediol sodium salt

Add 0.5L of methanol, 100g of nitromethane, and 103g of paraformaldehyde in the three-necked flask successively, start stirring, and after complete depolymerization, add 240g of 30% sodium hydroxide solution dropwise in the reaction flask, control the rate of addition, and make the reaction The temperature was kept at 25°C-30°C. After the dropwise addition was completed, the mixture was kept for 1 hour, filtered and dried to obtain 253g of 2-nitro-1,3-propanediol sodium salt.

Step 2: Preparation of Serinol by Catalytic Reduction

Add 0.8L of methanol, 253g of 2-nitro-1,3-propanediol sodium salt, 100g of ammonium chloride, 15g of ionic liquid, and 12.6g of 5% palladium/carbon into the reaction kettle, and feed hydrogen with a pressure of 1MPa, 15 Incubate at -20°C for 48 hours to prepare a serinol methanol solution. The palladium/carbon was filtered off, washed and reused.

Step 3: Purification by high vacuum distillation

The methanol solution of serinol prepared in step 2 was recovered under normal pressure for methanol, and then distilled under reduced pressure to obtain 138 g of pure serinol with a yield of 92.6%.

Example 2

The amount of ionic liquid added was changed to 0.5% of the mass of 2-nitro-1,3-propanediol sodium salt, and other conditions were the same as in Example 1, and the yield of serinol was 79.8%.

Example 3

The amount of ionic liquid added was changed to 3% of the mass of 2-nitro-1,3-propanediol sodium salt, and other conditions were the same as in Example 1, and the yield of serinol was 85.8%.

Example 4

The amount of ionic liquid added was changed to 10% of the mass of 2-nitro-1,3-propanediol sodium salt, and other conditions were the same as in Example 1, and the yield of serinol was 87.2%.

It should be noted that the above summary of the invention and specific implementation methods are intended to demonstrate the practical application of the technical solution provided by the present invention, and should not be construed as limiting the protection scope of the present invention. Those skilled in the art may make various modifications, equivalent replacements, or improvements within the spirit and principles of the present invention. The protection scope of the present invention shall be determined by the appended claims.

Description of drawings:

Figure 1 is the carbon spectrum of the by-product trishydroxymethylaminomethane.

Claims (2)

1. A novel process for preparing serinol is characterized in that ionic liquid is added in the catalytic hydrogenation reaction of 2-nitro-1, 3-propanediol sodium salt, so that the decomposition of the 2-nitro-1, 3-propanediol sodium salt is reduced, and the yield of serinol is improved.

2. The novel process as claimed in claim 1, wherein the ionic liquid is added in an amount of 0.5% -10%, preferably 3% -10%, more preferably 6% of the mass of the 2-nitro-1, 3-propanediol sodium salt cake.

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