CN103664705A - Citrulline nitrate synthesizing method - Google Patents

Abstract

The invention discloses a citrulline nitrate synthesizing method, belonging to the field of derivatives of carbamide which is further substituted with carboxyl groups. The citrulline nitrate synthesizing method comprises the following steps of heating a diluted nitric solution to 30-80 DEG C, then adding citrulline and reacting for 1-5 hours at 30-80 DEG C; after the reaction is completed, cooling to room temperature, adding an organic solvent the weight of which is 2-5 times the weight of the citrulline; cooling to 5-15 DEG C, precipitating a crystal, filtering for separation, washing, and drying in vacuum to obtain a solid product of citrulline nitrate; adjusting the pH value of the rest mother solution to be neutral or weakly alkaline, cooling, filtering, and drying in vacuum to obtain a crude citrulline product; and separating the mother solution of the citrulline and then performing ethanol-based rectifying recovery. The citrulline nitrate synthesizing method provided by the invention lays the foundation for scale production and is high in yield and purity, mild in control condition and free of waste gas and waste residue; a product is detected and verified to be consistent with theoretical results in terms of molecular structure and molecular weight.

Description

The synthetic method of citrulline nitrate

Technical field

The invention belongs to further by the derivative of the urea of carboxyl substituted, be specifically related to a kind of synthetic method of citrulline nitrate.

Background technology

Amino acid is the base substance that forms Animal nutrition desired protein, generally by people self, is generated or is obtained by food, to meet each seed amino acid of human body needs.But under special circumstances, in the situation of taking exercise as sick, injured or large amount of exercise, in order to recover the balance of various metabolism in body, strengthening immunity and regaining one's strength as early as possible, just needs extra supplementary each seed amino acid.

Citrulline is a kind of alpha amino acid, because obtaining from watermelon at first, and gain the name " citrulline ".Citrulline is to generate ornithine cycle from ornithine and amido formyl phosphoric acid salt, or by nitricoxide synthase (NOS) catalysis arginine, generates the by product of NO.First, arginine can be oxidized to N-hydroxyl-arginine, then row is oxidized to citrulline and disengages nitrogen protoxide.

When citrulline remains amino acid, because it is not for DNA encodes, thus be can be in protein biosynthesizing in embedded protein, but still have part protein to contain citrulline.These citrulline are produced by spermine acid imide enzyme (PAD), in the process of melon ammonification, by conversion of Arginine, are citrulline.The protein that generally contains citrulline includes Human Brain Myelin Basic Protein (MBP), poly-Keratin sulfate microfilament protein and some histones.As Mierocrystalline cellulose and vimentin can be by melon ammonifications from necrocytosis and tissue inflammation.

During citrulline reasonable quantity, for keeping muscle and liver health to play an important role, citrulline still helps the important nutritional supplementation of the interior nitrogen of body and metabolic balance, lacks this element and is called as citrulline deficiency disease, and this disease can only check out by vitamin deficiency detection means.The nitrate that citrulline is synthetic, is more conducive to body supplementary for the absorption of citrulline.

The anti-bad citrulline peptide antibody of < < China rheumatology impurity interim < < delivering of > > calendar year 2001 the 5th detects in meaning > > mono-literary composition in rheumatoid arthritis to be paid, and suffers from the patient of rheumatoid arthritis approximately 80% people and can develop a set of immune response antagonism with the protein of citrulline.Although this reaction mechanism is start from some unknown cause, discover the diagnosis that antibody can help this class disease.

Although citrulline is present in organism, play in vivo very important effect, and extract in plant materials, citrulline nitrate has not only been strengthened the stability of the external form of citrulline, has more promoted the absorption of form in citrulline body.

Summary of the invention

The present invention exists shortcoming unstable, that be difficult for being absorbed by the body to propose in order to overcome the citrulline existing in prior art, its objective is the synthetic method that a kind of citrulline nitrate is provided.

Principle of design of the present invention: take citrulline solid and aqueous nitric acid as raw material, by adjusting concentration, reacting by heating, insulation, cooling, then add organic solvent ethanol, crystallisation by cooling and obtaining.

Technical scheme of the present invention is:

A synthetic method for citrulline nitrate, comprises the following steps:

A. the nitric acid that is 65% by quality for number adds in purified water, and the mass ratio of nitric acid and purified water is 1:0.2 ~ 1;

B. mixed salpeter solution is heated to after 30 ~ 80 ℃, add citrulline, the mol ratio 1 ~ 1.5:1 of nitric acid and citrulline;

C. add after citrulline, in 30 ~ 80 ℃ of reactions 1 ~ 5 hour;

D. after above-mentioned reaction completes, question response liquid temp is down to room temperature, then adds wherein the organic solvent of 2 ~ 5 times of citrulline quality;

E. be cooled to 5 ~ 15 ℃, crystallize out, filtering separation, the organic solvent washing in steps d for filter cake, carries out vacuum-drying after washing, obtain citrulline nitrate solid phase prod;

F. the remaining mother liquor of step e regulates its pH to neutrality or weakly alkaline, separates out the crystallization of citrulline, is cooled to after 15 ℃, filters, and vacuum-drying, obtains citrulline crude product; The mother liquor of isolating citrulline carries out the rectifying recovery of organic solvent again.

Described organic solvent is ethanol.

The invention has the beneficial effects as follows:

The invention provides a kind of synthetic method of citrulline nitrate, and lay a good foundation for large-scale production, this synthetic method yield is high, purity is high; control condition is gentle, without waste water, without waste gas; without waste residue, product after testing, checking, molecular structure is consistent with notional result with molecular weight.

Embodiment

Below in conjunction with embodiment, the synthetic method of a kind of citrulline nitrate of the present invention is described in detail.

A synthetic method for citrulline nitrate, comprises the following steps:

A. the nitric acid that is 65% by quality for number adds in purified water, and the mass ratio of nitric acid and purified water is 1:0.2 ~ 1;

B. mixed salpeter solution is heated to after 30 ~ 80 ℃, add citrulline, the mol ratio 1 ~ 1.5:1 of nitric acid and citrulline;

C. add after citrulline, in 30 ~ 80 ℃ of reactions 1 ~ 5 hour;

D. after above-mentioned reaction completes, question response liquid temp is down to room temperature, then adds wherein the organic solvent of 2 ~ 5 times of citrulline quality;

E. be cooled to 5 ~ 15 ℃, crystallize out, filtering separation, the organic solvent washing in steps d for filter cake, carries out vacuum-drying after washing, obtain citrulline nitrate solid phase prod;

F. the remaining mother liquor of step e regulates its pH to neutrality or weakly alkaline, separates out the crystallization of citrulline, is cooled to after 15 ℃, filters, and vacuum-drying, obtains citrulline crude product; The mother liquor of isolating citrulline carries out the rectifying recovery of organic solvent again.

Described organic solvent is ethanol.

Embodiment 1

A synthetic method for citrulline nitrate, comprises the following steps:

A. the nitric acid 20g that is 65% by quality for number adds in 4g purified water;

B. mixed salpeter solution is heated to after 80 ℃, add citrulline, the mol ratio 1.5:1 of nitric acid and citrulline;

C. add after citrulline, in 80 ℃ of reactions 1 hour;

D. after above-mentioned reaction completes, question response liquid temp is down to room temperature, then adds wherein the ethanol of 2 times of citrulline quality;

E. be cooled to 5 ℃, crystallize out, filtering separation, filter cake washing with alcohol is carried out vacuum-drying at 60 ℃ after washing, obtain citrulline nitrate solid phase prod, and molar yield is 94.5%;

The theoretical element correlation data of the results of elemental analyses of products obtained therefrom and citrulline nitrate is as following table:

From above-mentioned Data Comparison, the theoretical numerical value of the citrulline nitrate product being obtained by method provided by the present invention and citrulline nitrate is basically identical.

F. the remaining mother liquor of step e regulates its pH to 7 ~ 7.5, separates out the crystallization of citrulline, is cooled to after 15 ℃, filters, and vacuum-drying, obtains citrulline crude product; The mother liquor of isolating citrulline carries out the rectifying recovery of ethanol again.

Embodiment 2

A synthetic method for citrulline nitrate, comprises the following steps:

A. the nitric acid 20g that is 65% by quality for number adds in 20g purified water;

B. mixed salpeter solution is heated to after 30 ℃, add citrulline, the mol ratio 1:1 of nitric acid and citrulline;

C. add after citrulline, in 30 ℃ of reactions 5 hours;

D. after above-mentioned reaction completes, question response liquid temp is down to room temperature, then adds wherein the ethanol of 5 times of citrulline quality; ;

E. be cooled to 15 ℃, crystallize out, filtering separation, filter cake washing with alcohol is carried out vacuum-drying at 60 ℃ after washing, obtain citrulline nitrate solid phase prod, and molar yield is 92.4%;

The theoretical element correlation data of the results of elemental analyses of products obtained therefrom and citrulline nitrate is as following table:

Claims (2)

1. a synthetic method for citrulline nitrate, is characterized in that: comprise the following steps:

A. the nitric acid that is 65% by quality for number adds in purified water, and the mass ratio of nitric acid and purified water is 1:0.2 ~ 1;

B. mixed salpeter solution is heated to after 30 ~ 80 ℃, add citrulline, the mol ratio 1 ~ 1.5:1 of nitric acid and citrulline;

C. add after citrulline, in 30 ~ 80 ℃ of reactions 1 ~ 5 hour;

D. after above-mentioned reaction completes, question response liquid temp is down to room temperature, then adds wherein the organic solvent of 2 ~ 5 times of citrulline quality;

E. be cooled to 5 ~ 15 ℃, crystallize out, filtering separation, the organic solvent washing in steps d for filter cake, carries out vacuum-drying after washing, obtain citrulline nitrate solid phase prod;

F. the remaining mother liquor of step e regulates its pH to neutrality or weakly alkaline, separates out the crystallization of citrulline, is cooled to after 15 ℃, filters, and vacuum-drying, obtains citrulline crude product; The mother liquor of isolating citrulline carries out the rectifying recovery of organic solvent again.

2. the synthetic method of a kind of citrulline nitrate according to claim 1, is characterized in that: described organic solvent is ethanol.