L-Valine(link:https://www.bloomtechz.com/synthetic-chemical/api-researching-only/valine-powder-cas-72-18-4.html) is a white monoclinic crystal or crystalline powder, odorless, with a special bitter taste, the melting point is about 315 ℃. It is easily soluble in water (8.85g/100ml, 25°C), almost insoluble in ethanol and ether. It is one of the essential amino acids for human and animal growth and maintenance of health, and is an important intermediate substance for protein synthesis and catabolism in human and animal bodies. It participates in the protein metabolism process in the human body and helps to maintain the normal physiological function and health of the human body. In addition, it is also a nutritional supplement, which can be used together with other essential amino acids to prepare amino acid infusions and comprehensive amino acid preparations for nutritional supplements and adjuvant therapy. In the valine produced by fermentation, all the products are L-type, and no optical resolution is required. L-valine is an amino acid with important physiological functions and uses, and is widely used in human protein metabolism, nutritional supplement manufacturing and other fields.
It should be noted that the production of L-valine needs to go through strict quality inspection standards, such as content, heavy metals, loss on drying, optical rotation and other parameters must meet certain standards. Different production methods may affect the quality and usage of the product, so various parameters and conditions need to be strictly controlled during the production process.
There are many ways to synthesize L-valine:
method one:
Aminoisobutanol is prepared from isobutyraldehyde and ammonia, then aminoisobutyronitrile is produced by reacting with hydrogen cyanide, and finally L-valine (L-valine) is obtained by hydrolysis. Below are the detailed steps and their chemical equations:
1. Isobutyraldehyde and ammonia generate aminoisobutanol:
React isobutyraldehyde with ammonia under appropriate solvent and reaction conditions to produce aminoisobutanol.
Chemical reaction formula: (CH3)2CHCHO + NH3 → (CH3)2CHCH2OHNH2
2. Synthesis of aminoisobutyronitrile from aminoisobutanol and hydrogen cyanide:
Aminoisobutanol and hydrogen cyanide react under acidic conditions to undergo condensation reaction to produce aminoisobutyronitrile.
Chemical reaction formula: (CH3)2CHCH2OHNH2 + HCN → (CH3)2CHCH2CN + H2O
3. Hydrolysis of aminoisobutyronitrile to generate L-valine:
React aminoisobutyronitrile with alkaline aqueous solution (such as sodium hydroxide) to undergo hydrolysis to generate L-valine.
Chemical reaction formula: (CH3)2CHCH2CN + 2H2O → (CH3)2CHCH2COOH + NH3
Method Two:
Hydroxyisobutyronitrile is synthesized from isobutyraldehyde and hydrogen cyanide, reacted with ammonia and then hydrolyzed to produce aminoisobutyronitrile.
Since the direct reaction of isobutyraldehyde and hydrogen cyanide to generate hydroxyisobutyronitrile is very unstable and dangerous, there is no conventional chemical synthesis route. In laboratory synthesis, other methods are usually used to prepare hydroxyisobutyronitrile.
Starting from hydroxyisobutyronitrile, react with ammonia to generate aminoisobutyronitrile, and then obtain L-valine (L-valine) through hydrolysis. The following are the detailed steps of the synthetic route and its chemical equation:
1. Synthesis of Hydroxyisobutyronitrile:
Isobutyraldehyde is oxidized to hydroxyisobutyronitrile by an appropriate method (such as an oxidation reaction).
Chemical reaction formula: (CH3)2CHCHO + [O] → (CH3)2C(OH)CN
2. Aminoisobutyronitrile reacts with ammonia to generate aminoisobutyronitrile:
React hydroxyisobutyronitrile with ammonia to generate aminoisobutyronitrile under suitable reaction conditions.
Chemical reaction formula: (CH3)2C(OH)CN + NH3 → (CH3)2CHCNH2
3. Hydrolysis of aminoisobutyronitrile to generate L-valine:
The aminoisobutyronitrile is reacted with alkaline aqueous solution (such as sodium hydroxide), and a hydrolysis reaction occurs to generate L-valine.
Chemical reaction formula: (CH3)2CHCNH2 + 2H2O → (CH3)2CHCOOH + NH3
Method three:
The steps of direct synthesis of L-valine by isobutyraldehyde, sodium cyanide, ammonium chloride are as follows:
1. Dissolve sodium cyanide in water and add it to the ammonium chloride solution to obtain a mixture.
2. Interact the mixture of isobutyraldehyde, ethyl formate and ethanol with the mixture obtained in step 1.
3. The synthetic steps of generating N-Boc-isobutylglycine ethyl ester hydrochloride N-Boc-isobutylglycine ethyl ester by refining reaction are as follows:
Sodium cyanide (2.0 eq.) was dissolved in water, and ammonium chloride solution (1.0 eq.) at 25°C was added to obtain a mixture A.
4. Interact the mixture A obtained in step 1 with the mixture of isobutyraldehyde, ethyl formate and ethanol at 25° C. for one hour.
5. Remove solids with a filter, and recover ammonia water to obtain solution B.
6. Add sodium ethoxide and chloroform at 18°C and interact for one hour at 25°C to obtain C.
7. Add a mixture of ethanol and sodium hydroxide (8.0 eq.) to carry out transesterification at 30°C. The reaction is accomplished with a phase transfer catalyst.
8. Remove ethyl formate under the condition of diethyl ether and sodium hydroxide.
9. Add dilute hydrochloric acid and interact for half an hour at 30°C.
10. Add dilute hydrochloric acid at 5°C and maintain at 5°C for half an hour.
11. Add saturated sodium chloride solution at 25°C, stir evenly, let stand to separate layers, and take the organic phase.
12. Add saturated sodium bicarbonate solution to the organic phase, stir evenly, let stand to separate layers, and take the water phase.
13. Add saturated sodium chloride solution to the water phase and stir evenly, then let it stand and separate layers to take the upper organic phase to obtain crude N-Boc-isobutylglycine ethyl ester.
The yields of the above three methods are all 36% to 40%. It can also be synthesized by hydrolysis of isobutyraldehyde, sodium cyanide and ammonium carbonate. The yield of this method is about 49%. There are also many methods for the resolution of racemates, such as enzymatic hydrolysis of acyl DL amino acids, and then separation of free amino acids and acylates with poor solubility. The valerian amino acids produced by fermentation are all L-type, and no optical separation is required. The strains used in the fermentation method are Micrococcus glutamicum, Brevibacterium ammonia, Escherichia coli and Aerobacter. Use glucose, urea, inorganic salts and other media.