METHOD FOR OBTAINING GLYCINE Russian patent 1994 according to IPC C07C227/08 C07C229/08 

Glycine is a supplement taken to improve brain function and relaxation. From a chemical point of view, this is one of the simplest and most common amino acids, one of the twenty proteinogenic (necessary for protein synthesis). The largest amount of glycine is part of collagen, a connective tissue protein that provides strength and elasticity to the skin, tendons and ligaments, joints, blood vessels, etc.

In our body, glycine is produced from the amino acid serine. Under normal circumstances, this is sufficient, but during strenuous activity, such as active sports, the need for glycine may increase. This leads to the answer to the question why drink glycine - this supplement may not be necessary, but it helps to calm down better, relieve tension, make brain function more stable, and also helps strengthen ligaments and tendons, skin and blood vessel walls.

Who is it useful for?

Aminoacetic acid is actively used to treat schizophrenia, stroke, benign prostatic hyperplasia, and genetic metabolic disorders. And given the beneficial effect on the functioning of the nervous system, this substance is prescribed to those suffering from insomnia, and is also used to “pacify” drug addicts in the first stages of treatment.

This amino acid is also extremely important for the proper functioning of the kidneys. In particular, it protects against the side effects of certain medications used after organ transplantation. The positive effect of aminoacetic acid is also felt by the liver. Especially for people who abuse alcohol. This substance is also classified as an anti-cancer substance. Used to heal ulcers on different areas of the skin, and also as a means to improve memory.

Contraindications and side effects of glycine

As already mentioned, glycine is a natural substance that is constantly produced by our body and enters it in food, therefore glycine is familiar to the body and has no toxic effects. Only individual intolerance is indicated as a contraindication for glycine. In extremely rare cases, an allergy to glycine may occur and should be monitored for such reactions.

Considering that glycine has no serious contraindications or side effects, it is sometimes taken in large doses, but this can hardly be considered justified. It is better to follow the manufacturer's recommendations, and if you have any questions, consult your doctor.

Role in the body

Forming healthy muscle tissue and converting glucose into energy are important functions of glycine. This substance is also important for maintaining the health of the central nervous and digestive systems. And research results show that in tandem with antioxidants it protects against certain types of cancer.

Glycine is an important component for the construction of DNA and RNA strands, and they, in turn, act as a genetic building material, without which the proper functioning of the body is impossible. It is one of three amino acids that form creatine, which is essential for muscle growth and energy production during exercise.

This amino acid is also part of collagen, which is responsible for the normal condition of the skin, ligaments and tendons. By the way, almost a third of the collagen that provides the skin with plasticity and elasticity consists of glycine. It promotes calcium absorption, which prevents muscle degeneration. And also plays an important role in the production of hormones responsible for the functioning of the immune system.

Without glycine, the body would not be able to repair damaged tissue. Sagging skin, wounds that do not heal for a long time, the epidermis destroyed by UV rays, the body suffering from constant attacks of free radicals - all these are also possible consequences of the complete absence of aminoacetic acid in the body.

Glycine helps the body regulate sugar levels and the uptake of glucose into skeletal muscles for energy production. These abilities make the amino acid an important component for diabetics, those suffering from frequent hypoglycemia, people with anemia or chronic fatigue.

Aminoacetic acid ensures normal functioning of the digestive tract. Concentrated in the gallbladder, glycine promotes the production of an enzyme necessary for the digestion of dietary fats. Another benefit of glycine is the ability to regulate the acid-base balance in the digestive tract, as well as protect against the harmful effects of alcohol.

The amino acid regulates the production of brain neurotransmitters, which affect a person’s emotional state and brain functionality. It is worth remembering this substance for people suffering from insomnia or sleep rhythm disturbances.

Functions of glycine.

1. For the nervous system, it acts as an inhibitory neurotransmitter that prevents epileptic seizures.
2. Used in the treatment of manic depression and hyperactivity.
3. Participates in many biochemical processes in the body.
4. Promotes normal functioning of the prostate.
5. It is part of glutathione, a coenzyme involved in many biochemical reactions.
6. Has antioxidant properties.
7. Helps the functioning of the central nervous system.

Suction

The human body functions in such a way that it will not accumulate more glycine than is needed. This feature determines the speed and intensity of absorption of the substance. The only time the body makes a mistake is when there are certain genetic diseases that affect the body's ability to detect a lack of a substance.

Glycine is a heme precursor

Why is blood red? Because it contains hemoglobin - a red protein that contains heme. This is an iron-containing porphyrin system, on which oxygen sits, from the lungs with the blood flowing to various tissues. Glycine is one of the precursors of heme in animals. The reaction involving glycine is shown in Figure 5.

Figure 5. Role of glycine in heme synthesis. a - Erythrocytes (“red blood cells”) - cells containing the red protein hemoglobin. b - The color of hemoglobin, as well as its transport function, are provided by the presence of heme. c — Synthesis of delta-aminolevulinic acid from succinyl-CoA and glycine is the first reaction in the synthesis of porphyrin systems in animals.

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The synthesis of porphyrins is a separate large “opera”, and glycine is involved only in the first “aria”, and in this article we will not study the full “score”. Nevertheless, the role of glycine in this fundamental process is enormous.

Daily requirement

It is believed that the human body is capable of synthesizing about 3 grams of glycine, and additionally receives at least 1.5-3 g of the substance from the diet.

But these doses cannot satisfy the body’s daily amino acid needs. According to scientists, an adult needs approximately 10-13 g of aminoacetic acid daily. This is exactly how much glycine, according to some estimates, is needed to ensure normal collagen synthesis. And, as you know, it consists of almost 22 percent glycine.

According to other recommendations, adults should receive about 0.3 g of the substance daily, and children - about 0.1 g. For heavy physical activity, the daily norm is increased to 0.8 g. Also, people with disorders of the central nervous system should receive a little more than the generally accepted daily norm. nervous system and brain, after heart attacks and strokes, during intoxication (caused by medications or alcohol poisoning), in stressful situations. But pregnant women, nursing mothers, people with hypotension or intolerance to aminoacetic acid should treat glycine with caution. You should not abuse dietary supplements containing amino acids or those whose work requires a quick reaction.

Application of glycine:

• 16-60 mg daily – for schizophrenia;
• 1-2 g per day – within 6 hours after a stroke;
• 10 mg (in cream form) – leg ulcers;
• 3 g before bedtime – for insomnia;
• 2-12 g – in the treatment of drug addiction.

And although glycine poisoning is an extraordinary phenomenon, it is still believed that the maximum daily dose of aminoacetic acid should not exceed 50 g.

Who is recommended to take glycine?

Considering the nootropic and proteinogenic properties of glycine, it is successfully used in many cases:

• athletes and everyone who suffers from overwork,
• those who experience increased stress on joints and tendons,
• students and people engaged in intense mental work,
• those who suffer from brain damage (only as prescribed by a doctor and as part of medical therapy).

Taking glycine can improve mental stability, increase performance, both mental and physical, reduce the negative effects of taking alcohol or medications, improve mood and relaxation, protect the ligaments and improve the health of the joints and vascular system.

In general, glycine is an affordable, safe and well-known remedy that is gentle and provides many benefits.

Food sources

The main sources of glycine are foods rich in protein.

A typical diet contains about 2 grams of glycine daily. It is also worth remembering that glycine is a non-essential amino acid. This means that it is regularly produced in the liver from other amino acids. Therefore, there is no urgent need to monitor the exact amount of glycine in the diet.

Animal sources: fish, dairy products, meat, cheese and others.

Plant sources: beans, soybeans, spinach, pumpkin, cabbage, cauliflower, burdock root, cucumbers, kiwi, bananas.

Other sources: aspic, marmalade, soy, chickpeas, pumpkin and sesame seeds, nuts (walnuts, peanuts, pistachios, pine), basil, fennel, ginger.

You can provide yourself with higher doses of glycine by consuming skin and bones (for example, preparing broths, jellied poultry meat with skin) or special nutritional supplements. It is important to remember that only natural ingredients are used to create glycine.

But it would be wrong to talk about food sources of glycine without remembering the factors that influence more complete absorption of the substance.

The first recommendation is nothing new - standard, but, in fact, very important advice: maintain a healthy lifestyle and eat a balanced menu.

Secondly, water is necessary for normal absorption of glycine. Proper drinking regimen (at least one and a half liters of fluid per day) will help the body extract more benefits from food.

And the third tip: an active lifestyle and regular walks in the fresh air.

general characteristics

Glycine (aminoacetic acid) has no stereoisomers and is involved in the formation of proteins and purine compounds such as guanine, xanthine, adenine. It is obtained from gelatin and is used to make dietary supplements. To obtain glycine, hydrolysis of proteins or the method of chlorination of carboxylic acids with further interaction with ammonia is used. In the pharmaceutical industry you can find other names - glycine, E640, paraoxyphenylglycine, p-hydroxyphenylaminoacetic or aminoethanoic acid.

This substance is also produced in the human body - glycine is synthesized in the liver from serine and threonine. Its greatest concentration is found in muscles, connective tissue and skin.

Note! The main source for the synthesis of glycine is serine.

Interaction with other substances

You must be extremely careful when taking glycine and clozapine (a drug for the treatment of schizophrenia) at the same time, since this drug stops working against the background of the amino acid. The combination of glycine and cysteine ​​enhances the synthesis of glutathione and increases insulin sensitivity. It is important to know that aminoacetic acid enhances the absorption of aspirin, and in combination with calcium or iron improves their absorption. But for glycine itself, the presence of B-group vitamins in the body, which contribute to the processes of amino acid synthesis, is important.

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Use of glycine in medicine

When taken under the tongue, the drug is quickly absorbed into the blood and signals to the brain that it needs to increase the production of its own glycine. In this way, the lack of endogenous amino acid is compensated.

The anti-stress and trophic properties of glycine allow it to be used as an effective drug in neurology, cardiology, psychiatry, and narcology. The natural protective mechanism, which is activated with the help of this amino acid, provides the cells with the necessary energy. Since taking Glycine stimulates the synthesis of amino acids in the body, and does not replace it, addiction and a decrease in the effect of the drug does not occur.

In conditions of impaired blood circulation and brain hypoxia, the amino acid glycine ensures a sufficient level of metabolic processes in neurons. This allows the use of the drug Glycine to reduce the consequences of stroke in the first 3-5 hours after the onset of cerebral ischemia. Glycine is the only over-the-counter drug that is recommended for use in case of stroke before the arrival of an ambulance .

Dosage and overdose

Glycine is available in three forms: 1) as a food additive in 23 kilogram bags - the best option in terms of price and quality ratio; 2) as dietary supplements in the form of pills or powdered mixtures that can be added to cocktails and smoothies; 3) and as tablets.

In terms of composition, supplements differ from “pharmacy drugs” only in that vitamins and flavorings are sometimes mixed into them. As a rule, there is no difference in dosage either. It is usually recommended to take 1 100 mg tablet three times daily. So, if you decide to replace the missing 10 grams of glycine for collagen synthesis in this way, you will need 100 tablets per day.

Glycine appears to have no side effects. There is a documented case where a subject took 64 grams of glycine per day without any health consequences, which is equivalent to more than three kilograms of fruit jelly. However, according to some observations, such an obvious overdose can still cause undesirable reactions from the gastrointestinal tract.

The effect of glycine and its sodium salt on the human body

Aminoacetic acid as a neurotransmitter performs regulatory functions and primarily affects the central and peripheral nervous system. Glycine has nootropic properties, normalizes metabolism, activates the protective functions of the central nervous system and has a mild calming effect.

Positive effects of glycine on the human body:

• reduction of emotional tension, anxiety, stress, aggressiveness;
• improved mood and normalization of sleep;
• relaxation of muscles and relief of cramps;
• increased performance;
• reducing the side effects of taking psychotropic drugs;
• reducing the severity of vegetative-vascular disorders;
• reducing cravings for alcohol and sweets.

As part of the E640 supplement, glycine and its salt do not have the above properties and have neither positive nor negative effects on the human body when consumed within normal limits. The food additive does not pose a threat to health, but in case of individual intolerance it can provoke an allergic reaction.

Potential dangers may come from impurities in the additive and low-quality food products, in the manufacture of which taste and aroma optimizers are used.

Method for producing glycine

The essence of the invention: product - aminoacetic acid, yield 98.5 - 99%, productivity up to 125 - 130 kg/m3h, mp. 233C. Reagent 1: monochloroacetic acid. Reagent 2: ammonia gas. Reaction conditions: at 40 - 70 C in the presence of hexamethylenetetramine in methanol containing 10% water, at a molar ratio of monochloroacetic acid: hexamethylenetetramine equal to (9 - 15) : 1, with an additional addition of 3 - 5 wt. % chloroform based on monochloroacetic acid. 1 table

The invention relates to methods for producing α-amino acids, namely glycine, which is widely used in technology, medicine and the food industry.

There are known methods for producing glycine through ammonolysis and subsequent saponification of aqueous solutions of glycolonitrile [1] HO-CH2-CN H2NCH2CN____COOH The original glycolonitrile is formed by the reaction of formaldehyde with hydrocyanic acid or its salts. The need to use this highly toxic reagent is the main disadvantage of the described method. The subsequent stages of ammonolysis and saponification are carried out in dilute aqueous solutions and require at least equimolar consumption of alkalis and acids, which leads to the formation of large quantities of contaminated wastewater. The yield of glycine is low - 69% [1]. There is a known method for producing glycine by alkaline hydrolysis of hydractoin with subsequent isolation of the free amino acid. The yield of glycine is 95%. However, hydractoin is not one of the reagents available for industrial synthesis; moreover, HCN (Strecker synthesis) is also required for its production. In industrial practice, the most common method for synthesizing glycine is ammonolysis of monochloroacetic acid (MCCA), which is available large-scale reagent, in an aqueous solution in the presence of equimolar amounts of hexamethylenetetramine ClCH2COOH + NH3 -> NH2CH2COOH + + NH4Cl For example, there is a known method for producing glycine by treating MCA or its ammonium or sodium salt with ammonia and NaOH in an aqueous medium containing hexamethylenetetramine and NH4+ ions in molar ratio with MCA is not less than 1: 3 [2]. The first half of an aqueous solution of 238 g of MCA is added dropwise over 1 hour at 65-70°C to a solution containing 52.5 parts of hexamethylenetetramine, 42.5 parts of NH4Cl, 180 parts - water, the pH of the solution is maintained at 6.5-7.0 by passing ammonia gas into the solution. Then, at the same temperature, the second half of the solution is added over the course of an hour and at the same time a solution of 100 parts of NaOH in 234 parts of water is introduced. The mixture is heated for another 1 hour at 65-70°C, after which 2000 parts of water are added and analyzed. They get 175.5 hours. glycine, yield 93.0%. An example is given with 2-fold use of stock solutions. The total yield of glycine is 88%. Disadvantages of the method: high consumption coefficients: 0.57 g of NaOH, 0.30 t of hexamethylenetetramine, 2.85 t of water per 1 t of crude glycine. Particularly noteworthy is the presence of a large volume of wastewater, which is unacceptable in the current environmental situation. The closest in technical essence and achieved effect to the proposed method is the method for the synthesis of glycine from MCA and ammonia, carried out in a medium of methyl or ethyl alcohol [3 - prototype]. According to In the prototype method, 189 kg of MCCA in 80 l of 90% CH3OH and 68 kg of NH3 are simultaneously added to 70 kg of hexamethylenetetramine in 1000 l of 90% CH3OH at 40-70°C and the ratio of hexamethylenetetramine: MCCA = 1: 4. Then from the resulting reaction mixtures, crystalline glycine is removed in a mixture with NH4Cl. The yield of glycine based on the spent MCA is 95%, the purity of the product after additional purification is 99.5%. The disadvantages of the prototype are: the yield of glycine is not high enough; low productivity of the process: (glycine removal from 1 m3 of reaction space is 36 kg/h. m3); low technical and economic indicators (consumption indicators per 1 ton of glycine after synthesis are: 100% methanol 5.7 t Hexamethylenetetramine 0.5 t Water 0.64 t MCA 1.35 t NH3 0.5 t significant volume of contaminated hexamethylenetetramine and NH4 wastewater 1.5 tons per 1 ton of glycine, which is unacceptable in the modern environmental situation. The purpose of the invention is to increase the yield of the target product, productivity and technical and economic indicators of the process, and reduce the amount of wastewater. This goal is achieved by the proposed method, which is carried out as follows. MCA and hexamethylenetetramine, taken in a molar ratio (9-15): 1, are dissolved in methanol containing 10 wt.% water, chloroform is added in an amount of 3-5% by weight of the introduced MCA and ammonia gas is bubbled into the resulting mixture at 40-70 ° C in for 1.5-2 hours. The resulting glycine in a mixture with NH4Cl precipitates into a crystalline precipitate, which, after cooling the reaction mixture to 20°C, is separated by centrifugation. The mother reaction liquid is used again as a reaction medium instead of a methanol solution of hexamethylenetetramine after replenishing the entrainment with the methanol precipitate of hexamethylenetetramine and chloroform. Next, the synthesis is carried out as described above. Distinctive features of the proposed method: the use of chloroform as a cocatalyst for the reaction in an amount of 3-5 wt. % of the weight of the loaded MCA; molar ratio of MCA: hexamethylenetetramine = 9-15: 1. The advantages of the proposed method are as follows: the yield of glycine at the synthesis stage increases to 98.5-99.0%, the productivity of the process increases to 125-130 kg of glycine/m3.h versus 36 kg/ m3.h according to a known method; the technical and economic indicators of the process are improved (consumption indicators for synthesis per 1 ton of glycine are, taking into account the 6-fold use of the reaction mother liquor: 100% methanol 0.320 t H2O 0.035 t Hexamethylenetetramine 0.046 t MCA 1.28 t NH3 0.50 t Chloroform 0.14 t the amount of wastewater is approximately 0.10 t per 1 t of glycine, i.e. it decreases by 15 times compared to the known method. EXAMPLE 1. Into a reaction vessel equipped with a stirrer, reflux condenser and a gas-conducting tube is loaded with 250 ml of methanol containing 10 wt.% water, 95.0% MCA of 99.5% purity, 11.7 g of hexamethylenetetramine (molar ratio of MCA: hexamethylenetetramine 12), 3.8 g of chloroform (4.0 wt.% of the mass of the loaded MCA) is stirred until complete dissolution. The ammonolysis reaction is carried out at 40-70°C, bubbling ammonia gas at a rate that ensures its complete absorption within 1.5 hours. The product formed during the reaction precipitates in the form of a fine-crystalline precipitate, which is mixture of glycine and NH4Cl. The reaction mixture is cooled to 20°C, the precipitate is separated in a centrifuge, washed with 50 ml of 90% methanol, dried at 100°C for an hour and analyzed for glycine content. 113.6 g of precipitate containing 73.9 g of glycine are obtained. The yield of glycine for the taken MCA is 98.5%. At the same time, the productivity of 1 m3 of the reaction space is 125 kg/h. Consumption indicators in terms of 1 ton of glycine obtained after synthesis are: CH3OH (100%) 2.51, water 0, 28 t, hexamethylenetetramine 0.16 t, MCA 1.28 t, NH3 0.50 t, chloroform 0.051 t. Purification of glycine is carried out similarly to the prototype, washing the resulting precipitate with aqueous methanol. Purity of the product after purification is 99.5%. Melting point of the product is - 233°C, which corresponds to literature data. Examples 2-3. The experiment is carried out under the conditions of example 1, with the exception that the boundary values ​​​​of the stated ranges of the molar ratio of MCA and hexamethylenetetramine (9 and 15) and chloroform (3 and 5% by weight of the taken MCA) are taken. The yield of glycine for examples 2 and 3 is 98.3 and 98.0%, respectively. EXAMPLES 4 and 5. Experiments are carried out under the conditions of example 1, except that the prohibitive values ​​for the amount of chloroform are taken: 5.5 and 2.5 wt. % relative to the taken MHUK. The glycine yield is 98.5 and 94.0%, respectively. Increasing the amount of chloroform above 5 wt. % is impractical, since it does not lead to an increase in product yield. EXAMPLES 6 and 7. Experiments are carried out under the conditions of example 1, except that exorbitant values ​​from the declared range of molar ratios MCCA: hexamethylenetetramine - 16 and 8, respectively, for examples 6 and 7. The yield of glycine is 90.5 and 98.0, respectively. Thus, reducing the molar ratio of MCA: hexamethylenetetramine below the stated one is environmentally unfeasible, since it increases the consumption of hexamethylenetetramine and does not lead to an increase in the yield of the product, and an increase in the ratio leads to a decrease in the yield. EXAMPLE 8. In a reactor equipped with a reflux condenser , with a device for stirring with a gas pipe, 185 g of the reaction mother solution from the stage of separating the sediment of the experiment of example 1, 95 g of 99.5% crystalline MCA, 2.0 g of hexamethylenetetramine and 0.6 g of chloroform are loaded with stirring to replenish their removal with the sediment experience of example 1 and 50 ml of 90% methanol after washing the sediment of experience of example 1 and stirred until completely dissolved. Next, the reaction is carried out similarly to example 1. 126.3 g are obtained, containing 74.5 g of glycine. The yield of glycine from the taken MCA is 99.2%. EXAMPLES 9-13. The experiments are carried out under the conditions of example 1 with the difference that the mother reaction solution obtained from the previous experiment is used as the reaction medium. The consumption indicators of the glycine synthesis process according to the proposed method, taking into account the 6-fold use of the mother reaction solution per 1 ton of glycine, are: methanol 100% 0.319 t; water 0.035 t; hexamethylenetetramine 0.046 t; MHUK 1.28 t; ammonia 0.5 t; chloroform 0.014 t. The amount of wastewater is 0.10 t per 1 t of glycine. The data is shown in the table. (56) UK Patent N 1157393, cl. C 2 C, 1969. Application of the Netherlands N 6515522, class. Since 07 C, 1967. Hungarian Patent N 161938, class. C 07 C 101/06, 1974.

Claim

METHOD FOR OBTAINING GLYCINE by ammonolysis of monochloroacetic acid at 40 - 70oC in the presence of hexamethylenetetramine in methanol containing 10% water, followed by isolation of the target product from the mother solution, characterized in that for ammonolysis a pre-prepared solution of monochloroacetic acid and hexamethylenetetramine is taken at a molar ratio of 9 - 15: 1, additionally containing 3 - 5 wt. % chloroform based on monochloroacetic acid, followed by passing ammonia gas through the reaction mass.

DRAWINGS

Use in the food industry

Glycine is also used as a flavor and aroma enhancer. This substance is known as E640.

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