|Company Name:||MP Biomedicals Gold|
|Glycine Chemical Properties|
|Melting point ||240 °C (dec.)(lit.)|
|Boiling point ||233°C|
|storage temp. ||2-8°C|
|solubility ||H2O: 100 mg/mL|
|color ||<5 (200 mg/mL)(APHA)|
|Water Solubility ||25 g/100 mL (25 ºC)|
|Stability:||Stable. Combustible. Incompatible with strong oxidizing agents.|
|CAS DataBase Reference||56-40-6(CAS DataBase Reference)|
|NIST Chemistry Reference||Glycine(56-40-6)|
|EPA Substance Registry System||Glycine(56-40-6)|
|Glycine Usage And Synthesis|
|Amino acids with the simplest structure||Glycine is of the simplest structure in the 20 members of amino acid series, also known as amino acetate. It is a non-essential amino acid for the human body and contains both acidic and basic functional group inside its molecule. It exhibits as a strong electrolyte an aqueous solution, and has a large solubility in strong polar solvents but almost insoluble in non-polar solvents. Moreover, it also has a relative high melting point and boiling point. The adjustment of the pH of the aqueous solution can make glycine exhibit different molecular forms. The side chain of glycine contains only a hydrogen atom. Owing to another hydrogen atom connecting to the α-carbon atom, the glycine is not optical isomer. Since the side bond of glycine is very small, it can occupy space which can’t be occupied by other amino acids, such as those amino acids located within the collagen helix. At room temperature, it exhibits as white crystal or light yellow crystalline powder and has a unique sweet taste which can ease the taste of acid and alkaline taste, masking the bitter taste of saccharin in food and enhance the sweetness. However, if an excessive amount of glycine is absorbed by body, they not only can’t be totally absorbed by the body, but will also break the balance of the body's absorption of amino acids as well as affect the absorption of other kinds of amino acids, leading to nutrient imbalances and negatively affected health. The milk drink with glycine being the major raw material can easily does harm to the normal growth and development of young people and children. It has a density of 1.1607, melting point of 232~236 °C (decomposition). It is soluble in water but insoluble in alcohol and ether. It is capable of acting together with hydrochloric acid to form hydrochloride salt. It is presented in the muscles of animals. IT can be produced from the reaction between monochloro acetate and ammonium hydroxide as well as from the hydrolysis of gelation with further refining.
|History of discovery||Amino acids are organic acids containing an amino group and are the basic units of protein. They are generally colorless crystals with a relative high melting point (over 200 °C). It is soluble in water with amphiprotic ionization characteristics and can have sensitive colorimetric reaction with ninhydrin reagent. In 1820, glycine with the simplest structure was first discovered in a protein hydrolysis product. Until 1940, it has been found that there were about 20 kinds of amino acids in nature. They are necessary for the protein synthesis of both human and animal. They are mostly α-L-type amino acids. According to the different number of amino groups and carboxyl groups contained in amino acids, we classify amino acids into neutral amino acids (glycine, alanine, leucine, isoleucine, valine, cystine, cysteine, A methionine, threonine, serine, phenylalanine, tyrosine, tryptophan, proline and hydroxyproline, etc.) with the amino acid molecules containing only one amino group and a carboxyl group; acidic amino acid (glutamate, aspartate) which contains two carboxyl and one amino group; alkaline amino acids (lysine, arginine) which molecularly contains one carboxyl group and two amino groups; Histidine contains a nitrogen ring which exhibits weakly alkaline and thus also belonging to alkaline amino acids. Amino acids can be obtained both from protein hydrolysis and from chemical synthesis. Since the 1960s, industrial production mainly applied microbial fermentation, such as monosodium glutamate factory has been widely applied fermentation method for production of glutamate. In recent years, people has also applied petroleum hydrocarbons and other chemical products as raw materials of fermentation for production of amino acids.|
The above information is edited by the Chemicalbook of Dai Xiongfeng.
|Content Analysis||Accurately weigh 175 mg of sample which has undergone drying for 2 h at 105 °C and place it in a 250m1 flask, add 50 mL of glacial acetic acid for dissolving; add 2 drops of crystal violet test solution (TS-74); titrate with 0.1ml/L perchloric acid to blue-green endpoint. At the same time carry out a blank test, and make the necessary corrections. Each mL of 0.1mol/L perchloric acid is equivalent to glycine (C2H5NO2) 7.507mg.
|Toxicity||LD50:7930 mg/kg (rat, oral administration). |
It is safe for being applied to food (FDA, §172.812 2000).
|Limited use||As the source of amino acids, it accounts for 3.5% of total protein mass in food (FDA, §172.320, 2000). |
As the bitterness masking agent for beverage added with sodium saccharin, Limitation 0.2% (in terms of finished drink); as the stabilizer for mono-, di-glycerides in edible fats, Limitation 0.02%, calculated according to the amount of single, and diglycerides meter (FDA§ 172.812,2000).
FEMA: beverages, candy, baked goods, meat, watching sausage, broth, seasonings, all 150 (mg/kg).
|Biosynthesis of glycine production||In the late 1980s, Japan's Mitsubishi Corporation added the screened aerobic Agrobacterium, Brevibacterium, Corynebacterium genus to the medium containing carbon, nitrogen and inorganic nutrient solution for cultivation, and then applied this class of bacteria for converting ethanolamine to glycine in 25~45 °C and pH value from 4 to 9 and further applied concentration, neutralization ion exchange treatment to get the glycine product.|
After entering the 1990s, there had been new progress on the production technology of glycine in foreign countries. The Nitto Chemical Industry Co (Japan) add cultured pseudomonas genus, casein bacteria genus, and alcaligenes genus and other species in 0.5% (mass fraction, dry weight) to the glycine amine-containing matrix for reaction of 45 h under 30 °C and pH value of 7.9 to 8.1 with almost all glycine amine being hydrolyzed into glycine with the conversion rate of 99%. Although biological methods are still in the research stage, however, owing to its high selectivity, non-pollution property, it will be a synthetic route with highly development potential.
|The maximum amount allowed for food additives and maximal allowable residue limits|
|Uses||1. It can be used for the pharmaceutical industry, organic synthesis and biochemical analysis. |
2. It can be used as a buffer for the preparation of tissue culture media and the testing of copper, gold and silver. In medicine, it is used for the treatment of myasthenia gravis and progressive muscular atrophy, hyperacidity, chronic enteritis, and children hyperprolinemia diseases.
3. It can be used for the treatment of myasthenia gravis and progressive muscular atrophy; treatment of excess stomach acid ester disease, chronic enteritis (often in combination antacid); using in combination with aspirin can reduce the irritation of the stomach; treatment of children hyperprolinemia; as the nitrogen source for generating non-essential amino acid and can be added to a mixed amino acid injection.
4. Glycine is primarily used as a nutritional additive in chicken feed.
5. It can be used as a kind of nutritional supplement which is mainly used for flavoring.
Flavoring agent: Used for alcoholic beverage in combination with alanine; the addition amount: grape wine: 0.4%, whiskey: 0.2%, champagne: 1.0%. Others such as powder soup: 2%; lees marinated foods: 1%. Because it is tasted like shrimp and cuttlefish, and thus can be used in sauces.
It has some certain inhibitory effects on the Bacillus subtilis and E. coli and thus can be used as the preservatives of surimi products and peanut butter with the added amount being 1% to 2%.
Buffering effect: Because glycine is amphiprotic ions containing both amino and carboxyl groups, it has a strong buffering property on the taste feeling of salt and vinegar. The added amount is: salted products: 0.3% to 0.7%, acid stain product: 0.05% to 0.5%.
Antioxidant effect (with its metal chelation): being added to butter, cheese, and margarine extend the storage duration by 3 to 4 times. To make the lard oil in baked food be stable, we can add 2.5% glucose and 0.5% glycine. Adding 0.1% to 0.5% glycine to the wheat flour for making convenient noodles can play a role of flavoring. In pharmacy, it is used as antacids (hyperacidity), therapeutic agent for muscle nutritional disorder as well as antidotes. Moreover, glycine can also be used as the raw material for synthesizing amino acids like threonine.
It can be used as a spice according to the provisions of GB 2760-96.
6. Glycine is also known as aminoacetic acid. In the field of pesticide production, it is used for synthesizing the glycine ethyl ester hydrochloride which is the intermediate for the synthesis of pyrethroid insecticides. Moreover, it can also be used for synthesizing fungicides iprodione and solid glyphosate herbicide; in addition it is also used in various kinds of other industries such as fertilizer, medicine, food additives, and spices.
7. The product is used as a solvent to remove carbon dioxide in the fertilizer industry. In the pharmaceutical industry, it can be used as amino acid preparations, the buffer of chlortetracycline buffer and as the raw material for synthesizing the anti-Parkinson's disease drugs L-dopa. Moreover, it is also the intermediate for producing ethyl imidazole. It is also an adjunct therapy medicine for treating neural hyperacidity and effectively suppressing excess amount of gastric ulcer acid. In the food industry, it is used for the synthesis of alcohol, brewing products, meat processing and cold drinks formula. As a food additive, glycine can be used alone as a condiment and also used in combination with sodium glutamate, DL-alanine acid, and citric acid. In other industries, it can be used as a pH adjusting agent, being added to the plating solution, or used as the raw material for making other amino acids. It can further be used as biochemical reagents and solvent in organic synthesis and biochemistry.
8. It can be used as the intermediates of pharmaceutical and pesticide, decarbonation solvents of fertilizers, plating fluid, etc.
9. It can be used as a solvent for removing carbon dioxide in the fertilizer industry. In pharmaceutical industry, it is used as the buffer of chlortetracycline, amino antacids, and used for the preparation of L-dopa. In food industry, it can be used as flavoring agents, agent for removing saccharine bitter taste, for brewing, meat processing, and preparation of soft drinks. In addition, it can also be used as a pH adjusting agent and used in the preparation of the plating solution.
10. It can be used as biochemical reagents for the pharmaceutical, food and feed additives; it can also be used as a non-toxic decarbonization agent in the field of fertilizer industry.
|Production method||1. Strecker method |
Have formaldehyde, sodium cyanide, ammonium chloride to react together, and then add acetic acid to precipitate out the methyleneamino acetonitrile; Add ethanol to the methyleneamino acetonitrile in the presence of sulfuric acid for decomposition to give aminoacetonitrile sulfate; use barium hydroxide to decompose this sulfates to obtain the barium glycine salt; then add sulfate to precipitate the barium, filter, and concentrate the filtrate, and the glycine crystals will be precipitated after cooling.
HCHO [NaCN] → [NH4Cl] CH2 = N-CH2CN
CH2 = N-CH2CN [H2SO4] → [C2H5OH] H2NCH2CN • H1SO4
H2NCH2CN • H2SO4 [Ba (OH) 2] → (NH2CH2COO) 2Ba
(NH2CH2COO) 2Ba [H2SO4] → H2NCH2COOH
2. Acid amide Method
Mix the ammonia and ammonium bicarbonate and heat to 55 °C; add chloro acid aqueous solution to have reaction for 2h, and then heat to 80 °C to remove the residual ammonia, decolorize with charcoal and filter. Add 95% ethanol to the bleaching solution to precipitate out the glycine crystal, filtrate, wash with ethanol and dry to obtain the crude product; then dissolve in hot water, plus recrystallization from ethanol to obtain the finished glycine. ClCH2COOH [NH4HCO3] → [NH4OH] H2NCH2COOH
3. Extract the hydrolysis product of 25 kg waste silk, add 75 L of 6N industrial hydrochloric acid, heat at 110-120 °C for reflux for 22h, fully hydrolyze it until biuret reaction doesn’t further exhibit purple color.
Before the end of hydrolysis reaction, add one volume of water plus 30-40 g of powdered activated carbon per liter, stir at 60 °C for 30min. Use polyester cloth to filter out impurities in the filter cylinder to obtain about 150 L of brown hydrolysis solution. Use activated carbon to adhere tyrosine in the hydrolysis solution and then use ion-exchange column separate out the glycine which can also separate out the alanine and serine. In the above production process, the monochloro acetic acid method is relatively simple. In fact, adding monochloro acid to the ammonia storage tank can generate glycine after a long time at room temperature. In the industrial production, take hexamine solution as the medium, have monochloro acid with a high concentration of ammonia reaction for 2 h at 70 °C through methanol (or ethanol) precipitation, refinement treatment to obtain a white crystallized glycine with this yield being 92-94% and the product content being 99%. Material fixed consumption amount: monochloroacetic acid (95%) 1600kg/t, liquid ammonia 880kg/t, methenamine 350kg/t, and methanol (95%) 1100kg/t. In addition, take raw materials as gelatin, after the hydrolysis, refinement and filtering, drying can also used for preparing glycine.
4. Take formaldehyde as the raw material, have reaction together with sodium cyanide and ammonium chloride for synthesis of N-methylene amino acetonitrile, then has reaction with ethanol and sulfuric acid for synthesizing amino acetonitrile which further have reaction with barium hydroxide to synthesize barium amino acetic acid; add sulfuric acid to obtain the final product . This cost of this method is relatively low, but because of the relation of cyanide (or hydrocyanic acid), it is generally not applied domestically. It is synthesized from chloro acetic acid with adding excess ammonia to obtain. This method is mature with raw material easily available, and thus it is generally applied domestically.
5. The by-product ammonium chloride is removed by ion exchange resin method, or removed by using methanol to salt out the glycine.
6. Obtain by the single hydrolysis of Gelatin.
7. Bucherer method. The trioxane is added to the aqueous solution of ammonium carbonate and sodium nitrile; after the stirring and dissolution, have them reaction at room temperature after at 80-85 °C for 3h to obtain the hydantoin solution. Then simply add 30% NaOH aqueous solution for hydrolysis at 170 °C for 3h. Finally, with the treatment of the cation exchange resin, we obtain a glycine yield of 83.2%.
8. Phase Transfer Catalysis. Add 2 kg of aqueous ammonia into 1L of methanol, further add 0.3 kg of hexamethylene tetramine for six times until the solution becomes clear; add 2 L of methanol containing 10 kg dissolved chloroacetic acid 10kg with the temperature of the system rising significantly together with a large number of crystals being precipitated out upon 58 °C. When the temperature was dropped to room temperature and the clear up-layer supernatant, filter to obtain the crystals; the filtrate was placed two days with part of the crystals being precipitated out again. Add 2-3 fold the amount of deionized water to the above crude product; heat to 70-75 °C; add 2-fold the volumes of methanol after the dissolution and cool to precipitate the crystals. Dry at 70 °C for 2h to obtain the fine product with the yield being 68.6% and the purity being 99.6 %.
9. chlorine acid ammoniation method
Amination main reaction: Side reaction:
Ingredients ratio: chloro acetic acid: aqueous ammonia = 1: 60,50 °C, reaction for 4h with yield of 84.50%; chloro acetic acid: ammonia: carbon dioxide = 1: 12: 3,60 °C, reaction for 4h with yield of 80.5%; chloro acetic acid: formaldehyde: ammonia = 1: 1.5: 3, 30 °C, reaction for 4h with yield of 92%; chloro acetic acid: bicarbonate: aqueous ammonia = 1: 3.0: 4.5, take chloro acetic acid, ammonium bicarbonate to separately dissolve in water, stir and mix the two solutions, 45 °C, add ammonia, rose to 55 °C; the reaction was stirred for 2h; heat to remove the left ammonia; decolorize with charcoal; filter and add 95% ethanol to the filtrate, precipitate out the glycine crystal; filter to obtain the crystals; wash with ethanol to give crude glycine.
Refinement: take the above crude to dissolve in water and heat to 85 °C; filter and take the filtrate; add three to five times the volume of 95% ethanol and place it in cold storage to stand overnight for crystallization; filter and collect the crystal; wash with ethanol; add 1 to 1.25 times the weight of distilled water to the crystal and heat to 80 °C, dissolve, further add 3 to 5 times the volumes of 95% ethanol, cool and crystal for 12h; filter and collect the crystals; wash with ethanol 80%; dry to obtain the refined glycine product with the total yield of 41.9% (calculated from chloro acetic acid).
|Chemical Properties||White crystalline powder|
|Usage||Non-essential amino acid for human development. An inhibitory neurotransmitter in spinal cord, allosteric regulator of NMDA receptors.|
|Usage||Glycine is a non-essential amino acid for human development. Glycine is an inhibitory neurotransmitter in spinal cord, allosteric regulator of NMDA receptors.|
|Definition||ChEBI: The simplest (and the only achiral) proteinogenic amino acid, with a hydrogen atom as its side chain.|
|General Description||White crystals.|
|Air & Water Reactions||Water soluble.|
|Reactivity Profile||An amino acid. A 0.2M aqueous solution has a pH of 4.0., so acts as a weak acid. Has characteristics of both acid and base.|
|Fire Hazard||LOW. Ignites at very high temperatures.|
|Biological Activity||One of the major inhibitory neurotransmitters in the mammalian CNS, predominantly active in the spinal cord and brain stem. Also acts as a modulator of excitatory amino acid transmission mediated by NMDA receptors. Also available as part of the NMDA Receptor - Glycine Site Tocriset™ .|
|Glycine Preparation Products And Raw materials|
|Raw materials||Etanol-->Methanol-->Acetic acid glacial-->Ammonium hydroxide-->Ammonia-->Ammonium chloride -->Sodium cyanide-->POTASSIUM CYANIDE-->Ammonium bicarbonate-->Activated carbon-->Chloroacetic acid-->Hexamethylenetetramine-->Activated carbon,decolor-->Barium hydroxide -->HYDROGEN CYANIDE-->Ammonium carbonate-->Gelatin-->AMBERLITE(R) IRC-50-->s-Trioxane-->D-Alanine-->Storage tank-->Boc-D-Tyrosine-->DL-Serine-->Hydantoin-->hydracide-->AMINOACETONITRILE-->Barium acetate-->terylene-->Biuret-->SILK-->Methylenaminoacetonitrile-->Aminoacetonitrile sulfate |
|Preparation Products||(6-ETHYL-THIENO[2,3-D]PYRIMIDIN-4-YLAMINO)-ACETIC ACID-->6-Methoxyindole-->6-Methoxy-1H-indole-3-carbaldehyde-->DL-Threonine-->Glycine methyl ester hydrochloride-->3-Chlorobenzylamine-->2,2-Dimethyl-3-(2-methylpropyl)cyclopropanecarboxylic acid p-(methoxymethyl)benzyl ester-->Dimethoxymethane-->HIPPURIC ACID-->DL-Serine-->Tiopronin-->1,2,3,4-TETRAHYDRO-9-ACRIDINAMINE-->Iprodione-->2,2,3,3-TETRAMETHYLCYCLOPROPANECARBOXYLIC ACID-->Ciclopirox-->TOSUFLOXACIN TOSILATE-->Leflunomide-->4-METHYLHIPPURIC ACID-->2-(Acetylamino)-3-phenyl-2-propenoic acid-->5-Methoxy-2-methylaniline-->4-Chloro-2-methylaniline-->H-TYR-GLY-GLY-PHE-MET-OH-->Antistaling agent-->3,4,5-Trimethoxybenzylamine-->Synthetic greasing agent-->4-Methyl-3-nitroanisole-->3-METHYLHIPPURIC ACID-->BETA-(2-THIENYL)-DL-SERINE-->Thiamphenicol-->Glyphosine-->2'-IODOHIPPURIC ACID-->HYDANTOIC ACID-->2,4,6-TRIFLUOROPHENYL ISOTHIOCYANATE-->N-Carbobenzyloxyglycine-->BOC-Glycine-->novel anticancer microsphere with multifunction-->N-(2-CYANOETHYL)GLYCINE-->Zinc glycinate-->1H-TETRAZOLE-1-ACETYL CHLORIDE-->2-hydroxy-3-phenyl-L-alanine|