59-30-3

Basic information

• Product Name: Folic acid
• Synonyms: EZNA KIT FUNGAL DNA MINI;KIT BLOOD DNA EZNA 5 TESTS;2-amino-6-((p-((1,3-dicarboxypropyl)carbamoyl)anilino)methyl)-4-pteridino PteGlu Pteroyl-L-glutamic acid Vitamin M PGA Pteroylglutamic acid Folic Acid Hydrate;PTEROYL-L-GLUTAMIC ACID;PTEROYLMONOGLUTAMIC ACID;PTEROYLGLUTAMIC ACID;PTEROYGLUTAMIC ACID;PTEGLU
• CAS NO: 59-30-3
• Molecular Formula: C₁₉H₁₉N₇O₆
• Molecular Weight: 441.4
• EINECS: 200-419-0
• Product Categories: Food and Feed Additive;Biochemistry;Vitamins;Nutritional Supplements;Vitamin Ingredients;Intermediates & Fine Chemicals;Pharmaceuticals;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;FOLICET;vitamin;food or feed additives;Inhibitors
• Mol File: 59-30-3.mol

Chemical Properties

• Melting Point: 250 °C
• Boiling Point: 552.35°C (rough estimate)
• Appearance: Yellow to orange/Crystalline Powder
• Density: 1.4704 (rough estimate)
• Refractive Index: 1.6800 (estimate)
• Storage Temp.: 2-8°C
• Solubility: boiling water: soluble1%
• PKA: pKa 2.5 (Uncertain)
• Water Solubility: 1.6 mg/L (25 ºC)
• Stability: Stable. Incompatible with heavy metal ions, strong oxidizing agents, strong reducing agents. Solutions may be light and heat sen
• Merck: 14,4221
• BRN: 100781
• CAS DataBase Reference: Folic acid(CAS DataBase Reference)
• NIST Chemistry Reference: Folic acid(59-30-3)
• EPA Substance Registry System: Folic acid(59-30-3)

Safety Data

• Statements: 33-62-68
• Safety Statements: 24/25
• WGK Germany: 1
• RTECS: LP5425000
• F: 8
• TSCA: Yes
• Hazardous Substances Data: 59-30-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Folic acid is used as a hematopoietic vitamin, which aids in the formation of red blood cells and prevents certain anemias. It is essential for normal metabolism and is involved in the metabolism of some amino acids needed for protein synthesis.
Used in Cosmetics Industry:
Folic acid is used as an emollient in the cosmetics industry. It has been shown to aid in DNA synthesis and repair, promote cellular turnover, reduce wrinkles, and promote skin firmness. There is some indication that folic acid may also protect DNA from UV-induced damage.
Used in Nutritional Supplements:
Folic acid is used as a nutritional supplement to prevent deficiency, which can lead to a range of developmental and cognitive disorders, most prominently neural tube defects and congenital heart defects. It is especially important during periods of rapid cell division, such as in pregnancy.
Used in Anticancer Applications:
Folic acid plays a role in the synthesis of aminopterin, a folate antagonist, which was one of the first anticancer drugs produced. Aminopterin and methotrexate, derivatives of folic acid, are used as antineoplastic agents.
Used in Fertility and Pregnancy:
Folic acid plays an important role in fertility by contributing to spermatogenesis and can effectively prevent neural tube defects in babies during pregnancy. It also reduces the incidence of heart disease, stroke, and cancer.

Originator

Folvite, Lederle, US ,1946

Manufacturing Process

The following description is taken from US Patent 2,956,057. 100 grams of 1,3,3-trichloroacetone are heated on a boiling water bath and 95 grams of bromine are added thereto in drops while being stirred and the stirring is continued for about 1 hour. The resulting reaction solution is distilled under reduced pressure. 115 grams of 1-bromo-1,3,3- trichloroacetone are obtained having a boiling point of 85° to 95°C/17 mm (Hg). For the preparation of the hydrate, 100 grams of water are added to 100 grams of 1bromo-1,3,3-trichloroacetone, which is agitated and cooled. A white scaly crystal of hydrate of 1-bromo-1,3,3-trichloroacetone is obtained (100 grams), having a melting point of 52° to 53°C. 8.9 grams of 2,4,5-triamino-6-hydroxypyrimidine hydrochloride and 8 grams of p-aminobenzoylglutamic acid are dissolved in 400 cc warm water, which is cooled at 35° to 27°C and adjusted to pH 4 by using 20% caustic soda solution. To this solution was simultaneously added dropwise a solution obtained by dissolving 13.4 grams of 1-bromo-1,3,3-trichloroacetone hydrate in 90 cc of 50% methanol and 24 grams of 35% aqueous sodium bisulfite solution over a period of approximately 2 hours. During this period, in order to maintain the pH value of the reaction solution at 4 to 5, 20% caustic soda solution is added from time to time. The precipitate, formed by stirring for 5 hours after dropping was finished, is filtered, and the filtrated precipitate is refined; 5.6 grams of pure pteroylglutamic acid is obtained.

Therapeutic Function

Treatment of B vitamin (folacin) deficiency

Air & Water Reactions

Insoluble in water. Aqueous solutions have pHs of 4.0-4.8.

Reactivity Profile

Acid solutions of Folic acid are sensitive to heat, but towards neutrality, stability progressively increases. Solutions are inactivated by ultraviolet light and alkaline solutions are sensitive to oxidation. Folic acid is also inactivated by light. Folic acid is incompatible with oxidizing agents, reducing agents and heavy metal ions.

Fire Hazard

Flash point data for Folic acid are not available; however, Folic acid is probably combustible.

Biochem/physiol Actions

A nutritional delivery form of folate. Folic acid and its derivatives are essential mediators of one-carbon metabolism within cells.

Clinical Use

Folate-deficient megaloblastic anaemiaSupplement in HD patients

Safety Profile

Poison by intraperitoneal and intravenous routes. Experimental teratogenic effects. Mutation data reported. When heated to decomposition it emits toxic fumes of NOx.

Veterinary Drugs and Treatments

Folic acid is used to treat folic acid deficiency in dogs, cats, and horses (theoretically in other animal species as well) often due to small intestinal disease. Cats with exocrine pancreatic insufficiency appear to be most at risk for folate and cobalamin deficiencies secondary to malabsorption of folic acid in the diet. Dogs with exocrine pancreatic insufficiency often are noted to have increased folate levels secondary to overgrowths of folate-synthesizing bacteria in the proximal small intestine. Chronic administration of dihydrofolate reductase inhibiting drugs such as pyrimethamine, ormetoprim or trimethoprim can potentially lead to reduced activated folic acid (tetrahydrofolic acid); folic acid supplementation is sometimes prescribed in an attempt to alleviate this situation.

Drug interactions

Potentially hazardous interactions with other drugs Antiepileptics: reduces phenytoin, primidone and phenobarbital levels. Cytotoxics: avoid with raltitrexed.

Metabolism

Folic acid given therapeutically enters the portal circulation largely unchanged, since it is a poor substrate for reduction by dihydrofolate reductase. It is converted to the metabolically active form 5-methyltetrahydrofolate in the plasma and liver. Folate undergoes enterohepatic circulation. Folate metabolites are eliminated in the urine and folate in excess of body requirements is excreted unchanged in the urine.

Purification Methods

If paper chromatography indicates impurities, then recrystallise it from hot H2O or from dilute acid [Walker et al. J Am Chem Soc 70 19 1948]. Impurities may be removed by repeated extraction with n-BuOH of a neutral aqueous solution of folic acid (by suspending in H2O and adding N NaOH dropwise till the solid dissolves, then adjusting the pH to ~7.0-7.5) followed by precipitation with acid, filtration, or better collected by centrifugation and recrystallised form hot H2O. [Blakley Biochem J 65 331 1975, Kalifa et al. Helv Chim Acta 6 1 2739 1978.] Chromatography on cellulose followed by filtration through charcoal has also been used to obtain pure acid. [Sakami & Knowles Science 129 274 1959.] UV: max 247 and 296nm ( 12,800 and 18,700) in H2O pH 1.0; 282 and 346nm ( 27.600 and 7,200) in H2O pH 7.0; 256, 284 and 366nm ( 24600, 24,500 and 86,00) in H2O pH 13 [Rabinowitz in The Enzymes (Boyer et al. Eds), 2 185 1960]. [Beilstein 26 III/IV 3944.]

InChI:InChI=1/C19H19N7O6/c20-19-25-15-14(17(30)26-19)23-11(8-22-15)7-21-10-3-1-9(2-4-10)16(29)24-12(18(31)32)5-6-13(27)28/h1-4,8,12,21H,5-7H2,(H,24,29)(H,27,28)(H,31,32)(H3,20,22,25,26,30)/p-2/t12-/m1/s1

Synthetic route

N-(4-aminobenzoyl)-L-glutamic acid (4271-30-1) + 2,5,6-triamino-1,4-dihydropyrimidin-4-one hydrochloride → folate (59-30-3)

Conditions	Yield
With 1,1,1-trichloroacetone; sodium sulfite In water at 40 - 50℃; for 1h; pH=3 - 4; pH-value; Temperature;	85%

1,1,3-trichloroacetone (921-03-9) + N-(4-aminobenzoyl)-L-glutamic acid (4271-30-1) + 2,4,5-triamino-6-hydroxypyrimidine sulfate (35011-47-3) → folate (59-30-3)

Conditions	Yield
With sodium metabisulfite at 20 - 30℃; for 2h; Temperature; Ionic liquid;	83.2%
With sodium metabisulfite; sodium acetate at 45℃; for 3h; Temperature;	46.2%

1,1,1-trichloroacetone (918-00-3) + p-Nitrobenzoyl-L-(+)-glutamic acid (6758-40-3) + 2,4-diamino-5-nitroso-6-hydroxypyrimidine (2387-48-6) → folate (59-30-3)

Conditions	Yield
Stage #1: p-Nitrobenzoyl-L-(+)-glutamic acid; 2,4-diamino6-hydroxy-5-nitroso pyrimidine With hydrogen In water at 82℃; under 6000.6 Torr; Stage #2: 1,1,1-trichloroacetone With sodium metabisulfite; sodium hydroxide In water at 45℃; pH=4.5; pH-value; Pressure; Temperature;	80%

1,1,1-trichloroacetone (918-00-3) + N-(4-aminobenzoyl)-L-glutamic acid (4271-30-1) + 2,4,5-triamino-6-hydroxypyrimidine sulfate (35011-47-3) → folate (59-30-3)

Conditions	Yield
Stage #1: 1,1,1-trichloroacetone; N-(4-aminobenzoyl)-L-glutamic acid With sodium acetate; sodium sulfite In acetic acid at 43℃; for 0.5h; Stage #2: 2,4,5-triamino-6-hydroxypyrimidine sulfate In acetic acid at 38℃; for 5h;	75.5%

1,1,3-tribromoacetone (3475-39-6) + N-(4-aminobenzoyl)-L-glutamic acid (4271-30-1) + 2,4,5-triamino-6-hydroxypyrimidine sulfate (35011-47-3) → folate (59-30-3)

Conditions	Yield
With sodium carbonate In ethanol; water at 40℃; pH=7.5; Temperature; pH-value;	60%

folate (65165-92-6) + 2-hydroxy-3-oxopropionaldehyde (497-15-4) + N-(4-aminobenzoyl)-L-glutamic acid (4271-30-1) → folate (59-30-3)

7,8-dihydrofolic acid (188497-71-4) + Na-folate + sodium citrate (68-04-2) → folate (59-30-3)

Conditions	Yield
With sodium hydroxide

folinic acid (58-05-9) + alpha cyclodextrin (10016-20-3) → folate (59-30-3)

Conditions	Yield
In water

folate (59-30-3) + N-tert-butoxycarbonyl cystamine (485800-26-8) → tert-butyl 2-{[2-({N2-(4-{[(2-amino-4-hydroxypteridin-6-yl)methyl]amino}benzoyl)-N1-[2-({2-[(tert-butoxycarbonyl)amino]ethyl}dithio)ethyl]-α-glutaminyl}amino)ethyl]dithio}ethylcarbamate (1301165-94-5)

Conditions	Yield
With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In water at 100℃;	96%

folate (59-30-3) + calcium chloride → C19H17N7O6(2-)*Ca(2+)

Conditions	Yield
Stage #1: folate With sodium hydroxide at 50℃; for 2h; pH=7.4; Stage #2: calcium chloride In ethanol; water at 50℃; for 1h;	96%

folate (59-30-3) + strontium chloride → C19H17N7O6(2-)*Sr(2+)

Conditions	Yield
Stage #1: folate With sodium hydroxide at 50℃; for 2h; pH=7.4; Stage #2: strontium chloride In ethanol; water at 50℃; for 1h;	95%

ethanol (64-17-5) + folate (59-30-3) → C23H27N7O6

Conditions	Yield
With methanesulfonic acid at 20℃;	95%

1-hydroxy-pyrrolidine-2,5-dione (6066-82-6) + folate (59-30-3) → N-hydroxysuccinimide folate (153445-05-7)

Conditions	Yield
With dicyclohexyl-carbodiimide In dimethyl sulfoxide at 20℃; for 24h; Darkness;	94%
With dicyclohexyl-carbodiimide In dimethyl sulfoxide at 20℃; for 0.0833333h; Inert atmosphere;	53%
With dicyclohexyl-carbodiimide In dimethyl sulfoxide at 50℃; for 6h;

1-amino-2-azidoethane (87156-40-9) + folate (59-30-3) → C21H23N11O5

Conditions	Yield
Stage #1: folate With 4-methyl-morpholine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In dimethyl sulfoxide; N,N-dimethyl-formamide at 0℃; for 1h; Inert atmosphere; Cooling with ice; Stage #2: 1-amino-2-azidoethane In dimethyl sulfoxide; N,N-dimethyl-formamide at 0℃; for 2h; Inert atmosphere; Cooling with ice;	94%
Stage #1: folate With 1-hydroxy-pyrrolidine-2,5-dione; dicyclohexyl-carbodiimide In dimethyl sulfoxide at 20℃; Inert atmosphere; Darkness; Stage #2: 1-amino-2-azidoethane In dimethyl sulfoxide for 24h; Inert atmosphere; Darkness;	84%

folate (59-30-3) + Propargylamine (2450-71-7) → propargylfolate

Conditions	Yield
Stage #1: folate With 1-hydroxy-pyrrolidine-2,5-dione; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide for 0.5h; Cooling with ice; Stage #2: Propargylamine In N,N-dimethyl-formamide at 20℃; for 24h;	93%

folate (59-30-3) + butan-1-ol (71-36-3) → C27H35N7O6

Conditions	Yield
With methanesulfonic acid at 20℃;	92%

formaldehyd (50-00-0) + folate (59-30-3) → calcium 5-methyl-tetrahydrofolate

Conditions	Yield
Stage #1: folate With sodium tetrahydroborate; edetate disodium; sodium hydroxide In water at 25 - 92℃; Stage #2: formaldehyd With hydrogenchloride In water at 0 - 10℃; pH=9; Further stages;	91.35%

tert-butyl N-(6-aminohexyl)carbamate (51857-17-1) + folate (59-30-3) → γ-{[tert-butyl-N-(6-aminohexyl)]carbamate}folic acid (850754-81-3)

Conditions	Yield
With pyridine; dicyclohexyl-carbodiimide In dimethyl sulfoxide at 20℃; for 18h; Inert atmosphere;	91%

folate (59-30-3) + Propargylamine (2450-71-7) → propargyl folic acid (1009599-12-5)

Conditions	Yield
Stage #1: folate With 1-hydroxy-pyrrolidine-2,5-dione; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide for 0.5h; Cooling with ice; Stage #2: Propargylamine In N,N-dimethyl-formamide at 20℃; Cooling with ice;	90%
Stage #1: folate With 1-hydroxy-pyrrolidine-2,5-dione; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide for 0.5h; Cooling with ice; Stage #2: Propargylamine In N,N-dimethyl-formamide at 25℃; for 24h;	71.2%
Stage #1: folate With 1-hydroxy-pyrrolidine-2,5-dione; 1,2-dichloro-ethane In N,N-dimethyl-formamide for 0.5h; Cooling with ice; Stage #2: Propargylamine In N,N-dimethyl-formamide at 20℃; for 24h;

nickel(II) chloride hexahydrate + water (7732-18-5) + hydrazine hydrate (7803-57-8) + folate (59-30-3) → [Ni2(FA)(N2H4)3(H2O)2(OH-)2]

Conditions	Yield
Stage #1: nickel(II) chloride hexahydrate; water; folate In ethanol for 0.166667h; Sonication; Stage #2: hydrazine hydrate In ethanol at 120℃; for 12h; pH=10.5; Autoclave;	90%

propan-1-ol (71-23-8) + folate (59-30-3) → C25H31N7O6

Conditions	Yield
With methanesulfonic acid at 20℃;	89%

methanol (67-56-1) + folate (59-30-3) → C21H23N7O6 (319919-60-3)

Conditions	Yield
With methanesulfonic acid at 20℃;	87%

adamantylmethylamine (17768-41-1) + folate (59-30-3) → C30H36N8O5

Conditions	Yield
Stage #1: folate With 1-hydroxy-pyrrolidine-2,5-dione; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dimethyl sulfoxide for 1h; Inert atmosphere; Darkness; Stage #2: adamantylmethylamine With triethylamine In dimethyl sulfoxide for 48h; Inert atmosphere; Darkness;	86%

Upstream product

• 1004-75-7 2,5,6-triamino-3,4-dihydro-4-pyrimidinone 
• 921-03-9 1,1,3-trichloroacetone 
• 4271-30-1 N-(4-aminobenzoyl)-L-glutamic acid 
• 3475-39-6 1,1,3-tribromoacetone 
• 26944-17-2 2,2,3-tribromopropanal 
• 712-30-1 6-formylpterin 
• 120568-20-9 (2-amino-4-oxo-3,4-dihydro-pteridin-6-yl)-acetic acid 
• 54-62-6 aminopterin 
• 103508-85-6 N-{4-[(2-amino-4-dimethylamino-pteridin-6-ylmethyl)-amino]-benzoyl}-L-glutamic acid 
• 2544-29-8 N⁽²⁾-acetylfolic acid 
• 3946-50-7 N-(N²-acetyl-10-formyl-pteroyl)-L-glutamic acid 
• 59212-10-1 2-amino-6-(bromomethyl)-4(1H)-pteridinone hydrobromide 
• 56-86-0 L-glutamic acid 
• 197151-79-4 pteroyl azide 

Downstream Products

• 111612-17-0 5-(-)-menthyloxycarbonyl-(6R)-tetrahydrofolic acid 
• 135-16-0 tetrahydrofolic acid 
• 4033-27-6 (S)-2-{4-[(2-Amino-4-oxo-3,4,7,8-tetrahydro-pteridin-6-ylmethyl)-amino]-benzoylamino}-pentanedioic acid 
• 35695-16-0 6-methyl-5,6,7,8-tetrahydropterin hydrochloride 
• 223378-68-5 N¹⁰-(trifluoroacetyl)pyrofolic acid 
• 119-24-4 pteroic acid 
• 153445-05-7 folic acid, N-hydroxysuccinimide ester 
• 135-16-0 (6S,S)-5,6,7,8-tetrahydrofolic acid 
• 74708-38-6 (6R,S)-5,6,7,8-tetrahydrofolic acid 
• 712-30-1 6-formylpterin 
• 4271-30-1 N-(4-aminobenzoyl)-L-glutamic acid 
• 712-29-8 6-(hydroxymethyl)pterin 
• 292045-48-8 (6-([4-(imidazol-1-ylcarbonyl)phenylamino]methyl)-4-oxo-3,4-dihydro-pteridin-2-yl)-carbamic acid 2-trimethylsilylethyl ester 
• 292045-47-7 α-[2-(trimethylsilyl)ethoxy]-2-N-[2-(trimethylsilyl)ethoxycarbonyl]folic acid 

Relevant articles and documents

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Method for preparing folic acid by virtue of micro-channel reaction (by machine translation)

The invention belongs to the technical field of chemical synthesis of drugs, and relates to a synthesis method for preparing folic acid through a microchannel reactor. An intermediate 6 is prepared from cyanoethyl acetate as a raw material by one-step continuous operation, and the folic acid bulk drug is prepared through one-step reaction of the intermediate 6 and L - glutamate. The synthesis method uses the microchannel reactor to prepare the folic acid intermediate 2,triamino -4 - hydroxypyrimidine and folic acid, is safe and environment-friendly, and ensures the tasteless system. The method guarantees that the operation is simple and feasible, the solvent consumption is greatly reduced, 2,triamino -4 - hydroxyl pyrimidine yield and purity are obviously improved. (by machine translation)

Heteropolyacid catalyzed safe and green folic acid synthesis method

The invention belongs to the technical field of pharmaceutical chemistry synthesis, and relates to a heteropolyacid catalyzed safe and green folic acid synthesis method. The folic acid synthesis method comprises the following steps that (1), acrolein, heteropoly acid, 2,5,6-triamino-4-hydroxypyrimidine, p-aminobenzoate and alcoholic solvents are added into a reactor, stirring and warming are conducted, a reaction is conducted, material cooling is conducted after the reaction is finished, filtration is conducted, a filter cake is washed with the solvents, filtrate and washing liquid are combined, activated carbon is used for decoloration, the solvents are dried through distillation after extraction filtration is conducted, and a yellowish solid intermediate 6 is obtained; (2), sodium hydrogen glutamate and the intermediate 6 are dissolved into an alcohol-water mixed solution, stirring and a temperature reaction are conducted, after the reaction is finished, material cooling and coolingare conducted, heat preservation and crystallization are conducted, extraction filtration is conducted, the filter cake is washed with water, a crude folic acid product is obtained, and folic acid isobtained through refining. According to the synthesis method, acrolein which is low in price and easy to obtain is used as a raw material, the reaction is complete and rapid, no residue exists, it isguaranteed that the system is tasteless, and the yield and purity are obviously increased.

Preparation method of folic acid

The invention discloses a preparation method of folic acid. 2,4,5-triamino-6-hydroxypyrimidine hydrochloride is adopted as a reaction raw material, the compound has the great solubility in water, thusin the reaction process, the reaction area is increased, reaction selectivity is improved, a product is precipitated from a water solution, the obvious purification effect is achieved, and the yieldof a crude product reaches 90% or above; meanwhile, the using amount of a solvent, namely the water is remarkably lowered, compared with a traditional process, the water amount is lowered from 40-50 times to 5-10 times (relative to the mass ratio of N-(4-aminobenzoyl)-L-glutamic acid), and the yield is increased by 15-20%; and the yield of the synthesized folic acid is high, the product purity ishigh, reaction conditions are mild, the reaction speed is high, all the crude product water is reused, wastewater is less, safety and environmental friendliness are achieved, and thus the requirementof industrialization for environmental friendliness is met.

Preparation method of 2,4,5-triamino-6-hydroxypyrimidine sulfate and folic acid

The invention relates to a preparation method of 2,4,5-triamino-6-hydroxypyrimidine sulfate and folic acid. The preparation method comprises the following steps: enabling cyanoacetate and sodium nitrite to be subjected to reaction under the action of an organic solvent and/or an inorganic solvent and an acidic substance to obtain 2-oximidocyanoacetate; then, enabling the 2-oximidocyanoacetate andguanidine hydrochloride to be subjected to reaction under an alkaline condition to obtain 2,4-diamino-5-isonitroso-6-oxopyrimidine; enabling the 2,4-diamino-5-isonitroso-6-oxopyrimidine and hydrogen gas to be subjected to reaction under an alkaline condition by means of action of Pd/C to obtain 2,4,5-triamino-6-hydroxypyrimidine, and adding sulfuric acid to adjust the pH value to obtain 2,4,5-triamino-6-hydroxypyrimidine sulfate; and then, adding trichloroacetone and N-(4-aminobenzoyl)-L-glutamic acid to be subjected to reaction in a buffer solution under the action of a catalyst molecular sieve so as to obtain the folic acid. Based on the process route, the invention explores the influences of different reaction steps and refining conditions on the preparation route of 2,4,5-triamino-6-hydroxypyrimidine sulfate and the folic acid so as to reduce the wastewater pollution while increasing the yield.

Environment-friendly production method of folic acid

The invention provides a simple environment-friendly production method of folic acid. The method comprises the following steps: performing reaction of 2,4,5-triamino-6-hydroxypyrimidine sulfate, 1,1,3-trichloroacetone and N-p-aminobenzoyl-L-glutamic acid in a mixed solvent system of water and organic solvents to generate folic acid crude product, then refining by thionyl chloride in an organic solvent system to obtain a purified folic acid product, wherein the organic solvent used can be recycled by distillation. The purification method provided by the invention is simple in operation and lowin cost, and effectively reduces the generation of wastewater in folic acid production, and is suitable for requirements of industrialization to environmental protection.

Production method of folic acid

The invention relates to a production method folic acid. The production method sequentially includes following steps: synthesizing a crude product: using N-(p-aminobenzoyl)-L-glutamic acid shown as a compound A in a formula I, 2, 4, 5-triamino-6-hydroxy pyrimidine sulfate shown as a compound B in the formula I and trichloroacetone shown as a compound C in the formula I as raw material, sodium metabisulfite as an antioxidant and water as a solvent, and adopting a mode of charging in batches for graded cyclization reaction to obtain reaction liquid; subjecting the reaction liquid to cooling and press filtering to obtain a crude folic acid product; subjecting the crude folic acid product to acid dissolution, alkali dissolution and refining to obtain the folic acid. The mode of charging in batches is adopted to maintain concentration of materials in the reaction liquid within a reasonable range, so that water amount needed at the stage of synthesizing the crude folic acid product is reduced to 1/4 of that needed by existing synthesis processes.

Environmentally friendly preparation method of synthetic folic acid

The invention relates to an environmentally friendly preparation method of synthetic folic acid. 2, 4, 5-triamino-6-hydroxypyrimidine sulfate, 1, 1, 2, 2, 3-pentachloropropane and N-P-aminobenzoyl-L-glutamic acid undergo a reaction to produce folic acid. Cheap and easily available 1, 1, 2, 2, 3-pentachloropropane replaces 1, 1, 3-trichloroacetone which is not easy to acquire and has low purity. The reaction process is simple and has characteristics of good regional selectivity, environmental friendliness, simple purification and low cost. The environmentally friendly preparation method has a good industrial production prospect.

Folic acid preparation technology

The invention belongs to the technical field of medicine and chemical engineering, and particularly relates to a folic acid preparation technology. The technology comprises the steps of 1, dissolving 2,4-diamino-6-hydroxy-5-nitrosopyrimidine and nitrophenylcarbimide formylglutamicacid in water, adding NiAl2 to serve as a catalyst, and conducting hydrogenation reaction; 2, filtering a reaction solution obtained in step 1, taking filtrate, and recovering a NiAl2 catalyst obtained from filtration; 3, directly adding sodium metabisulfite into the filtrate, adding a trichloroacetone aqueous solution dropwise at 30-60 DEG C, and adding a sodium hydroxide solution to regulate pH; 4, conducting cooling crystallization and filter pressing on a solution obtained after reaction in step 3 to obtain a crude product, and refining the crude product to obtain pure folic acid. By the adoption of the technology, reaction efficiency is improved greatly, the preparing process is simplified, yield is increased, and generation of liquid waste and solid water is reduced greatly.

New folic acid preparation method

The invention discloses a new folic acid preparation method, wherein folic acid is subjected to one-pot low temperature synthesis by using an ion liquid as a solvent. According to the present invention, the reaction condition is mild, the problems of more side reactions, high water consumption and complex refining process of the existing folic acid preparation method using the water as the solvent are solved, and the good foundation is established for the production capacity improving in the industrial production.