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%
• 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
• 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

Definition

ChEBI: An N-acyl-amino acid that is a form of the water-soluble vitamin B9. Its biologically active forms (tetrahydrofolate and others) are essential for nucleotide biosynthesis and homocysteine remethylation.

General Description

Odorless orange-yellow needles or platelets. Darkens and chars from approximately 482°F.

Description

Folic acid (folate) is a kind of B-vitamin which is mainly present in the liver and kidney. It has various kinds of pharmacological and physiological effects. It is involved in amino acid metabolism, purine and pyrimidine synthesis, and is also essential for hematopoiesis and red blood cell generation. In women pregnancy, folate can effectively prevent neural tube defects in the baby. It plays important role in fertility through contributing to spermatogenesis. It can also reduce the incidence of heart disease, stroke and cancer. 
Folate deficiency may lead to various kinds of diseases including glossitis, diarrhea, depression, confusion, anemia, and fetal neural tube defectsand brain defects (during pregnancy). Other symptoms may include fatigue, gray hair, mouth sores, poor growth, and swollen tongue.

Uses

A vitamin needed to synthesize DNA, conduct DNA repair and methylate DNA, it also acts as a cofactor in biological reactions involving folate.

Air & Water Reactions

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

Chemical Properties

orange to yellow crystalline powder

Uses

hematopoietic vitamin

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.]

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.

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

• 532-82-1 Basic Orange 2 
• 1603-02-7 2,5,6-Triaminopyrimidin-4-ol sulphate 
• 921-03-9 1,1,3-Trichloroacetone 
• 5221-17-0 3,5-DI-T-BUTYL-4-METHOXYBENZALDEHYDE 
• 7681-57-4 Sodium metabisulfite 

Downstream Products

• 59303-03-6 3-Methyl-2-propionylthiophene 
• 59303-05-8 methylfurfurylthiol,5-methyl-2-furfurylthiol 
• 59303-07-0 2-FURFURYLTHIO-3-METHYLPYRAZINE 
• 59303-08-1 Pyrazine, 2-(2-furanylmethyl)thio-5-methyl- 
• 59303-09-2 Pyrazine, 2-(2-furanylmethyl)thio-6-methyl- 
• 59303-10-5 2-CHLORO-5-METHYLPYRAZINE 
• 59303-12-7 2-(methoxymethyl)-6-methylpyridine 
• 59303-13-8 2-Methyl-5-propionylthiophene 
• 59303-17-2 Ethanone, 1-(5-methyl-2-thiazolyl)- (9CI) 
• 59303-19-4 propyl thiophene-2-carboxylate 
• 593-03-3 3-Hexadecanol 
• 5930-37-0 N-{2-methyl-4-[(2-nitrophenyl)sulfanyl]phenyl}acetamide 
• 5930-38-1 1-{5-[(1H-benzimidazol-2-ylsulfanyl)methyl]furan-2-yl}-2,2,2-trifluoroethanone 
• 59303-93-4 4-methyl-N'-[2-(2-toluidino)benzoyl]benzenesulfonohydrazide