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Folic acid

Chemical Name:
Folic acid
Molecular Formula:
Molecular Weight:
MDL Number:
MOL File:
MSDS File:
Last updated:2023-12-26 17:07:23

Folic acid Properties

Melting point 250 °C
alpha 20 º (c=1, 0.1N NaOH)
Boiling point 552.35°C (rough estimate)
Density 1.4704 (rough estimate)
refractive index 1.6800 (estimate)
storage temp. 2-8°C
solubility boiling water: soluble1%
form Crystalline Powder
pka pKa 2.5 (Uncertain)
color Yellow to orange
Odor Odorless
PH Range 4
Water Solubility 1.6 mg/L (25 ºC)
Merck 14,4221
BRN 100781
BCS Class 3
Stability Stable. Incompatible with heavy metal ions, strong oxidizing agents, strong reducing agents. Solutions may be light and heat sensitive.
LogP -0.990 (est)
FDA 21 CFR 172.345; 102.23; 104.20; 310.545
Substances Added to Food (formerly EAFUS) FOLIC ACID
CAS DataBase Reference 59-30-3(CAS DataBase Reference)
EWG's Food Scores 1
NCI Dictionary of Cancer Terms folate; folic acid
NCI Drug Dictionary folic acid
ATC code B03BB01,B03BB51,V04CX02
NIST Chemistry Reference Folic acid(59-30-3)
EPA Substance Registry System L-Glutamic acid, N-[4-[[(2-amino-3,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]- (59-30-3)

Folic acid price More Price(55)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich F7876 Folic acid ≥97% 59-30-3 1g $23.2 2024-03-01 Buy
Sigma-Aldrich 1286005 Folic acid United States Pharmacopeia (USP) Reference Standard 59-30-3 500mg $447 2024-03-01 Buy
Sigma-Aldrich BP937 Folic acid British Pharmacopoeia (BP) Reference Standard 59-30-3 150MG $266 2023-06-20 Buy
TCI Chemical F0043 Folic Acid Hydrate >98.0%(HPLC)(T) 59-30-3 25g $65 2024-03-01 Buy
Alfa Aesar J60833 Folic acid, crystalline 59-30-3 25g $80.2 2024-03-01 Buy
Product number Packaging Price Buy
F7876 1g $23.2 Buy
1286005 500mg $447 Buy
BP937 150MG $266 Buy
F0043 25g $65 Buy
J60833 25g $80.2 Buy

Folic acid Chemical Properties,Uses,Production


Folic acid (folate,59-30-3) 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.


In the 1930s, brewer’s yeast was found to prevent anemia. Folic acid was later discovered to be the nutrient responsible for this effect and was purified in 1941 by Mitchell and coworkers (Mitchell et al., 1941). Folate is needed for biosynthesis of purines and thymidine for DNA and RNA synthesis in all cells. It is also involved in metabolism of some of the amino acids needed for protein synthesis, especially the conversions of serine to glycine and homocysteine to methionine. This makes the nutrient especially important during periods of rapid cell division, such as in pregnancy. Folate is also involved in transfer of one-carbon groups for methylation reactions. The role of folate in cell division was capitalized upon in the synthesis of aminopterin, a folate antagonist, which was one of the first anticancer drugs produced.


Folic acid is an essential B vitamin. It is converted to folate in vivo, which is a necessary cofactor for a variety of biological processes, including nucleotide synthesis and, thus, DNA synthesis and repair, among others. A deficiency in dietary folic acid can lead to a range of developmental and cognitive disorders, most prominently neural tube defects and congenital heart defects.

Chemical Properties

orange to yellow crystalline powder

Physical properties

The folates include a large number of chemically related species, each differing with respect to the various substituents possible at three sites on the pteroylglutamic acid basic structure. More than 170 different folates are theoretically possible. Not all of these occur in nature; but it has been estimated that as many as 100 different forms are found in animals. The folates from most natural sources usually have a single carbon unit at N-5 and/or N-10; these forms participate in the metabolism of the single-carbon pool.
Folic acid (pteroylmonoglutamic acid) is an orange-yellow crystalline substance that is soluble in water but insoluble in ethanol or less polar organic solvents. It is unstable to light, to acidic or alkaline conditions, to reducing agents, and, except in dry form, to heat. It is reduced in vivo enzymatically (or in vitro with a reductant such as dithionite) first to 7,8-dihydrofolic acid (FH2) and then to FH4; both of these compounds are unstable in aerobic environments and must be protected by the pres ence of an antioxidant (e.g., ascorbic acid, 2-mer
Two derivatives of folic acid, each having an amino group in the place of the hydroxyl at C-4, are folate antagonists of biomedical use: aminopterin (4-aminofolic acid) and methotrexate (4-amino-N10-methylfolic acid). Aminopterin is used as a rodenticide; methotrexate is an antineoplastic agent.


Folvite, Lederle, US ,1946




folic acid is generally used as an emollient. In vitro and in vivo skin studies now indicate its capacity 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. Folic acid is a member of the vitamin B complex and is naturally occurring in leafy greens.


Literature tends to indicate that B vitamins cannot pass through the layers of the skin and, therefore, are of no value in the skin surface. Current experiments demonstrate, however, that vitamin B2 acts as a chemical reaction accelerator, enhancing the performance of tyrosine derivatives in suntan-accelerating preparations.


Folic Acid is a water-soluble b-complex vitamin that aids in the for- mation of red blood cells, prevents certain anemias, and is essential in normal metabolism. high-temperature processing affects its sta- bility. it is best stored at lower than room temperatures. it is also termed folacin. it is found in liver, nuts, and green vegetables.


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


hematopoietic vitamin


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.

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

General Description

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

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 anaemia
Supplement 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.


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.]

Folic acid Preparation Products And Raw materials

Raw materials

Preparation Products

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