2-(4-Aminobenzenesulfonamido)-4,6-dimethylpyrimidine CAS 57-68-1

Introduction：Basic information about 2-(4-Aminobenzenesulfonamido)-4,6-dimethylpyrimidine CAS 57-68-1, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

2-(4-Aminobenzenesulfonamido)-4,6-dimethylpyrimidine Basic information

• Product Name: 2-(4-Aminobenzenesulfonamido)-4,6-dimethylpyrimidine
• Synonyms: (p-Aminobenzolsulfonyl)-2-amino-4,6-dimethylpyrimidin;2-(4-Aminobenzenesulfonamido)-4,6-dimethylpyrimidine;6-(4’-aminobenzol-sulfonamido)-2,4-dimethylpyrimidin;6-(4'-Aminobenzol-sulfonamido)-2,4-dimethylpyrimidin;A-502;Azolmetazin;Benzenesulfonamide, 4-amino-N-(4,6-dimethyl-2-pyrimidinyl)-;benzenesulfonamide,4-amino-N-(4,6-dimethyl-2-pyrimiidinyl)-
• CAS: 57-68-1
• MF: C12H14N4O2S
• MW: 278.33
• EINECS: 200-346-4
• Product Categories: Active Pharmaceutical Ingredients;Intermediates & Fine Chemicals;Antibiotics for Research and Experimental Use;Biochemistry;Pharmaceuticals;Sulfur & Selenium Compounds;Sulfonamides (Antibiotics for Research and Experimental Use);Pharmaceutical intermediate;SULFASURE;Animal medication;57-68-1
• Mol File: 57-68-1.mol

2-(4-Aminobenzenesulfonamido)-4,6-dimethylpyrimidine Chemical Properties

• Melting point: 197 °C
• Boiling point: 294°C (rough estimate)
• density: 1.2997 (rough estimate)
• refractive index: 1.6440 (estimate)
• storage temp.: 2-8°C
• solubility: acetone: soluble50mg/mL
• pka: 7.4, 2.65(at 25℃)
• form: Crystalline Powder
• color: white to off-white
• Water Solubility: 150mg/100mL (29 ºC)
• Merck: 14,8905
• BRN: 261304
• Stability: Stable, but light sensitive. Incompatible with strong oxidizing agents.
• InChI: 1S/C12H14N4O2S/c1-8-7-9(2)15-12(14-8)16-19(17,18)11-5-3-10(13)4-6-11/h3-7H,13H2,1-2H3,(H,14,15,16)
• InChIKey: ASWVTGNCAZCNNR-UHFFFAOYSA-N
• SMILES: Cc1cc(C)nc(NS(=O)(=O)c2ccc(N)cc2)n1
• CAS DataBase Reference: 57-68-1(CAS DataBase Reference)
• IARC: 3 (Vol. 79) 2001
• NIST Chemistry Reference: Sulfamethazine(57-68-1)
• EPA Substance Registry System: Sulfamethazine (57-68-1)

Safety Information

• Hazard Codes: Xi
• Risk Statements: 36/37/38
• Safety Statements: 23-24/25-36-26
• WGK Germany: 2
• RTECS: WO9275000
• F: 10
• TSCA: TSCA listed
• HS Code: 29350090
• Storage Class: 11 - Combustible Solids
• Hazardous Substances Data: 57-68-1(Hazardous Substances Data)
• Toxicity: LD50 i.p. in mice: 1.06 g/kg (Bobranski)

2-(4-Aminobenzenesulfonamido)-4,6-dimethylpyrimidine Usage And Synthesis

Brand Name(s) in US

Brand Name(s) in US

Description

Sulfamethazine is an antibacterial sulfonamide. Like other sulfonamides, sulfamethazine is bacteriostatic, competitively inhibiting dihydropteroate synthase to block folate synthesis and inhibit growth and multiplication. Sulfamethazine is metabolized by cytochrome P450 isoforms and arylamine N-acetyltransferase 2 in a sex-dependent manner.

Chemical Properties

White to Off-Solid

Originator

Cremomethazine,MSD,US,1947

Uses

Sulfamethazine is an antibacterial.This compound is a contaminant of emerging concern (CECs).

Definition

ChEBI: A sulfonamide consisting of pyrimidine with methyl substituents at the 4- and 6-positions and a 4-aminobenzenesulfonamido group at the 2-position.

Manufacturing Process

A flask heated in an oil bath is filled with 600 ml water and 60 g (1 mol)glacial acetic acid (or an equivalent quantity of diluted acetic acid). Whilestirring 235 g (1.1 mols) anhydrous p-aminobenzenesulfonamidoguanidine (oran equivalent quantity of a nonanhydrous product) and 122 g (1 mol) sodiumacetylacetonate 100% purity (or an equivalent quantity of product of a lowerpurity) are introduced into the flask while stirring.
The temperature of the reaction mixture is brought to 102°C to 103°C, themixture is further stirred at this temperature during 24 hours. The pH value ofthe mixture, which should range between 5 and 6 is checked during thereaction.
On expiry of the reaction period heating is cut off, the mass being cooled orallowed to cool down to 60°C.
Filtering under suction is effected, the solids on the filter being washed with100 ml water at 80°C.
After drying of the product on the filter 256 g of 2-paminobenzenesulfonamido-4,6-dimethylpyrimidine, melting point 196°C to197°C, purity 99.5% are obtained. The output is 92% of the theory calculatedwith respect to the sodium acetylacetonate employed.

Brand name

Calfspan Tablets [Veterinary] (Fort Dodge Animal Health); Sulka S Boluses [Veterinary] (Fort Dodge Animal Health); SulfaSURE SR Bolus [Veterinary] (Boehringer Ingelheim Animal Health);Crermomethazine;Deladine;Dimezathine;Hava-span;Intradin;Neotrizine;Rigesol;Rivodin;S-dimidine;Spanbolet;Sulka-s;Sulphamezathine;Sulphfmezatine;Superseptyl;Sustain iii;Tersulpha;Trisulfaminic;Trisulfaminie.

Therapeutic Function

Antimicrobial

World Health Organization (WHO)

Sulfadimidine, a sulfonamide anti-infective agent, was introducedin 1942 for the treatment of bacterial infections. The importance of sulfonamideshas subsequently decreased as a result of increasing resistance and theirreplacement by antibiotics which are generally more active and less toxic. Thesulfonamides are known to cause serious adverse effects such as renal toxicity,sometimes fatal exfoliative dermatitis and erythema multiforma and dangerousadverse reactions affecting blood formation such as agranulocytosis andhaemolytic or aplastic anaemia. Sulfadimidine is still used in some countries as ainjectable or oral antimicrobial for susceptible infections.

Antimicrobial activity

This drug is used for pneumococcal, staphylococcal, and streptococcal infections as wellas for sepsis, gonorrhea, and other infectious diseases. Synonyms of this drug are sulfadiamezin and sulfadimidin.

General Description

Sulfamethazine’splasma half-life is 7 hours. This compound is similar inchemical properties to sulfamerazine and sulfadiazine butdoes have greater water solubility than either. Its pKa is 7.2.Because it is more soluble in acid urine than sulfamerazineis, the possibility of kidney damage from use of the drug isdecreased. The human body appears to handle the drugunpredictably; hence, there is some disfavor to its use in thiscountry except in combination sulfa therapy (in trisulfapyrimidines,USP) and in veterinary medicine.

General Description

Odorless sticky, white or creamy-white crystalline powder. Slightly bitter taste. An antibacterial.

Air & Water Reactions

Water solubility increases rapidly with increasing pH [Merck]. Insoluble in water.

Reactivity Profile

Sulfamethazine is sensitive to light and may also be sensitive to heat. The presence of oxygen and moisture may accelerate the effects of heat and light .

Fire Hazard

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

Pharmaceutical Applications

2-Sulfanilamido-4,6-methylpyrimidine (syn: sulphamethazine,sulfamezathine). A water-soluble compound, unstableon exposure to light. It is usually administered bymouth and is a component of some triple sulfonamidecombinations.
The spectrum is typical of the group, but sulfadimidineexhibits relatively low potency. It is well absorbedafter oral administration. It is extensively metabolized,predominantlyby acetylation. The mean plasma half-life(1.5–5 h) varies with acetylator status.
In addition to side effects common to the group, a seriousinteraction between ciclosporin (cyclosporin A) and sulfadimidine,leading to reduced ciclosporin levels, has beenreported.

Biochem/physiol Actions

Sulfamethazine is an antimicrobial sulfur drug that blocks the synthesis of dihydrofolic acid by inhibiting the enzyme dihydropteroate synthase. Sulfamethazine is a competitive inhibitor of bacterial para-aminobenzoic acid (PABA), which is required for bacterial synthesis of folic acid. It induces CYP3A4 expression and is acetylated by N-acetyltransferase. It exhibits sex dependent pharmacokinetics, metabolized by the male specific isoform CYP2C11. Sulfamethazine is bacteriostatic.

Safety Profile

Moderately toxic by intravenous and intraperitoneal routes. Experimental teratogenic and reproductive effects. Questionable carcinogen with experimental tumorigenic data. When heated to decomposition it emits very toxic fumes of SOx and NOx.

Synthesis

Sulfamethazine, N1-(4,6-dimethyl-2-pyrimidinyl)sulfanilamide (33.1.13),is also synthesized in the aforementioned manner by reacting 4-acetylaminobenzenesulfonylchloride with 2-amino-4,6-dimethylpyrimidine, which is in turn synthesized by condensingacetylacetone with guanidine followed by hydrolysis of the acetylamino group using a base.

Purification Methods

Crystallise it from dioxane or aqueous dioxane. [Caldwell et al. J Am Chem Soc 63 2188 1941, Roblin et al. J Am Chem Soc 64 567 1942, Beilstein 25 III/IV 2215.]

References

[1] C J ALLEGRA. Interaction of sulfonamide and sulfone compounds with Toxoplasma gondii dihydropteroate synthase.[J]. Journal of Clinical Investigation, 1990, 85 2: 371-379. DOI: 10.1172/jci114448
[2] S A SALMON. Comparison of MICs of ceftiofur and other antimicrobial agents against bacterial pathogens of swine from the United States, Canada, and Denmark.[J]. Journal of Clinical Microbiology, 1995, 33 9: 2435-2444. DOI: 10.1128/jcm.33.9.2435-2444.1995
[3] M.J.B. MENGELERS. Structure-activity relationships between antibacterial activities and physicochemical properties of sulfonamides[J]. Journal of veterinary pharmacology and therapeutics, 2003, 20 4: 276-283. DOI: 10.1046/j.1365-2885.1997.00063.x
[4] FENG-JIAO PENG. Joint antibacterial activity of soil-adsorbed antibiotics trimethoprim and sulfamethazine[J]. Science of the Total Environment, 2015, 506: Pages 58-65. DOI: 10.1016/j.scitotenv.2014.10.117
[5] REBECA LóPEZ-SERNA  Damià B  Mira Petrovi?. Direct analysis of pharmaceuticals, their metabolites and transformation products in environmental waters using on-line TurboFlow? chromatography–liquid chromatography–tandem mass spectrometry[J]. Journal of Chromatography A, 2012, 1252: Pages 115-129. DOI: 10.1016/j.chroma.2012.06.078

2-(4-Aminobenzenesulfonamido)-4,6-dimethylpyrimidine Preparation Products And Raw materials

• Raw materials: Sodium carbonate-->Acetylacetone-->Cyclohexanone-->Sulfaguanidine-->SODIUM 2,4-PENTANEDIONATE
• Preparation Products: 2-Amino-4,6-dimethylpyrimidine-->4-[[4-[[(4,6-dimethyl-2-pyrimidinyl)amino]sulphonyl]phenyl]amino]-4-oxoisocrotonic acid