68-89-3

Basic information

• Product Name: Dipyrone
• Synonyms: (antipyrinylmethylamino)methanesulfonicacidsodiumsalt;(antipyrinylmethylamino)-methanesulfonicacimonosodiumsalt;(antipyrinylmethylamino)-methanesulfonicacisodiumsalt;1-phenyl-2,3-dimethyl-4-methylamino-5-pyrazolon-n-methanesulfonsaeurennatriu;1-phenyl-2,3-dimethyl-5-pyrazolone-4-methylaminomethanesulfonatesodium;1-phenyl-2,3-dimethylpyrazolone-(5)-4-methylaminomethanesulfonicacidsodium;4-methylamino-1,5-dimethyl-2-phenyl-3-pyrazolonesodiummethanesulfonate;4-sodiummethanesulfonatemethylamine-antipyrine
• CAS NO: 68-89-3
• Molecular Formula: C₁₃H₁₆N₃O₄S*Na
• Molecular Weight: 333.34
• EINECS: 200-694-7
• Product Categories: PHARMACEUTICALS;DIO - DIZForensic and Veterinary Standards;Alphabetic;D;Drugs&Metabolites;Neat Compounds;Cosmetic Ingredients & Chemicals;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Sulfur & Selenium Compounds
• Mol File: 68-89-3.mol
• Article Data: 0

Chemical Properties

• Melting Point: 227 °C
• Appearance: solid
• Density: 1.388 g/cm3
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly), Water (Slightly)
• Stability: Stable. Incompatible with strong oxidizing agents.
• CAS DataBase Reference: Dipyrone(CAS DataBase Reference)
• NIST Chemistry Reference: Dipyrone(68-89-3)
• EPA Substance Registry System: Dipyrone(68-89-3)

Safety Data

• Hazard Codes: Xn
• Statements: 42/43
• Safety Statements: 36
• WGK Germany: 2
• RTECS: PB1300000
• Hazardous Substances Data: 68-89-3(Hazardous Substances Data)

Usage

Description

Dipyrone is a water soluble pyrazolone derivative available in oral, rectal and injectable forms. It has analgesic, antipyretic, antispasmodic, and anti-inflammatory properties. Dipyrone is used most commonly to treat severe pain, particularly, for pain associated with smooth muscle spasm or colic affecting the gastrointestinal, biliary or urinary tracts. It is useful for fever that is refractory to other treatment. Because of the risk of serious adverse effects, such as agranulocytosis, its use is justified only in serious situations where no alternative is available or suitable.

Drug Instructions

Alias: dipyrone, NOVALGIN; Noramidopyrine, Metamizole sodium,metamizole Property: This product is white or yellow-white crystal or crystalline powder, odorless, slightly bitter taste, soluble in water. Action: Dipyrone is the derivative of aminopyrine, its has a significant effect of antipyretic analgesia. The antipyretic effect of it is three times as aminopyrine, the analgesic effect is similar to that of aminopyrine. Process vivo: Easily absorbed orally, mainly metabolized by the liver and excreted of renal Indications: It is mainly used for cooling, acute arthritis, headache, rheumatic neuralgia, toothache and muscle pain etc. Dosage Oral or intranasal administration. For oral, the adult should take 0.5g of the medicine and three times a day, the amount of the child is 8-10mg/ kg, the number of the times is according to the necessary. For intranasal, the child under 5 years old can take 1-2drops for each nostril, can take the medicine another time if necessary,for the patient above 5 years old increase the dosage appropriately. Note 1, The dosage should be controled strictly to prevent collapse. 2, The intramuscular injection can cause atrophy and erosion to the local muscle, it is abandoned now. 3, The patient who has a allergy to the praziquantel can not use the dipyrone 4, It not suitable for a long-term application, Please pay attention to the granulocytes. Specification Tablets:each table is weight for 0.25g or 0.5g; Injection: each ingection has the specification of 0.25g/1ml or 0.5g/2ml; Drops: solution with the concentration of 10%~20%

Side effects of dipyrone

1, The side effects contain the allergies, exhaustion, leukopenia, thrombocytopenia even the severe aplastic anemia. 2, Some people may also suffering the nephrotoxicity and gastrointestinal bleeding after they take the dipyrone.The most serious side effect is lethal agranulocytosis.

Uses

Different sources of media describe the Uses of 68-89-3 differently. You can refer to the following data:
1. It has the effect of detoxification, analgesic and anti-rheumatic etc and mainly used for cooling, but also can be applied to cure the acute arthritis, rheumatic pain, muscle pain and headache etc.
2. A non-steroidal anti-inflammatory drug that, when coadministered with morphine, potentiates its antinociceptive action and delays the development of tolerance. Dipyrone is a relatively selective inhibitor of cyclooxygenase-3 (COX-3), with lower activity against COX-1 and no activity against COX-2. Blocks PGE2-induced hyperalgesia in several models.
3. Dipyrone is a non-steroidal anti-inflammatory drug that, when coadministered with morphine, potentiates its antinociceptive action and delays the development of tolerance. Dipyrone is a relatively sel ective inhibitor of cyclooxygenase-3 (COX-3), with lower activity against COX-1 and no activity against COX-2. Dipyrone blocks PGE2-induced hyperalgesia in several models.
4. Methamizole sodium has expressed analgesic and fever-reducing properties and poorly expressed anti-inflammatory action, and is very convenient in cases where high concentrations of drug need to be quickly reached. Methamizole sodium is used for relieving pain of various origins (renal and biliary colic, neuralgia, myalgia, trauma, burns, headaches, and toothaches). Use of this drug may cause allergic reactions, and long-term use may cause granulocytopenia.

Hazards & Safety Information

Category Toxic Chemicals Acute toxicity For oral – the lethal dose for rat LD50: 3000 mg/kg; For oral – the lethal dose for mouse LD50: 2891 mg/kg Toxicity grading Moderately toxic Flammability hazard characteristic It is combustible and can produce the toxic fumes contained nitrogen oxides, sulfur oxides and sodium oxide during the combustion Storage Characteristic The storeroom should be airy, low-temperature and dried. Extinguishing agent Dry powder, foam, sand, carbon dioxide, water mist

References

[1] Micha Levy, Ester Zylber-Katz and Bernd Rosenkranz, Clinical Pharmacokinetics of Dipyrone and its Metabolites, Clinical Pharmacokinetics, 1995, vol. 28, 216-234 [2] JE Edwards, F. Meseguer, CC Faura, RA Moore and HJ McQuay, Single-dose dipyrone for acute postoperative pain, Cochrane Database Syst Rev., 2010, vol. 9, CD003227

Chemical Properties

solid

Definition

ChEBI: An organic sodium salt of antipyrine substituted at C-4 by a methyl(sulfonatomethyl)amino group, commonly used as a powerful analgesic and antipyretic.

Brand name

Diprofarn (Farmitalia, Societa Farmaceutici Italia, Italy); Novaldin (Sterling Winthrop);Abalgine;Acabel compositum;Acefalgin;Acrobal;Acrogesico;Adolkin;Algia-nil;Alginodia compose;Algisedal;Algobuscopan;Algopriv;Algopyriv;Alkozin;Amiglan;Aminocid;Amitralil;Ampi tumisan;Anadex;Analcedor;Analject;Anarinyl;Anchrina;Anespas cpto;Angiter;Ankaljin;An-t;Apasmo;Arantil;Arquidon;Artritex;Ascorbalgine;Ascortin;Aseptobron;Atecilina;Atn-020/2;Avafortan;Ayoral;Bayer 1387;Bebealjin;Bebigut;Belatropin;Belflex/2;Beneurin;Bexopirona;Biogamma2;Biotangin;Bipasmin compuesto;Bort;Bristacilia;Britercina;Bromalgin;Bromalgon;Broncofenil;Broncolysin;Bucarboxal;Buscapina comp.;Buscapina compuesto;Buscapina compuestum;Buscol compositum;Buscopan composto;Buscopan compostum;Buscopina compostum;Butalgine;Butylpan;Calgayan-c;Calmetron;Camizol;Causalon;Cessantyl;Chini-med;Cintaverin compuesto;Clizim;Clofexan;Codalgin;Codasal injetavel;Colgenol;Comaril 5000;Corilin pediatric;Cortempirol;Cortitracin;Cronopen balsamico;Deltricin;Devalgin;Dexa butarin;Di-bal-rone;Dimethedon;Dinopirina;Dioxadol;Dipirona;Diprofarm;Dipyrivo;Dispalgine;Divarin;Divarmin;Do-ba-rone;Dolatets;Dolazon;Dolemicin;Dolispasmo;Dolo adamon;Dolo baralgine;Dolo buscopan;Dolo nerv;Dolo neurobion forte;Dolo pangavit;Dolo raptalgin;Dolo spasuret;Dolojudolor;Dolo-neurobion;Dolopirina;Doloscopin;Dopiral;Dorflex merrell;Dorlisin;Doron;Dorscopena;D-pron;Dumalgin;Duralnordin;Dya-tran;Edgartet;Eespanal;Enzipan combinado;Espasfher;Espasmir;Espasmo-cibalgina;Espasmoqual;Espasmotex;Espasmoviral;Espyre;Farbinol;Flogolisin;G.r. ulix compuesto;Genservet;Gentil;Geralgine;Glutisal;Greplicina belsa;H 116;H 117;H 118;Hagalgin;Hasain;Indextron;Influbene;Kb-502;Kefren;Kesan;Killgrip;Kipyrone;Kitax alpha;Kitax n;Konitan;Labymetacincpo;Lactmicina;Lagalgine;Lamprcsnum;Lapalgine;Larq 731;Lasain;Lavaciclina;Levapa;Levismon;Lisalgil;Magdor;Magnalsa;Magnemidon;Mapir;Mecoten;Megal;Melpen;Menalgine;Mialgan;Minalgine;Minoval;Miocitalgan;Nadalgine;Naftalgin;Naltrium;Napasone;Nartate;Natralgin;Natric;Neo-melubrim;Neo-melubrina;Neo-melubrine;Neo-oxipen;Neosal-n;Neosoldina;Neuro-fortamin;Nisidina;Nlo conicilina balsamica;Nobelgin;Nolotil composirum;Notermin;Novacid;Novalcina;Novalgetol;Novalgin quinine;Novalgina;Novalgine;Nova-lyseen;Novamidazofen;Novamidazophen;Novamideazophene;Novaminophenazone;Novaminsulfon ratiopharm;Novaminsulfone sodium;Novaminsulfonium;Novaminsulfonum;Novaminsulton;Novazolon dexametasona;Noveltex;Novemida;Novemina;Novil;Oftlamin;Orphalginen;Ortopirona;Oxiquiunazine;Pabron gold;Panalvon;Patalgin;Pentrodin;Phanalgin;Pharmalgine;Porbiot;Pplan 2500;Probaphen;Prodol;Prydonnal;Pydirone;Pyralgine;Pyrilgin;Pyriligin;Pyrisan;Quarelin;Reflex rectal;Relexal compuesto;Repriman;Resquim;Rheuma-spalt;Ridol;Rumalisine;Rupalgin;Santeprednisan a;Sebon;Sedabel;Sedarel;Sedarene;Sedazepane;Selpiran;Sertalanalgesico;Severen;Sinalgex;Sintaverin;Sinvirol;Spasdolsom;Spaslar;Spasmalgon;Spasmium-comp.;Spasmizol;Spasmodor;Spasmopyralgin;Spasmothil;Sufonovin;Sulfonovin;Supadol;Supergine;Surpyrine;Tanper;Tapal;Tega-pyrone;Tempil;Tepal;Termonil;Tetrabal-hosbon;Tetraspasmil;Tiadexol;Tiartan;Toloxin andromaco;Trenteron;Triartan;Trinalgen.

World Health Organization (WHO)

Metamizole sodium, a pyrazolone derivative with analgesic, antipyretic and antinflammatory activity, was introduced in 1921 and has since been widely available in over-the-counter products. By the early 1970s its use had been associated, as with some other pyrazolones, with serious and sometimes fatal adverse reactions, notably cases of blood dyscrasias including agranulocytosis, which led to its withdrawal by some regulatory authorities. Although preparations of metamirole sodium are prohibited in certain countries, they remain widely available in others and, in some cases, in over-the-counter products.

Safety Profile

Poison by subcutaneous route. Moderately toxic by several other routes. An experimental teratogen. Other experimental reproductive effects. Human mutation data reported. Questionable carcinogen with experimental neoplastigenic data. See also SULFONATES. When heated to decomposition it emits very toxic fumes of NOx,, Na2O, and SOx,.

Synthesis

Methamizole sodium, 1-phenyl-2,3-dimethyl-4-methylaminopyrazolone-5-N-sodium methansulfonate (3.2.16), is synthesized in a multi-stage synthesis from acetoacetic ester and phenylhydrazine. Their reaction leads to the formation of 1-phenyl- 3-methylpyrazolone-5 (3.2.9). Methylation of this product with methyl iodide gives 1-phenyl- 2,3-dimethylpyrazolone-5 (3.2.10). This compound is used independently in medicine as a fever-reducing and anti-inflammatory analgesic under the name antipyrin. It undergoes nitrozation by sodium nitrite in an acidic medium, forming 1-phenyl-2,3-dimethyl-4- nitrozopyrazolone-5 (3.2.11). Reduction of the nitrous derivative (3.2.11) by different reducing agents leads to the formation of 1-phenyl-2,3-dimethyl-4-aminopyrazolone-5 (3.2.12). This product is reacted with benzaldehyde, forming an easily separable crystalline 1-phenyl- 2,3-dimethyl-4-benzylidenaminopyrazolone-5 (3.2.13), which is methylated at the imine atom of nitrogen by dimethylsulfate, giving a quaternary salt (3.2.14). Hydrolysis of the resulting salt gives 1-phenyl-2,3-dimethyl-4-methylaminopyrazolone-5 (3.2.15). Treating the product with a water solution of a mixture of sodium bisulfite and formaldehyde leads to the formation of 1-phenyl-2,3-dimethyl-4-methylaminopyrazolone-5-N-sodium methanesulfonate (3.2.16), the desired sodium methamizole [72–75].

InChI:InChI=1/C13H19N3O4S.Na/c1-10-12(14(2)9-21(18,19)20)13(17)16(15(10)3)11-7-5-4-6-8-11;/h4-8,10,12H,9H2,1-3H3,(H,18,19,20);/q;+1/p-1/rC13H18N3NaO4S/c1-10-12(14(2)9-22(19,20)21-17)13(18)16(15(10)3)11-7-5-4-6-8-11/h4-8,10,12H,9H2,1-3H3

Synthetic route

metamizol (68-89-3) → Metamizol (50567-35-6)

Conditions	Yield
With hydrogenchloride In ethanol at 20 - 30℃; for 1h; Solvent; Reagent/catalyst;	93.3%

metamizol (68-89-3) → 4-methylaminoantipyrine (519-98-2)

Conditions	Yield
With hydrogenchloride In methanol; water at 60℃; for 3h;	86.7%
In water for 4h; Irradiation; Yield given;

bromopentacarbonylmanganese(I) (14516-54-2) + metamizol (68-89-3) → fac-[Mn(CO)3(metamizole)]

Conditions	Yield
With acetone for 0.333333h; Inert atmosphere; Darkness; Reflux;	82%

metamizol (68-89-3) → Oxalsaeure-mono(2-acetyl-2-methyl-1-phenyl)hydrazid (38988-02-2)

Conditions	Yield
With dihydrogen peroxide for 0.0833333h;	79%

metamizol (68-89-3) + nickel(II) acetate tetrahydrate (6018-89-9) → (1-phenyl-2,3-dimethyl-5-pyrazolone-4-methylaminomethane sulphonate)nickel(II) (84110-66-7)

Conditions	Yield
In ethanol for 1 - 3h; Reflux;	77%

cobalt(II) nitrate hexahydrate + metamizol (68-89-3) → (1-phenyl-2,3-dimethyl-5-pyrazolone-4-methylaminomethane sulphonate)cobalt(II) (84110-65-6)

Conditions	Yield
In ethanol for 1 - 3h; Reflux;	73%

copper(II) nitrate trihydrate + metamizol (68-89-3) → Cu([(1,5-dimethyl-3-oxo-2-phenylpyrazol-4-yl)-methylamino]methanesulfonate)2

Conditions	Yield
In ethanol for 1 - 3h; Reflux;	68%

diammonium hexachlororhenate(IV) + metamizol (68-89-3) → 2C13H17N3O4S*2H(1+)*{ReCl6}(2-)=(C13H18N3O4S)2{ReCl6}

Conditions	Yield
In hydrogenchloride satg. 6 M HCl with (NH4)2(ReCl6); treating soln. with ethanol satd. with NaC13H16N3O4S (25°C, magnetic stirring);; pptn.; rinsing with 6 M HCl; drying to const. wt. at 105°C; elem. anal. (Re is partially oxidized);;	50%

tetracyanodinitrosylmanganate(0) (125841-54-5) + metamizol (68-89-3) → Mn(2+)*2NO*2CN(1-)*2Na(1+)*2C13H16N3O4S(1-)*H2O = [Mn(NO)2(CN)2Na2(C13H16N3O4S)2]*H2O

Conditions	Yield
In acetic acid aq. acetic acid; refluxing (80°C, 2 h); ppt. washing (dild. acetic acid, water), drying (vac.); elem. anal.;	40%

potassium hexabromorhenate (IV) + metamizol (68-89-3) → 2C13H17N3O4S*2H(1+)*{ReBr6}(2-)=(C13H18N3O4S)2{ReBr6}

Conditions	Yield
In hydrogen bromide aq. HBr; satg. 6 M HBr with K2(ReBr6); treating soln. with ethanol satd. with NaC13H16N3O4S (25°C, magnetic stirring);; pptn.; rinsing with 6 M HBr; drying to const. wt. at 105°C; elem. anal. (Re is partially oxidized);;	35%

metamizol (68-89-3) → 1-phenyl-3,4-dimethyl-5-hydroxy-imidazoline-2-on (96337-48-3)

Conditions	Yield
In water at 20℃; for 1.5h; Product distribution; Irradiation; photochemical decomposition studies to different products at different times;	32%
In water at 20℃; for 1.5h; Irradiation;	32%

metamizol (68-89-3) → 3-Methyl-1-phenyl-2-pyrazoline-4,5-dione (881-05-0) + 1-acetyl-1-methyl-2-phenylhydrazine (38604-70-5) + Sodium; [methyl-(3-methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-4-yl)-amino]-methanesulfonate + Glyoxilic acid (298-12-4) + 4-hydroxyantipyrine (1672-63-5) + 5-hydroxy-1,5-dimethyl-3-phenyl-imidazolidine-2,4-dione (50871-97-1)

Conditions	Yield
In water Kinetics; Irradiation; photochemical decomposition, λ=254 nm;

metamizol (68-89-3) → 4-amino-2,3-dimethyl-1-phenylpyrazolin-5-one (83-07-8) + 4-methylaminoantipyrine (519-98-2)

Conditions	Yield
In water Kinetics; Irradiation; photochemical decomposition, λ=254 nm;

metamizol (68-89-3) → formaldehyd (50-00-0) + 4-methylaminoantipyrine (519-98-2)

Conditions	Yield
With sodium hydroxide at 100℃; for 0.5h;

metamizol (68-89-3) → phenyl isocyanate (1197040-29-1) + 1,5-dimethyl-3-phenyl-2,4-imidazolidinedione (2221-10-5) + Sodium; [(2,3-dihydroxy-1,3-dimethyl-aziridin-2-yl)-methyl-amino]-methanesulfonate + Sodium; [methyl-(2-{1-[(E)-methylimino]-ethyl}-3-oxo-1-phenyl-aziridin-2-yl)-amino]-methanesulfonate + Sodium; [(4-hydroxy-1,5-dimethyl-3-oxo-2-phenyl-pyrazolidin-4-yl)-methyl-amino]-methanesulfonate + Formanilid (103-70-8)

Conditions	Yield
In water Kinetics; Irradiation; photochemical decomposition, λ=254 nm;

metamizol (68-89-3) → phenyl isocyanate (1197040-29-1) + Sodium; [(2,3-dihydroxy-1,3-dimethyl-aziridin-2-yl)-methyl-amino]-methanesulfonate + Sodium; [methyl-(2-{1-[(E)-methylimino]-ethyl}-3-oxo-1-phenyl-aziridin-2-yl)-amino]-methanesulfonate + Sodium; [(4-hydroxy-1,5-dimethyl-3-oxo-2-phenyl-pyrazolidin-4-yl)-methyl-amino]-methanesulfonate + 1-phenyl-3,4-dimethylimidazol-2(1H)-one (16939-00-7) + Formanilid (103-70-8)

Conditions	Yield
In water Kinetics; Irradiation; photochemical decomposition, λ=254 nm;

metamizol (68-89-3) → 1,5,1',5'-tetramethyl-2,2'-diphenyl-1,2,1',2'-tetrahydro-4,4'-(N,N'-dimethyl-N,N'-methanediyl-diamino)-bis-pyrazol-3-one (810-16-2)

Conditions	Yield
With sodium hydroxide Ambient temperature;

metamizol (68-89-3) → 1-acetyl-1-methyl-2-phenylhydrazine (38604-70-5) + Methylaminooxoessigsaeure-2-acetyl-2-methyl-1-phenylhydrazid (92569-10-3) + Oxalsaeure-mono(2-acetyl-2-methyl-1-phenyl)hydrazid (38988-02-2)

Conditions	Yield
With sodium hydroxide; phosphate buffer; dihydrogen peroxide In water for 24h; Product distribution; Ambient temperature; var. of pH;

hydrogenchloride (7647-01-0) + water (7732-18-5) + metamizol (68-89-3) → 4-methylaminoantipyrine (519-98-2) + aminopyrine (58-15-1)

hydrogenchloride (7647-01-0) + water (7732-18-5) + metamizol (68-89-3) → 4-methylaminoantipyrine (519-98-2) + 1,5,1',5'-tetramethyl-2,2'-diphenyl-1,2,1',2'-tetrahydro-4,4'-(N,N'-dimethyl-N,N'-methanediyl-diamino)-bis-pyrazol-3-one (810-16-2)

metamizol (68-89-3) → formaldehyd (50-00-0) + 4-methylaminoantipyrine (519-98-2) + NaHSO3

Conditions	Yield
With sodium hydroxide at 100℃; for 0.5h; Mechanism; dependence from temperature;

(±)-3-(1-(dimethylamino)-2-methylpentan-3-yl)phenol (515114-52-0) + metamizol (68-89-3) → 3-(1-(dimethylamino)-2-methylpentan-3-yl)phenol ((1,5-dimethyl-3-oxo-2-phenylpyrazolidin-4-yl)(methyl)amino)methanesulfonate

Conditions	Yield
In acetone at 20 - 40℃;

metamizol (68-89-3) → 1-phenyl-2,3-dimethyl-4-methylaminopyrazoline-5-one N-methylsulfonate magnesium hexahydrate

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / ethanol / 1 h / 20 - 30 °C 2: magnesium oxide / isopropyl alcohol / 3 h / 20 - 30 °C View Scheme

Downstream Products

• 519-98-2 4-methylaminoantipyrine 
• 810-16-2 1,5,1',5'-tetramethyl-2,2'-diphenyl-1,2,1',2'-tetrahydro-4,4'-(N,N'-dimethyl-N,N'-methanediyl-diamino)-bis-pyrazol-3-one 
• 50-00-0 formaldehyd 
• 50567-35-6 Metamizol 
• 84110-66-7 (1-phenyl-2,3-dimethyl-5-pyrazolone-4-methylaminomethane sulphonate)nickel(II) 
• 84110-65-6 (1-phenyl-2,3-dimethyl-5-pyrazolone-4-methylaminomethane sulphonate)cobalt(II) 
• 58-15-1 aminopyrine 
• 38988-02-2 Oxalsaeure-mono(2-acetyl-2-methyl-1-phenyl)hydrazid 
• 38604-70-5 1-acetyl-1-methyl-2-phenylhydrazine 
• 92569-10-3 Methylaminooxoessigsaeure-2-acetyl-2-methyl-1-phenylhydrazid 
• 1197040-29-1 phenyl isocyanate 
• 16939-00-7 1-phenyl-3,4-dimethylimidazol-2(1H)-one 
• 103-70-8 Formanilid 
• 96337-48-3 1-phenyl-3,4-dimethyl-5-hydroxy-imidazoline-2-on