Sulfadimethoxine Sodium(link:https://www.bloomtechz.com/synthetic-chemical/api-researching-only/sulfadimethoxine-sodium-cas-1037-50-9.html) is a white crystalline powder with good solubility. Molecular formula: C12H14N4O4SNa, molecular weight: 330.32 g/mol. Good solubility in water makes it easy to use as an ingredient in pharmaceutical preparations. It is also soluble in some organic solvents such as methanol, ethanol and acetone. pH is usually in the neutral or alkaline range. It is a relatively stable pharmaceutical compound. Exposure to strong light, heat and humidity should be avoided to prevent it from breaking down or degrading.
The following is a brief description of the three laboratory synthesis methods of Sulfadimethoxine Sodium and their corresponding chemical equations:
1. N4-aromatic sulfonyl-N1-methoxypyrazole-2-carboxylate method:
a. Synthesis of dimethyl sulfate (Dimethyl sulfate): Dimethyl sulfate is produced by reacting dioxane with concentrated sulfuric acid.
The reaction equation is as follows: C4H8O2 + H2O4S → methyleneated dioxane
b. Reaction with pyrazole: react methylene dioxane with pyrazole under appropriate reaction conditions to generate methoxypyrazole compound. This step also includes the use of solvents and catalysts.
Methyleneated dioxane + C3H4N2 → methoxypyrazole compound
c. Reaction with p-nitrobenzenesulfonyl chloride: react methoxypyrazole compound with p-nitrobenzenesulfonyl chloride under appropriate reaction conditions to generate N4-arylsulfonyl-N1-methoxypyrazole-2- Carboxylate.
Methoxypyrazole compound + C6H4ClNO4S → N4-arylsulfonyl-N1-methoxypyrazole-2-carboxylate
d. Neutralization to generate sodium salt: react N4-arylsulfonyl-N1-methoxypyrazole-2-carboxylate with sodium hydroxide to generate Sulfadimethoxine Sodium. This step is aimed at generating the sodium salt form of the drug.
N4-arylsulfonyl-N1-methoxypyrazole-2-carboxylate + NaOH → C12H15N4NaO4S
2. p-Nitrobenzenesulfonate method:
The p-nitrobenzenesulfonate method is one of the commonly used methods for the synthesis of Sulfadimethoxine Sodium, which involves the following steps:
a. Synthesis of p-nitrobenzenesulfonic acid (p-Nitrobenzenesulfonic acid): react p-nitrobenzene with concentrated sulfuric acid to generate p-nitrobenzenesulfonic acid. The reaction equation is as follows:
C6H4ClNO4S + H2O4S → C6H5NO5S + H2O
b. Reaction with N4-aminobenzoic acid methyl ester: react p-nitrobenzenesulfonic acid with N4-aminobenzoic acid methyl ester under alkaline conditions to generate N4-nitrobenzenesulfonyl-N1-methoxypyrazole - Methyl 2-carboxylate. This step requires the use of appropriate solvents and catalysts.
C6H5NO5S + N4-aminobenzoic acid methyl ester → N4-nitrobenzenesulfonyl-N1-methoxypyrazole-2-carboxylic acid methyl ester
c. Hydrogenation reduction reaction: Catalytic hydrogenation reduction reaction of N4-nitrobenzenesulfonyl-N1-methoxypyrazole-2-carboxylic acid methyl ester to remove the nitro group and generate N4-arylsulfonyl-N1-methyl Oxypyrazole-2-carboxylic acid methyl ester.
N4-nitrobenzenesulfonyl-N1-methoxypyrazole-2-carboxylic acid methyl ester + catalyst + H2 → N4-arylsulfonyl-N1-methoxypyrazole-2-carboxylic acid methyl ester
d. Neutralization to generate sodium salt: react N4-arylsulfonyl-N1-methoxypyrazole-2-carboxylic acid methyl ester with sodium hydroxide to generate Sulfadimethoxine Sodium. This step is aimed at generating the sodium salt form of the drug.
N4-arylsulfonyl-N1-methoxypyrazole-2-carboxylic acid methyl ester + NaOH → C12H15N4NaO4S
3. 4-aminobenzenesulfonate method:
The 4-aminobenzenesulfonate method is a common method for the synthesis of Sulfadimethoxine Sodium (sulfadimethoxypyrimidine sodium). The method involves the following main steps:
a. Synthesis of 4-aminobenzenesulfonic acid (4-aminobenzenesulfonic acid):
- Reaction of p-nitrobenzene with nitrous acid.
- Formation of 4-aminobenzenesulfonic acid and water products.
Chemical equation: C6H5NO3 + HNO2 → C6H7NO3S + H2O
b. Reaction with methyl N4-methoxybenzoate:
- Reaction of 4-aminobenzenesulfonic acid with methyl N4-methoxybenzoate under basic conditions.
- The product resulting in methyl N4-aminobenzenesulfonyl-N1-methoxypyrazole-2-carboxylate.
Chemical formula: C6H7NO3S + N4-methoxybenzylamine methanesulfonate → N4-sulfanilamido-N1-methoxyisotxazole-2-methanesulfonate
c. Hydrogenation reduction reaction:
- Catalytic hydrogenation reduction of methyl N4-aminobenzenesulfonyl-N1-methoxypyrazole-2-carboxylate.
- Removal of the amino and sulfonyl groups yields the Sulfadimethoxine (sulfadimethoxypyrimidine) product.
Chemical formula: N4-sulfanilamido-N1-methoxyisotxazole-2-methane sulfonate + H2 + Pd/C → C12H14N4O4S + CH3OH
d. Sodium salinization:
- Reaction of sulfadimethoxine with sodium hydroxide.
- A product that produces Sulfadimethoxine Sodium.
Chemical equation: C12H14N4O4S + NaOH → C12H15N4N4O4S + H2O
4. Normally, the synthetic method of Sulfadimethoxine Sodium comprises the following steps:
a. Nitration reaction: Methylsulfonic acid (Methylsulfonic acid) is reacted with nitric acid to generate Methylsulfonic acid nitrate. The reaction equation is as follows:
CH3SO3H + HNO3 → CH3SO3NO2 + H2O
b. Reduction reaction: The reduction reaction of nitromethanesulfonic acid and sodium bisulfite (Sodium bisulfite) produces methylsulfonic acid (Methylsulfonic acid) and sodium nitrosomethanesulfonate (Sodium methylsulfonate). The reaction equation is as follows:
CH3SO3NO2 + NaHSO3 → CH3SO3H + NaCH3SO3
c. Acetylation reaction: react sodium nitrosomethylsulfonate with acetic anhydride (Acetic anhydride) to generate sodium nitrosoacetyl methylsulfonate (Sodium acetyl methylsulfonate). The reaction equation is as follows:
NaCH3SO3 + (CH3CO)2O → NaO2CCH3 + CH3SO3CH3 + CH3COOH
d. Sulfonation reaction: react sodium nitrosoacetylmethylsulfonate with sulfonic acid to generate Sulfadimethoxine Sodium. The reaction equation is as follows:
NaO2CCH3 + CH3SO3H → CH3SO2NHCH2COONa + CH3COOH
These steps are only a brief overview of the synthetic method. The actual synthesis process may also involve the optimization of intermediate steps and reaction conditions. For specific detailed steps and chemical equations, please refer to relevant literature or professional information. Please note that when performing this synthetic reaction, it is important to follow safe operating procedures and perform it in a professional laboratory environment. In addition, it is recommended that an experienced chemist guide the synthesis process.