N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide 4-hydroxybenzoate | 1236289-97-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide 4-hydroxybenzoate
• CAS: 1236289-97-6
• 化学式: C₄H₆N₄O₃S₂*C₇H₆O₃
• 分子量: 360.371
• InChiKey: UTXPKDOGEQVSFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.23
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  172.57
• 氢给体数：
  4.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  乙酰唑胺 、 对羟基苯甲酸 以 水 为溶剂， 生成 N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide 4-hydroxybenzoate
  参考文献：
  名称：

  Co-Crystals of Active Pharmaceutical Ingredients - Acetazolamide

  摘要：

  A total of 20 co-crystal formers have been combined with acetazolamide (ACZ) via solvent drop grinding in acetone, acetonitrile, and water. The screening experiments provided co-crystals with 4-hydroxybenzoic acid (4HBA) and nicotinamide (NA) (ACZ-4HBA and ACZ-NA-H2O), which were identified by X-ray powder diffraction (XRPD) and further characterized by IR spectroscopy and differential scanning calorimetry-thermogravimetric analysis (DSC-TGA). Both co-crystals could be prepared also by neat grinding (NG) and reaction crystallization (RC). Single-crystal X-ray diffraction analyses allowed for an examination of the dominant hydrogen bonding patterns in the co-crystals, showing that 4HBA binds to the thiadiazole acetamide fragment of ACZ via C(N)NH center dot center dot center dot HOOC and O-H center dot center dot center dot N interactions, while NA is linked through N-H center dot center dot center dot N and N-H center dot center dot center dot O contacts. In ACZ-NA-H2O, the components are connected further by crystal lattice water molecules through N-H center dot center dot center dot O-w and O-w-H center dot center dot center dot N hydrogen bonds. Phase stability assays in water at physiological pH values ranging from 1.2 to 6.8 showed that for ACZ-4HBA the crystalline solid phase did not transform to ACZ within 72 h, while for ACZ-NA-H2O a gradual transformation occurred. Thermal treatment of ACZ-NA-H2O and reaction crystallization experiments in methanol and anhydrous ethanol gave the dehydrated crystalline phase ACZ-NA, which is stable at ambient conditions for at least four months but transforms to the corresponding co-crystal monohydrate when stirred with deionized water.

  DOI：

  10.1021/cg1005693

文献信息

• Modification of the Supramolecular Hydrogen-Bonding Patterns of Acetazolamide in the Presence of Different Cocrystal Formers: 3:1, 2:1, 1:1, and 1:2 Cocrystals from Screening with the Structural Isomers of Hydroxybenzoic Acids, Aminobenzoic Acids, Hydroxybenzamides, Aminobenzamides, Nicotinic Acids, Nicotinamides, and 2,3-Dihydroxybenzoic Acids
  作者：Jenniffer I. Arenas-García、Dea Herrera-Ruiz、Karina Mondragón-Vásquez、Hugo Morales-Rojas、Herbert Höpfl

  DOI：10.1021/cg201140g

  日期：2012.2.1

  Acetazolamide (ACZ) has been combined via liquid-assisted grinding in water with a library of cocrystal formers derived from benzoic and nicotinic acid, which provided novel cocrystals with 2-hydroxybenzamide, 2-aminobenzamide, picolinamide, and 2,3-dihydroxybenzoic acid. The cocrystalline phases were identified first by XRPD analysis and then structurally characterized by IR spectroscopy and single-crystal X-ray diffraction analysis. These cocrystals and the previously reported cocrystalline phases obtained from 4-hydroxybenzoic acid and nicotinamide constitute a series of six cocrystals of varied stoichiometric ratios (3:1, 2:1, 1:1, and 1:2), which allowed for a profound an of the structural and chemical factors that govern their formation. The structural analysis has shown that the ACZ molecules participate in the dominant hydrogen-bonding patterns within the crystal structures: three cocrystal structures exhibit extended supramolecular aggregates of ACZ having channels, pores, or semispherical voids, in which the cocrystal formers are included as guest molecules, and can, therefore, be described as inclusion or clathrate complexes. One cocrystal can be considered as a pillared or intercalation compound, and the remaining two cocrystals are true two-component 2D or 3D networks. In addition, a variety of alternative preparative methods (liquid-assisted grinding, neat grinding, reaction crystallization, solution-mediated phase transformation, and solution crystallization) have been employed, showing that four of the six cocrystals required the presence of water for successful cocrystal formation.