1. The impurity of diuretic hydrochlorothiazide 04, also be a medical intermediate.
2. It’s mainly used for the detection of drug impurities, the synthesis of hydrochlorothiazide and the screening of medical structural fragments.
3. Presents a weak alkaline,refrigeration.
. Recommended Products is: 5250-72-6 and 22503-72-6.
The mechanism of chlorination and bromination of dihydrochlorothiazides (I) and related compounds in a mixture of H2O and CCl4, as well as bromination in dry HCONMe2, was discussed. Dropwise addition of equimolar Br in CCl4 to 3-chloro-4,6-disulfamoylaniline (II) suspended in H2O gave 97% the 2-bromo derivative (III), m. 284-9¡ã (decomposition). Recrystallization from 1:1 aqueous ethanol gave a product, m. 304¡ã (decomposition). Addition of II to a Br solution in aqueous KBr gave, after 4 hrs., quant. III, m. 287¡ã. III was also prepared in 72% yield with 100% excess Br. Treating I in a similar manner with 1 or 2 moles Br gave 94% the 5-bromo derivative (IV), m. 300¡ã. Neither 6-chloro-7-sulfamoyl-1,2,4-benzothiadiazine 1,1-dioxide, nor 3-oxo-6-chloro-7-sulfamoyl-1,2,4-dihydrobenzothiadiazine 1,1-dioxide could be brominated by this method. Chlorination of II under similar conditions resulted in a pink powder, m. 226¡ã (black foaming melt). This was extracted with Na2SO3 solutions in 1:1 aqueous MeOH to remove 15-20% N-chloro compounds and to give 33% V, m. 285-7¡ã. Similar chlorination of I with 1 mole Cl gave a 1:1 mixture of the 5-Cl derivative (VI) and the 2,5-Cl2 derivative (VII) of I, sintered at 155¡ã and became a red foam at 210-13¡ã, while chlorination with 2 moles Cl gave 98% VII. 154-6¡ã. With equimolar Br and H2O-CCl4 mixtures I (R = Me) gave 87% the 5-bromo derivative, m. 250¡ã. In a similar manner was prepared the 5-bromo deriv, of I (R = Et), m. 255¡ã (decomposition). Bromination under similar conditions of I (R = MeCH:CH), obtained by the action of crotonaldehyde on II, gave a 2: 1 mixture of the mono-brominated product and the starting product. The 3,3-dimethyl-derivative of I gave 80% the 5-bromo derivative, 216-20¡ã (decomposition), but neither the 3,3-pentamethylene derivative (VIIa) nor its p-methyl derivative could be brominated. Since 4-methyldihydrochlorothiazide readily gave 87% the 5-bromo derivative, m. 200¡ã (decomposition), the supposition that the presence of H on N-4 was necessary for the bromination of the benzene ring was ruled out. VIII (R = H) was brominated to a 1:1 mixture of VIII (R = H and R = Br), m. 259-60¡ã (decomposition), whereas IX was easily brominated to 96% 5-bromo-6-amino-7-sulfamoyl-3,3-pentamethylene1,2,4-dihydrobenzothiadiazine 1,1-dioxide, m. 198-200¡ã. Brominations in homogeneous media was effected in dry HCONMe2, with N, N’-dibromo-4,4-dimethylhydantoine (X) as the brominating agent, in order to avoid HBr formation. VIIa was successfully brominated by 0.5 mole at 5¡ã to give 98% the 5-bromo derivative (XI), m. 250-1¡ã (decomposition). The position of the Br atom was established by cleaving XI with boiling N HCl to III in 94% yield and to cyclohexanone, identified as its 2,4-dinitrophenylhydrazone. When VIIa was brominated with equimol. amounts of X, 95% 5,7-dibromo-6-chloro-3,3-pentamethylene-1,2,4-dihydrobenzothiadiazine 1,1-dioxide (XII), m. 173-7¡ã, was isolated. Cleavage of XII with boiling N HCl gave 2,4-dibromo-3-chloro-6-sulfamoylaniline (XIII) in theoretical yield and cyclohexanone. XII was also obtained by similar bromination of VIIa with 1.5 moles X in 10% yield and of XI with 0.5 mole X in 95% yield. Formation of XII was consistently accompanied by formation of strongly acidic compounds III with X gave a mixture of compounds from which XIII and 2,4,6-tribromo-3-chloroaniline were isolated. IV gave excellent yields of 5,7-dibromo-6-chloro-1,2,4- dihydrobenzothiadiazine 1,1-dioxide, m. 242-4¡ã.
Halogenation of dihydrochlorothiazides and related compounds. Recommended basis is hydrochlorothiazide 20. Products is: https://www.ambeed.com/products/742-20-1.html, 432499-63-3
Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem