3D Mol Similar

Xipamide

Iupac Name：4-chloro-N-(2,6-dimethylphenyl)-2-hydroxy-5-sulfamoylbenzamide

CAS No.: 14293-44-8

Molecular Weight：354.805

Modify Date.: 2022-11-23 01:58

Introduction: Xipamide is a diuretic and antihypertensive agent. View more+

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1. Names and Identifiers

1.1 Name: Xipamide
1.2 Synonyms: 4-Chloro-2',6'-dimethyl-5-sulfamoylsalicylanilide 4-chloro-2',6-dimethyl-5-sulfamoylsalicylanilide 4-Chloro-2-hydroxy-N-(2,6-dimethylphenyl)-5-sulfamoylbenzamide 4-Chloro-5-sulfamoyl-2',6'-salicyloxylidide 4-Chloro-5-sulfamylsalicyloyl-2',6'-dimethylanilide 4-Chloro-N-(2,6-dimethylphenyl)-2-hydroxy-5-sulfamoylbenzamide 5-(Aminosulfonyl)-4-chloro-N-(2,6-dimethylphenyl)-2-hydroxybenzamide 5-(Aminosulfonyl)-4-chloro-N-(2,6-dimethylphenyl)-2-hydroxy-benzamide Aquaphor Aquaphor(diuretic) Aquaphoril Benzamide, 5-(aminosulfonyl)-4-chloro-N-(2,6-dimethylphenyl)-2-hydroxy- Benzamide,5-(aminosulfonyl)-4-chloro-N-(2,6-dimethylphenyl)-2-hydroxy- Diurexan EINECS 238-216-4 Xipamid XIPAMIDE (IN HOUSE) Zipix

1.3 CAS No.: 14293-44-8

1.4 CID: 26618

1.5 EINECS(EC#): 238-216-4

1.6 Molecular Formula: C15H15ClN2O4S (isomer)

1.7 Inchi: InChI=1S/C15H15ClN2O4S/c1-8-4-3-5-9(2)14(8)18-15(20)10-6-13(23(17,21)22)11(16)7-12(10)19/h3-7,19H,1-2H3,(H,18,20)(H2,17,21,22)

1.8 InChkey: MTZBBNMLMNBNJL-UHFFFAOYSA-N

1.9 Canonical Smiles: CC1=C(C(=CC=C1)C)NC(=O)C2=CC(=C(C=C2O)Cl)S(=O)(=O)N

1.10 Isomers Smiles: CC1=C(C(=CC=C1)C)NC(=O)C2=CC(=C(C=C2O)Cl)S(=O)(=O)N

2. Properties

2.1 Density: 1.477

2.1 Melting point: 255-256℃

2.1 Refractive index: 1.652

2.1 Precise Quality: 354.04400

2.1 PSA: 117.87000

2.1 logP: 4.41620

2.1 Solubility: DMSO: soluble20mg/mL, clear

2.2 Appearance: white to beige

2.3 Storage: Refrigerator

2.4 Chemical Properties: Off-White Solid

2.5 Color/Form: white to beige

2.6 pKa: pKa 4.75±0.04(0.4% MeOH in H2O) (Uncertain)

2.7 Water Solubility: DMSO: soluble20mg/mL, clear

2.8 StorageTemp: Inert atmosphere,Store in freezer, under -20°C

3. Use and Manufacturing

3.1 GHS Classification: Signal: Warning
GHS Hazard Statements
Aggregated GHS information provided by 31 companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria by 1 of 31 companies. For more detailed information, please visit ECHA C&L website

Of the 6 notification(s) provided by 30 of 31 companies with hazard statement code(s):

H302 (23.33%): Harmful if swallowed [Warning Acute toxicity, oral]
H315 (80%): Causes skin irritation [Warning Skin corrosion/irritation]
H319 (80%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]
H335 (80%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

Precautionary Statement Codes
P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501

3.2 Methods of Manufacturing: General procedure: The complexes [Ti(XPD)2(H2O)2]Cl (1), [Ni(XPD)2(H2O)2] (2), [ZrO(XPD)2H2O]·H2O (2), [Pd(XPD)2(H2O)2]·H2O(4), [Ce(XPD)2SO4] (5), and [UO2(XPD)2]·3H2O (6) were synthesized as follows: 0.5 mmol of the corresponding metal salt, TiCl3, NiSO4·6H2O, ZrOCl2·8H2O, PdCl2, Ce(SO4)2, or UO2(NO3)2·6H2O, was dissolved in 20 mL of bidistilled water and added to 1mmol (0.35 g) of XPD and 1 mmol (0.40 g) of NaOHin 25 mL of acetone. The mixture was stirred at room temperature for 3 days, and then left for slow evaporation. The formed precipitates were filtered off, washed several times with bidistilled water, and dried over CaCl2 in a desiccator under vacuum.General procedure: The complexes [Ti(XPD)2(H2O)2]Cl (1), [Ni(XPD)2(H2O)2] (2), [ZrO(XPD)2H2O]·H2O (2), [Pd(XPD)2(H2O)2]·H2O(4), [Ce(XPD)2SO4] (5), and [UO2(XPD)2]·3H2O (6) were synthesized as follows: 0.5 mmol of the corresponding metal salt, TiCl3, NiSO4·6H2O, ZrOCl2·8H2O, PdCl2, Ce(SO4)2, or UO2(NO3)2·6H2O, was dissolved in 20 mL of bidistilled water and added to 1mmol (0.35 g) of XPD and 1 mmol (0.40 g) of NaOHin 25 mL of acetone. The mixture was stirred at room temperature for 3 days, and then left for slow evaporation. The formed precipitates were filtered off, washed several times with bidistilled water, and dried over CaCl2 in a desiccator under vacuum.General procedure: The complexes [Ti(XPD)2(H2O)2]Cl (1), [Ni(XPD)2(H2O)2] (2), [ZrO(XPD)2H2O]·H2O (2), [Pd(XPD)2(H2O)2]·H2O(4), [Ce(XPD)2SO4] (5), and [UO2(XPD)2]·3H2O (6) were synthesized as follows: 0.5 mmol of the corresponding metal salt, TiCl3, NiSO4·6H2O, ZrOCl2·8H2O, PdCl2, Ce(SO4)2, or UO2(NO3)2·6H2O, was dissolved in 20 mL of bidistilled water and added to 1mmol (0.35 g) of XPD and 1 mmol (0.40 g) of NaOHin 25 mL of acetone. The mixture was stirred at room temperature for 3 days, and then left for slow evaporation. The formed precipitates were filtered off, washed several times with bidistilled water, and dried over CaCl2 in a desiccator under vacuum.General procedure: The complexes [Ti(XPD)2(H2O)2]Cl (1), [Ni(XPD)2(H2O)2] (2), [ZrO(XPD)2H2O]·H2O (2), [Pd(XPD)2(H2O)2]·H2O(4), [Ce(XPD)2SO4] (5), and [UO2(XPD)2]·3H2O (6) were synthesized as follows: 0.5 mmol of the corresponding metal salt, TiCl3, NiSO4·6H2O, ZrOCl2·8H2O, PdCl2, Ce(SO4)2, or UO2(NO3)2·6H2O, was dissolved in 20 mL of bidistilled water and added to 1mmol (0.35 g) of XPD and 1 mmol (0.40 g) of NaOHin 25 mL of acetone. The mixture was stirred at room temperature for 3 days, and then left for slow evaporation. The formed precipitates were filtered off, washed several times with bidistilled water, and dried over CaCl2 in a desiccator under vacuum.General procedure: The complexes [Ti(XPD)2(H2O)2]Cl (1), [Ni(XPD)2(H2O)2] (2), [ZrO(XPD)2H2O]·H2O (2), [Pd(XPD)2(H2O)2]·H2O(4), [Ce(XPD)2SO4] (5), and [UO2(XPD)2]·3H2O (6) were synthesized as follows: 0.5 mmol of the corresponding metal salt, TiCl3, NiSO4·6H2O, ZrOCl2·8H2O, PdCl2, Ce(SO4)2, or UO2(NO3)2·6H2O, was dissolved in 20 mL of bidistilled water and added to 1mmol (0.35 g) of XPD and 1 mmol (0.40 g) of NaOHin 25 mL of acetone. The mixture was stirred at room temperature for 3 days, and then left for slow evaporation. The formed precipitates were filtered off, washed several times with bidistilled water, and dried over CaCl2 in a desiccator under vacuum.General procedure: The complexes [Ti(XPD)2(H2O)2]Cl (1), [Ni(XPD)2(H2O)2] (2), [ZrO(XPD)2H2O]·H2O (2), [Pd(XPD)2(H2O)2]·H2O(4), [Ce(XPD)2SO4] (5), and [UO2(XPD)2]·3H2O (6) were synthesized as follows: 0.5 mmol of the corresponding metal salt, TiCl3, NiSO4·6H2O, ZrOCl2·8H2O, PdCl2, Ce(SO4)2, or UO2(NO3)2·6H2O, was dissolved in 20 mL of bidistilled water and added to 1mmol (0.35 g) of XPD and 1 mmol (0.40 g) of NaOHin 25 mL of acetone. The mixture was stirred at room temperature for 3 days, and then left for slow evaporation. The formed precipitates were filtered off, washed several times with bidistilled water, and dried over CaCl2 in a desiccator under vacuum.

3.3 Usage: Xipamide is a diuretic and antihypertensive agent.

4. Safety and Handling

4.1 Symbol: GHS07;

4.1 Hazard Codes: Xi

4.1 Signal Word: Warning

4.1 Risk Statements: 36/37/38

4.1 Safety Statements: 26

4.1 Hazard Declaration: H315; H319; H335

4.1 RIDADR: NONH for all modes of transport

4.1 Caution Statement: P261-P305 + P351 + P338

4.1 WGK Germany: 3

4.1 Safety: Poison by intraperitoneal route. Moderately toxic by ingestion and subcutaneous routes. When heated to decomposition it emits toxic fumes of Cl⁻, SO_x, and NO_x.

4.2 Specification: Xipamide , its CAS NO. is 14293-44-8, the synonyms are 4-Chloro-2',6'-dimethyl-5-sulfamoylsalicylanilide ; 4-Chloro-5-sulfamylsalicyloyl-2',6'-dimethylanilide ; 4-chloro-N-(2,6-dimethylphenyl)-2-hydroxy-5-sulfamoylbenzamide ; 5-(Aminosulfonyl)-4-chloro-N-(2,6-dimethylphenyl)-2-hydroxybenzamide ; Benzamide, 5-(aminosulfonyl)-4-chloro-N-(2,6-dimethylphenyl)-2-hydroxy- ; 2',6'-Salicyloxylidide, 4-chloro-5-sulfamoyl- .

4.3 Toxicity

Organism	Test Type	Route	Reported Dose (Normalized Dose)	Effect	Source
dog	LD50	intravenous	> 50mg/kg (50mg/kg)		Arzneimittel-Forschung. Drug Research. Vol. 25, Pg. 245, 1975.
dog	LD50	oral	> 1500mg/kg (1500mg/kg)		Arzneimittel-Forschung. Drug Research. Vol. 25, Pg. 245, 1975.
mouse	LD50	intraperitoneal	520mg/kg (520mg/kg)	BEHAVIORAL: ATAXIA BEHAVIORAL: COMA LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION	Arzneimittel-Forschung. Drug Research. Vol. 25, Pg. 245, 1975.
mouse	LD50	oral	877mg/kg (877mg/kg)		United States Patent Document. Vol. #4490368,
mouse	LD50	subcutaneous	1480mg/kg (1480mg/kg)	BEHAVIORAL: ATAXIA BEHAVIORAL: COMA LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION	Arzneimittel-Forschung. Drug Research. Vol. 25, Pg. 245, 1975.
rat	LD50	intraperitoneal	320mg/kg (320mg/kg)	BEHAVIORAL: ATAXIA BEHAVIORAL: COMA LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION	Arzneimittel-Forschung. Drug Research. Vol. 25, Pg. 245, 1975.
rat	LD50	oral	1640mg/kg (1640mg/kg)	BEHAVIORAL: ATAXIA BEHAVIORAL: COMA LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION	Arzneimittel-Forschung. Drug Research. Vol. 25, Pg. 245, 1975.

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5. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

Skin irritation, Category 2

Eye irritation, Category 2

Specific target organ toxicity \u2013 single exposure, Category 3

2.2 GHS label elements, including precautionary statements

Pictogram(s)
Signal word	Warning
Hazard statement(s)	H315 Causes skin irritation H319 Causes serious eye irritation H335 May cause respiratory irritation
Precautionary statement(s)
Prevention	P264 Wash ... thoroughly after handling. P280 Wear protective gloves/protective clothing/eye protection/face protection. P261 Avoid breathing dust/fume/gas/mist/vapours/spray. P271 Use only outdoors or in a well-ventilated area.
Response	P302+P352 IF ON SKIN: Wash with plenty of water/... P321 Specific treatment (see ... on this label). P332+P313 If skin irritation occurs: Get medical advice/attention. P362+P364 Take off contaminated clothing and wash it before reuse. P305+P351+P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. P337+P313 If eye irritation persists: Get medical advice/attention. P304+P340 IF INHALED: Remove person to fresh air and keep comfortable for breathing. P312 Call a POISON CENTER/doctor/\u2026if you feel unwell.
Storage	P403+P233 Store in a well-ventilated place. Keep container tightly closed. P405 Store locked up.
Disposal	P501 Dispose of contents/container to ...

2.3 Other hazards which do not result in classification

none

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6. NMR Spectrum

13C NMR : Predict

1H NMR : Predict

Predict 1H proton NMR

7. Other Information

7.0 Chemical Properties: Off-White Solid

7.1 Uses: Xipamide is a diuretic and antihypertensive agent.

7.2 Storage Conditions: General procedure: The complexes [Ti(XPD)2(H2O)2]Cl (1), [Ni(XPD)2(H2O)2] (2), [ZrO(XPD)2H2O]·H2O (2), [Pd(XPD)2(H2O)2]·H2O(4), [Ce(XPD)2SO4] (5), and [UO2(XPD)2]·3H2O (6) were synthesized as follows: 0.5 mmol of the corresponding metal salt, TiCl3, NiSO4·6H2O, ZrOCl2·8H2O, PdCl2, Ce(SO4)2, or UO2(NO3)2·6H2O, was dissolved in 20 mL of bidistilled water and added to 1mmol (0.35 g) of XPD and 1 mmol (0.40 g) of NaOHin 25 mL of acetone. The mixture was stirred at room temperature for 3 days, and then left for slow evaporation. The formed precipitates were filtered off, washed several times with bidistilled water, and dried over CaCl2 in a desiccator under vacuum.General procedure: The complexes [Ti(XPD)2(H2O)2]Cl (1), [Ni(XPD)2(H2O)2] (2), [ZrO(XPD)2H2O]·H2O (2), [Pd(XPD)2(H2O)2]·H2O(4), [Ce(XPD)2SO4] (5), and [UO2(XPD)2]·3H2O (6) were synthesized as follows: 0.5 mmol of the corresponding metal salt, TiCl3, NiSO4·6H2O, ZrOCl2·8H2O, PdCl2, Ce(SO4)2, or UO2(NO3)2·6H2O, was dissolved in 20 mL of bidistilled water and added to 1mmol (0.35 g) of XPD and 1 mmol (0.40 g) of NaOHin 25 mL of acetone. The mixture was stirred at room temperature for 3 days, and then left for slow evaporation. The formed precipitates were filtered off, washed several times with bidistilled water, and dried over CaCl2 in a desiccator under vacuum.General procedure: The complexes [Ti(XPD)2(H2O)2]Cl (1), [Ni(XPD)2(H2O)2] (2), [ZrO(XPD)2H2O]·H2O (2), [Pd(XPD)2(H2O)2]·H2O(4), [Ce(XPD)2SO4] (5), and [UO2(XPD)2]·3H2O (6) were synthesized as follows: 0.5 mmol of the corresponding metal salt, TiCl3, NiSO4·6H2O, ZrOCl2·8H2O, PdCl2, Ce(SO4)2, or UO2(NO3)2·6H2O, was dissolved in 20 mL of bidistilled water and added to 1mmol (0.35 g) of XPD and 1 mmol (0.40 g) of NaOHin 25 mL of acetone. The mixture was stirred at room temperature for 3 days, and then left for slow evaporation. The formed precipitates were filtered off, washed several times with bidistilled water, and dried over CaCl2 in a desiccator under vacuum.General procedure: The complexes [Ti(XPD)2(H2O)2]Cl (1), [Ni(XPD)2(H2O)2] (2), [ZrO(XPD)2H2O]·H2O (2), [Pd(XPD)2(H2O)2]·H2O(4), [Ce(XPD)2SO4] (5), and [UO2(XPD)2]·3H2O (6) were synthesized as follows: 0.5 mmol of the corresponding metal salt, TiCl3, NiSO4·6H2O, ZrOCl2·8H2O, PdCl2, Ce(SO4)2, or UO2(NO3)2·6H2O, was dissolved in 20 mL of bidistilled water and added to 1mmol (0.35 g) of XPD and 1 mmol (0.40 g) of NaOHin 25 mL of acetone. The mixture was stirred at room temperature for 3 days, and then left for slow evaporation. The formed precipitates were filtered off, washed several times with bidistilled water, and dried over CaCl2 in a desiccator under vacuum.General procedure: The complexes [Ti(XPD)2(H2O)2]Cl (1), [Ni(XPD)2(H2O)2] (2), [ZrO(XPD)2H2O]·H2O (2), [Pd(XPD)2(H2O)2]·H2O(4), [Ce(XPD)2SO4] (5), and [UO2(XPD)2]·3H2O (6) were synthesized as follows: 0.5 mmol of the corresponding metal salt, TiCl3, NiSO4·6H2O, ZrOCl2·8H2O, PdCl2, Ce(SO4)2, or UO2(NO3)2·6H2O, was dissolved in 20 mL of bidistilled water and added to 1mmol (0.35 g) of XPD and 1 mmol (0.40 g) of NaOHin 25 mL of acetone. The mixture was stirred at room temperature for 3 days, and then left for slow evaporation. The formed precipitates were filtered off, washed several times with bidistilled water, and dried over CaCl2 in a desiccator under vacuum.General procedure: The complexes [Ti(XPD)2(H2O)2]Cl (1), [Ni(XPD)2(H2O)2] (2), [ZrO(XPD)2H2O]·H2O (2), [Pd(XPD)2(H2O)2]·H2O(4), [Ce(XPD)2SO4] (5), and [UO2(XPD)2]·3H2O (6) were synthesized as follows: 0.5 mmol of the corresponding metal salt, TiCl3, NiSO4·6H2O, ZrOCl2·8H2O, PdCl2, Ce(SO4)2, or UO2(NO3)2·6H2O, was dissolved in 20 mL of bidistilled water and added to 1mmol (0.35 g) of XPD and 1 mmol (0.40 g) of NaOHin 25 mL of acetone. The mixture was stirred at room temperature for 3 days, and then left for slow evaporation. The formed precipitates were filtered off, washed several times with bidistilled water, and dried over CaCl2 in a desiccator under vacuum.

7.3 Mesh: Agents that promote the excretion of urine through their effects on kidney function. (See all compounds classified as Diuretics.)|Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)

7.4 Originator: Aquaphor,Beiersdorf,W. Germany ,1971

7.5 Manufacturing Process: The 4-chloro-5-sulfamyl salicylic acid used as starting point was prepared in the following way:
(a) 4-Chloro-5-Chlorosulfonyl Salicylic Acid: 100 grams 4-chloro salicylic acid was added portionwise with stirring at about -5°C to 275 ml chlorosulfonic acid. The temperature was not allowed to rise above +3°C. At the end of the addition, the solution formed was stirred for 1 hour in an ice bath, then for 1 hour at 20°C and finally for 2 1/2 hours at 80°C oil bath temperature. Then the dark brown solution, after ensuing slow cooling with vigorous stirring, was poured onto ice; the precipitate was vacuum filtered, washed with water and dried. After recrystallization from toluene the compound formed had a melting point of 181° to 183°C.
(b) 4-Chloro-5-Sulfamyl Salicylic Acid: 40 grams 4-chloro-5-chlorosulfonyl salicylic acid obtained from (a) was added portionwise with stirring to 250 ml liquid ammonia. This was allowed to stand for 2 hours, then the precipitate was vacuum filtered and dissolved in 500 ml water. The solution was filtered and the filtrate was treated with 2 N hydrochloric acid until no more precipitation occurred. The 4-chloro-5-sulfamyl salicylic acid obtained as the precipitate was filtered off and finally recrystallized from water, MP 258° to 260°C.
5.0 grams 4-chloro-5-sulfamyl salicylic acid was suspended in 100 ml water- free chlorobenzene and then 2.44 grams of 2,6-dimethylaniline and 0.9 ml phosphorus trichloride were added to the suspension in turn. The reaction mixture was heated under reflux for 5 hours. After cooling, the chlorobenzene was separated from the precipitate by decantation. The latter was finally collected on a filter and washed, first with chlorobenzene and, after drying, with 2 N hydrochloric acid and water. The compound obtained by recrystallization from methanol had a melting point of 256°C.

7.6 Therapeutic Function: Diuretic, Antihypertensive

8. Computational chemical data

Molecular Weight: 354.805g/mol
Molecular Formula: C₁₅H₁₅ClN₂O₄S
Compound Is Canonicalized: True
XLogP3-AA: 2.9
Exact Mass: 354.0441058
Monoisotopic Mass: 354.0441058
Complexity: 526
Rotatable Bond Count: 3
Hydrogen Bond Donor Count: 3
Hydrogen Bond Acceptor Count: 5
Topological Polar Surface Area: 118
Heavy Atom Count: 23
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Isotope Atom Count: 0
Covalently-Bonded Unit Count: 1
CACTVS Substructure Key Fingerprint: AAADccBzOABEAAAAAAAAAAAAAAAAAAAAAAAwYAAAAAAAAAABQAAAHgYQSAAADA6B2CAyx4LAAgKIAiVSUHDCABAlJQAIiBkGTsgIJjbDl5OEcUhm5BHI2YeYyGCOBIACgQAKAIAJAAUCABQBAAAAAAAAAA==