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Trazodone hydrochloride

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Name

Trazodone hydrochloride

EINECS 246-855-5
CAS No. 25332-39-2 Density N/A
PSA 45.78000 LogP 3.16660
Solubility Soluble at 25mg/ml in methanol. Also soluble in 0.1M HCl or DMSO. Insoluble in water /n Melting Point 223oC
Formula C19H23Cl2N5O Boiling Point 528.5 °C at 760 mmHg
Molecular Weight 408.331 Flash Point 273.4 °C
Transport Information UN 3249 Appearance N/A
Safety 22-36-37/39-26 Risk Codes 22-40-36/37/38
Molecular Structure Molecular Structure of 25332-39-2 (Trazodone hydrochloride) Hazard Symbols HarmfulXn,IrritantXi
Synonyms

s-Triazolo[4,3-a]pyridin-3(2H)-one,2-[3-[4-(m-chlorophenyl)-1-piperazinyl]propyl]-, monohydrochloride (8CI);AF1161;Bimaran;Desyrel;KB 831;Mesyrel;Molipaxin;Pragmazone;Thombran;Tombran;Trazolan;Trittico;Trazodone HCL;

Article Data 5

Trazodone hydrochloride Synthetic route

2-(3-bromopropyl)-1,2,4-triazolo[4,3-a]pyridin-3-(2H)-one

13078-15-4

1-(3-chlorophenyl)piperazine hydrochloride

25332-39-2

trazodone hydrochloride

Conditions
ConditionsYield
Stage #1: 2-(3-bromopropyl)[1,2,4]triazolo[4,3-a]pyridine-3(2H)-one; 1-(3-chlorophenyl)piperazine hydrochloride With tetrabutylammomium bromide; potassium carbonate In N,N-dimethyl-formamide for 0.0166667h; Microwave irradiation;
Stage #2: With hydrogenchloride In 1,4-dioxane; acetone Solvent; Reagent/catalyst;
98%
19794-93-5

trazodone

25332-39-2

trazodone hydrochloride

Conditions
ConditionsYield
With hydrogenchloride In ethanol; water at 60℃; for 2h; pH=3;93%
With hydrogenchloride In water; acetone at 50℃; pH=3 - 4;90%
With hydrogenchloride In water; acetone pH=3 - 4; Product distribution / selectivity;87%
13078-15-4

1-(3-chlorophenyl)piperazine hydrochloride

19666-40-1

2-(3-chloropropyl)-1,2,4-triazolo<4,3-a>pyridin-3-one

25332-39-2

trazodone hydrochloride

Conditions
ConditionsYield
Stage #1: 1-(3-chlorophenyl)piperazine hydrochloride; 2-(3-chloropropyl)-1,2,4-triazolo<4,3-a>pyridin-3-one With tetrabutylammomium bromide; potassium carbonate In acetonitrile for 0.0166667h; Microwave irradiation;
Stage #2: With hydrogenchloride In 1,4-dioxane; acetone Solvent;
90%
52605-52-4

1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride

1,2,4-triazolo<4,3-a>pyridin-3(2H)-one sodium salt

25332-39-2

trazodone hydrochloride

Conditions
ConditionsYield
With tetrabutylammomium bromide; sodium carbonate In isopropyl alcohol at 80 - 85℃; for 12h; Reagent/catalyst;83%
109-09-1

2-chloropyridine

25332-39-2

trazodone hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: sulfuric acid / 2-ethoxy-ethanol / 0.03 h / Microwave irradiation
2: potassium carbonate; tetrabutylammomium bromide / acetonitrile / Microwave irradiation
View Scheme
Multi-step reaction with 3 steps
1: sulfuric acid / 2-ethoxy-ethanol / 0.03 h / Microwave irradiation
2: potassium carbonate; tetrabutylammomium bromide / acetonitrile / 0.02 h / Microwave irradiation
3: potassium carbonate; tetrabutylammomium bromide / acetonitrile / 0.02 h / Microwave irradiation
View Scheme
Multi-step reaction with 3 steps
1: sulfuric acid / 2-ethoxy-ethanol / 0.03 h / Microwave irradiation
2: potassium carbonate; tetrabutylammomium bromide / acetonitrile / 0.03 h / Microwave irradiation
3: potassium carbonate; tetrabutylammomium bromide / N,N-dimethyl-formamide / 0.02 h / Microwave irradiation
View Scheme
6969-71-7

[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

25332-39-2

trazodone hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: potassium carbonate; tetrabutylammomium bromide / acetonitrile / 0.02 h / Microwave irradiation
2: potassium carbonate; tetrabutylammomium bromide / acetonitrile / 0.02 h / Microwave irradiation
View Scheme
52605-52-4

1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride

6969-71-7

[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

25332-39-2

trazodone hydrochloride

Conditions
ConditionsYield
Stage #1: 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride; [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one With tetrabutylammomium bromide; potassium carbonate In acetonitrile Microwave irradiation;
Stage #2: With hydrogenchloride In 1,4-dioxane; acetone
109-04-6

2-bromo-pyridine

25332-39-2

trazodone hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: sulfuric acid / 2-ethoxy-ethanol / 0.03 h / Microwave irradiation
2: potassium carbonate; tetrabutylammomium bromide / acetonitrile / Microwave irradiation
View Scheme
Multi-step reaction with 3 steps
1: sulfuric acid / 2-ethoxy-ethanol / 0.03 h / Microwave irradiation
2: potassium carbonate; tetrabutylammomium bromide / acetonitrile / 0.02 h / Microwave irradiation
3: potassium carbonate; tetrabutylammomium bromide / acetonitrile / 0.02 h / Microwave irradiation
View Scheme
Multi-step reaction with 3 steps
1: sulfuric acid / 2-ethoxy-ethanol / 0.03 h / Microwave irradiation
2: potassium carbonate; tetrabutylammomium bromide / acetonitrile / 0.03 h / Microwave irradiation
3: potassium carbonate; tetrabutylammomium bromide / N,N-dimethyl-formamide / 0.02 h / Microwave irradiation
View Scheme
4930-98-7

pyrid-2-ylhydrazine

25332-39-2

trazodone hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: neat (no solvent) / 0.01 h / Microwave irradiation
2: potassium carbonate; tetrabutylammomium bromide / acetonitrile / Microwave irradiation
View Scheme
Multi-step reaction with 3 steps
1: neat (no solvent) / 0.01 h / Microwave irradiation
2: potassium carbonate; tetrabutylammomium bromide / acetonitrile / 0.02 h / Microwave irradiation
3: potassium carbonate; tetrabutylammomium bromide / acetonitrile / 0.02 h / Microwave irradiation
View Scheme
Multi-step reaction with 3 steps
1: neat (no solvent) / 0.01 h / Microwave irradiation
2: potassium carbonate; tetrabutylammomium bromide / acetonitrile / 0.03 h / Microwave irradiation
3: potassium carbonate; tetrabutylammomium bromide / N,N-dimethyl-formamide / 0.02 h / Microwave irradiation
View Scheme
6640-24-0

N-(m-chlorophenyl)piperazine

25332-39-2

trazodone hydrochloride

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: sodium hydroxide / water; 1-methyl-pyrrolidin-2-one / 88 °C / Flow reactor
2: sodium hydroxide / water; acetonitrile / 150 °C / Flow reactor
3: hydrogenchloride / water; acetone / 50 °C / pH 3 - 4
View Scheme

Trazodone hydrochloride Standards and Recommendations

ASSAY: 99.0min
RESIDUE ON IGNITION: 0.1% max
LOSS ON DRYING: 0.5% max
HEAVY METALS: 20ppm max

Trazodone hydrochloride Specification

The CAS registry number of Trazodone hydrochloride is 25332-39-2. The IUPAC name is 2-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one hydrochloride (1:1). Its EINECS registry number is 246-855-5. In addition, the formula is C19H23Cl2N5O and the molecular weight is 408.32482. It is a kind of off-white powder.

Physical properties about this chemical are: (1)ACD/LogP: 1.66; (2)# of Rule of 5 Violations: 0; (3)ACD/LogD (pH 5.5): 0.67; (4)ACD/LogD (pH 7.4): 1.61; (5)ACD/BCF (pH 5.5): 1.09; (6)ACD/BCF (pH 7.4): 9.68; (7)ACD/KOC (pH 5.5): 19.33; (8)ACD/KOC (pH 7.4): 171.45; (9)#H bond acceptors: 6; (10)#H bond donors: 0; (11)#Freely Rotating Bonds: 5; (12)Polar Surface Area: 42.39 Å2 ; (13)Flash Point: 273.4 °C; (14)Enthalpy of Vaporization: 80.34 kJ/mol; (15)Boiling Point: 528.5 °C at 760 mmHg; (16)Vapour Pressure: 2.94E-11 mmHg at 25°C.

Preparation of Trazodone hydrochloride: at first, we should use 2-chloropyridine and hydratehydrazine to prepare pyridinehydrazine. The reaction time is 24 hours by stirring. In this reaction, we should use diethyl ether to extract the product. Then we can use urea and pyridinehydrazine to prepare 1,2,4-triazolo-[4,3-a]pyridine-3(2H)-one. The reaction time is 2 hours by heating at reaction temperature of 155-160 °C. The yield is about 86.5%. At last, trazodone hydrochloride can be prepared by 1,2,4-triazolo-[4,3-a]pyridine-3(2H)-one and 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazinehydrochloride. This reaction will need reagent ethanol and solvent NaOH. The product should be extracted by dichloromethane and dried by Na2SO4. The yield is about 67.5%.

Uses of Trazodone hydrochloride: it is a kind of antidepressants. The effect is similar with tricyclic drugs, but smaller toxicity to the cardiovascular system and no anticholinergic side effects. In addition, it is more applicable to the older or the depression with cardiovascular disease. It can treat the depression, anxiety disorders and schizophrenia in clinical.

When you are using this chemical, please be cautious about it as the following:
It is harmful if swallowed and irritating to eyes, respiratory system and skin. You should  not breathe dust. Limited evidence of a carcinogenic effect. When you are using it, wear suitable gloves and eye/face protection. In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.

You can still convert the following datas into molecular structure:
(1)SMILES: Cl.Clc4cccc(N3CCN(CCCN1/N=C2/C=C\C=C/N2C1=O)CC3)c4
(2)InChI: InChI=1/C19H22ClN5O.ClH/c20-16-5-3-6-17(15-16)23-13-11-22(12-14-23)8-4-10-25-19(26)24-9-2-1-7-18(24)21-25;/h1-3,5-7,9,15H,4,8,10-14H2;1H
(3)InChIKey: OHHDIOKRWWOXMT-UHFFFAOYAR

The toxicity data is as follows:

Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
dog LD50 intravenous > 40mg/kg (40mg/kg)   Modern Problems of Pharmacopsychiatry. Vol. 9, Pg. 76, 1974.
dog LD50 oral 500mg/kg (500mg/kg) BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX)

BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD

BEHAVIORAL: AGGRESSION
Modern Problems of Pharmacopsychiatry. Vol. 9, Pg. 76, 1974.
man TDLo oral 667ug/kg (0.667mg/kg) CARDIAC: CARDIOMYOPATHY INCLUDING INFARCTION American Journal of Psychiatry. Vol. 141, Pg. 1472, 1984.
man TDLo oral 5714ug/kg/4D- (5.714mg/kg) BEHAVIORAL: EUPHORIA

BEHAVIORAL: EXCITEMENT
British Journal of Psychiatry. Vol. 158, Pg. 275, 1991.
man TDLo oral 43mg/kg/30D-I (43mg/kg) BLOOD: AGRANULOCYTOSIS

BLOOD: OTHER CHANGES
American Journal of Psychiatry. Vol. 150, Pg. 1563, 1993.
man TDLo oral 46mg/kg/8D-I (46mg/kg) BEHAVIORAL: EXCITEMENT

CARDIAC: PULSE RATE INCREASE WITHOUT FALL IN BP

KIDNEY, URETER, AND BLADDER: URINE VOLUME INCREASED
Journal of Clinical Pyschopharmacology. Vol. 6, Pg. 117, 1986.
monkey LD50 intravenous 25mg/kg (25mg/kg) BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD

GASTROINTESTINAL: CHANGES IN STRUCTURE OR FUNCTION OF SALIVARY GLANDS

LUNGS, THORAX, OR RESPIRATION: CYANOSIS
Pharmacological and Biochemical Properties of Drug Substances. Vol. 3, Pg. 94, 1981.
mouse LD50 intraperitoneal 255mg/kg (255mg/kg)   Journal of Pharmaceutical Sciences. Vol. 81, Pg. 99, 1992.
mouse LD50 intravenous 91mg/kg (91mg/kg) BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD

LUNGS, THORAX, OR RESPIRATION: CYANOSIS

GASTROINTESTINAL: CHANGES IN STRUCTURE OR FUNCTION OF SALIVARY GLANDS
Modern Problems of Pharmacopsychiatry. Vol. 9, Pg. 76, 1974.
mouse LD50 oral 584mg/kg (584mg/kg)   Drug Development Research. Vol. 22, Pg. 385, 1991.
mouse LD50 subcutaneous > 1500mg/kg (1500mg/kg)   Iyakuhin Kenkyu. Study of Medical Supplies. Vol. 22, Pg. 967, 1991.
rabbit LD50 intravenous 52mg/kg (52mg/kg) BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD

LUNGS, THORAX, OR RESPIRATION: CYANOSIS

GASTROINTESTINAL: CHANGES IN STRUCTURE OR FUNCTION OF SALIVARY GLANDS
Modern Problems of Pharmacopsychiatry. Vol. 9, Pg. 76, 1974.
rabbit LD50 oral 560mg/kg (560mg/kg) BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD

LUNGS, THORAX, OR RESPIRATION: CYANOSIS

GASTROINTESTINAL: CHANGES IN STRUCTURE OR FUNCTION OF SALIVARY GLANDS
Modern Problems of Pharmacopsychiatry. Vol. 9, Pg. 76, 1974.
rat LD50 intraperitoneal 178mg/kg (178mg/kg) BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD

GASTROINTESTINAL: CHANGES IN STRUCTURE OR FUNCTION OF SALIVARY GLANDS

LUNGS, THORAX, OR RESPIRATION: CYANOSIS
Modern Problems of Pharmacopsychiatry. Vol. 9, Pg. 76, 1974.
rat LD50 intravenous 91mg/kg (91mg/kg) BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD

LUNGS, THORAX, OR RESPIRATION: CYANOSIS

GASTROINTESTINAL: CHANGES IN STRUCTURE OR FUNCTION OF SALIVARY GLANDS
Modern Problems of Pharmacopsychiatry. Vol. 9, Pg. 76, 1974.
rat LD50 oral 690mg/kg (690mg/kg) BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD

GASTROINTESTINAL: CHANGES IN STRUCTURE OR FUNCTION OF SALIVARY GLANDS

LUNGS, THORAX, OR RESPIRATION: CYANOSIS
Modern Problems of Pharmacopsychiatry. Vol. 9, Pg. 76, 1974.
rat LD50 subcutaneous 2729mg/kg (2729mg/kg)   Iyakuhin Kenkyu. Study of Medical Supplies. Vol. 22, Pg. 967, 1991.
women TDLo oral 750ug/kg (0.75mg/kg) BEHAVIORAL: "HALLUCINATIONS, DISTORTED PERCEPTIONS" American Journal of Psychiatry. Vol. 141, Pg. 434, 1984.
women TDLo oral 80mg/kg (80mg/kg) BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

VASCULAR: BP LOWERING NOT CHARACTERIZED IN AUTONOMIC SECTION

LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION
Journal of Analytical Toxicology. Vol. 8, Pg. 91, 1984.
women TDLo oral 100mg/kg (100mg/kg) BEHAVIORAL: SLEEP

BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

VASCULAR: BP ELEVATION NOT CHARACTERIZED IN AUTONOMIC SECTION
Clinical Pharmacy. Vol. 4, Pg. 97, 1985.
women TDLo oral 720mg/kg/34W- (720mg/kg) LIVER: "HEPATITIS (HEPATOCELLULAR NECROSIS), ZONAL"

KIDNEY, URETER, AND BLADDER: OTHER CHANGES IN URINE COMPOSITION
Annals of Internal Medicine. Vol. 118, Pg. 791, 1993.

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