50-49-7

Basic information

• Product Name: IMIPRAMINE
• Synonyms: IM;Imidobenzyle;Imipramina;Imiprin;Imizin;Imizine;Imizinum;Impramine
• CAS NO: 50-49-7
• Molecular Formula: C₁₉H₂₄N₂
• Molecular Weight: 280.41
• EINECS: 200-042-1
• Product Categories: TOFRANIL
• Mol File: 50-49-7.mol
• Article Data: 23

Chemical Properties

• Melting Point: 174°C
• Boiling Point: bp0.1 160°
• Flash Point: 179.7°C
• Appearance: /
• Density: 0.9935 (rough estimate)
• Vapor Pressure: 1.04E-06mmHg at 25°C
• Refractive Index: 1.5640 (estimate)
• PKA: pKa 9.66(H2O,t = 25,I=0.025) (Uncertain)
• Water Solubility: 18.23mg/L(24 oC)
• CAS DataBase Reference: IMIPRAMINE(CAS DataBase Reference)
• NIST Chemistry Reference: IMIPRAMINE(50-49-7)
• EPA Substance Registry System: IMIPRAMINE(50-49-7)

Safety Data

• Hazardous Substances Data: 50-49-7(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 50-49-7 differently. You can refer to the following data:
1. Imipramine is used in depression of various etiology accompanied by motor clumsiness and enuresis in children and Parkinson’s disease.
2. antidepressant

Therapeutic Function

Antidepressant

Mechanism of action

Besides being used in the clinical treatment of depression, imipramine also has been used for the treatment of functional enuresis in children who are at least 6 years of age (25 mg daily administered 1 hour before bedtime, not to exceed 2.5 mg/kg daily).

Clinical Use

Imipramine is a 10,11-dihydrodibenzazepine tertiary amine TCA that is marketed as hydrochloride and pamoate salts, both of which are administered orally. Although the hydrochloride salt may be administered in divided daily doses, imipramine's long duration of action suggests that the entire oral daily dose may be administered at one time.On the other hand, imipramine pamoate usually is administered as a single daily oral dose.

Synthesis

Imipramine, 5-[3-(dimethylamino)propyl]-10,11-dihydro-5H-dibenz[b,f] azepine (7.1.1), is synthesized by the alkylation of 10,11-dihydro-5H-dibenz[b,f]azepine using 3-dimethylaminopropylchloride in the presence of sodium amide [1–3].

InChI:InChI=1/C19H24N2/c1-20(2)14-7-15-21-18-10-5-3-8-16(18)12-13-17-9-4-6-11-19(17)21/h3-6,8-11H,7,12-15H2,1-2H3

Synthetic route

imipramine N-oxide (6829-98-7) → impramine (50-49-7)

Conditions	Yield
With sodium tetrahydroborate In water at 50 - 60℃; chemoselective reaction;	96%

desipramine (50-47-5) + carbon dioxide (124-38-9) → impramine (50-49-7)

Conditions	Yield
With hydrogen In octane at 150℃; for 30h; Autoclave;	89%
With hydrogen; tris(acetylacetonato)ruthenium(III); lithium chloride; [2-((diphenylphospino)methyl)-2-methyl-1,3-propanediyl]bis[diphenylphosphine] In tetrahydrofuran at 140℃; for 24h; Autoclave; Inert atmosphere;	83 %Chromat.
With proazaphosphatrane; 9-bora-bicyclo[3.3.1]nonane In tetrahydrofuran at 90℃; under 750.075 Torr; for 1h; Inert atmosphere; Schlenk technique; chemoselective reaction;	99 %Spectr.

N'-(4-carbomethoxy)desimipramine (876124-39-9) → impramine (50-49-7)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 0.5h; Heating;	79%

formaldehyd (50-00-0) + didesmethylimipramine (2095-95-6) → impramine (50-49-7)

Conditions	Yield
With formic acid In water at 100℃; for 1h; Eschweiler-Clark Amine Methylation; Microwave irradiation;	61%

1,2-bis(2-bromophenyl)ethane (59485-34-6) + 1-amino-3-(dimethylamino)propane (109-55-7) → impramine (50-49-7)

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; XPhos In toluene at 110℃; Buchwald-Hartwig Coupling;	60%

methanol (67-56-1) + desipramine (50-47-5) → impramine (50-49-7)

Conditions	Yield
With rhodium(III) chloride hydrate; potassium tert-butylate at 150℃; for 60h; Sealed tube; High pressure;	49%

Clomipramine (303-49-1) → clomipramine N-oxide (14171-67-6) + impramine (50-49-7) + 3-hydroxyimipramine + 3-hydroxyimipramine-N-oxide

Conditions	Yield
With oxygen In methanol; phosphate buffer at 25 - 28℃; pH=7.4; Product distribution; Further Variations:; Reagents; Photolysis; UV-irradiation;	A 15% B 15% C 40% D 20%

9,10-dihydrodibenzazepine (494-19-9) → impramine (50-49-7)

Conditions	Yield
With sodium amide; benzene und Erwaermen der Reaktionsloesung mit <3-Chlor-propyl>-dimethyl-amin;

9,10-dihydrodibenzazepine (494-19-9) + 3-(Dimethylamino)propyl chloride (109-54-6) → impramine (50-49-7)

Conditions	Yield
With sodium hydroxide; potassium carbonate DMSO 1.) room temp., 2 h, 2.) 110 deg C, 18 h; Yield given. Multistep reaction;
With potassium hydroxide; ammonium acetate In toluene at 20℃; Heating / reflux;

carbon dioxide (124-38-9) + [3-(10,11-Dihydro-dibenzo[b,f]azepin-5-yl)-propyl]-methyl-trimethylsilanyl-amine → impramine (50-49-7)

Conditions	Yield
With lithium aluminium tetrahydride 1.) THF, -45 deg C - 60 deg C, 2.) 60 deg C, 10 min; Yield given. Multistep reaction;

desipramine (50-47-5) + carbon dioxide (124-38-9) + methyl chloroformate (79-22-1) → impramine (50-49-7)

Conditions	Yield
Mechanism; multistep reaction; labelled with 11C;

desipramine hydrochloride (58-28-6) → impramine (50-49-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: (NH4)2SO4 / 110 °C 2: 2.) LiAlH4 / 1.) THF, -45 deg C - 60 deg C, 2.) 60 deg C, 10 min View Scheme

desipramine (50-47-5) → impramine (50-49-7)

Conditions	Yield
Multi-step reaction with 2 steps 2: 79 percent / LiAlH4 / tetrahydrofuran / 0.5 h / Heating View Scheme

formic acid (64-18-6) + desipramine (50-47-5) → impramine (50-49-7)

Conditions	Yield
With platinum(0)-1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex; 1,3-bis-(diphenylphosphino)propane; phenylsilane In dibutyl ether at 60℃; for 18h; Schlenk technique; Inert atmosphere;	92 %Chromat.

Imipramine hydrochloride (113-52-0) → impramine (50-49-7)

Conditions	Yield
With sodium hydroxide In water

Imipramine N-glucuronide (165602-94-8) → impramine (50-49-7)

Conditions	Yield
With hydrogenchloride In water at 90℃;

impramine (50-49-7) + methyl iodide (74-88-4) → Trimethyl-imipramine Iodide (16870-81-8)

Conditions	Yield
In diethyl ether at 20℃; for 20h;	98%

impramine (50-49-7) + Pamoic acid (130-85-8) → imipramine pamoate

Conditions	Yield
In ethyl acetate at 20 - 50℃; Solvent; Temperature;	96%

impramine (50-49-7) + (6-bromohexyl)dimethyl-[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propyl]ammonium bromide → C38H52N4O2(2+)*2Br(1-)

Conditions	Yield
In acetonitrile Heating;	90%

1 ,6-dibromohexane (629-03-8) + impramine (50-49-7) → (6-bromo-hexyl)-[3-(10,11-dihydro-dibenzo[b,f]azepin-5-yl)-propyl]-dimethyl-ammonium; bromide

Conditions	Yield
at 20℃;	86%

impramine (50-49-7) → C19H16(2)H8N2

Conditions	Yield
With deuterium In tetrahydrofuran for 36h; Glovebox; Inert atmosphere; regioselective reaction;	84%

impramine (50-49-7) → C19H16(2)H8N2

Conditions	Yield
With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; deuterium In tetrahydrofuran at 55℃; under 750.075 Torr; for 22h; Inert atmosphere;	80%

impramine (50-49-7) + methyl iodide (74-88-4) → imipramine methiodide (129344-89-4)

Conditions	Yield
In butanone for 1h; Ambient temperature;	77%

Koshlands reagent I (772-33-8) + impramine (50-49-7) → 2-((5-(3-(dimethylamino)propyl)-10,11-dihydro-5H-dibenzo[b,f]azepin-2-yl)methyl)-4-nitrophenol

Conditions	Yield
With dipotassium hydrogenphosphate In dichloromethane at 20℃; for 48h;	73%

impramine (50-49-7) + C24H30N2O5S → C43H54N4O5S

Conditions	Yield
With (4s,6s)-2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile; sodium acetate In N,N-dimethyl-formamide at 20℃; for 16h; Irradiation; Inert atmosphere; diastereoselective reaction;	64%

impramine (50-49-7) + 1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester (21085-72-3) → ((2R,3R,4S,5S,6S)-6-Carboxy-3,4,5-trihydroxy-tetrahydro-pyran-2-yl)-[3-(10,11-dihydro-dibenzo[b,f]azepin-5-yl)-propyl]-dimethyl-ammonium; chloride (86492-48-0)

Conditions	Yield
With XAD-2 ion-exchange resin; sodium hydrogencarbonate In water; benzene for 72h; Ambient temperature;	55%

sodium cyanide (773837-37-9) + impramine (50-49-7) → 9,10-dihydrodibenzazepine (494-19-9) + 2-((3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-(methyl)amino)acetonitrile + 2-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-4-(dimethylamino)butanenitrile

Conditions	Yield
With [4,4’-bis(1,1-dimethylethyl)-2,2’-bipyridine-N1,N1‘]bis [3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate; acetic acid In acetonitrile at 20℃; for 24h; Irradiation; Sealed tube;	A 50% B 22% C 23%

potassium cyanide + impramine (50-49-7) → 9,10-dihydrodibenzazepine (494-19-9) + 2-((3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-(methyl)amino)acetonitrile + 2-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-4-(dimethylamino)butanenitrile

Conditions	Yield
With 2-Picolinic acid; iron(III) chloride; tert-Butyl peroxybenzoate; 18-crown-6 ether In acetonitrile at 50℃; for 48h;	A 6% B 35% C 15%

1 ,6-dibromohexane (629-03-8) + impramine (50-49-7) → C44H60N4(2+)*2Br(1-)

Conditions	Yield
In acetonitrile Heating;	24%

impramine (50-49-7) → 10-Hydroxyimipramine (796-28-1) + 2-hydroxyimipramine (303-70-8) + 4-hydroxyimipramine (94436-87-0)

Conditions	Yield
Stage #1: impramine With ethylenediaminetetraacetic acid trisodium salt; oxygen; manganese (II) acetate tetrahydrate; ascorbic acid In water pH=4; Udenfriend reaction; Stage #2: With ferrous(II) sulfate heptahydrate; ethylenediaminetetraacetic acid trisodium salt; oxygen In water at 45℃; for 2h; Udenfriend reaction;	A 2.56% B 1.46% C 3.47%

impramine (50-49-7) + [14C]methanol (3046-50-2) → C18(14)CH22N2O

Conditions	Yield
With oxygen; palladium on activated charcoal for 24h; Ambient temperature;

impramine (50-49-7) → desipramine (50-47-5)

Conditions	Yield
With D-glucose; corn steep liquor; S. aureus; peptone; yeast extract In water at 37℃; Product distribution; other reagents;
With oxygen; palladium on activated charcoal In methanol for 24h; Ambient temperature;
With pooled human liver microsomes; Tris buffer; NADPH; magnesium chloride at 37℃; pH=7.4; Enzyme kinetics;
With human hepatic CYP1A2; human hepatic CYP2C9; human hepatic CYP3A4 Enzymatic reaction;
Multi-step reaction with 2 steps 1: N,N,N',N'-tetramethyl-1,8-diaminonaphthalene / 1,2-dichloro-ethane / 1 h / Reflux 2: 2 h / Reflux View Scheme

impramine (50-49-7) → 2,8-dibromoimipramine (144434-72-0)

Conditions	Yield
With N-Bromosuccinimide; silica gel In dichloromethane at 18℃;

Upstream product

• 494-19-9 9,10-dihydrodibenzazepine 
• 50-47-5 desipramine 
• 124-38-9 carbon dioxide 
• 67-56-1 methanol 
• 50-00-0 formaldehyd 
• 2095-95-6 didesmethylimipramine 
• 113-52-0 Imipramine hydrochloride 
• 59485-34-6 1,2-bis(2-bromophenyl)ethane 
• 109-55-7 1-amino-3-(dimethylamino)propane 
• 64-18-6 formic acid 
• 6829-98-7 imipramine N-oxide 
• 58-28-6 desipramine hydrochloride 
• 303-49-1 Clomipramine 
• 79-22-1 methyl chloroformate 

Downstream Products

• 50-47-5 desipramine 
• 6829-98-7 imipramine N-oxide 
• 2095-95-6 didesmethylimipramine 
• 494-19-9 9,10-dihydrodibenzazepine 
• 1027983-95-4 N-[3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl]-2-(4-methoxyphenyl)-N-methylacetamide 
• 1026480-32-9 3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N-[2-(4-methoxyphenyl)ethyl]-N-methylpropan-1-amine 
• 311332-81-7 3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylpropan-1-amine 
• 10075-24-8 imipramine pamoate 
• 86492-48-0 ((2R,3R,4S,5S,6S)-6-Carboxy-3,4,5-trihydroxy-tetrahydro-pyran-2-yl)-[3-(10,11-dihydro-dibenzo[b,f]azepin-5-yl)-propyl]-dimethyl-ammonium; chloride 

Relevant articles and documents

Simple RuCl3-catalyzed N-Methylation of Amines and Transfer Hydrogenation of Nitroarenes using Methanol

Methanol is a potential hydrogen source and C1 synthon, which finds interesting applications in both chemical synthesis and energy technologies. The effective utilization of this simple alcohol in organic synthesis is of central importance and attracts scientific interest. Herein, we report a clean and cost-competitive method with the use of methanol as both C1 synthon and H2 source for selective N-methylation of amines by employing relatively cheap RuCl3.xH2O as a ligand-free catalyst. This readily available catalyst tolerates various amines comprising electron-deficient and electron-donating groups and allows them to transform into corresponding N-methylated products in moderate to excellent yields. In addition, few marketed pharmaceutical agents (e. g., venlafaxine and imipramine) were also successfully synthesized via late-stage functionalization from readily available feedstock chemicals, highlighting synthetic value of this advanced N-methylation reaction. Using this platform, we also attempted tandem reactions with selected nitroarenes to convert them into corresponding N-methylated amines using MeOH under H2-free conditions including transfer hydrogenation of nitroarenes-to-anilines and prepared drug molecules (e. g., benzocaine and butamben) as well as key pharmaceutical intermediates. We further enable one-shot selective and green syntheses of 1-methylbenzimidazole using ortho-phenylenediamine (OPDA) and methanol as coupling partners.

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The present invention is in relation to preparation of Imipramine Pamoate by a simple two-step process. The process provides new form of Imipramine Pamoate. The present invention is cost effective, involves mild conditions to beget said compound.