537-26-8

Basic information

• Product Name: tropacocaine
• Synonyms: tropacocaine;benzoylpseudotropine;Benzoyl-psi-tropeine;Pseudotropine benzoate;psi-Tropine benzoate;Tropacaine
• CAS NO: 537-26-8
• Molecular Formula: C₁₅H₁₉NO₂
• Molecular Weight: 245.32
• EINECS: 208-662-4
• Mol File: 537-26-8.mol
• Article Data: 9

Chemical Properties

• Melting Point: 49°
• Boiling Point: 388.28°C (rough estimate)
• Flash Point: 122.3°C
• Appearance: /
• Density: 1.0426
• Vapor Pressure: 8.92E-05mmHg at 25°C
• Refractive Index: 1.5080 (estimate)
• PKA: 4.32(at 15℃)
• Water Solubility: 1.055g/L(15 oC)
• CAS DataBase Reference: tropacocaine(CAS DataBase Reference)
• NIST Chemistry Reference: tropacocaine(537-26-8)
• EPA Substance Registry System: tropacocaine(537-26-8)

Safety Data

• Hazardous Substances Data: 537-26-8(Hazardous Substances Data)

Usage

General Description

Tropacocaine, also known as benzoyltropine, is a synthetic alkaloid and is a derivative of cocaine. It is a local anesthetic and a stimulant with similar pharmacological effects as cocaine, but with a shorter duration of action. Tropacocaine is not regulated under international drug control treaties, making it a popular alternative to cocaine in some illicit drug markets. However, its use carries significant health risks, including potential addiction and overdose, as well as adverse psychological and cardiovascular effects. Tropacocaine's chemical structure and pharmacological activity make it a concerning substance in the context of drug abuse and public health.

InChI:InChI=1/C15H19NO2/c1-16-12-7-8-13(16)10-14(9-12)18-15(17)11-5-3-2-4-6-11/h2-6,12-14H,7-10H2,1H3/t12-,13+,14?

Synthetic route

benzoyl chloride (98-88-4) + pseudotropine (135-97-7) → tropacocain (537-26-8)

Conditions	Yield
With triethylamine In toluene for 4h; Reflux;	90%
With TEA In toluene for 3h; Heating;

benzoyl chloride (98-88-4) + 3β-hydroxy-8-methyl-8-azabicyclo[3.2.1]octane → tropacocain (537-26-8)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 20 - 30℃; for 2h;	54%

benzoic acid anhydride (93-97-0) + pseudotropine (135-97-7) → tropacocain (537-26-8)

Conditions	Yield
With water

formaldehyd (50-00-0) + Nortropacocaine (18470-33-2, 20811-95-4, 123202-90-4) → tropacocain (537-26-8)

Conditions	Yield
With formic acid for 10h; Heating; Yield given;

Nortropacocaine (18470-33-2, 20811-95-4, 123202-90-4) → tropacocain (537-26-8)

Conditions	Yield
With formaldehyd; formic acid Heating; Yield given;

tropacocaine-N oxide (35772-45-3) + sulphurous acid (7782-99-2) → tropacocain (537-26-8)

benzoic acid (65-85-0) + 3-tropanol (120-29-6) → tropacocain (537-26-8)

Conditions	Yield
With di-tert-butyl-diazodicarboxylate; polimer-immobilized triphenylphosphine In dichloromethane at 20℃; for 24h;

cyclohepta-3,5-dien-1-yl benzoate (59171-91-4) → tropacocain (537-26-8)

Conditions

Yield

Multi-step reaction with 7 steps 1: 57 percent / ethanol; CCl4 / 1.) -20 deg C, 5 h, 2.) -10 deg C, 14 d 2: 98 percent / H2 / 5percent Pd/C / methanol / 7 h 3: Na2CO3 / 1.) chloroform, water, 0 deg C, 30 min, 2.) RT, 2h 4: 36 percent / pyridine, SOCl2 / CHCl3 / 1 h / Heating 5: 75 percent / potassium tert-butoxide / benzene; hexamethylphosphoric acid triamide / 2 h / Ambient temperature 6: H2 / 5percent Pd/C / methanol / 8 h / 760 Torr 7: aq. formic acid / 10 h / Heating View Scheme

N-<(benzyloxy)carbonyl>nortropacocaine (95687-87-9) → tropacocain (537-26-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2 / 5percent Pd/C / methanol / 8 h / 760 Torr 2: aq. formic acid / 10 h / Heating View Scheme
Multi-step reaction with 2 steps 1: H2 / Pd/C / methanol 2: HCHO, HCO2H / Heating View Scheme

all-cis-3-(benzoyloxy)-5-(<(benzyloxy)carbonyl>amino)-cycloheptanol (95687-98-2) → tropacocain (537-26-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: 36 percent / pyridine, SOCl2 / CHCl3 / 1 h / Heating 2: 75 percent / potassium tert-butoxide / benzene; hexamethylphosphoric acid triamide / 2 h / Ambient temperature 3: H2 / 5percent Pd/C / methanol / 8 h / 760 Torr 4: aq. formic acid / 10 h / Heating View Scheme

3β-(benzoyloxy)-1β(<(benzyloxy)carbonyl>amino)-5α-chlorocycloheptane (95687-97-1) → tropacocain (537-26-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 75 percent / potassium tert-butoxide / benzene; hexamethylphosphoric acid triamide / 2 h / Ambient temperature 2: H2 / 5percent Pd/C / methanol / 8 h / 760 Torr 3: aq. formic acid / 10 h / Heating View Scheme

all-cis-5-amino-3-(benzoyloxy)cycloheptanol hydrochloride (95687-94-8) → tropacocain (537-26-8)

Conditions	Yield
Multi-step reaction with 5 steps 1: Na2CO3 / 1.) chloroform, water, 0 deg C, 30 min, 2.) RT, 2h 2: 36 percent / pyridine, SOCl2 / CHCl3 / 1 h / Heating 3: 75 percent / potassium tert-butoxide / benzene; hexamethylphosphoric acid triamide / 2 h / Ambient temperature 4: H2 / 5percent Pd/C / methanol / 8 h / 760 Torr 5: aq. formic acid / 10 h / Heating View Scheme

exo-3-(benzoyloxy)-8-oxa-9-azabicyclo<3.2.2.>-non-6-ene hydrochloride (95687-89-1, 95782-70-0) → tropacocain (537-26-8)

Conditions

Yield

Multi-step reaction with 6 steps 1: 98 percent / H2 / 5percent Pd/C / methanol / 7 h 2: Na2CO3 / 1.) chloroform, water, 0 deg C, 30 min, 2.) RT, 2h 3: 36 percent / pyridine, SOCl2 / CHCl3 / 1 h / Heating 4: 75 percent / potassium tert-butoxide / benzene; hexamethylphosphoric acid triamide / 2 h / Ambient temperature 5: H2 / 5percent Pd/C / methanol / 8 h / 760 Torr 6: aq. formic acid / 10 h / Heating View Scheme

Benzoic acid (1R,3R,6S)-3-benzyloxycarbonylamino-6-hydroxy-cycloheptyl ester (95687-98-2) → tropacocain (537-26-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: 36 percent / thionyl chloride, pyridine / CHCl3 / 0 °C 2: 75 percent 3: H2 / Pd/C / methanol 4: HCHO, HCO2H / Heating View Scheme

Benzoic acid (1R,3R,6R)-3-benzyloxycarbonylamino-6-chloro-cycloheptyl ester (95687-97-1) → tropacocain (537-26-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 75 percent 2: H2 / Pd/C / methanol 3: HCHO, HCO2H / Heating View Scheme

benzyl chloroformate (501-53-1) → tropacocain (537-26-8)

Conditions	Yield
Multi-step reaction with 5 steps 1: 96 percent / aq. Na2CO3 / CHCl3 / 0 - 25 °C 2: 36 percent / thionyl chloride, pyridine / CHCl3 / 0 °C 3: 75 percent 4: H2 / Pd/C / methanol 5: HCHO, HCO2H / Heating View Scheme

Tropacocaine hydrochloride (637-23-0) → tropacocain (537-26-8)

Conditions	Yield
With ammonia In water
With ammonia In water

benzoic acid (65-85-0) + pseudotropine (135-97-7) → tropacocain (537-26-8)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃;

tropacocain (537-26-8) → C29H33N2O4(1+) + N-Formyl-nor-tropacocaine (89100-81-2) + Nortropacocaine (18470-33-2, 20811-95-4, 123202-90-4)

Conditions	Yield
With sodium perchlorate; water for 7h; Electrochemical reaction; Green chemistry;	A n/a B n/a C 73%

tropacocain (537-26-8) → N-Formyl-nor-tropacocaine (89100-81-2) + Nortropacocaine (18470-33-2, 20811-95-4, 123202-90-4)

Conditions	Yield
With sodium periodate; ruthenium tetroxide In tetrachloromethane; water for 3h;	A 45% B 25%

tropacocain (537-26-8) → tropacocaine-N oxide (35772-45-3)

Conditions	Yield
With dihydrogen peroxide; acetone

tropacocain (537-26-8) → tropidine (529-18-0, 122709-67-5)

Conditions	Yield
at 525℃; flash vacuum thermolysis;

tropacocain (537-26-8) → Nortropacocaine (18470-33-2, 20811-95-4, 123202-90-4)

Conditions	Yield
With potassium permanganate; sulfuric acid; sodium hydrogencarbonate In water at 30℃; for 1h;
Multi-step reaction with 2 steps 1: K2CO3 / toluene / 2.33 h / Heating 2: Zn; acetic acid / 2 h / 20 °C View Scheme

dihydrogen peroxide (7722-84-1) + acetone (67-64-1) + tropacocain (537-26-8) → tropacocaine-N oxide (35772-45-3) + pseudotropine (135-97-7)

hydrogenchloride (7647-01-0) + tropacocain (537-26-8) → benzoic acid (65-85-0) + pseudotropine (135-97-7)

tropacocain (537-26-8) + 2,2,2-Trichloroethyl chloroformate (17341-93-4) → endo-3-benzoyloxy-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid 2,2,2-trichloroethyl ester

Conditions	Yield
With potassium carbonate In toluene for 2.33333h; Heating;
In toluene at 20 - 100℃; for 16h;
In toluene at 20 - 100℃; for 16h;
In toluene at 20 - 100℃; for 16h;

tropacocain (537-26-8) → N-ethyl-3β-benzoyloxynortropane (6814-72-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: K2CO3 / toluene / 2.33 h / Heating 2: Zn; acetic acid / 2 h / 20 °C 3: 20 °C View Scheme

tropacocain (537-26-8) → pseudotropine (135-97-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogen peroxide; acetone 2: concentrated hydrochloric acid 3: sulfur dioxide View Scheme

tropacocain (537-26-8) → tropane-3exo-ol-8-oxide (32663-70-0, 32663-71-1, 35772-43-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen peroxide; acetone 2: concentrated hydrochloric acid View Scheme

tropacocain (537-26-8) → 8-acetyl-nortropan-3-ol (4030-20-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen peroxide; acetone 2: und folgenden Verseifen mit 1n-alkoholischer Kalilauge View Scheme

Upstream product

• 93-97-0 benzoic acid anhydride 
• 135-97-7 pseudotropine 
• 50-00-0 formaldehyd 
• 18470-33-2 Nortropacocaine 
• 35772-45-3 tropacocaine-N oxide 
• 7782-99-2 sulphurous acid 
• 95687-89-1 exo-3-(benzoyloxy)-8-oxa-9-azabicyclo<3.2.2.>-non-6-ene hydrochloride 
• 95687-94-8 all-cis-5-amino-3-(benzoyloxy)cycloheptanol hydrochloride 
• 95687-97-1 3β-(benzoyloxy)-1β(<(benzyloxy)carbonyl>amino)-5α-chlorocycloheptane 
• 95687-98-2 all-cis-3-(benzoyloxy)-5-(<(benzyloxy)carbonyl>amino)-cycloheptanol 
• 95687-87-9 N-<(benzyloxy)carbonyl>nortropacocaine 
• 59171-91-4 cyclohepta-3,5-dien-1-yl benzoate 
• 98-88-4 benzoyl chloride 
• 65-85-0 benzoic acid 

Downstream Products

• 18470-33-2 Nortropacocaine 
• 89100-81-2 N-Formyl-nor-tropacocaine 
• 17366-47-1 3α-benzoyloxy-8-azabicyclo[3.2.1]octane hydrochloride 
• 4030-20-0 N-Acetyl-nortropin 
• 32663-70-0 tropane-3exo-ol-8-oxide 
• 135-97-7 pseudotropine 
• 6814-72-8 N-ethyl-3β-benzoyloxynortropane 
• 65-85-0 benzoic acid 
• 35772-45-3 tropacocaine-N oxide 

Relevant articles and documents

Bioactivity-guided synthesis of tropine derivatives as new agonists for melatonin receptors

Twenty-three tropine derivatives as new melatonin receptor (MT1 and MT2) agonists were synthesized and evaluated on HEK293 cells in vitro. Derivatives 1f, 1i, 1j, 1m-1s and 1t exhibited increased agonisting activities on MT1 and MT2 receptors compared to the substrate tropine. Particularly, compound 1r showed significant agonistic activities on MT1 and MT2 receptors with EC50 values of 0.20 and 0.24 mM, respectively. The preliminary structure-activity relationships (SARs) of tropine derivatives were summarized for further investigation on melatonin receptor agonists.

NOVEL BENZOOXAZOL- AND BENZOOXATHIOL-2-ONE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS

This invention relates to novel benzooxazol- and benzooxathiol-2-one derivatives useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.

8-AZA-BICYCLO[3.2.1]OCTANE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS

This invention relates to novel 8-aza-bicyclo[3.2.1]octane derivatives useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.