643-20-9

Basic information

• Product Name: Hexahydro-1H-pyrrolizine
• Synonyms: 1-Azabicyclo[3.3.0]octane;Hexahydro-1H-pyrrolizine;Hexahydropyrrolizine;Pyrrolizidine;2,3,5,6,7,8-hexahydro-1H-pyrrolizine
• CAS NO: 643-20-9
• Molecular Formula: C₇H₁₃N
• Molecular Weight: 111.18
• Mol File: 643-20-9.mol
• Article Data: 12

Chemical Properties

• Boiling Point: 198.35°C (rough estimate)
• Flash Point: 34.2°C
• Appearance: /
• Density: 0.8928 (rough estimate)
• Vapor Pressure: 4.78mmHg at 25°C
• Refractive Index: 1.4731 (estimate)
• CAS DataBase Reference: Hexahydro-1H-pyrrolizine(CAS DataBase Reference)
• NIST Chemistry Reference: Hexahydro-1H-pyrrolizine(643-20-9)
• EPA Substance Registry System: Hexahydro-1H-pyrrolizine(643-20-9)

Safety Data

• Hazardous Substances Data: 643-20-9(Hazardous Substances Data)

Usage

Definition

ChEBI: A bicyclic organonitrogen heterocyclic compound comprised of two ortho-fused pyrrolidine rings which share a common nitrogen atom.

World Health Organization (WHO)

Plants containing pyrrolizidine alkaloids have traditionally been made into teas in the Caribbean and South-East Asia and several of these active substances have been incorporated into medicines for use in treatment for a variety of illnesses. The decision to prohibit use of these products was based on their association with a variety of adverse effects and on their hepatotoxic and carcinogenic potential as seen in both laboratory animals and in communities that commonly use plants containing these compounds to prepare teas and other beverages.

Synthesis Reference(s)

Canadian Journal of Chemistry, 50, p. 1167, 1972 DOI: 10.1139/v72-184Journal of the American Chemical Society, 82, p. 1466, 1960 DOI: 10.1021/ja01491a047

InChI:InChI=1/C7H13N/c1-3-7-4-2-6-8(7)5-1/h7H,1-6H2

Synthetic route

1-Benzyloxycarbonyl-5-oxoperhydroazocine (80662-83-5) → pyrrolizidine (643-20-9)

Conditions	Yield
With perchloric acid; hydrogen; palladium on activated charcoal In methanol under 760.2 Torr; for 6h; Ambient temperature;	95%

1,2,5,6,7,8-hexahydro-3H-pyrrolizin-3-one (32548-24-6) → pyrrolizidine (643-20-9)

Conditions	Yield
With dimethylsulfide borane complex In tetrahydrofuran at 20℃; for 16h;	77%
With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether Cooling with ice; Reflux;

2-(3-Oxo-propyl)-pyrrolidine-1-carboxylic acid benzyl ester (209409-40-5) → pyrrolizidine (643-20-9)

Conditions	Yield
With ammonium formate; palladium on activated charcoal In methanol for 0.5h; Heating;	55%

heptamethyleneimine (1121-92-2) → pyrrolizidine (643-20-9)

Conditions	Yield
With lithium bromide In water; acetonitrile for 2.5h; bicyclization by electrochemical oxidation; other cyclic amines;	52%
With lithium bromide In water; acetonitrile for 2.5h; electrochemical oxidation, C anode, 100 mA;	52%

tetrahydro-pyrrolizin-3,5-dione (18356-28-0) → pyrrolizidine (643-20-9)

Conditions	Yield
With lithium aluminium tetrahydride; diethyl ether

1,4,7-tribromo-heptane (3981-10-0) → pyrrolizidine (643-20-9)

Conditions	Yield
With methanol; ammonia at 140℃;

4-hydroxyimino-heptanedioic acid diethyl ester (34999-74-1) → pyrrolizidine (643-20-9)

Conditions	Yield
With 1,4-dioxane; copper oxide-chromium oxide at 265℃; under 257428 Torr; Hydrogenation;

dimethyl 4-nitro-1,7-heptanedioate (7766-83-8) → pyrrolizidine (643-20-9)

Conditions	Yield
With methanol; platinum Hydrogenation.Hydrierung des Reaktionsprodukts an Kupferoxid-Chromoxid bei 250grad/340-400at;

pyrrol-2-ylmethyl-malonic acid diethyl ester (100371-16-2) → pyrrolizidine (643-20-9)

Conditions	Yield
With 1,4-dioxane; copper oxide-chromium oxide at 260℃; under 176522 Torr; Hydrogenation;

1-iodo-3-chloro-propane (6940-76-7) + pyrrolidine tert-butylformamidine (85152-51-8) → pyrrolizidine (643-20-9)

Conditions	Yield
Yield given. Multistep reaction;

1-aza-1--4-cyclooctene (129885-44-5) → pyrrolizidine (643-20-9) + (Z)-5-azacyclooctene (57502-48-4) + 1-(2-pyridylthio)pyrrolizidine (129885-57-0)

Conditions	Yield
With malonic acid; 2-methylpropan-2-thiol In acetonitrile at 25℃; Irradiation;	A 28 % Chromat. B 45 % Chromat. C 24 % Chromat.

8-chloro-8-azabicyclo<3.2.1>octane (74327-95-0) → pyrrolizidine (643-20-9)

Conditions	Yield
With sodium tetrahydroborate; silver tetrafluoroborate 1.) Benzene, room temp, 4h; Yield given. Multistep reaction;

4-Azido-7-chloro-hept-1-ene → pyrrolizidine (643-20-9)

Conditions	Yield
Yield given. Multistep reaction;

2-<3-bromo-propyl>-pyrrolidine → pyrrolizidine (643-20-9)

Conditions	Yield
With sodium hydroxide

4,7-dibromo-heptylamine → pyrrolizidine (643-20-9)

Conditions	Yield
With sodium hydroxide

4-amino-1,7-dibromo-heptane hydrobromide → pyrrolizidine (643-20-9)

Conditions	Yield
With sodium hydroxide

1,4-dioxane (123-91-1) + 3-(5-oxo-4,5-dihydro-pyrrol-2-yl)-propionic acid amide (98334-70-4) + copper oxide-chromium oxide → pyrrolizidine (643-20-9)

Conditions	Yield
at 250℃; under 95616 Torr; Hydrogenation;

methanol (67-56-1) + methyl β-(5-oxo-2-pyrrolidyl)propionate (81980-11-2) + copper oxide-chromium oxide → pyrrolizidine (643-20-9)

Conditions	Yield
at 250℃; under 250073 - 301558 Torr; Irradiation;

1,4-dioxane (123-91-1) + 4-hydroxyimino-heptanedioic acid diethyl ester (34999-74-1) + copper oxide-chromium oxide → pyrrolizidine (643-20-9)

Conditions	Yield
at 265℃; under 257428 Torr; Hydrogenation;

1-azoniabicyclo[3.3.0]oct-1(5)-ene perchlorate → pyrrolizidine (643-20-9)

Conditions	Yield
With lithium aluminium tetrahydride In diethyl ether	0.09 g

(+/-)-3-(2-pyrrolidinyl)-1-propanol (7699-50-5) → pyrrolizidine (643-20-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 65 percent / NaHCO3 / H2O / 1.5 h / Ambient temperature 2: 86 percent / PCC / CH2Cl2 / 3 h / Ambient temperature 3: 55 percent / ammonium formate / Pd/C / methanol / 0.5 h / Heating View Scheme

3-Pyrrolidin-(2Z)-ylidene-dihydro-furan-2-one → pyrrolizidine (643-20-9)

Conditions	Yield
Multi-step reaction with 5 steps 1: 90 percent / 3N aq. HCl / 12 h / 60 °C 2: 90 percent / NaBH4 / ethanol / 48 h 3: 65 percent / NaHCO3 / H2O / 1.5 h / Ambient temperature 4: 86 percent / PCC / CH2Cl2 / 3 h / Ambient temperature 5: 55 percent / ammonium formate / Pd/C / methanol / 0.5 h / Heating View Scheme

3-(3,4-dihydro-2H-pyrrol-5-yl)propan-1-ol (209409-18-7) → pyrrolizidine (643-20-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 90 percent / NaBH4 / ethanol / 48 h 2: 65 percent / NaHCO3 / H2O / 1.5 h / Ambient temperature 3: 86 percent / PCC / CH2Cl2 / 3 h / Ambient temperature 4: 55 percent / ammonium formate / Pd/C / methanol / 0.5 h / Heating View Scheme

2-(3-Hydroxy-propyl)-pyrrolidine-1-carboxylic acid benzyl ester (1026417-23-1) → pyrrolizidine (643-20-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 86 percent / PCC / CH2Cl2 / 3 h / Ambient temperature 2: 55 percent / ammonium formate / Pd/C / methanol / 0.5 h / Heating View Scheme

7-Chloro-hept-1-en-4-ol → pyrrolizidine (643-20-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 68 percent / PPh3, HN3, E-N=N-E View Scheme

benzyl diallylcarbamate (25070-76-2) → pyrrolizidine (643-20-9)

Conditions	Yield
Multi-step reaction with 2 steps 2: 95 percent / perchloric acid, hydrogen / 10percent Pd/C / methanol / 6 h / 760.2 Torr / Ambient temperature View Scheme
Multi-step reaction with 2 steps 2: 95 percent / perchloric acid, hydrogen / 10percent Pd/C / methanol / 6 h / 760.2 Torr / Ambient temperature View Scheme
Multi-step reaction with 2 steps 2: 95 percent / perchloric acid, hydrogen / 10percent Pd/C / methanol / 6 h / 760.2 Torr / Ambient temperature View Scheme

2-(N,N-dimethylaminomethyl)pyrrole (14745-84-7) → pyrrolizidine (643-20-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: ethanol / anschliessendes Erwaermen mit der Natrium-Verbindung des Malonsaeure-diaethylesters in Aethanol 2: copper oxide-chromium oxide; dioxane / 260 °C / 176522 Torr / Hydrogenation View Scheme

3-(5-oxo-pyrrolidin-2-yl)-propionic acid (7766-86-1) → pyrrolizidine (643-20-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid anhydride / Erhitzen auf Siedetemperatur 2: lithium alanate; diethyl ether View Scheme

3H-pyrrolizine (251-60-5) → pyrrolizidine (643-20-9) + 2-n-propylpyrrole (1551-08-2) + 1,2-dihydro-3H-pyrrolo<1,2-a>pyrrole (13618-87-6)

Conditions	Yield
With 5% Pd(II)/C(eggshell); hydrogen In ethanol at 20℃; under 2844.39 Torr; for 8h;	A n/a B 7 mg C 16 mg

pyrrolizidine (643-20-9) + (5-bromopentyl)triethylammonium bromide (104304-09-8) → C18H38N2(2+)*2Br(1-)

Conditions	Yield
In propan-1-ol Heating;	56%

pyrrolizidine (643-20-9) + 2-Bromoethyl cyclopentylphenylacetate (73330-89-9) → 1-(2-Hydroxyethyl)pyrrolizidinium bromide α-phenylcyclopentaneacetate (73330-90-2)

Conditions	Yield
In diethyl ether	40%

pyrrolizidine (643-20-9) + methyl iodide (74-88-4) → cis-4-methyl-hexahydro-pyrrolizinium; iodide (22529-67-5)

Conditions	Yield
With diethyl ether

Upstream product

• 18356-28-0 tetrahydro-pyrrolizin-3,5-dione 
• 123-91-1 1,4-dioxane 
• 34999-74-1 4-hydroxyimino-heptanedioic acid diethyl ester 
• 209409-18-7 3-(3,4-dihydro-2H-pyrrol-5-yl)propan-1-ol 
• 7766-86-1 3-(5-oxo-pyrrolidin-2-yl)-propionic acid 
• 251-60-5 3H-pyrrolizine 
• 126424-79-1 (R)-(+)-3,4-dihydropyrrolam A 
• 87184-80-3 5-tert-butyldimethylsilyloxypentanal 
• 32548-24-6 1,2,5,6,7,8-hexahydro-3H-pyrrolizin-3-one 
• 14745-84-7 2-(N,N-dimethylaminomethyl)pyrrole 
• 25070-76-2 benzyl diallylcarbamate 
• 1026417-23-1 2-(3-Hydroxy-propyl)-pyrrolidine-1-carboxylic acid benzyl ester 
• 7699-50-5 (+/-)-3-(2-pyrrolidinyl)-1-propanol 
• 67-56-1 methanol 

Downstream Products

• 14129-07-8 pyrrolizidinium picrate 
• 73330-90-2 1-(2-Hydroxyethyl)pyrrolizidinium bromide α-phenylcyclopentaneacetate 

Relevant articles and documents

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Synthesis of indolizidine, pyrrolizidine and quinolizidine ring systems by proline-catalyzed sequential α-amination and HWE olefination of an aldehyde

A general procedure for the synthesis of azabicyclic ring systems viz. indolizidine, pyrrolizidine and quinolizidine has been developed utilizing proline-catalyzed sequential α-amination and Horner-Wadsworth-Emmons (HWE) olefination of an aldehyde as the key step. This method can be further extended to the synthesis of various biologically active natural products containing azabicyclic ring systems.

Hydrogenation of pyrrolizin-3-ones; New routes to pyrrolizidines

Pyrrolizin-3-ones (e.g.1) can be easily hydrogenated to their hexahydro (pyrrolizidin-3-one) derivatives in the presence of heterogeneous catalysts. Good diastereoselectivity (up to >97:3, depending on catalysts and solvent) can be achieved if the pyrroli

Stereochemistry of β-deuterium isotope effects on amine basicity

Secondary β-deuterium isotope effects on amine basicities are measured using a remarkably precise NMR titration method. Deuteration is found to increase the basicity of methylamine, dimethylamine, benzylamine, N,N-dimethylaniline, 2-methyl-2-azanorbornane, and pyrrolizidine. The increase in dimethylamine arises entirely from enthalpy, contrary to a previous report. The method permits a determination of intramolecular isotope effects in 1-benzyl-4-methylpiperidine and 2-benzyl-2-azanorbornane. It is found that deuteration has a larger isotope effect when either antiperiplanar or synperiplanar to a lone pair, but the synperiplanar effect is smaller, as confirmed by computations. The isotope effect is attributed to a lowered zero-point energy of a C-H bond adjacent to an amine nitrogen, arising from delocalization of either a syn or an anti lone pair, and with no detectable angle-independent inductive effect.