31252-42-3

Basic information

• Product Name: 4-BENZYLPIPERIDINE
• Synonyms: 4-(phenylmethyl)-piperidin;4-benzyl-piperidin;Piperidine, 4-(phenylmethyl)-;Piperidine, 4-benzyl-;4-BENZYLPIPERIDINE;4-(PHENYLMETHYL)PIPERIDINE;ALPHA-(4-PIPERIDYL)TOLUENE;AKOS BBS-00003617
• CAS NO: 31252-42-3
• Molecular Formula: C₁₂H₁₇N
• Molecular Weight: 175.27
• EINECS: 250-535-0
• Product Categories: Piperidine;Piperidine Series;B;Bioactive Small Molecules;Building Blocks;C12;Cell Biology;Chemical Synthesis;Heterocyclic Building Blocks;Piperidines
• Mol File: 31252-42-3.mol
• Article Data: 15

Chemical Properties

• Melting Point: 6-7 °C(lit.)
• Boiling Point: 279 °C(lit.)
• Flash Point: >230 °F
• Appearance: Clear colorless to yellow/Viscous Liquid
• Density: 0.997 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.00397mmHg at 25°C
• Refractive Index: n20/D 1.537(lit.)
• Storage Temp.: Store below +30°C.
• PKA: 10.58±0.10(Predicted)
• BRN: 132339
• CAS DataBase Reference: 4-BENZYLPIPERIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-BENZYLPIPERIDINE(31252-42-3)
• EPA Substance Registry System: 4-BENZYLPIPERIDINE(31252-42-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: TM4728000
• TSCA: Yes
• HazardClass: IRRITANT
• Hazardous Substances Data: 31252-42-3(Hazardous Substances Data)

Usage

Chemical Properties

clear colourless to yellow viscous liquid.

Uses

4-Benzylpiperidine was studied as acid corrosion inhibitor for iron. It was also used to study potential utility of dopamine-welective releaser as a treatment for cocaine dependence. In an assay of cocaine discrimination, 4-Benzylpiperidine had the most rapid onset and shortest duration of action.

Preparation

4-Benzylpiperidine can be prepared by reacting 4-cyanopyridine with toluene. Catalytic hydrogenation of the pyridine ring then completes the synthesis.

Application

Reactant for synthesis of:AntiproliferativesGABA uptake inhibitorsPyridinesHistamine H3 antagonistsMultipotent drugs with cholinergic and neuroprotective properties for the treatment of Alzheimer′s and neuronal vascular diseasesAntiserotoninergic, antiplatelet, hemorheologic, antiarrythmic and antioxidant molecules via nucleophilic substitution

Synthesis Reference(s)

Synthesis, p. 741, 1980 DOI: 10.1055/s-1980-29196

General Description

4-Benzylpiperidine is dopamine-selective releaser. It is a potential candidate for treatments for cocaine dependence.

Biochem/physiol Actions

4-Benzylpiperidine inhibits the activity of rat brain monoamine oxidase-A and -B, with IC50 values of 0.02 mM and 2 mM respectively. It acts as a monoamine releasing agent with 20- to 48-fold selectivity for releasing dopamine versus serotonin. It is most efficacious as a releaser of norepinephrine, with an ec50 of 109/41.4/5246nM for DA/NE/5HT, respectively . It has a fast onset of action and a short duration. It also functions as a monoamine oxidase inhibitor (MAOI) with preference for MAO-A.

InChI:InChI=1/C12H17N/c1-2-4-11(5-3-1)10-12-6-8-13-9-7-12/h1-5,12-13H,6-10H2/p+1

Synthetic route

4-benzyl-1-[(4-methylphenyl)sulfonyl]piperidine (205641-99-2) → 4-benzylpyperidine (31252-42-3)

Conditions	Yield
Stage #1: 4-benzyl-1-[(4-methylphenyl)sulfonyl]piperidine With Na/K absorbed into silica gel In tetrahydrofuran at 20℃; Inert atmosphere; Stage #2: With water In tetrahydrofuran	96%
	92%
With dimethyl(phenyl)silyl lithium In tetrahydrofuran at 0℃;	78%

piperidine (110-89-4) + benzaldehyde (100-52-7) → 4-benzylpyperidine (31252-42-3)

Conditions	Yield
With sodium tetrahydroborate; cetyltrimethylammonim bromide at 20℃; for 14h;	96%

4-benzyl-N-tritylpiperidine (544478-05-9) → 4-benzylpyperidine (31252-42-3)

Conditions	Yield
Stage #1: 4-benzyl-N-tritylpiperidine With naphthalene; lithium In tetrahydrofuran at 0℃; for 1h; Stage #2: With water In tetrahydrofuran at 0 - 20℃;	91%

1-nitroso-4-(phenylmethyl)piperidine (15104-07-1) → 4-benzylpyperidine (31252-42-3)

Conditions	Yield
With sodium tetrahydroborate; titanium tetrachloride In 1,2-dimethoxyethane for 14h; Ambient temperature;	90%
With sodium tetrahydroborate; nickel dichloride In tetrahydrofuran for 6h; Ambient temperature;	90%

4-benzyl-N-(triphenylsilyl)piperidine → 4-benzylpyperidine (31252-42-3)

Conditions	Yield
With naphthalene; lithium In tetrahydrofuran; methanol at 20℃; for 5h;	89%

4-benzyl-1-(methanesulfonyl)piperidine (132251-82-2) → 4-benzylpyperidine (31252-42-3)

Conditions	Yield
Stage #1: 4-benzyl-1-(methanesulfonyl)piperidine With Na/K absorbed into silica gel In tetrahydrofuran at 20℃; Inert atmosphere; Stage #2: With water In tetrahydrofuran	89%
Product distribution / selectivity;	83%

4-benzyl pyridine (2116-65-6) → 4-Cyclohexylmethyl-piperidine (78197-28-1) + 4-benzylpyperidine (31252-42-3)

Conditions	Yield
With hydrogenchloride; platinum Hydrogenation;

4-benzyl pyridine (2116-65-6) → 4-benzylpyperidine (31252-42-3)

Conditions	Yield
With ethanol; sodium
With acetic acid; platinum Hydrogenation;
With nickel at 100℃; under 110326 - 220652 Torr; Hydrogenation;
With platinum(IV) oxide; hydrogen In acetic acid at 20℃; under 2585.81 Torr; for 12h;
Stage #1: 4-benzyl pyridine With hydrogen; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In octane at 120℃; under 15001.5 Torr; for 40h; Stage #2: With water Catalytic behavior; chemoselective reaction;	> 99 %Chromat.

4-benzyl pyridine (2116-65-6) + ethanol (64-17-5) + sodium → 4-benzylpyperidine (31252-42-3) + 4-benzyl-piperideine

1-(4-benzylpiperidin-1-yl)-2,2-dimethylpropan-1-one → 4-benzylpyperidine (31252-42-3)

Conditions	Yield
With naphthalene; lithium In tetrahydrofuran at 0℃; for 1h;	95 % Chromat.

4-bromopyridin (1120-87-2) → 4-benzylpyperidine (31252-42-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1,3-bis[(diphenylphosphino)propane]dichloronickel(II) / tetrahydrofuran / 15 h / 20 °C 2: platinum(IV) oxide; hydrogen / acetic acid / 12 h / 20 °C / 2585.81 Torr View Scheme

3-((4-benzylpiperidin-1-yl)methyl)-N,N-diethylaniline → 4-benzylpyperidine (31252-42-3)

Conditions	Yield
With acetic acid In water-d2 for 0.25h; Solvent; Irradiation;	96 %Spectr.

4-benzylpyperidine (31252-42-3) + trifluoroacetic acid (76-05-1) + Wang resin-linked N1-tert-butyloxycarbonyl-N2-triflylguanidine → 4-benzyl-piperidine-1-carboxamidine; compound with trifluoro-acetic acid

Conditions	Yield
Stage #1: 4-benzylpyperidine; Wang resin-linked N1-tert-butyloxycarbonyl-N2-triflylguanidine In dichloromethane at 20℃; Stage #2: trifluoroacetic acid In dichloromethane Further stages.;	100%

4-benzylpyperidine (31252-42-3) + epichlorohydrin (106-89-8) → 1-chloro-3-(4-benzylpiperidin-1-yl)propan-2-ol (438634-79-8)

Conditions	Yield
	100%
In ethanol for 3h;

4-benzylpyperidine (31252-42-3) + trifluoroacetic anhydride (407-25-0) → 1-(trifluoroacetyl)-4-benzylpiperidine (157338-47-1)

Conditions	Yield
In dichloromethane at 20℃;	100%
In ethyl acetate at 20℃; for 3h;	97%
In dichloromethane	88%
In dichloromethane at 20℃; for 1.5h;
In dichloromethane for 0.5h;

4-benzylpyperidine (31252-42-3) + acetic anhydride (108-24-7) → 1-(4-benzylpiperidin-1-yl)ethan-1-one (101997-42-6)

Conditions	Yield
at 20℃; for 1h;	100%

2-bromo-N-(1,3-dibromo-6-oxo-5,6-dihydro-4H-cyclopenta[c]thien-4-yl)acetamide (872408-08-7) + 4-benzylpyperidine (31252-42-3) → 2-(4-benzyl-piperidin-1-yl)-N-(1,3-dibromo-6-oxo-5,6-dihydro-4H-cyclopenta[c]thiophen-4-yl)-acetamide

Conditions	Yield
With potassium carbonate at 20℃; for 12h;	100%

4-benzylpyperidine (31252-42-3) + 2-chloro-6-fluorobenzaldehyde (387-45-1) → 2-chloro-6-(4-benzylpiperidine)benzaldehyde (793706-92-0)

Conditions	Yield
With potassium carbonate In DMF (N,N-dimethyl-formamide) at 130℃; for 3.5h;	100%

4-benzylpyperidine (31252-42-3) + Benzyl bromoacetate (5437-45-6) → (4-benzylpiperidin-1-yl)acetic acid benzyl ester (438634-63-0)

Conditions	Yield
With triethylamine In dichloromethane; ethyl acetate	100%

formaldehyd (50-00-0) + 4-benzylpyperidine (31252-42-3) + (4-nitrophenyl)ethanone (100-19-6) → C34H41N3O3 (1037020-24-8)

Conditions	Yield
With hydrogenchloride In ethanol Mannich reaction; Heating;	100%

formaldehyd (50-00-0) + 4-benzylpyperidine (31252-42-3) + 1-(4-methoxyphenyl)ethanone (100-06-1) → C35H44N2O2 (1037020-22-6)

Conditions	Yield
With hydrogenchloride In ethanol Mannich reaction; Heating;	100%

4-benzylpyperidine (31252-42-3) + S-(3-phenylpropyl) 4-(p-tolyl)benzenecarbothioate (1178916-74-9) → (4-benzyl-1-piperidyl)-[4-(p-tolyl)phenyl]methanone (1178916-75-0)

Conditions	Yield
With potassium phosphate; silver trifluoromethanesulfonate In acetonitrile at 70℃; for 16h;	100%

4-benzylpyperidine (31252-42-3) + benzaldehyde (100-52-7) → N-benzyl-4-benzylpiperidine

Conditions	Yield
With sodium tris(acetoxy)borohydride In 2-methyltetrahydrofuran at 18℃; for 1h; Solvent; Reagent/catalyst; Green chemistry;	100%

3-phenyl-propionaldehyde (104-53-0) + 4-benzylpyperidine (31252-42-3) → 4-benzyl-1-(3-phenylpropyl)piperidine

Conditions	Yield
With sodium tris(acetoxy)borohydride In 2-methyltetrahydrofuran at 18℃; for 1h; Solvent; Reagent/catalyst; Green chemistry;	100%

4-benzylpyperidine (31252-42-3) + (E)-4-(4-isopropylphenyl)-4-oxo-2-butenoic acid phenylamide (1220094-90-5) → 2-(4-benzylpiperidinyl)-4-(4-isopropylphenyl)-4-oxo-N-phenylbutanamide

Conditions	Yield
In dichloromethane; toluene Michael Addition;	100%

4-benzylpyperidine (31252-42-3) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → 3-(4-benzylpiperidin-1-yl)-4-chloro-1,2,5-thiadiazole

Conditions	Yield
at 110 - 120℃;	100%

4-benzylpyperidine (31252-42-3) + p-Toluic acid (99-94-5) → (4-benzylpiperidin-1-yl)(p-tolyl)methanone

Conditions	Yield
Stage #1: p-Toluic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate at 20℃; for 0.166667h; Stage #2: 4-benzylpyperidine at 20℃; for 1h;	100%

4-benzylpyperidine (31252-42-3) + Ethyl oxalyl chloride (4755-77-5) → (4-benzylpiperidin-1-yl)-oxoacetic acid ethyl ester (349119-55-7)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h;	99%
With TEA In chloroform at 10℃; for 2h;
With N-ethyl-N,N-diisopropylamine In dichloromethane	15.5 g (99%)

4-benzylpyperidine (31252-42-3) + toluene-4-sulfonic acid Chroman-3-ylmethyl ester (113771-46-3) → 4-benzyl-1-chroman-3-ylmethyl-piperidine

Conditions	Yield
In toluene for 12h; Heating;	99%

formaldehyd (50-00-0) + 4-benzylpyperidine (31252-42-3) → 4-benzyl-1-methylpiperidine (1557-31-9)

Conditions	Yield
With formic acid at 0 - 20℃; for 16h; Reflux;	98%
With formic acid
With formic acid for 18h; Heating;
With formic acid In water for 24h; Reflux;

4-benzylpyperidine (31252-42-3) + ortho-nitrofluorobenzene (1493-27-2) → 4-benzyl-1-(2-nitro-phenyl)piperidine (455260-04-5)

Conditions	Yield
Stage #1: 4-benzylpyperidine With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 1h; Stage #2: ortho-nitrofluorobenzene In N,N-dimethyl-formamide at 0 - 20℃; Further stages.;	98%

formaldehyd (50-00-0) + 4-benzylpyperidine (31252-42-3) + potassium (benzo[b]thiophene-2-yl)trifluoroborate → 1-benzo[b]thiophen-2-ylmethyl-4-benzyl-piperidine

Conditions	Yield
Stage #1: formaldehyd; 4-benzylpyperidine In toluene at 90℃; Stage #2: potassium (benzo[b]thiophene-2-yl)trifluoroborate With boron trifluoride diethyl etherate In toluene at 90℃; for 5h; Further stages.;	98%

C12H15NO3S2 + 4-benzylpyperidine (31252-42-3) → C24H32N2O3S2 (865432-96-8)

Conditions	Yield
In dichloromethane	98%

4-benzylpyperidine (31252-42-3) + C16H15ClOS (1178916-14-7) → (4-benzylpiperidin-1-yl)(4-chlorophenyl)methanone

Conditions	Yield
With potassium phosphate; silver trifluoromethanesulfonate In acetonitrile at 70℃; for 16h;	98%

4-benzylpyperidine (31252-42-3) + 3-acetyl-2-chloropyridine (55676-21-6) → 1-[2-(4-benzylpiperidin-1-yl)pyridin-3-yl]ethanone (1260147-79-2)

Conditions	Yield
In N,N-dimethyl-formamide at 200℃; under 12929 Torr; for 0.25h; Microwave irradiation;	98%

4-benzylpyperidine (31252-42-3) + N-(2-methoxybenzyl)-6-(4-phenylpiperidin-1-yl)-N-(pyridin-2-ylmethyl)hexan-1-amine (1258447-85-6) → 6-(4-benzylpiperidin-1-yl)-N-(2-methoxybenzyl)-N-(pyridin-2-ylmethyl)hexan-1-amine (1258447-87-8)

Conditions	Yield
	98%

4-benzylpyperidine (31252-42-3) + 4-fluorophenyl N-[5-[(tert-butyldimethylsilyl)oxy]pyridin-2-yl]carbamate → 4-benzyl-N-[5-[(tert-butyldimethylsilyl)oxy]pyridin-2-yl]piperidine-1-carboxamide

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 2h;	98%

4-benzylpyperidine (31252-42-3) + di-tert-butyl dicarbonate (24424-99-5) → 1-t-butyloxycarbonyl-4-benzylpiperidine (251107-37-6)

Conditions	Yield
With citric acid In tetrahydrofuran; ethyl acetate	97.9%
With citric acid In tetrahydrofuran; ethyl acetate	97.9%
In tetrahydrofuran for 20h; Heating / reflux;	91%

formaldehyd (50-00-0) + 4-benzylpyperidine (31252-42-3) + 11-methylene-6,11-dihydrodibenzoxepin-2-acetic acid methyl ester (113836-34-3) → {11-[2-(4-Benzyl-piperidin-1-yl)-eth-(E)-ylidene]-6,11-dihydro-dibenzo[b,e]oxepin-2-yl}-acetic acid methyl ester

Conditions	Yield
With acetic acid; trifluoroacetic acid In dichloromethane	97%

4-benzylpyperidine (31252-42-3) + methyl thioisocyanate (556-61-6) → 4-benzyl-piperidine-1-carbothioic acid methylamide

Conditions	Yield
In dichloromethane at 20℃; for 0.333333h; Addition;	97%

4-benzylpyperidine (31252-42-3) + (4-chloro-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-dimethyl-amine (461670-34-8) → 4-(4-benzyl-1-piperidinyl)-6-dimethylamino-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine

Conditions	Yield
In tetrahydrofuran Heating;	97%

4-benzylpyperidine (31252-42-3) + (S)-2-((tert-butoxycarbonyl)(methyl)amino)-3-(4-hydroxyphenyl)propanoic acid (82038-34-4) → 1-[(S)-N-tert-butyloxycarbonyl-N-methyltyrosyl]-4-benzylpiperidine (516473-08-8)

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 20℃; for 24h;	97%

Upstream product

• 2116-65-6 4-benzyl pyridine 
• 64-17-5 ethanol 
• 1120-87-2 4-bromopyridin 
• 132251-82-2 4-benzyl-1-(methanesulfonyl)piperidine 
• 110-89-4 piperidine 
• 100-52-7 benzaldehyde 
• 544478-05-9 4-benzyl-N-tritylpiperidine 
• 205641-99-2 4-benzyl-1-[(4-methylphenyl)sulfonyl]piperidine 
• 15104-07-1 1-nitroso-4-(phenylmethyl)piperidine 

Downstream Products

• 1557-31-9 N-methyl-4-benzylpiperidine 
• 3565-03-5 [2-(4-benzyl-piperidin-1-yl)-ethyl]-dimethyl-amine 
• 74071-10-6 2,6-bis-(4-benzylpiperidino-acetylamino)-benzo[1,2-d:5,4-d']bisthiazole 
• 129190-27-8 2,6-bis(4'-benzylpiperidin-1'-ylmethyl)-4-nitrophenol 
• 134896-47-2 4-acetamido-2-(4'-benzylpiperidin-1'-ylmethyl)-5,6,7,8-tetrahydronaphthalen-1-ol 
• 144220-90-6 3-(4-Benzyl-piperidin-1-ylmethyl)-6-(3-fluoro-benzoyl)-3H-benzooxazol-2-one 
• 144220-79-1 3-(4-Benzyl-piperidin-1-ylmethyl)-6-(2-fluoro-benzoyl)-3H-benzooxazol-2-one 
• 79512-31-5 1,3-Diacetyl-2-hydroxy-6-methyl-4-(4-benzylpiperidino)-benzol 
• 35133-39-2 1-(4-(benzyloxy)phenyl)-2-(4-benzylpiperidin-1-yl)propan-1-one 
• 103892-76-8 [(S)-6-(4-Benzyl-piperidin-1-yl)-5-tert-butoxycarbonylamino-6-oxo-hexyl]-carbamic acid benzyl ester 
• 100222-11-5 3-(4-Benzyl-piperidin-1-yl)-N-phenyl-propionamide 
• 100222-09-1 3-(4-Benzyl-piperidin-1-yl)-N-(2-chloro-phenyl)-propionamide 
• 140135-28-0 C₂₆H₃₄N₆O₅ 
• 100222-10-4 3-(4-Benzyl-piperidin-1-yl)-N-(2-fluoro-phenyl)-propionamide 

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