86-21-5

Basic information

• Product Name: Pheniramine
• Synonyms: n,n-dimethyl-3-phenyl-3-(2-pyridyl)propylamine;PHENIRAMINE;2-(alpha-(2-(dimethylamino)ethyl)benzyl)-pyridin;2-(alpha-(2-dimethylaminoethyl)benzyl)pyridine;2-[alpha-[2-(Dimethylamino)ethyl]benzyl]pyridine;2-Pyridinepropanamine, N,N-dimethyl-gamma-phenyl-;3-Phenyl-3-(2-pyridyl)-N,N-dimethylpropylamine;3-phenyl-3-(2-pyridyl)-n,n-dimethylpropylanine
• CAS NO: 86-21-5
• Molecular Formula: C₁₆H₂₀N₂
• Molecular Weight: 240.34
• EINECS: 201-656-2
• Mol File: 86-21-5.mol
• Article Data: 9

Chemical Properties

• Melting Point: <25 °C
• Boiling Point: bp13 181°; bp2 142°; bp0.5 135°
• Flash Point: 9℃
• Appearance: /
• Density: 1.0081
• Vapor Pressure: 5.07E-05mmHg at 25°C
• Refractive Index: nD25 1.5519 to 1.5521
• Storage Temp.: ?20°C
• PKA: pKa 4.03± 0.08;9.32± 0.06(H2O,t undefined,I=0.30(NaCl)) (Uncertain)
• CAS DataBase Reference: Pheniramine(CAS DataBase Reference)
• NIST Chemistry Reference: Pheniramine(86-21-5)
• EPA Substance Registry System: Pheniramine(86-21-5)

Safety Data

• Hazard Codes: F,T
• Statements: 11-23/24/25-39/23/24/25
• Safety Statements: 16-36/37-45
• RIDADR: UN1230 - class 3 - PG 2 - Methanol, solution
• WGK Germany: 1
• Hazardous Substances Data: 86-21-5(Hazardous Substances Data)

Usage

Therapeutic Function

Antihistaminic

Safety Profile

Poison by intravenous route. Human systemic effects by ingestion: central nervous system effects. When heated to decomposition it emits toxic fumes of NOx.

Enzyme inhibitor

This antihistamine (FWfree-base = 240.35 g/mol; CAS 86-21-5; insoluble in water; maleate and p-aminosalicylate salts are water-soluble), also known as N,N-dimethyl-g-phenyl-2-pyridinepropanamide, is more frequently abused than other antihistamines relative to its market share. One of the histamine H1 antagonists with little sedative action, pheniramine is often used in treatment of hay fever, rhinitis, allergic dermatoses, and pruritus. Target(s): H1 histamine receptor; and histamine Nmethyltransferase, mildly inhibited.

InChI:InChI=1/C16H20N2/c1-18(2)13-11-15(14-8-4-3-5-9-14)16-10-6-7-12-17-16/h3-10,12,15H,11,13H2,1-2H3

Synthetic route

3-phenyl-3-(2-pyridyl)propanal (100866-24-8) + dimethyl amine (124-40-3) → pheniramine (86-21-5)

Conditions	Yield
With hydrogen; platinum(IV) oxide In toluene at 120℃; under 38000 Torr; for 12h; catalytic reductive amination;	100%

4-dimethylamino-2-phenyl-butyronitrile (50599-78-5) + acetylene (74-86-2) → pheniramine (86-21-5)

Conditions	Yield
(η5-cyclopentadienyl)-η4-cycloocta-1,5-dienecobalt(I) In toluene at 140℃; under 10640 Torr; for 36h;	85%

3-phenyl-3-pyridin-2-yl-propan-1-ol (46498-51-5) + dimethyl amine (124-40-3) → pheniramine (86-21-5)

Conditions	Yield
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; bis[2-(diphenylphosphino)phenyl] ether In toluene at 20℃; Inert atmosphere; Reflux;	84%

2-(1-phenylvinyl)pyridine (15260-65-8) + carbon monoxide (201230-82-2) + dimethyl amine (124-40-3) → pheniramine (86-21-5)

Conditions	Yield
With hydrogen; [Rh(1,3-dimesitylimidazole-2-ylidene)(cod)Cl] In toluene at 125℃; for 24h;	80%

N,N-dimethyl-3-phenyl-3-(pyridin-2-ylsulfinyl)propan-1-amine borane → pheniramine (86-21-5)

Conditions	Yield
With methylmagnesium bromide In tetrahydrofuran; diethyl ether at 20℃;	42%

2-(1-phenylvinyl)pyridine (15260-65-8) + C12H12N2O4 → pheniramine (86-21-5)

Conditions	Yield
With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; 0.8C12H6N2O4(2-)*HO(1-)*Al(3+)*0.4CF3O3S(1-)*0.1Ir(3+)*0.2C11H8N(1-)*0.1Cl(1-) In acetonitrile at 20℃; for 6h; Inert atmosphere; Irradiation;	38%

2-bromo-pyridine (109-04-6) + phenylacetonitrile (140-29-4) → pheniramine (86-21-5)

Conditions	Yield
With sodium amide; benzene anschl. mit <2-Chlor-aethyl>-dimethyl-amin und anschl. Erhitzen mit KOH in Butan-1-ol;

2-Benzylpyridine (101-82-6) + 2-(dimethylamino)ethyl chloride (107-99-3) → pheniramine (86-21-5)

Conditions	Yield
With potassium amide
With sodium
With sodium amide
With potassium amide

phenyl-pyridin-2-yl-acetonitrile (5005-36-7) → pheniramine (86-21-5)

Conditions	Yield
With sodium amide; toluene anschl. mit <2-Chlor-aethyl>-dimethyl-amin und anschl. Erwaermen mit H2SO4;

dimethyl-(3-phenyl-3-pyridin-2-yl-allyl)-amine (35344-68-4) → pheniramine (86-21-5)

Conditions	Yield
With palladium on activated charcoal; acetic acid Hydrogenation;
With nickel Hydrogenation;
With palladium on activated charcoal; acetic acid Hydrogenation;

2-(dimethylamino)ethyl chloride (107-99-3) + (2-pyridyl)phenylmethyl methyl ether → pheniramine (86-21-5)

Conditions	Yield
With potassium Sodium 1.) THF, 2.) THF, 0 deg C, 12 h; Yield given. Multistep reaction;

(+-)-3-dimethylamino-1-phenyl-1-<2>pyridyl-propan-1-ol → pheniramine (86-21-5)

Conditions	Yield
With thionyl chloride; benzene anschl. mit Zink-Pulver in Essigsaeure;

(+-)-3-phenyl-3-<2>pyridyl-propionic acid dimethylamide → pheniramine (86-21-5)

Conditions	Yield
With lithium aluminium tetrahydride; diethyl ether

(+-)-4-dimethylamino-2-phenyl-2-<2>pyridyl-butyric acid dimethylamide → pheniramine (86-21-5)

Conditions	Yield
With sulfuric acid; water

(+-)-4-dimethylamino-2-phenyl-2-<2>pyridyl-butyronitrile → pheniramine (86-21-5)

Conditions	Yield
With sulfuric acid; water
With ethylmagnesium bromide; methoxybenzene
With hydrogenchloride; water

formaldehyd (50-00-0) + (+-)-3-phenyl-3-<2>pyridyl-propylamine → pheniramine (86-21-5)

Conditions	Yield
With formic acid; water

dimethyl amine (124-40-3) + (+-)-3-phenyl-3-<2>pyridyl-propionaldehyde → pheniramine (86-21-5)

Conditions	Yield
With nickel at 160℃; under 61047.2 Torr; Hydrogenation;
With ethanol; platinum Hydrogenation;

2-(1-phenylvinyl)pyridine (15260-65-8) → pheniramine (86-21-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 85 percent / Na / 6 h / 20 °C 2: aq. potassium tert-butoxide / diethyl ether / 25 °C 3: 80 percent / tetrabutylammonium periodate / dioxane / 20 h / Heating 4: 100 percent / H2 / PtO2 / toluene / 12 h / 120 °C / 38000 Torr View Scheme

2-Benzylpyridine (101-82-6) → pheniramine (86-21-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: lithium diisopropylamide; HMPT / 2 h / 0 °C 1.2: 80 percent / HMPT / 3 h / -78 - 20 °C 2.1: 100 percent / 5 percent aq. HCl / methanol / 24 h / 20 °C 3.1: 100 percent / H2 / PtO2 / toluene / 12 h / 120 °C / 38000 Torr View Scheme

N,N-dimethyl-4-phenyl-4-(2-pyridyl)-2-hydroxybutanamide (233760-13-9) → pheniramine (86-21-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: aq. potassium tert-butoxide / diethyl ether / 25 °C 2: 80 percent / tetrabutylammonium periodate / dioxane / 20 h / Heating 3: 100 percent / H2 / PtO2 / toluene / 12 h / 120 °C / 38000 Torr View Scheme

3-phenyl-4,4-diethoxybutanenitrile (121504-36-7) → pheniramine (86-21-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 85 percent / (η5-cyclopentadienyl)<(1,5-η)-cyclooctadienyl>cobalt / toluene / 72 h / 120 °C / 9500 Torr 2: 100 percent / 5 percent aq. HCl / methanol / 24 h / 20 °C 3: 100 percent / H2 / PtO2 / toluene / 12 h / 120 °C / 38000 Torr View Scheme

3-[1,3]dioxolan-2-yl-2-phenyl-propionaldehyde oxime → pheniramine (86-21-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: tetrabutylammonium hydrogen sulfate; carbon disulfide; 15 percent aq. NaOH / benzene / 0.5 h / 20 °C 2: 85 percent / (η5-cyclopentadienyl)<(1,5-η)-cyclooctadienyl>cobalt / toluene / 72 h / 120 °C / 9500 Torr 3: 100 percent / 5 percent aq. HCl / methanol / 24 h / 20 °C 4: 100 percent / H2 / PtO2 / toluene / 12 h / 120 °C / 38000 Torr View Scheme

2-(2-[1,3]dioxolan-2-yl-1-phenyl-ethyl)-pyridine (233760-11-7) → pheniramine (86-21-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 100 percent / 5 percent aq. HCl / methanol / 24 h / 20 °C 2: 100 percent / H2 / PtO2 / toluene / 12 h / 120 °C / 38000 Torr View Scheme

2-hydroxy-4-phenyl-4-pyridin-2-yl-butyric acid → pheniramine (86-21-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / tetrabutylammonium periodate / dioxane / 20 h / Heating 2: 100 percent / H2 / PtO2 / toluene / 12 h / 120 °C / 38000 Torr View Scheme

(E)-N,N-dimethyl-3-phenylprop-2-en-1-amine (42817-44-7) → pheniramine (86-21-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: H2 / HRh(CO)(PPh3)3 / benzene / 24 h / 80 °C / 76000 Torr 2: NH2OH 3: 95 percent / CS2, n-Bu4N(1+)*HSO4(1-), 15percent aq. NaOH / CH2Cl2 / 0.5 h / Ambient temperature 4: 85 percent / (η5-cyclopentadienyl)<(1,5-η)-cyclopentadienyl>cobalt / toluene / 36 h / 140 °C / 10640 Torr View Scheme

4-Dimethylamino-2-phenyl-butyraldehyde (158696-48-1) → pheniramine (86-21-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: NH2OH 2: 95 percent / CS2, n-Bu4N(1+)*HSO4(1-), 15percent aq. NaOH / CH2Cl2 / 0.5 h / Ambient temperature 3: 85 percent / (η5-cyclopentadienyl)<(1,5-η)-cyclopentadienyl>cobalt / toluene / 36 h / 140 °C / 10640 Torr View Scheme

4-Dimethylamino-2-phenyl-butyraldehyde oxime (158696-51-6) → pheniramine (86-21-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / CS2, n-Bu4N(1+)*HSO4(1-), 15percent aq. NaOH / CH2Cl2 / 0.5 h / Ambient temperature 2: 85 percent / (η5-cyclopentadienyl)<(1,5-η)-cyclopentadienyl>cobalt / toluene / 36 h / 140 °C / 10640 Torr View Scheme

2-chloropyridine (109-09-1) → pheniramine (86-21-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaNH2; toluene 2: NaNH2; toluene / anschl. mit <2-Chlor-aethyl>-dimethyl-amin und anschl. Erwaermen mit H2SO4 View Scheme

phenylacetonitrile (140-29-4) → pheniramine (86-21-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaNH2; toluene 2: NaNH2; toluene / anschl. mit <2-Chlor-aethyl>-dimethyl-amin und anschl. Erwaermen mit H2SO4 View Scheme

pheniramine (86-21-5) + 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)-dimethyl-(3-phenyl-3-pyridin-2-yl-propyl)-ammonium; chloride (145823-17-2)

Conditions	Yield
With XAD-2 ion-exchange resin; sodium hydrogencarbonate In water; benzene for 144h; Ambient temperature;	13%

2,3-Dichloro-1,4-naphthoquinone (117-80-6) + pheniramine (86-21-5) → 2-chloro-3-(dimethylamino)naphthalene-1,4-dione (5350-26-5) + 2-Chlor-3-[methyl-(3-phenyl-3-pyridin-2-ylpropyl)amino]-1,4-naphthochinon

Conditions	Yield
In dichloromethane for 96h; Heating;	A n/a B 1.3%

Upstream product

• 50599-78-5 4-dimethylamino-2-phenyl-butyronitrile 
• 74-86-2 acetylene 
• 100866-24-8 3-phenyl-3-(2-pyridyl)propanal 
• 124-40-3 dimethyl amine 
• 46498-51-5 3-phenyl-3-pyridin-2-yl-propan-1-ol 
• 101-82-6 2-Benzylpyridine 
• 107-99-3 2-(dimethylamino)ethyl chloride 
• 109-04-6 2-bromo-pyridine 
• 140-29-4 phenylacetonitrile 
• 15260-65-8 2-(1-phenylvinyl)pyridine 
• 4463-42-7 benzyl boronic acid 
• 2862-39-7 2-(dimethylamino)ethyl bromide hydrobromide 
• 67-56-1 methanol 
• 76132-65-5 3-Phenyl-3-(2-pyridyl)propionitrile 

Downstream Products

• 132-20-7 pheniramine maleate 
• 56141-72-1 (R)-pheniramine 
• 23201-92-5 (S)-pheniramine 
• 5350-26-5 2-chloro-3-(dimethylamino)naphthalene-1,4-dione 
• 145823-17-2 ((2R,3R,4S,5S,6S)-6-Carboxy-3,4,5-trihydroxy-tetrahydro-pyran-2-yl)-dimethyl-(3-phenyl-3-pyridin-2-yl-propyl)-ammonium; chloride 

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