30339-30-1

Basic information

• Product Name: (S)-1-PHENYL-2-(P-TOLYL)ETHYLAMINE
• Synonyms: (S)-1-Phenyl-2-(4-methylphenyl)ethanamine;(S)-α-Phenyl-4-methylphenethylamine;(αS)-α-Phenyl-4-methylbenzeneethaneamine;[(S)-1-Phenyl-2-(4-methylphenyl)ethyl]amine;(S)-1-Phenyl-2-(p-toly)ethylamine;(S)-1-PHENYL-2-(P-TO;(S)-2-(4-Methylphenyl)-1-phenylethylamine;(S)-1-Phenyl-2-(p-tolyl)ethylamine
• CAS NO: 30339-30-1
• Molecular Formula: C₁₅H₁₇N
• Molecular Weight: 211.30218
• Product Categories: chiral;Amines (Chiral);Chiral Building Blocks;for Resolution of Acids;Optical Resolution;Synthetic Organic Chemistry
• Mol File: 30339-30-1.mol
• Article Data: 6

Chemical Properties

• Melting Point: 140.5 °C
• Boiling Point: 317.847 °C at 760 mmHg
• Flash Point: 164°C
• Appearance: /
• Density: 1,02 g/cm3
• Refractive Index: 11 ° (C=neat)
• PKA: 8.89±0.10(Predicted)
• CAS DataBase Reference: (S)-1-PHENYL-2-(P-TOLYL)ETHYLAMINE(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-1-PHENYL-2-(P-TOLYL)ETHYLAMINE(30339-30-1)
• EPA Substance Registry System: (S)-1-PHENYL-2-(P-TOLYL)ETHYLAMINE(30339-30-1)

Safety Data

• Statements: 36/37/38
• Safety Statements: 26-36/37/39
• Hazardous Substances Data: 30339-30-1(Hazardous Substances Data)

Synthetic route

(1R,2S)-norephedrine (492-41-1) + 1-Phenyl-2-p-tolyl-ethanone O-benzyl-oxime (113683-85-5, 136534-11-7) → (S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1)

Conditions	Yield
With borane In tetrahydrofuran at 20℃;	82%

(1R,2S)-norephedrine (492-41-1) + 1-Phenyl-2-p-tolyl-ethanone O-octyl-oxime (123982-65-0) → (S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1)

Conditions	Yield
With borane In tetrahydrofuran at 20℃;	64%

(1R,2S)-norephedrine (492-41-1) + phenyl p-tolylmethyl ketone O-methyloxime (111630-13-8) → (S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1)

Conditions	Yield
With borane In tetrahydrofuran at 20℃;	64%

1-phenyl-2-(p-tolyl)ethylamine (30275-30-0) → (S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1) + (R)-1-phenyl-(2-p-tolyl)ethylamine (30339-32-3)

Conditions	Yield
	A 36% B n/a
	A n/a B 16%
Stage #1: 1-phenyl-2-(p-tolyl)ethylamine With (R)-(2,2-Me2-1,3-dioxa-c-pentan-3-yl)methyl monophthalate In water; isopropyl alcohol at 20℃; for 4h; Stage #2: With sulfuric acid In ethyl acetate	A 600 mg B n/a
With chiral stationary phase including isopropyl-functionalized CF6 In methanol; acetic acid; triethylamine; acetonitrile at 20℃; Purification / work up;

(1R,2S)-norephedrine (492-41-1) + C18H23NOSi (123982-67-2) → (S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1)

Conditions	Yield
With borane In tetrahydrofuran at 20℃; Yield given;

(S)-3-(benzo[1,3]dioxol-5-yl)-2-methylpropionate (S)-1-phenyl-2-(p-tolyl)ethylammonium (1254780-66-9) → (S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1)

Conditions	Yield
With sodium hydroxide In water; toluene at 25℃; for 0.5h; pH=12;

S-2-pyridyl 3-cyanoandrosta-3,5-diene-17β-thiocarboxylate (153002-83-6) + (S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1) → N-[(1S)-2-(4-methylphenyl)-1-phenylethyl]-3-cyanoandrosta-3,5-diene-17β-carboxamide

Conditions	Yield
	77%

DL-3-(N-formylamino)-3-phenylpropionic acid (126575-05-1) + (S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1) → C10H11NO3*C15H17N

Conditions	Yield
In methanol	37.9%

ethyl 1-formylcyclopropane-1-carboxylate (33329-70-3) + (S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1) → 1-[(RS)-1-Cyano-[(S)-1-phenyl-2-p-tolylethylamino]methyl]-1-ethoxycarbonylcyclopropane

Conditions	Yield
With hydrogenchloride In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethanol; water	251 mg (67%)

p-toluenesulfonate monohydrate + (S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1) + 1,1-cyclopropanedicarboxaldehyde (136476-41-0) + orthoformic acid triethyl ester (122-51-0) → (2R)-2-[1-(diethoxymethyl)cyclopropyl]-2-{[(1S)-1-phenyl-2-(p-tolyl)ethyl]amino}acetonitrile + (2S)-2-[1-(diethoxymethyl)cyclopropyl]-2-{[(1S)-1-phenyl-2-(p-tolyl)ethyl]amino}acetonitrile

Conditions	Yield
With sodium hydrogencarbonate; sodium hydrogensulfite In ethanol; water; toluene

(S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1) + 1,1-cyclopropanedicarboxaldehyde (136476-41-0) + orthoformic acid triethyl ester (122-51-0) → (2R)-2-[1-(diethoxymethyl)cyclopropyl]-2-{[(1S)-1-phenyl-2-(p-tolyl)ethyl]amino}acetonitrile + (2S)-2-[1-(diethoxymethyl)cyclopropyl]-2-{[(1S)-1-phenyl-2-(p-tolyl)ethyl]amino}acetonitrile

Conditions	Yield
Stage #1: 1,1-cyclopropanedicarboxaldehyde; orthoformic acid triethyl ester With ethanol; toluene-4-sulfonic acid In toluene at 0 - 40℃; for 1h; Stage #2: (S)-2-(4-methylphenyl)-1-phenylethylamine With sodium hydrogencarbonate In water; toluene at 0℃; for 0.5h; Stage #3: With potassium cyanide; sodium hydrogensulfite In water; toluene at 50℃; for 2h;

3-(3,4-methylenedioxyphenyl)-2-methylpropionic acid (77269-66-0) + (S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1) → (S)-3-(benzo[1,3]dioxol-5-yl)-2-methylpropionate (S)-1-phenyl-2-(p-tolyl)ethylammonium (1254780-66-9) + (R)-3-(benzo[1,3]dioxol-5-yl)-2-methylpropionate (S)-1-phenyl-2-(p-tolyl)ethylammonium

Conditions	Yield
In methanol; isopropyl alcohol at 20 - 70℃; for 4.5h;

aquabis(dimethylglyoximato)[(racemic)-1-(ethoxycarbonyl)ethyl]cobalt(III) + (S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1) → bis(dimethylglyoximato)[(S)-1-(ethoxycarbonyl)ethyl][(S)-1-phenyl-2-(p-tolyl)ethylamine]cobalt(III)

Conditions	Yield
In methanol; water Co complex dissolved in aq. MeOH; ligand added; stirred for 1 h; recrystd. from aq. MeOH; Co complex with (S)-(ethoxycarbonyl)ethyl ligand obtained;

(S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1) + (S)-1-((R)-1-(tert-butoxycarbonyl)pyrrolidine-2-carbonyl)pyrrolidine-2-carboxylic acid (87603-13-2) → C30H39N3O4

Conditions	Yield
With 1-hydroxybenzotriazol-hydrate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 5h;

2,2'-dihydroxybenzil (85-26-7) + (S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1) → C44H40N2O2 + C44H40N2O2

Conditions	Yield
In ethanol at 80℃; for 6h; diastereoselective reaction;	A n/a B n/a

(S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1) → (S)-(6-methyl-2-phenylindolin-1-yl)(pyridin-2-yl)methanone

Conditions	Yield
Multi-step reaction with 2 steps 1: dmap; triethylamine / dichloromethane / 24 h / 20 °C / Inert atmosphere 2: copper diacetate / N,N-dimethyl-formamide / 0.67 h / 200 °C / Microwave irradiation View Scheme

2-picolinoyl chloride hydrochloride (39901-94-5) + (S)-2-(4-methylphenyl)-1-phenylethylamine (30339-30-1) → C21H20N2O

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; for 24h; Inert atmosphere;

Upstream product

• 1254780-66-9 (S)-3-(benzo[1,3]dioxol-5-yl)-2-methylpropionate (S)-1-phenyl-2-(p-tolyl)ethylammonium 
• 30275-30-0 1-phenyl-2-(p-tolyl)ethylamine 
• 492-41-1 (1R,2S)-norephedrine 
• 111630-13-8 phenyl p-tolylmethyl ketone O-methyloxime 
• 123982-65-0 1-Phenyl-2-p-tolyl-ethanone O-octyl-oxime 
• 113683-85-5 1-Phenyl-2-p-tolyl-ethanone O-benzyl-oxime 
• 123982-67-2 C₁₈H₂₃NOSi 

Downstream Products

• 1254780-66-9 (S)-3-(benzo[1,3]dioxol-5-yl)-2-methylpropionate (S)-1-phenyl-2-(p-tolyl)ethylammonium 

Relevant articles and documents

Resolution of 1-phenyl-2-(p-tolyl)ethylamine via diastereomeric salt formation

(S)-1-Phenyl-2-(p-tolyl)ethylamine (S)-1, used for the industrial scale resolution of chrysanthemic acids, was obtained via resolution of the racemate with the hemiphthalate of (S)-isopropylidene glycerol (R)-2. The maximum experimental efficiency [69% yield and >99% e.e. of (S)-1] was achieved by a simple precipitation of (S)-1·(R)-2 from the solution of the 1:1 diastereomeric salt mixture in 93/7 isopropanol/water at saturation of the more soluble (R)-1·(R)-2 salt. Such an experimental efficiency was consistent with 0.79 maximum theoretical resolvability, derived from the solubilities of the two diastereomeric salts, and with DSC data, which indicated that the (S)-1·(R)-2/(R)-1·(R)-2 system is a binary mixture exhibiting an eutectic with composition approximately corresponding to a 0.2 molar ratio of (S)-1·(R)-2.

COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS

The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.

Synthesis of enantiomerically pure amino-substituted fused bicyclic rings

This invention describes various processes for synthesis and resolution of racemic amino-substituted fused bicyclic ring systems. One process utilizes selective hydrogenation of an amino-substituted fused bicyclic aromatic ring system. An alternative process prepares the racemic amino-substituted fused bicyclic ring system via nitrosation. In addition, the present invention describes the enzymatic resolution of a racemic mixture to produce the (R)- and (S)-forms of amino-substituted fused bicyclic rings as well as a racemization process to recycle the unpreferred enantioner. Further provided by this invention is an asymmetric synthesis of the (R)- or (S)-enantiomer of primary amino-substituted fused bicyclic ring systems.