27298-98-2

Basic information

• Product Name: (S)-(-)-1-(P-TOLYL)ETHYLAMINE
• Synonyms: (S)-(-)-ALPHA,4-DIMETHYLBENZYLAMINE;(S)-(-)-A-(P-TOLYL)ETHYLAMINE;(S)-(-)-4-(1-AMINOETHYL)TOLUENE;(S)-4-METHYL-ALPHA-METHYLBENZYLAMINE;(S)-(-)-1-(4-METHYLPHENYL)ETHYLAMINE;(S)-1-(4-METHYLPHENYL)ETHYLAMINE;(S)-1-P-TOLYLETHANAMINE;(S)-(-)-1-(P-TOLYL)ETHYLAMINE
• CAS NO: 27298-98-2
• Molecular Formula: C₉H₁₃N
• Molecular Weight: 135.21
• EINECS: -0
• Product Categories: chiral;API intermediates;Amines (Chiral);Asymmetric Synthesis;Chiral Building Blocks;for Resolution of Acids;Optical Resolution;Synthetic Organic Chemistry;Amines;Chiral Building Blocks;Organic Building Blocks
• Mol File: 27298-98-2.mol
• Article Data: 58

Chemical Properties

• Melting Point: <-20°C
• Boiling Point: 205 °C(lit.)
• Flash Point: 180 °F
• Appearance: colorless to light yellow liquid
• Density: 0.919 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.212mmHg at 25°C
• Refractive Index: n20/D 1.521(lit.)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 9.20±0.10(Predicted)
• Sensitive: Air Sensitive
• BRN: 2422644
• CAS DataBase Reference: (S)-(-)-1-(P-TOLYL)ETHYLAMINE(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-(-)-1-(P-TOLYL)ETHYLAMINE(27298-98-2)
• EPA Substance Registry System: (S)-(-)-1-(P-TOLYL)ETHYLAMINE(27298-98-2)

Safety Data

• Hazard Codes: C
• Statements: 20/21/22-34
• Safety Statements: 16-26-27-36/37/39-45
• RIDADR: UN 2619 8/PG 2
• WGK Germany: 3
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 27298-98-2(Hazardous Substances Data)

Usage

Chemical Properties

Colorless to light yellow liqui

InChI:InChI=1/C9H13N/c1-7-3-5-9(6-4-7)8(2)10/h3-6,8H,10H2,1-2H3/t8-/m0/s1

Synthetic route

para-methylacetophenone (122-00-9) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2)

Conditions	Yield
With formate dehydrogenase; Arthrobacter citreus S9 ω-transaminase; ATA-113 ω-transaminase; sodium formate; isopropylamine; NADH; yeast alcohol dehydrogenase pH=7; aq. phosphate buffer; Enzymatic reaction; optical yield given as %ee;	99%
Stage #1: para-methylacetophenone With ochrobactrum anthropi ω-transaminases W58L/R417A; isopropylamine In aq. phosphate buffer; dimethyl sulfoxide at 37℃; under 460 Torr; for 8h; pH=7; Enzymatic reaction; Stage #2: With hydrogenchloride; perchloric acid In water; acetonitrile	92%
With pyridoxal 5'-phosphate; ω-transaminases from ochrobactrum anthropi mutant W58A; isopropylamine In aq. phosphate buffer; dimethyl sulfoxide at 37℃; under 300 Torr; for 7h; pH=7; Kinetics; Reagent/catalyst; Enzymatic reaction; enantioselective reaction;	n/a

(1R)-2-({[(1S)-1-(4-methylphenyl)ethyl]amino}oxy)-1-phenylethanol (757195-32-7) → (R)-1-phenyl-1,2-ethanediol (16355-00-3) + (S)-1-(4-methylphenyl)ethylamine (27298-98-2)

Conditions	Yield
With hexacarbonyl molybdenum In water; acetonitrile at 85℃; for 1h;	A n/a B 72%

1-(p-tolyl)ethylamine (42070-98-4) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2) + (R)-4'-methyl-1-phenylethylamine (586-70-9, 4187-38-6, 27298-98-2, 42070-98-4)

Conditions	Yield
With 6-(1,2:3,4-di-O-isopropylidene-α-D-galactopyranosyl) hydrogen phthalate In isopropyl alcohol Heating;	A 65.7% B n/a
Stage #1: 1-(p-tolyl)ethylamine With N-(1-(R)-phenylethyl)-malonamic acid In acetone Heating; Stage #2: With hydrogenchloride	A 55% B n/a
Stage #1: 1-(p-tolyl)ethylamine With 5-(1,2-O-C(CH3)2-3,6-anhydro-α-D-glucofuranose)-H-phthalate In methanol for 0.05h; Heating; Stage #2: With hydrogenchloride

isopropyl methoxyacetate (17640-21-0) + 1-(p-tolyl)ethylamine (42070-98-4) → 2-methoxy-N-[(1R)-1-(4-methylphenyl)ethyl]acetamide (296236-17-4) + (S)-1-(4-methylphenyl)ethylamine (27298-98-2)

Conditions	Yield
With Novozym 435 at 23℃; for 3h; Molecular sieve; Enzymatic reaction; optical yield given as %ee; enantioselective reaction;	A 45% B 45%
With Candida antacrtica lipase B at 20℃; Enzymatic reaction; optical yield given as %ee;

1-(p-tolyl)ethylamine (42070-98-4) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2)

Conditions	Yield
With D-(+)-camphoric acid
With N-Ac-Leu

(1S,2R)-1-Phenyl-2-[1-p-tolyl-eth-(E)-ylideneamino]-propan-1-ol → (S)-1-(4-methylphenyl)ethylamine (27298-98-2) + (R)-4'-methyl-1-phenylethylamine (586-70-9, 4187-38-6, 27298-98-2, 42070-98-4)

Conditions	Yield
With platinum(IV) oxide; sodium periodate; hydrogen 1.) C6H6, 2.) CH3OH, RT, 5 h; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;

(1R,2S)-1-Phenyl-2-[1-p-tolyl-eth-(E)-ylideneamino]-propan-1-ol → (S)-1-(4-methylphenyl)ethylamine (27298-98-2) + (R)-4'-methyl-1-phenylethylamine (586-70-9, 4187-38-6, 27298-98-2, 42070-98-4)

Conditions	Yield
With platinum(IV) oxide; sodium periodate; hydrogen 1.) C6H6, 2.) CH3OH, RT, 5 h; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;

para-methylacetophenone (122-00-9) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2) + (R)-4'-methyl-1-phenylethylamine (586-70-9, 4187-38-6, 27298-98-2, 42070-98-4)

Conditions	Yield
Stage #1: para-methylacetophenone With [((R)-tol-binap)RuCl2(DMF)x]; ammonia; ammonium formate In methanol at 85℃; for 21h; Leuckart-Wallach reaction; Stage #2: With hydrogenchloride In ethanol for 1h; Heating; Title compound not separated from byproducts;
Stage #1: para-methylacetophenone With ammonium acetate; sodium cyanoborohydride In methanol at 20℃; reductive amination; Stage #2: racemate resolution; Further stages.;
Stage #1: para-methylacetophenone With 2-Hydroxybenzylamine; C24H34N2O2 In toluene at 110℃; for 72h; Stage #2: With hydrogenchloride In tetrahydrofuran; water at 20℃; for 24h; Overall yield = 52 %;	A n/a B n/a

1-p-tolylethanone oxime (54582-23-9) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2) + (R)-4'-methyl-1-phenylethylamine (586-70-9, 4187-38-6, 27298-98-2, 42070-98-4)

Conditions	Yield
Stage #1: 1-p-tolylethanone oxime With diphenylsilane; silver trifluoromethanesulfonate In 1,2-dimethoxyethane at 20℃; for 40h; Stage #2: With hydrogenchloride In methanol; 1,2-dimethoxyethane Further stages. Title compound not separated from byproducts.;

(E)-1-(4-methylphenyl)ethanone O-benzyl oxime (937371-81-8) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2)

Conditions	Yield
With sodium tetrahydroborate; borane; enantiopure spiroborate ester In 1,4-dioxane for 36h;

1-p-tolylethanone oxime (54582-23-9) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaH / dimethylformamide / 20 °C 2: borane; NaBH4 / enantiopure spiroborate ester / dioxane / 36 h View Scheme

4-methylbenzaldehyde O-[(2R)-2-hydroxy-2-phenylethyl]oxime (757195-21-4) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene; diethyl ether / 0.42 h / -20 °C 2: 72 percent / Mo(CO)6 / acetonitrile; H2O / 1 h / 85 °C View Scheme

4-methyl-benzaldehyde (104-87-0) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 98 percent / TsOH / toluene / 0.5 h / Heating 2: toluene; diethyl ether / 0.42 h / -20 °C 3: 72 percent / Mo(CO)6 / acetonitrile; H2O / 1 h / 85 °C View Scheme

para-methylacetophenone (122-00-9) + KOH → (S)-1-(4-methylphenyl)ethylamine (27298-98-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 4 Angstroem molecular sieves / benzene / 24 h / Ambient temperature 2: 1.) H2, PtO2, 2.) NaIO4 / 1.) C6H6, 2.) CH3OH, RT, 5 h View Scheme
Multi-step reaction with 2 steps 1: 4 Angstroem molecular sieves / benzene / 24 h / Ambient temperature 2: 1.) H2, PtO2, 2.) NaIO4 / 1.) C6H6, 2.) CH3OH, RT, 5 h View Scheme

4-methylacethophenone oxime (2089-33-0) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: ethanol; sodium 2: (1R)-cis-camphoric acid View Scheme

Conditions	Yield
With Candida antarctica lipase B; hydrogen; nickel In toluene at 70℃; under 75.0075 Torr; for 72h; Autoclave; Enzymatic reaction; optical yield given as %ee;

+ para-methylacetophenone (122-00-9) → (R)-1-phenyl-ethyl-amine + (S)-1-(4-methylphenyl)ethylamine (27298-98-2) + 3-Carboxyphenol

Conditions	Yield
With Chromobacterium violaceum ω-transaminase variant W60C at 37℃; for 12h; pH=7; Reagent/catalyst; pH-value; enantioselective reaction;	A n/a B n/a C n/a

para-methylacetophenone (122-00-9) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2) + (R)-N-[1-(4-methylphenyl)ethyl]acetamide

Conditions	Yield
Multi-step reaction with 2 steps 1.1: formamide / water / 10 h / 210 °C 1.2: 1 h / 100 °C / Reflux 2.1: Candida antarctica B lipase CAL-B acrylic resin / toluene / 72 h / 50 °C / Enzymatic reaction View Scheme

1-(p-tolyl)ethylamine (42070-98-4) + ethyl acetate (141-78-6) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2) + (R)-N-[1-(4-methylphenyl)ethyl]acetamide

Conditions	Yield
With Candida antarctica B lipase CAL-B acrylic resin In toluene at 50℃; for 72h; Enzymatic reaction; enantioselective reaction;	A n/a B 50 %Chromat.

1-(p-tolyl)ethylamine (42070-98-4) + 3-Methyl-2,4-pentanedione (815-57-6) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2) + (R,Z)-3-methyl-4-((1-(p-tolyl)ethyl)amino)pent-3-en-2-one + (S,Z)-3-methyl-4-((1-(p-tolyl)ethyl)amino)pent-3-en-2-one + (R)-4'-methyl-1-phenylethylamine (586-70-9, 4187-38-6, 27298-98-2, 42070-98-4)

Conditions	Yield
With C74H89O4P In diethyl ether at -78 - -5℃; for 20h; Inert atmosphere; Molecular sieve; Resolution of racemate;	A n/a B n/a C n/a D n/a

2-amino-5-methylhexane (28292-43-5) + 3-Methyl-2,4-pentanedione (815-57-6) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2) + (R,Z)-3-methyl-4-((5-methylhexan-2-yl)amino)pent-3-en-2-one + (R)-4'-methyl-1-phenylethylamine (586-70-9, 4187-38-6, 27298-98-2, 42070-98-4)

Conditions	Yield
With C74H89O4P In diethyl ether at -78 - -5℃; for 20h; Inert atmosphere; Molecular sieve; Resolution of racemate;	A n/a B n/a C n/a

1-(p-tolyl)ethylamine (42070-98-4) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2) + para-methylacetophenone (122-00-9)

Conditions	Yield
With (R)-amine dehydrogenase In dimethyl sulfoxide at 37℃; pH=8.5; Catalytic behavior; Resolution of racemate; Microbiological reaction; Enzymatic reaction; enantioselective reaction;

4-methylethylbenzene (622-96-8) → (S)-1-(4-methylphenyl)ethylamine (27298-98-2) + (R)-4'-methyl-1-phenylethylamine (586-70-9, 4187-38-6, 27298-98-2, 42070-98-4) + 4-ethylbenzylamine (7441-43-2)

Conditions	Yield
With C5H11NO*CHF3O3S In ethanol; water at 10℃; for 12h; pH=7.4; Inert atmosphere; Sealed tube; Enzymatic reaction; Overall yield = 48 percent; enantioselective reaction;	A n/a B n/a C n/a

(S)-1-(4-methylphenyl)ethylamine (27298-98-2) + 2-oxopropanal (78-98-8) → N-[(S)-1-(4-methylphenyl)ethyl]-2-oxopropan-1-imine

Conditions	Yield
	100%

Upstream product

• 42070-98-4 1-(p-tolyl)ethylamine 
• 122-00-9 para-methylacetophenone 
• 54582-23-9 1-p-tolylethanone oxime 
• 757195-32-7 (1R)-2-({[(1S)-1-(4-methylphenyl)ethyl]amino}oxy)-1-phenylethanol 
• 937371-81-8 (E)-1-(4-methylphenyl)ethanone O-benzyl oxime 
• 757195-21-4 4-methylbenzaldehyde O-[(2R)-2-hydroxy-2-phenylethyl]oxime 
• 104-87-0 4-methyl-benzaldehyde 
• 2089-33-0 4-methylacethophenone oxime 
• 3938-96-3 ethyl 2-methoxyacetate 
• 177750-53-7 N-[(1R)-1-(4-bromophenyl)ethyl]acetamide 
• 3886-69-9 (R)-1-phenyl-ethyl-amine 
• 70249-37-5 3-aminocyclohexa-1,5-dienecarboxylic acid 
• 622-96-8 4-methylethylbenzene 
• 36283-44-0 N-acetyl-1-phenylethylamine 

Downstream Products

• 100-41-4 ethylbenzene 
• 586-70-9 (R)-4'-methyl-1-phenylethylamine 
• 214195-50-3 bis-(1-p-tolyl-ethyl)-amine 
• 1067652-30-5 (1R,2R,4S)-4-(methanesulfonyl-methyl-amino)-2-[(S)-1-p-tolyl-ethylcarbamoyl]-cyclopentanecarboxylic acid methyl ester 
• 42070-98-4 1-(p-tolyl)ethylamine 
• 52726-41-7 Bis-(1-p-tolyl-ethyl)-amine 
• 709613-20-7 (S)-5-(1-p-Tolyl-ethylcarbamoyl)-thiophene-2-carboxylic Acid Methyl Ester 
• 1187776-92-6 C₃₄H₄₇N₃O₂ 
• 444169-17-9 N-((R)-1-(4-methylphenyl)ethyl)pivalamide 
• 1257422-13-1 (R)-(-)-PAM * (S)-(-)-MePEA [(-)-p salt] 
• 1257422-12-0 (S)-(+)-PAM * (S)-(-)-MePEA [(+)-n salt] 

Relevant articles and documents

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Iterative Alanine Scanning Mutagenesis Confers Aromatic Ketone Specificity and Activity of L-Amine Dehydrogenases

Direct reductive amination of prochiral ketones catalyzed by amine dehydrogenases is attractive in the synthesis of active pharmaceutical ingredients. Here, we report the protein engineering of L-Bacillus cereus amine dehydrogenase to allow reactivity on synthetically useful aromatic ketone substrates using an iterative, multiple-site alanine scanning mutagenesis approach. Mutagenesis libraries based on molecular docking, iterative alanine scanning, and double-proximity filter approach significantly expand the scope of active pharmaceutical ingredients relevant building blocks. The eventual quintuple mutant (A115G/T136A/L42A/V296A/V293A) showed reactivity toward aromatic ketones 12 a (5-phenyl-pentan-2-one) and 13 a (6-phenyl-hexan-2-one), which have not been reported to serve as targets of reductive amination by currently available amine dehydrogenases. Docking simulation and tunnel analysis provided valuable insights into the source of the acquired specificity and activity.

Deracemization of Racemic Amines to Enantiopure (R)- and (S)-amines by Biocatalytic Cascade Employing ω-Transaminase and Amine Dehydrogenase

A one-pot deracemization strategy for α-chiral amines is reported involving an enantioselective deamination to the corresponding ketone followed by a stereoselective amination by enantiocomplementary biocatalysts. Notably, this cascade employing a ω-transaminase and amine dehydrogenase enabled the access to both (R)-and (S)-amine products, just by controlling the directions of the reactions catalyzed by them. A wide range of (R)-and (S)-amines was obtained with excellent conversions (>80 %) and enantiomeric excess (>99 % ee). Finally, preparative scale syntheses led to obtain enantiopure (R)- and (S)-13 with the isolated yields of 53 and 75 %, respectively.