586-70-9

Usage

Uses

Used in Pharmaceutical Industry:
1-(4-METHYLPHENYL)ETHYLAMINE 96 is used as a building block or intermediate for the synthesis of various pharmaceutical compounds. Its chiral nature allows it to be a key component in the development of enantiomerically pure drugs, which can have significant implications for the efficacy and safety of medications.
Used in Chemical Synthesis:
1-(4-METHYLPHENYL)ETHYLAMINE 96 is used as a reagent in the preparation of various organic compounds. For instance, it may be used in the synthesis of 1,1′-(2-thienylmethylene) di-2-naphthol ethyl acetate solvate and (R)-N-(1-p-tolylethyl)-2-methoxyacetamide. These compounds can have applications in different areas, such as materials science, agrochemicals, and pharmaceuticals.
Used in Research and Development:
Due to its unique structure and properties, 1-(4-METHYLPHENYL)ETHYLAMINE 96 can be employed in research and development for exploring new chemical reactions, understanding the behavior of chiral amines, and developing novel synthetic methods. This can lead to the discovery of new compounds with potential applications in various industries.

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

Upstream product

• 42070-98-4 1-(p-tolyl)ethylamine 
• 122-00-9 para-methylacetophenone 
• 54582-23-9 1-p-tolylethanone oxime 
• 368447-72-7 (2S)-2-({[(1R)-1-(4-methylphenyl)ethyl]amino}oxy)-2-phenylethanol 
• 27298-98-2 (S)-1-(4-methylphenyl)ethylamine 
• 2089-33-0 4-methylacethophenone oxime 
• 124709-71-3 R-(-)-2-(4'-methylphenyl)-propanoic acid 
• 2947-61-7 (4-methylphenyl)acetonitrile 
• 536-50-5 CH₃C₆H₄CH(CH₃)OH 
• 42070-92-8 (R)-1-(4-methylphenyl)ethanol 
• 536-50-5 (S)-1-(4-Methylphenyl)ethanol 
• 36283-44-0 N-acetyl-1-phenylethylamine 
• 622-96-8 4-methylethylbenzene 
• 3886-69-9 (R)-1-phenyl-ethyl-amine 

Downstream Products

• 177499-67-1 2-Amino-1-((R)-1-p-tolyl-ethyl)-4,5,6,7-tetrahydro-1H-indole-3-carbonitrile 
• 629657-92-7 6-chloro-N-[(1R)-1-(4-methylphenyl)ethyl]pyrazin-2-amine 
• 864162-71-0 (2R)-2-hydroxy-5-(4-methoxyphenyl)pentanoic acid (+)-tolylethylamine 
• 1187776-92-6 C₃₄H₄₇N₃O₂ 
• 444169-17-9 N-((R)-1-(4-methylphenyl)ethyl)pivalamide 
• 1410797-12-4 (R)-1-(p-tolyl)ethylammonium (R)-2-methoxy-2-(1-naphthyl)propanoate 

Relevant academic research and scientific papers

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.

Enzymatic Primary Amination of Benzylic and Allylic C(sp3)-H Bonds

Aliphatic primary amines are prevalent in natural products, pharmaceuticals, and functional materials. While a plethora of processes are reported for their synthesis, methods that directly install a free amine group into C(sp3)-H bonds remain unprecedented. Here, we report a set of new-to-nature enzymes that catalyze the direct primary amination of C(sp3)-H bonds with excellent chemo-, regio-, and enantioselectivity, using a readily available hydroxylamine derivative as the nitrogen source. Directed evolution of genetically encoded cytochrome P411 enzymes (P450s whose Cys axial ligand to the heme iron has been replaced with Ser) generated variants that selectively functionalize benzylic and allylic C-H bonds, affording a broad scope of enantioenriched primary amines. This biocatalytic process is efficient and selective (up to 3930 TTN and 96percent ee), and can be performed on preparative scale.

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.

Transition-Metal-Free Hydrogen Autotransfer: Diastereoselective N-Alkylation of Amines with Racemic Alcohols

A practical method for the synthesis of α-chiral amines by alkylation of amines with alcohols in the absence of any transition-metal catalysts has been developed. Under the co-catalysis of a ketone and NaOH, racemic secondary alcohols reacted with Ellman's chiral tert-butanesulfinamide by a hydrogen autotransfer process to afford chiral amines with high diastereoselectivities (up to >99:1). Broad substrate scope and up to a 10 gram scale production of chiral amines were demonstrated. The method was applied to the synthesis of chiral deuterium-labelled amines with high deuterium incorporation and optical purity, including examples of chiral deuterated drugs. The configuration of amine products is found to be determined solely by the configuration of the chiral tert-butanesulfinamide regardless of that of alcohols, and this is corroborated by DFT calculations. Further mechanistic studies showed that the reaction is initiated by the ketone catalyst and involves a transition state similar to that proposed for the Meerwein–Ponndorf–Verley (MPV) reduction, and importantly, it is the interaction of the sodium cation of the base with both the nitrogen and oxygen atoms of the sulfinamide moiety that makes feasible, and determines the diastereoselectivity of, the reaction.

Method for synthesizing chiral amine compound

The present invention provides a method for synthesizing a chiral amine compound. The method comprises the following steps: (1) reacting a compound of formula I with t-butylsulfonamide in the presenceof a catalyst to obtain a compound having a structure represented by formula II; 2) reacting the compound of the formula II in a hydrogen atmosphere in the presence of an iridium catalyst and a ligand to obtain a compound of formula III; and (3) carrying out a t-butylsulfonyl group removal reaction on the compound of the formula III to obtain the chiral amine compound. The method constructs the structure of sulfonamide by a keto carbonylgroup, and synthesizes the chiral amine compound with the aralkylamine structure by an asymmetric catalytic hydrogenation reaction of the sulfonamide structure, the ee value is generally 80% or above, the highest ee value is 99% or above, the yield of each step reaction can reach 90% or above, and the total yield is high.

Evaluation of the Edman degradation product of vancomycin bonded to core-shell particles as a new HPLC chiral stationary phase

A modified macrocyclic glycopeptide-based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide-based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide-based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary behavior with these glycopeptides. A screening procedure was used based on previous work for the enantiomeric separation of 50 chiral compounds including amino acids, pesticides, stimulants, and a variety of pharmaceuticals. Fast and efficient chiral separations resulted by using superficially porous (core-shell) particle supports. Overall, the vancomycin Edman degradation product (EDP) resembled TeicoShell with high enantioselectivity for acidic compounds in the polar ionic mode. The simultaneous enantiomeric separation of 5 racemic profens using liquid chromatography-mass spectrometry with EDP was performed in approximately 3?minutes. Other highlights include simultaneous liquid chromatography separations of rac-amphetamine and rac-methamphetamine with VancoShell, rac-pseudoephedrine and rac-ephedrine with NicoShell, and rac-dichlorprop and rac-haloxyfop with TeicoShell.

Method for synthesis of (R)-1-(4-methyl phenyl) ethylamine

The invention discloses a method for synthesis of (R)-1-(4-methyl phenyl) ethylamine. The method includes: subjecting a compound 3 to deacylation to obtain (R)-1-(4-methyl phenyl) ethylamine in a C4-C10 monoalcohol solvent and in the presence of alkali metal hydroxide, wherein R refers to ethanoyl, propionyl or butyryl. The method is low in synthesis cost, simple in step, safe in operation, low inby-products, simple in aftertreatment, easy to purify intermediate products and final products, high in whole yield, high in final product purity and easy in industrialization.

Mapping the substrate scope of monoamine oxidase (MAO-N) as a synthetic tool for the enantioselective synthesis of chiral amines

A library of 132 racemic chiral amines (α-substituted methylbenzylamines, benzhydrylamines, 1,2,3,4-tetrahydronaphthylamines (THNs), indanylamines, allylic and homoallylic amines, propargyl amines) was screened against the most versatile monoamine oxidase (MAO-N) variants D5, D9 and D11. MAO-N D9 exhibited the highest activity for most substrates and was applied to the deracemisation of a comprehensive set of selected primary amines. In all cases, excellent enantioselectivity was achieved (e.e. >99%) with moderate to good yields (55–80%). Conditions for the deracemisation of primary amines using a MAO-N/borane system were further optimised using THN as a template addressing substrate load, nature of the enzyme preparation, buffer systems, borane sources, and organic co-solvents.

Asymmetric Synthesis of Chiral Primary Amines by Ruthenium-Catalyzed Direct Reductive Amination of Alkyl Aryl Ketones with Ammonium Salts and Molecular H2

A ruthenium/C3-TunePhos catalytic system has been identified for highly efficient direct reductive amination of simple ketones. The strategy makes use of ammonium acetate as the amine source and H2 as the reductant and is a user-friendly and operatively simple access to industrially relevant primary amines. Excellent enantiocontrol (>90% ee for most cases) was achieved with a wide range of alkyl aryl ketones. The practicability of this methodology has been highlighted by scalable synthesis of key intermediates of three drug molecules. Moreover, an improved synthetic route to the optimal diphosphine ligand C3-TunePhos is also presented.

In vitro biocatalytic pathway design: Orthogonal network for the quantitative and stereospecific amination of alcohols

The direct and efficient conversion of alcohols into amines is a pivotal transformation in chemistry. Here, we present an artificial, oxidation-reduction, biocatalytic network that employs five enzymes (alcohol dehydrogenase, NADP-oxidase, catalase, amine dehydrogenase and formate dehydrogenase) in two concurrent and orthogonal cycles. The NADP-dependent oxidative cycle converts a diverse range of aromatic and aliphatic alcohol substrates to the carbonyl compound intermediates, whereas the NAD-dependent reductive aminating cycle generates the related amine products with >99% enantiomeric excess (R) and up to >99% conversion. The elevated conversions stem from the favorable thermodynamic equilibrium (K′eq = 1.88 × 1042 and 1.48 × 1041 for the amination of primary and secondary alcohols, respectively). This biocatalytic network possesses elevated atom efficiency, since the reaction buffer (ammonium formate) is both the aminating agent and the source of reducing equivalents. Additionally, only dioxygen is needed, whereas water and carbonate are the by-products. For the oxidative step, we have employed three variants of the NADP-dependent alcohol dehydrogenase from Thermoanaerobacter ethanolicus and we have elucidated the origin of the stereoselective properties of these variants with the aid of in silico computational models.