623-08-5

Usage

Chemical Properties

CLEAR YELLOW TO BROWN LIQUID

General Description

N-Methyl-p-toluidine is an aromatic secondary amine. It forms social isomers when encapsulated with a molecule of chloroform or benzene in a cylindrical capsule. 2-amino-4,6-dichloropyrimidine-5-carbaldehyde undergoes mono-amination with N-methyl-p-toluidine to form a precursor for the preparation of pyrazolo[3,4-d]pyrimidines. It annelates with dimethyl acetylenedicarboxylate via formation of toluidine radical cation intermediate.

InChI:InChI=1/C8H11N/c1-7-3-5-8(9-2)6-4-7/h3-6,9H,1-2H3

Upstream product

• 186581-53-3 diazomethane 
• 106-49-0 p-toluidine 
• 917-64-6 methyl magnesium iodide 
• 60-29-7 diethyl ether 
• 99-99-0 1-methyl-4-nitrobenzene 
• 64-17-5 ethanol 
• 17450-22-5 bis(4-methylphenylamino)methane 
• 540-23-8 p-toluidine hydrochloride 
• 6380-10-5 N-methyl-N-(4-methylphenyl)-p-toluenesulfonamide 
• 32111-89-0 methyl-p-tolyl-carbamonitrile 
• 67-56-1 methanol 
• 4727-41-7 dimethylsulfonioacetate 
• 80-48-8 methyl p-toluene sulfonate 
• 74-88-4 methyl iodide 

Downstream Products

• 16062-76-3 1,5-bis-(N-methyl-p-toluidino)-pentamethinium ; bromide 
• 53761-42-5 1,4,6-trimethylquinolin-2(1H)-one 
• 13020-97-8 N-methyl-N-(4-methylphenyl)carbamoyl chloride 
• 101092-33-5 N-methyl-N-(p-tolyl)benzo[d]thiazol-2-amine 
• 19732-23-1 4,N-dimethyl-6-(N-methyl-p-toluidinomethyl)aniline 
• 64672-68-0 2-[methyl(p-tolyl)amino]acetonitrile 
• 107521-44-8 bis-(N-methyl-p-toluidinomethyl)-peroxide 
• 7137-82-8 N,N'-dimethyl-N,N'-di-p-tolylmethanediamine 
• 101281-22-5 methyl-(6-methyl-benzothiazol-2-yl)-p-tolyl-amine 
• 115818-32-1 3-methyl-1-phenyl-3-p-tolyl-triazene 
• 55246-78-1 methyl(p-tolyl)carbamothioic chloride 
• 62166-71-6 (N-methyl-p-toluidino)-ethenetricarbonitrile 
• 114492-95-4 O⁴,O⁶-((R)-benzylidene)-1-(N-methyl-p-toluidino)-1-deoxy-D-fructose 
• 52853-54-0 3,6-dimethyl-3H-benzothiazol-2-ylideneamine 

Relevant academic research and scientific papers

SYNTHESIS OF CYCLOPROPYLAMINOOXOSULFONIUM SALTS BY THE REACTION OF DIAMINOOXOSULFONIUM YLIDES WITH ALDEHYDES

The title compounds have been synthesized by the reaction of diaminooxosulfonium methylides with aldehydes as isomeric mixtures in good yields.These ylides reacted with aldehydes to give betaines, which formed unusual four-membered cyclic alkoxyoxosulfonium salts.Another methylide further attacked α-carbon of these salts to afford cyclopropyldiaminooxosulfonium salts.

Electronically tuneable orthometalated RuII–NHC complexes as efficient catalysts for C–C and C–N bond formations via borrowing hydrogen strategy

The catalytic activities of a series of simple and electronically tuneable cyclometalated RuII–NHC complexes (2a–d) were explored in various C–C/N bond formations following the borrowing hydrogen process. Slight modifications in the ligand backbone were noted to tune the activities of these complexes. Among them, the complex 2d featuring a 1,2,4-triazolylidene donor with a 4-NO2–phenyl substituent displayed the highest activity for the coupling of diverse secondary and primary alcohols with a low catalyst loading of 0.01 mol% and a sub-stoichiometric amount of inexpensive KOH base. The efficacy of this simple system was further showcased in the challenging one-pot unsymmetrical double alkylation of secondary alcohols using different primary alcohols. Moreover, the complex 2d also effectively catalyses the selective mono-N-methylation of various aromatic and aliphatic primary amines using methanol to deliver a range of N-methyl amines. Mechanistically, the β-alkylation reaction follows a borrowing hydrogen pathway which was established by the deuterium labelling experiment in combination with various control experiments. Intriguingly, in situ1H NMR and ESI-MS analyses evidently suggested the involvement of a Ru–H species in the catalytic cycle and further, the kinetic studies revealed a first order dependence of the reaction rate on the catalyst as well as the alcohol concentrations.

Reusable Co-nanoparticles for general and selectiveN-alkylation of amines and ammonia with alcohols

A general cobalt-catalyzedN-alkylation of amines with alcohols by borrowing hydrogen methodology to prepare different kinds of amines is reported. The optimal catalyst for this transformation is prepared by pyrolysis of a specific templated material, which is generatedin situby mixing cobalt salts, nitrogen ligands and colloidal silica, and subsequent removal of silica. Applying this novel Co-nanoparticle-based material, >100 primary, secondary, and tertiary amines includingN-methylamines and selected drug molecules were conveniently prepared starting from inexpensive and easily accessible alcohols and amines or ammonia.

Novel hybrid conjugates with dual estrogen receptor α degradation and histone deacetylase inhibitory activities for breast cancer therapy

Hormone therapy targeting estrogen receptors is widely used clinically for the treatment of breast cancer, such as tamoxifen, but most of them are partial agonists, which can cause serious side effects after long-term use. The use of selective estrogen receptor down-regulators (SERDs) may be an effective alternative to breast cancer therapy by directly degrading ERα protein to shut down ERα signaling. However, the solely clinically used SERD fulvestrant, is low orally bioavailable and requires intravenous injection, which severely limits its clinical application. On the other hand, double- or multi-target conjugates, which are able to synergize antitumor activity by different pathways, thus may enhance therapeutic effect in comparison with single targeted therapy. In this study, we designed and synthesized a series of novel dual-functional conjugates targeting both ERα degradation and histone deacetylase inhibiton by combining a privileged SERD skeleton 7-oxabicyclo[2.2.1]heptane sulfonamide (OBHSA) with a histone deacetylase inhibitor side chain. We found that substituents on both the sulfonamide nitrogen and phenyl group of OBHSA unit had significant effect on biological activities. Among them, conjugate 16i with N-methyl and naphthyl groups exhibited potent antiproliferative activity against MCF-7 cells, and excellent ERα degradation activity and HDACs inhibitory ability. A further molecular docking study indicated the interaction patterns of these conjugates with ERα, which may provide guidance to design novel SERDs or PROTAC-like SERDs for breast cancer therapy.

Biobased Spiroimides from Itaconic Acid and Formamides: Molecular Targets for a Novel Synthetic Application of Renewable Chemicals

Spiroimides exhibit a wide range of biological activities, such as anticonvulsant, antiarrhythmic, and antihyperglycemic activities. Herein, a novel synthetic application of renewable chemicals, itaconic acid and formamides, is described. Proper exploitation of the reactivity of itaconic acid and formamide allows for the development of an efficient synthetic approach for the production of several new biobased spiroimides, spiro[dihydroquinolin-2-one-succinimides] and spiro[indolin-2-one-glutarimides], in excellent overall yields (up to 98%).

CO2-tuned highly selective reduction of formamides to the corresponding methylamines

We herein describe an efficient, CO2-tuned and highly selective C-O bond cleavage of N-methylated formanilides. With easy-to-handle and commercially available NaBH4 as the reductant, a variety of formanilides could be turned into the desired tertiary amines in moderate to excellent yields. The role of CO2 has been investigated in detail, and the mechanism is proposed on the basis of experiments.

Photoinduced Hydroarylation and Cyclization of Alkenes with Luminescent Platinum(II) Complexes

Photoinduced hydroarylation of alkenes is an appealing synthetic strategy for arene functionalization. Herein, we demonstrated that aryl radicals generated from electron-deficient aryl chlorides/bromides could be trapped by an array of terminal/internal aryl alkenes in the presence of [Pt(O^N^C^N)] under visible-light (410 nm) irradiation, affording anti-Markovnikov hydroarylated compounds in up to 95 % yield. Besides, a protocol for [Pt(O^N^C^N)]-catalyzed intramolecular photocyclization of acrylanilides to give structurally diverse 3,4-dihydroquinolinones has been developed.

Method for realizing N-alkylation by using alcohols as carbon source under photocatalysis

The invention discloses a method for realizing N-alkylation by using alcohols as a carbon source under photocatalysis, and belongs to the technical field of catalytic synthesis. Alcohol, a substrate raw material and a catalyst are placed in a reaction device, ultraviolet and/or visible light irradiation is carried out in an inert atmosphere, after the irradiation is finished, solid-liquid separation is carried out to remove the catalyst, and an N-alkylation product can be obtained through extraction, distillation and purification, wherein the substrate raw material comprises any one of an amine compound, an aromatic nitro compound or an aromatic nitrile compound, the alcohol comprises any one or more of soluble primary alcohols, and the catalyst is metal oxide/titanium dioxide or metal sulfide/titanium dioxide. The method is simple and easy to operate, can be used for efficient photocatalysis one-pot multi-step hydrogenation N-alkylation reaction, and is mild in reaction condition, high in chemical selectivity of N-alkylamine, good in catalyst stability and easy to recycle.

Additive-freeN-methylation of amines with methanol over supported iridium catalyst

An efficient and versatile zinc oxide-supported iridium (Ir/ZnO) catalyst was developed to catalyze the additive-freeN-methylation of amines with methanol. Mechanistic studies suggested that the high catalytic reactivity is rooted in the small sizes (1.4 nm) of Ir nanoparticles and the high ratio (93%) of oxidized iridium species (IrOx, Ir3+and Ir4+) on the catalyst. Moreover, the delicate cooperation between the IrOxand ZnO support also promoted its high reactivity. The selectivity of this catalyticN-methylation was controllable between dimethylation and monomethylation by carefully tuning the catalyst loading and reaction solvent. Specifically, neat methanol with high catalyst loading (2 mol% Ir) favored the formation ofN,N-dimethylated amine, while the mesitylene/methanol mixture with low catalyst loading (0.5 mol% Ir) was prone to producing mono-N-methylated amines. An environmentally benign continuous flow system with a recycled mode was also developed for the efficient production ofN-methylated amines. With optimal flow rates and amine concentrations, a variety ofN-methylamines were produced with good to excellent yields in this Ir/ZnO-based flow system, providing a starting point for the clean and efficient production ofN-methylamines with this cost-effective chemical process.

Ru-Catalyzed Selective Catalytic Methylation and Methylenation Reaction Employing Methanol as the C1 Source

Methanol can be employed as a green and sustainable methylating agent to form C-C and C-N bonds via borrowing hydrogen (BH) methodology. Herein we explored the activity of the acridine-derived SNS-Ru pincer for the activation of methanol to apply it as a C1 building block in different reactions. Our catalytic system shows great success toward the β-C(sp3)-methylation reaction of 2-phenylethanols to provide good to excellent yields of the methylated products. We investigated the mechanistic details, kinetic progress, and temperature-dependent product distribution, which revealed the slow and steady generation of in situ formed aldehyde, is the key factor to get the higher yield of the β-methylated product. To establish the environmental benefit of this reaction, green chemistry metrics are calculated. Furthermore, dimerization of 2-naphthol via methylene linkage and formation of N-methylation of amine are also described in this study, which offers a wide range of substrate scope with a good to excellent yield.