540-23-8

Usage

General Description

Off-white to grayish-white crystals.

Air & Water Reactions

Water soluble. May be sensitive to moisture.

Reactivity Profile

4-Methylaniline hydrochloride reacts with oxidizing and alkali materials. .

Fire Hazard

Flash point data for 4-Methylaniline hydrochloride are not available, but 4-Methylaniline hydrochloride is probably combustible.

Safety Profile

Poison by intraperitoneal route. Moderately toxic by ingestion. Questionable carcinogen with experimental carcinogenic and tumorigenic data. When heated to decomposition it emits very toxic fumes of NOx and HCl. See also p-TOLUIDINE.

Purification Methods

Crystallise the salt from MeOH containing a few drops of conc HCl or aqueous EtOH. Dry it under vacuum over paraffin chips. [Beilstein 12 II 587, 12 III 2021, 12 IV 1869.]

InChI:InChI=1/C7H9N.ClH/c1-6-2-4-7(8)5-3-6;/h2-5H,8H2,1H3;1H

Upstream product

• 106-49-0 p-toluidine 
• 79-11-8 chloroacetic acid 
• 99-99-0 1-methyl-4-nitrobenzene 
• 97-00-7 1-chloro-2,4-dinitro-benzene 
• 82054-47-5 1-(3-Phenyl-3-thioxo-thiopropionyl)-3-p-tolyl-urea 
• 67-56-1 methanol 
• 934-53-2 cumenyl chloride 
• 40473-10-7 2-chloro-2-(3'-chlorophenyl)propane 
• 13240-60-3 3-(2-Chloro-2-propyl)toluene 
• 42325-37-1 4-(α-chloro-isopropyl)-biphenyl 
• 14276-97-2 1-chloro-4-(α-chloro-isopropyl)-benzene 
• 10026-13-8 phosphorus pentachloride 
• 111141-29-8 N,N'-di-p-tolyl-malamide 
• 504405-07-6 (4,4,5,5-tetramethyl-[1,3]dioxolan-2-ylidene)-p-tolyl-amine 

Downstream Products

• 16379-95-6 5-p-toluidino-1-p-tolylimino-penta-2,4-dien-2-ol; hydrochloride 
• 94685-67-3 bis(4-methylphenylamino)phenylphosphine oxide 
• 608-05-9 5-methyl-indole-2,3-dione 
• 22896-78-2 3-methyl-1-phenyl-N-(p-tolyl)-1H-pyrazol-5-amine 
• 81759-22-0 Diethyl(p-tolylimido)carbonat 
• 14277-01-1 N-(4-methylphenyl)acetamidine 
• 5132-17-2 N,N'-di(p-tolyl)acetamidine 
• 103-89-9 4-Methylacetanilide 
• 79491-05-7 4-(4-methylphenyl)-1,2,4-triazolidine-3,5-dione 
• 81-48-1 1-hydroxy-4-(4-methylphenylamino)-9,10-anthraquinone 
• 36804-50-9 5-methyl-2,3-diphenyl-indole 
• 41120-12-1 N,N-diphenacylaniline 
• 840-59-5 6-methyl-3-(4-tolyl)-3,4-dihydroquinazoline 
• 623-08-5 N-methyl-p-toluidine 

Relevant academic research and scientific papers

Cobalt-Catalyzed Deoxygenative Hydroboration of Nitro Compounds and Applications to One-Pot Synthesis of Aldimines and Amides

The commercially available and bench-stable Co(acac)2 ligated with bis[(2-diphenylphosphino)phenyl] ether (dpephos) was employed for selective room temperature hydroboration of nitro compounds with HBPin (TOF up to 4615 h?1), tolerating halide, hydroxy, amino, ether, ester, lactone, amide and heteroaromatic functionalities. These reactions offered a direct access to a variety of N-borylamines RN(H)BPin, which were in situ treated with aldehydes and carboxylic acids to produce a series of aldimines and secondary carboxamides without the need for dehydrating and/or coupling reagents. Combination of these transformations in a sequential one-pot manner allowed for direct and selective synthesis of aldimines and secondary carboxamides from readily available and inexpensive nitro compounds.

Synthesis, Characterization, and Catalytic Reactivity of {CoNO}8PCP Pincer Complexes

The reaction of coordinatively unsaturated Co(II) PCP pincer complexes with nitric oxide leads to the formation of new, air-stable, diamagnetic mono nitrosyl compounds. The synthesis and characterization of five- and four-coordinate Co(III) and Co(I) nitrosyl pincer complexes based on three different ligand scaffolds is described. Passing NO through a solution of [Co(PCPNMe-iPr)Cl], [Co(PCPO-iPr)Cl] or [Co(PCPCH2-iPr)Br] led to the formation of the low-spin complex [Co(PCP-iPr)(NO)X] with a strongly bent NO ligand. Treatment of the latter species with (X = Cl, Br) AgBF4 led to chloride abstraction and formation of cationic square-planar Co(I) complexes of the type [Co(PCP-iPr)(NO)]+ featuring a linear NO group. This reaction could be viewed as a formal two electron reduction of the metal center by the NO radical from Co(III) to Co(I), if NO is counted as NO+. Hence, these systems can be described as {CoNO}8 according to the Enemark-Feltham convention. X-ray structures, spectroscopic and electrochemical data of all nitrosyl complexes are presented. Preliminary studies show that [Co(PCPNMe-iPr)(NO)]+ catalyzes efficiently the reductive hydroboration of nitriles with pinacolborane (HBpin) forming an intermediate {CoNO}8 hydride species.

Catalytic Staudinger Reduction at Room Temperature

We report an efficient catalytic Staudinger reduction at room temperature that enables the preparation of a structurally diverse set of amines from azides in excellent yields. The reaction is based on the use of catalytic amounts of triphenylphosphine as a phosphine source and diphenyldisiloxane as a reducing agent. Our catalytic Staudinger reduction exhibits a high chemoselectivity, as exemplified by reduction of azides over other common functionalities, including nitriles, alkenes, alkynes, esters, and ketones.

Reversible capture and release of aromatic amines by vicinal tricarbonyl compound

In this paper, we report reversible capture and release of aromatic amines by diphenylpropanetrione (DPPT). Addition of aromatic amines to the central carbonyl group occurred readily at ambient temperature to provide the aromatic amine adducts of DPPT (DPPT-aromatic amines), which has a hemiaminal structure. On the other hand, washing a solution of DPPT-aromatic amine with diluted hydrochloric acid (HCl) enabled successful recovery of DPPT to demonstrate the reversible nature of this system.

High graphite N content in nitrogen-doped graphene as an efficient metal-free catalyst for reduction of nitroarenes in water

Four kinds of nitrogen-doped graphene (NG) as metal-free catalysts are synthesized by a one-step hydrothermal reaction and thermal treatment using graphene oxide and urea as precursors. It is found that the reduction of nitroarenes can be catalyzed by using a low NG loading and a small amount of NaBH4 in water with high yield. The type of nitrogen species in NG has an important effect on the reduction reaction. The NG catalyst containing the most graphite N shows the highest catalytic activity during reduction of nitroarenes, which demonstrates that the graphite N of NG plays a key role in impelling this reaction. The reaction mechanism is proven by GC-MS experiments, and DFT calculations reveal the reasons for the graphite N showing better catalytic activity. It is worth noting that no dehalogenation phenomenon occurs during the reduction process for halogen-substituted nitroarenes in contrast to conventional metal catalysts. In addition, the NG catalyst can be simply recycled and efficiently used for eight consecutive runs with no significant decrease in activity.

Development and evaluation of ST-1829 based on 5-benzylidene-2-phenylthiazolones as promising agent for anti-leukotriene therapy

Different inflammatory diseases and allergic reactions are mediated by leukotrienes, which arise from the oxygenation of arachidonic acid catalyzed by 5-lipoxygenase (5-LO). One promising approach for an effective anti-leukotriene therapy is the inhibition of this key enzyme. This study presents the synthesis and development of a potent and direct 5-LO inhibitor based on the well characterized 5-benzylidene-2-phenylthiazolone C06, whose further pharmacological investigation was precluded due to its low solubility. Through optimization of C06, evaluation of structure-activity relationships including profound assessment of the thiazolone core and consideration of the solubility, the 5-benzyl-2-phenyl-4-hydroxythiazoles represented by 46 (ST-1829, 5-(4-chlorobenzyl)-2-p-tolylthiazol-4-ol) were developed. Compound 46 showed an improved 5-LO inhibitory activity in cell-based (ICinf50/inf values 0.141/4M) and cell-free assays (ICinf50/inf values 0.03 1/4M) as well as a prominent enhanced solubility. Furthermore, it kept its promising inhibitory potency in the presence of blood serum, excluding excessive binding to serum proteins. These facts combined with the non-cytotoxic profile mark a major step towards an effective anti-inflammatory therapy.

The ortho effect on the acidic and alkaline hydrolysis of substituted formanilides

The kinetics of formanilides hydrolysis were determined under first-order conditions in hydrochloric acid (0.01-8 M, 20-60°C) and in hydroxide solutions (0.01-3 M, 25 and 40°C). Under acidic conditions, second-order specific acid catalytic constants were used to construct Hammett plots. The ortho effect was analyzed using the Fujita-Nishioka method. In alkaline solutions, hydrolysis displayed both first- and second-order dependence in the hydroxide concentration. The specific base catalytic constants were used to construct Hammett plots. Ortho effects were evaluated for the first-order dependence on the hydroxide concentration. Formanilide hydrolyzes in acidic solutions by specific acid catalysis, and the kinetic study results were consistent with the AAC2 mechanism. Ortho substitution led to a decrease in the rates of reaction due to steric inhibition of resonance, retardation due to steric bulk, and through space interactions. The primary hydrolytic pathway in alkaline solutions was consistent with a modified BAC2 mechanism. The Hammett plots for hydrolysis of meta- and para-substituted formanilides in 0.10 M sodium hydroxide solutions did not show substituent effects; however, ortho substitution led to a decrease in rate constants proportional to the steric bulk of the substituent.

Synthesis, cytotoxic evaluation, and in silico studies of substituted N-alkylbromo-benzothiazoles

In efforts to develop a new class of anticancer agents with improved efficacy and selective action, a series of N-alkylbromo-benzothiazoles were synthesized and evaluated for in vitro cytotoxic activity against various human cancer cell lines such as lung (A-549), prostate (PC-3), leukemia (THP-1), and colon (Caco-2). They were found to be highly active against prostate (PC-3) and leukemia (THP-1) cancer cells, moderately active against colon (Caco-2) cancer cells and less active against lung (A-549) cancer cells. Of the 12 compounds, two (11d, 11j) exhibit IC50 values of ≤ 1 μM against leukemia (THP-1) cancer cell lines. Compound 11l showed significant cytotoxic activity against the PC-3 (IC50 = 0.6 μM), THP-1 (IC50 = 3 μM) and Caco-2 cell lines (IC50 = 9.9 μM), respectively. Docking study of the synthesized ligand was done on epidermal growth factor receptor using ArgusLab flexible docking, to determine their observed activity. Further QSAR investigations with stepwise multiple linear regression analysis were applied to find correlation between various physicochemical parameters and anticancer activity. The QSAR results showed that anticancer activity could be modeled with descriptors. The predictive ability of models was cross-validated by observation of the low residual activity values and adjusted coefficient of variation (radj2) obtained by leave-one-out technique.

A facile and efficient method for the selective deacylation of N-arylacetamides and 2-chloro-Narylacetamides catalyzed by SOCl2

Thionyl chloride efficiently and selectively promoted the deacylation of N-arylacetamides and 2-chloro-N-arylacetamides, under anhydrous conditions, without effecting the ester group, aminosulfonyl group, or benzyloxyamide group. This method, which has been successfully applied to a variety of substrates including different N-arylacetamides and 2-chloro-N-arylacetamides, has the attractive advantages of inexpensive reagents, satisfactory selectivity, excellent yields, short reaction time, and convenient workup. This new method can probably be used to selectively deacylate between aromatic amides and alkyl amides. Springer Science+Business Media B.V. 2011.