7175-47-5

Usage

Preparation

To a flask containing 5.4 gm (0.05 mole) of p-toluidine in 100 ml of dry 1,2-dimethoxyethane is added 28 gm (0.15 mole) of sodium trichloroacetate. The reaction is slightly exothermic. The reaction mixture is refluxed for ? hr, whereupon carbon dioxide is copiously evolved. The reaction mixture is filtered, the solid (10 gm) is washed with ether, and the combined reddish black filtrate concentrated. The residue is extracted with ether, washed with water, dried, and concentrated to afford a red-black oil, which, upon distillation, gives 2.5 gm (43%), b.p. 38°C (1 mm Hg), m.p. 19-20°C of a yellow liquid, IR, 4.69 μ (—NC).

InChI:InChI=1/C8H7N/c1-7-3-5-8(9-2)6-4-7/h3-6H,1H3

Upstream product

• 589-93-5 2,5-dimethylpyridine 
• 67-66-3 chloroform 
• 3085-54-9 N-(4-methylphenyl)formamide 
• 15296-47-6 N-p-tolyl-formimidic acid ethyl ester 
• 106-49-0 p-toluidine 
• 109499-74-3 Diethyl--orthopropionat 
• 622-59-3 1-isothiocyanato-4-methylbenzene 
• 64-17-5 ethanol 
• 7647-01-0 hydrogenchloride 
• 16519-45-2 N,N'-di-p-tolylselenourea 
• 86119-84-8 phosphoric acid 
• 64-19-7 acetic acid 
• 81-88-9 rhodamine B 
• 113779-60-5 bis(4-methylphenylisocyanide)(tetra(2,3-pyrido)porphyrazinato)iron(II) 

Downstream Products

• 27429-31-8 N-(4-methylphenyl)-N'-(2-pyridyl)thiourea 
• 42793-96-4 dihydroxy-malonic acid di-p-toluidide 
• 15296-47-6 N-p-tolyl-formimidic acid ethyl ester 
• 57585-32-7 N-p-tolyl-formimidic acid methyl ester 
• 16596-03-5 N,N'-di-p-tolylformamidine 
• 16001-28-8 N-4-methylphenyl isocyanodichloride 
• 38308-69-9 p-Tolyl-(4,4,4-trifluoro-3-methoxy-2-trifluoromethyl-but-1-enylidene)-amine 
• 76669-11-9 1,1''-Dimethyl-5'(4-tolylimino)dispiro-2(1H),2''(1''H),4,4''-tetron 
• 106-49-0 p-toluidine 
• 89-62-3 4-methyl-2-nitroaniline 
• 115930-29-5 2-p-tolyl-3-(p-tolylamino)-6,7-di-(p-tolyl)pyrrolo<3,4-g>quinoxaline-4,9-dione 
• 92883-94-8 N,N,N',N'-Tetramethyl-3-p-tolylimino-cycloprop-1-ene-1,2-diamine 
• 18169-42-1 [2-Methyl-prop-(E)-ylidene]-p-tolyl-amine 
• 129801-41-8 (Z)-3-p-Tolyl-2-p-tolyliminomethyleneamino-acrylic acid ethyl ester 

Relevant academic research and scientific papers

Silver-Catalyzed Selective Multicomponent Coupling Reactions of Arynes with Nitriles and Isonitriles

Pathway selective aryne-based novel multicomponent coupling reactions with isonitriles and nitriles are described. Crucial to these reactions is the formation of a silver-aryne complex, which shows differential reactivity toward isonitriles and nitriles to form two different forms of ortho-nitrilium organosilver arene species. Interception of the nitrilium of an aryne-isonitrile adduct with another isonitrile leads to the formation of benzocyclobutene-1,2-diimines, whereas the nitrilium of an aryne-nitrile adduct renders selective formation of 3H-indol-3-imines or 3-iminoindolin-2-ol depending on the structure of the nitrile employed.

Isocyanide 2.0

The isocyanide functionality due to its dichotomy between carbenoid and triple bond characters, with a nucleophilic and electrophilic terminal carbon, exhibits unusual reactivity in organic chemistry exemplified for example in the Ugi reaction. Unfortunately, the over proportional use of only a few isocyanides hampers novel discoveries about the fascinating reactivity of this functional group. The synthesis of a broad range of isocyanides with multiple functional groups is lengthy, inefficient, and exposes the chemist to hazardous fumes. Here we present an innovative isocyanide synthesis overcoming these problems by avoiding the aqueous workup which we exemplify by parallel synthesis from a 0.2 mmol scale performed in 96-well microtiter plates up to a 0.5 mol multigram scale. The advantages of our methodology include an increased synthesis speed, very mild conditions giving access to hitherto unknown or highly reactive classes of isocyanides, rapid access to large numbers of functionalized isocyanides, increased yields, high purity, proven scalability over 5 orders of magnitude, increased safety and less reaction waste resulting in a highly reduced environmental footprint. For example, the hitherto believed to be unstable 2-isocyanopyrimidine, 2-acylphenylisocyanides and even o-isocyanobenzaldehyde could be accessed on a preparative scale and their chemistry was explored. Our new isocyanide synthesis will enable easy access to uncharted isocyanide space and will result in many discoveries about the unusual reactivity of this functional group. This journal is

Palladium-Catalyzed Diarylation of Isocyanides with Tetraarylleads for the Selective Synthesis of Imines and α-Diimines

Using tetraaryllead compounds (PbAr4) as arylating reagents, isocyanides undergo selective diarylation in the presence of palladium catalysts such as Pd(OAc)2 or Pd(PPh3)4 to afford imines and/or α-diimines based on the isocyanide employed. With aliphatic isocyanides, imines are obtained preferentially, whereas α-diimines are formed in the case of electron-rich aromatic isocyanides. The differences in imine/α-diimine selectivity can be attributed to the stability of imidoylpalladium intermediates formed in this catalytic reaction. Compared with other arylating reagents, tetraaryllead compounds are excellent candidates for use in the selective transformations to imines and/or α-diimines, especially in terms of inhibiting the oligomerization of isocyanides, which results in a lower product selectivity in many transition-metal-catalyzed reactions of isocyanides.

Visible-light-induced radical cascade cyclization of oxime esters and aryl isonitriles: Synthesis of cyclopenta[: B] quinoxalines

A visible-light-induced radical cascade cyclization of aryl isonitriles and cyclobutanone oxime esters for the synthesis of cyclopenta[b]quinoxalines has been accomplished for the first time. The key to the success of this process was the integration of the in situ-formed nitrile radical followed by the cascade radical isonitrile/nitrile insertion-cyclization. The easy introduction of substituents for both substrates and the high functional group tolerance of the reaction make it an efficient strategy to give various quinoxaline derivatives in moderate to good yields.

Selective Gold-Catalysed Synthesis of Cyanamides and 1-Substituted 1H-Tetrazol-5-Amines from Isocyanides

The newly discovered gold-catalysed reaction of isocyanides with hydrazoic acid generated in situ from trimethylsilyl azide and methanol (or, alternatively, from NaN3/AcOH) produces either cyanamides or 1-substituted 1H-tetrazol-5-amines, depending on the amount of available HN3. The reaction proceeds selectively and in generally high yields of either product, thus providing a particularly convenient access to a wide range of substituted 1H-tetrazol-5-amines that are rather difficult to access otherwise.

Visible-Light-Induced Radical Cascade Cyclization: Synthesis of the ABCD Ring Cores of Camptothecins

A new strategy for constructing indolizino[1,2-b]quinolin-9(11H)-ones (ring cores of camptothecins) from readily available isocyanoarenes and N-(alkyl-2-yn-1-yl)pyridin-2(1H)-ones has been developed through a visible-light-induced radical cascade cyclization process. The reaction proceeds under mild conditions with fair to excellent yields. The easy introduction of substituents for both reactants and the broad functional group tolerance of the reaction make it a straightforward route to the cores of the marketed camptothecins and their derivatives.

One-step synthesis of N, N′-substituted 4-imidazolidinones by an isocyanide-based pseudo-five-multicomponent reaction

A pseudo-five-multicomponent reaction involving an isocyanide, a primary amine, two molecules of formaldehyde and water is reported, which gives N,N′-substituted 4-imidazolidinones when trifluoroethanol is used as the solvent. The reaction proceeds with good yields and with a wide variety of amines and isocyanides, providing an efficient new entry to these heterocycles. A preliminary study of the reaction mechanism suggests that trifluoroethanol, although acting as the solvent, is directly involved as a reagent in the reaction pathway.

Development of an Industrial Process Based on the Groebke-Blackburn-Bienaymé Multicomponent Reaction: Efficient Preparation- of 3-Aminoimidazo[1,2-a]pyrazines

3-Aminoimidazo[1,2-a]pyrazine is an important scaffold that is found in many drugs. This scaffold is rapidly accessible through a Groebke-Blackburn-Bienaymé cyclisation starting from an aminopyrazine, an aldehyde and an isocyanide. A scale-up process of this multicomponent reaction has been achieved in high yield and with excellent purity. The scope and limitations of this process leading to various 3-aminoimidazo[1,2-a]pyrazines are disclosed.

An isocyanide based multi-component reaction under catalyst- and solvent-free conditions for the synthesis of unsymmetrical thioureas

A new and efficient method for the synthesis of thiourea derivatives by a sequential one-pot, three-component reaction between aromatic isocyanides, amines, and 1,2-di-tert-butyldisulfane (DTBS) was developed and 27 different examples were synthesized in good to excellent yields. DTBS was identified as an effective sulfur surrogate without the use of both catalysts and solvents. This protocol does not employ any transition metal catalyst or special experimental setup.

Cobalt(II)-Catalyzed Isocyanide Insertion Reaction with Sulfonyl Azides in Alcohols: Synthesis of Sulfonyl Isoureas

A Co(II)-catalyzed isocyanide insertion reaction with sulfonyl azides in alcohols to form sulfonyl isoureas via nitrene intermediate has been developed. This protocol provides a new, environmentally friendly, and simple strategy for the synthesis of sulfonyl isourea derivatives by employing a range of substrates under mild conditions.