14271-73-9

Usage

Uses

Used in Pharmaceutical Industry:
4-METHYLBENZOYL CYANIDE is used as a reactant for the synthesis of a muscarinic acetylcholine receptor (mAChR) modulator. It plays a crucial role in the development of drugs targeting the central nervous system, particularly those aimed at treating conditions such as Alzheimer's disease, schizophrenia, and other cognitive disorders.
In the synthesis process, 4-METHYLBENZOYL CYANIDE serves as a key building block, providing the necessary structural framework for the final mAChR modulator. Its reactivity and functional groups enable the formation of various chemical bonds, allowing for the creation of complex molecules with specific biological activities.
The use of 4-METHYLBENZOYL CYANIDE in the pharmaceutical industry highlights its importance as a versatile and valuable chemical intermediate. Its application in the synthesis of mAChR modulators demonstrates its potential in contributing to the development of novel therapeutic agents for a range of neurological and psychiatric conditions.

Synthesis Reference(s)

Tetrahedron Letters, 26, p. 925, 1985 DOI: 10.1016/S0040-4039(00)61966-4Synthesis, p. 637, 1983 DOI: 10.1055/s-1983-30454

Upstream product

• 106-43-4 para-chlorotoluene 
• 460-19-5 ethanedinitrile 
• 108-88-3 toluene 
• 544-92-3 copper(I) cyanide 
• 874-60-2 4-methyl-benzoyl chloride 
• 1115-12-4 carbonyl cyanide 
• 1075-47-4 4-methylphenylglyoxal 
• 201230-82-2 carbon monoxide 
• 624-31-7 4-tolyl iodide 
• 151-50-8 potassium cyanide 
• 1904-60-5 3-amino-2-phenylquinazolin-4(3H)-one 
• 619-41-0 4-(bromoacetyl)toluene 
• 33534-88-2 2-(4-methylphenyl)malononitrile 
• 4815-10-5 2-hydroxy-2-(4-methylphenyl)acetonitrile 

Downstream Products

• 6833-18-7 4-methyl-N-phenylbenzamide 
• 5955-79-3 p-Tolyl-glyoxylsaeure-thionamid 
• 68019-84-1 2-ethoxy-3-ethyl-2,4-dioxo-5-p-tolyl-2λ⁵-[1,3,2]oxazaphospholidine-5-carbonitrile 
• 99817-28-4 3-amino-4-(p-tolyl)-1,2,5-oxadiazole 
• 149403-05-4 (S)-1-(4'-methylphenyl)-2-aminoethanol 
• 97642-98-3 (R)-1-(4'-methylphenyl)-2-aminoethanol 
• 7163-50-0 (4-methylphenyl)(oxo)acetic acid 
• 75599-79-0 2-(4′-methylbenzoyloxy)-2-(4-methylphenyl)acetonitrile 
• 104-85-8 para-methylbenzonitrile 
• 121019-54-3 4-amino-2-p-chlorophenyl-5-p-tolyloxazole 
• 121019-56-5 4-amino-2-p-nitrophenyl-5-p-tolyloxazole 
• 82461-61-8 C₁₄H₁₃NO₂ 
• 125654-19-5 2-Phenyl-5-p-tolyl-2H-[1,2,3]triazol-4-ylamine 
• 121019-55-4 4-amino-2-o-nitrophenyl-5-p-tolyloxazole 

Relevant academic research and scientific papers

Anomalous Reaction of Arylmalononitriles with Nitric Acid. Para-Directing Nature of Dicyanomethyl Group and a Through-Ring Nitro/aci-Nitro Tautomerism of 4-Nitrophenylmalononitrile

Phenylmalononitrile reacts with nitric acid in dichloromethane at room temperature to afford 1,2-bis(4-nitrophenyl)-1,1,2,2-tetracyanoethane as an initial product, which readily suffers oxidative cleavage to give 4-nitrobenzoyl cyanide.Contrary to common

Novel synthesis method of alpha-carbonyl acid ester

The invention discloses a novel synthesis method of alpha-carbonyl acid ester. The method comprises the following steps: carrying out chlorination reaction on an alpha-methylene-containing nitrile compound and chlorine to obtain dichloronitrile, reacting the dichloronitrile product in a sulfuric acid and water system to obtain formyl cyanide, then acquiring an imino sulfate compound in the same reaction system, and finally performing esterification to obtain the target product. The adopted reaction raw materials are wide in sources and low in price, highly toxic solid sodium cyanide can be prevented from being used in the prior art, the method is environmentally friendly, and the method is easy to operate, mild in condition and easy to industrialize.

Palladium-Catalyzed One-Pot Four-Component Synthesis of β-Cyano-α,β-unsaturated Ketones Using Calcium Carbide as an Acetylene Source and Potassium Hexacyanoferrate(II) as an Eco-Friendly Cyanide Source

Palladium-catalyzed one-pot four-component synthesis of β-cyano-α,β-unsaturated ketones by the reactions of aryl halides, calcium carbide, potassium hexacyanoferrate(II) and aroyl chlorides is described. The salient features of this protocol are the direct use of easy-to-handle acetylene source and eco-friendly cyanide source, wide scope of substrates with good functional group tolerance, and simple work-up procedure. (Figure presented.).

Acceptorless and Base-free Dehydrogenation of Cyanohydrin with (η6-Arene)halide(Bidentate Phosphine)ruthenium(II) Complex

Ruthenium-catalyzed dehydrogenation of cyanohydrins under acceptorless and base-free conditions was demonstrated for the first time in the synthesis of acyl cyanide. As opposed to the thermodynamically preferred elimination of hydrogen cyanide, the dehydrogenation of cyanohydrins could be kinetically controlled with ruthenium (II) bidentate phosphine complexes. The effects of the arene, phosphine ligands and counter anions were investigated in regard to catalytic activity and selectivity. Selective dehydrogenation can occur via β-hydride elimination with the experimentally observed [(alkoxide)Ru] complex. (Figure presented.).

Rh-Catalyzed Asymmetric Hydrogenation of 1,2-Dicyanoalkenes

A highly efficient enantioselective hydrogenation of 1,2-dicyanoalkenes catalyzed by the complex of rhodium and f-spiroPhos has been developed. A series of 1,2-dicyanoalkenes were successfully hydrogenated to the corresponding chiral 1,2-dicyanoalkanes under mild conditions with excellent enantioselectivities (up to 98% ee). This methodology provides efficient access to the asymmetric synthesis of chiral diamines.

Dual Lewis Acid/Lewis Base Catalyzed Acylcyanation of Aldehydes: A Mechanistic Study

A mechanistic investigation, which included a Hammett correlation analysis, evaluation of the effect of variation of catalyst composition, and low-temperature NMR spectroscopy studies, of the Lewis acid-Lewis base catalyzed addition of acetyl cyanide to prochiral aldehydes provides support for a reaction route that involves Lewis base activation of the acyl cyanide with formation of a potent acylating agent and cyanide ion. The cyanide ion adds to the carbonyl group of the Lewis acid activated aldehyde. O-Acylation by the acylated Lewis base to form the final cyanohydrin ester occurs prior to decomplexation from titanium. For less reactive aldehydes, the addition of cyanide is the rate-determining step, whereas, for more reactive, electron-deficient aldehydes, cyanide addition is rapid and reversible and is followed by rate-limiting acylation. The resting state of the catalyst lies outside the catalytic cycle and is believed to be a monomeric titanium complex with two alcoholate ligands, which only slowly converts into the product.

Reactions of Zirconocene-1-Aza-1,3-diene Complexes with Acyl Cyanides: Substrate-Dependent Synthesis of Acyl- or Non-Acyl-Substituted Pyrroles

Insertion of acyl cyanides into azazirconacyclopentenes derived from 1,3-azadienes has been described, which affords acyl- or non-acyl-substituted pyrroles upon acidic quenching. These reactions are initialized through C=O insertion into the azazirconacycle to afford seven-membered oxaazazirconacycles. In the cases of 1,4- or 1,2,4-substituted azadienes, addition of a second molecule of acyl cyanide followed by cyclization upon acidic quenching leads to acyl-substituted pyrroles. In the cases of 1,3,4-substituted azadienes, the addition of a second molecule of acyl cyanide cannot proceed due to the steric hindrance caused by the R3 group on the zirconium intermediate. Acidic quenching of the resulting zirconium intermediate affords non-acyl-substituted pyrroles.

ZnI2-catalyzed cyanation of acyl chlorides with TMS-CN: An interesting role of iodine

Both aliphatic and aromatic acyl cyanides have been synthesized with TMSCN and acyl chloride with ZnI2 (0.5 mol%). However the in situ generated I2 is proposed accounting for the formation of by-product O-TMS enolate at high catalyst loading rather than 0.5 mol%. Asymmetric reduction of benzoyl cyanide with borane has been explored in 82% yield and 24% ee.

A new convenient synthesis of aroyl cyanides via the formation of cyanohydrin nitrate intermediates

The treatment of α-bromoarylacetonitriles with AgNO3 generates cyanohydrin nitrate intermediates, which easily eliminate nitrous acid with the formation of carbonyl bond to afford aroyl cyanides in good to high yields.

o-iodoxybenzoic acid- and tetraethylammonium bromide-mediated oxidative transformation of primary carboxamides to one-carbon dehomologated nitriles

A clean and efficient method for the oxidative transformations of primary carboxamides to one-carbon dehomologated nitriles using the combination of o-iodoxybenzoic acid and tetraethylammonium bromide has been developed. This method exhibits a broad scope and is expected to be of great utility in organic synthesis.