20359-56-2

Usage

Synthesis Reference(s)

Tetrahedron Letters, 27, p. 929, 1986 DOI: 10.1016/S0040-4039(00)84140-4

InChI:InChI=1/C12H16O/c1-3-4-9-12(13)11-8-6-5-7-10(11)2/h5-8H,3-4,9H2,1-2H3

Upstream product

• 875856-17-0 1-(o-tolyl)pentan-1-imine 
• 74571-46-3 2-Benzyloxy-hexanenitrile 
• 693-03-8 n-butyl magnesium bromide 
• 933-88-0 ortho-toluoyl chloride 
• 118-90-1 ortho-methylbenzoic acid 
• 109-72-8 n-butyllithium 
• 107-12-0 propiononitrile 
• 623-03-0 4-Cyanochlorobenzene 
• 529-19-1 2-Methylbenzonitrile 
• 693-04-9 butyl magnesium bromide 
• 42930-39-2 n-butylzinc chloride 
• 87-24-1 ethyl 2-methylbenzoate 
• 16419-60-6 2-Methylphenylboronic acid 
• 100-39-0 benzyl bromide 

Downstream Products

• 3413-15-8 butylphthalide 

Relevant academic research and scientific papers

A Fast and General Route to Ketones from Amides and Organolithium Compounds under Aerobic Conditions: Synthetic and Mechanistic Aspects

We report that the nucleophilic acyl substitution reaction of aliphatic and (hetero)aromatic amides by organolithium reagents proceeds quickly (20 s reaction time), efficiently, and chemoselectively with a broad substrate scope in the environmentally responsible cyclopentyl methyl ether, at ambient temperature and under air, to provide ketones in up to 93 % yield with an effective suppression of the notorious over-addition reaction. Detailed DFT calculations and NMR investigations support the experimental results. The described methodology was proven to be amenable to scale-up and recyclability protocols. Contrasting classical procedures carried out under inert atmospheres, this work lays the foundation for a profound paradigm shift of the reactivity of carboxylic acid amides with organolithiums, with ketones being straightforwardly obtained by simply combining the reagents under aerobic conditions and with no need of using previously modified or pre-activated amides, as recommended.

Iron-Catalyzed ortho C?H Arylation and Methylation of Pivalophenone N?H Imines

Iron-catalyzed ortho C?H arylation and methylation reactions of pivalophenone N?H imines are reported. The pivaloyl N?H imine proved an excellent directing group for the arylation with diarylzinc reagents in the presence of an iron-diphosphine catalyst an

Controlled photo-flow oxidative reaction (UV-FOR) platform for ultra-fast phthalide and API synthesis

An integrated photo-flow oxidative reaction (UV-FOR) platform approach is presented for the synthesis of phthalides. The current protocol is catalyst-free, and uses economical and abundant hydro-carbons and hydrocarbon derivatives such as benzoic acid, benzene, and xylene, as starting materials. The reaction is performed using oxygen as a green oxidant in a time- and labour-efficient manner. This integrated approach has been shown to be successful in making a UV-FOR platform suitable for the on-demand synthesis of phthalides and their further syntheses to 2-arylmethylbenzoic acids and arylogous Michael addition products under relatively mild conditions. The current protocol was further extended to the gram scale synthesis of an ischemic stroke-relevant active pharmaceutical ingredient (API), 3-N-butylphthalide (NBP), in a continuous flow process.

Pd-catalyzed Oxidative Cross-coupling of Alkyl Chromium(0) Fischer Carbene Complexes with Organoboronic Acids

Alkyl chromium(0) carbene complexes have been explored as the cross-coupling partners in the palladium-catalyzed reaction with aryl or alkenyl boronic acids. This coupling reaction displays the versatile reactivities of alkyl chromium(0) carbenes under palladium catalysis. Mechanistically, this transformation is proposed to involve deprotonation of the alkyl chromium carbene substrate to generate a vinyl chromium anion intermediate that undergoes transmetalation to organopalladium species and reductive elimination.

Mild and direct conversion of esters to morpholine amides using diisobutyl(morpholino)aluminum: Application to efficient one-pot synthesis of ketones and aldehydes from esters

Morpholine amide intermediates, which are easily prepared by aminolysis of various esters with diisobutyl(morpholino)aluminum, react with organolithium and reducing agents (DIBALH or LDBMA) without isolation of the aminolysis intermediates to give ketones in 83-95% yields and aldehydes quantitatively.

A Palladium Bipyridyl Complex Grafted onto Nanosized MCM-41 as a Heterogeneous Catalyst for Negishi Coupling

The Negishi coupling of aryl bromides or acyl chlorides with organozinc chlorides catalyzed by a palladium bipyridyl complex anchored on nanosized mobile crystalline material 41 (MCM-41) were investigated. The reactions proceeded smoothly with a very low catalyst loading in THF at 70°C for electron-deficient aryl bromides, which gave good to high yields of the Negishi coupling products. However, reactions in toluene at 110°C were required if electron-rich aryl bromides were employed. For acyl chlorides, the reactions could be performed in THF at 50°C and the corresponding ketones and ynones were obtained in high yields. After centrifugation, it was possible to easily recover the supported catalyst from the reaction mixture, and this could be reused several times without any retreatment or regeneration with only a slight decrease in activity.

1-(4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (pyrovalerone) analogues: A promising class of monoamine uptake inhibitors

Dopamine, serotonin, and norepinephrine are essential for neurotransmission in the mammalian system. These three neurotransmitters have been the focus of considerable research because the modulation of their production and their interaction at monoamine receptors has profound effects upon a multitude of pharmacological outcomes. Our interest has focused on neurotransmitter reuptake mechanisms in a search for medications for cocaine abuse. Herein we describe the synthesis and biological evaluation of an array of 2-aminopentanophenones. This array has yielded selective inhibitors of the dopamine and norepinephrine transporters with little effect upon serotonin trafficking. A subset of compounds had no significant affinity at 5HT1A, 5HT1B, 5HT1C, D1, D2, or D3 receptors. The lead compound, racemic 1-(4-methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one 4a, was resolved into its enantiomers and the S isomer was found to be the most biologically active enantiomer. Among the most potent of these DAT/NET selective compounds are the 1-(3,4-dichlorophenyl)- (4u) and the 1-naphthyl- (4t) 2-pyrrolidin-1-yl-pentan-1-one analogues.

A new synthetic method to 2-pyridones

We report here a simple procedure for the preparation of 4,6- disubstituted- and 3,4,6-trisubstituted-2-pyridones and 3-substituted- isoquinol-1-ones, in good yields, from lithium diene-diolates and nitriles.

Directed Lithiation of Tertiary β-Amino Benzamides

The directed ortho-lithiation-alkylation of several tertiary β-amino benzamides was studied.The ortho-substituted β-amino benzamides were hydrolyzed directly with 6 N hydrochloric acid, or by a three-step, one-pot reaction involving methylation, elimination, and treatment with aqueous acid. o-Toluic acid, 2-n-butylbenzoic acid, 2-methoxy-6-methylbenzoic aicd, and 4-methoxy-2-methylbenzoic acid were prepared by using this ortho-metalation-hydrolysis methodology.Ortho-lithiation and reaction with benzaldehyde or dimethylformamide followed by hydrolysis with aqueous acid gave lactones in good yield.Methanolysis of N-(4-methoxy-2-methyl benzoyl)-N'-methylpiperizine with sulfuric acid/methanol gave methyl 4-methoxy-2-methylbenzoate in 71percent yield.The conversion of tertiary benzamides into ketones and aldehydes was examined.Treatment of certain tertiary benzamides with alkyllithium reagents gave ketones, while reaction with a modified aluminum hydride reagent gave aldehydes

HIGHLY CHEMOSELECTIVE COUPLING REACTIONS OF ORGANOVANADIUM COMPOUNDS

Organovanadium compounds generated in dichloromethane from equimolar amounts of vanadium trichloride and Grignard reagents underwent the chemoselective cross-coupling reaction with acid chlorides leading to the corresponding ketones.Treatment with allyl halides resulted in allylation of organovanadium compounds.In the case of propargyl bromide, regioselective displacement occured to produce allene derivatives.