10354-50-4

Basic information

• Product Name: 2-Pyridinecarboxamide, N-cyclohexyl-
• CAS NO: 10354-50-4
• Molecular Formula: C12H16N2O
• Molecular Weight: 204.272
• Mol File: 10354-50-4.mol

Chemical Properties

• CAS DataBase Reference: 2-Pyridinecarboxamide, N-cyclohexyl-(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Pyridinecarboxamide, N-cyclohexyl-(10354-50-4)
• EPA Substance Registry System: 2-Pyridinecarboxamide, N-cyclohexyl-(10354-50-4)

Safety Data

• Hazardous Substances Data: 10354-50-4(Hazardous Substances Data)

Upstream product

• 110-86-1 pyridine 
• 931-53-3 Cyclohexyl isocyanide 
• 98-98-6 2-Picolinic acid 
• 108-91-8 cyclohexylamine 
• 69157-32-0 picolinic acid 
• 1452-77-3 pyridine-2-carboxylic acid amide 
• 110-82-7 cyclohexane 
• 29745-44-6 pyridine-2-carbonyl chloride 
• 109-09-1 2-chloropyridine 

Relevant articles and documents

Amidation via ligand-free direct oxidative C(sp3)-H/N[sbnd]H coupling with Cu-CPO-27 metal-organic framework as a recyclable heterogeneous catalyst

A copper-based metal-organic framework Cu-CPO-27 was synthesized, and used as a recyclable catalyst for the amidation of unactivated alkanes by benzamides via direct oxidative C(sp3)-H/N[sbnd]H coupling under ligand-free conditions. Using a catalytic amount of the Cu-CPO-27 for the transformation, high yields of N-cyclohexyl benzamides were achieved. The Cu-CPO-27 was more catalytically active than other Cu-MOFs such as Cu3(BTC)2, Cu(BDC), Cu(EDB), Cu2(BPDC)2(BPY), Cu2(BDC)2(DABCO), and Cu2(EDB)2(BPY). The Cu-CPO-27 also exhibited advantages as compared to several copper-based salts, including Cu(OAc)2, CuCl2, CuBr, CuI, CuCl, Cu(NO3)2, and CuSO4. The Cu-CPO-27 catalyst could be reused several times for the amidation transformation while its catalytic activity was not decreased significantly. To the best of our knowledge, the amidation of unactivated alkanes by benzamides via direct oxidative C(sp3)-H/N[sbnd]H coupling was not previously performed under heterogeneous catalysis conditions.

Tuning Reactivity in Pd-catalysed C(sp3)-H Arylations via Directing Group Modifications and Solvent Selection

The palladium-catalysed sp3 C?H arylation of a selection of saturated amine scaffolds was investigated using substituted picolinamide directing groups. On the bornylamine scaffold, highly selective monoarylation takes place using unsubstituted picolinamide or 3-methylpicolinamide, whereas a double C?H arylation occurs with other substituents present, becoming a significant product with 3-trifluoromethylpicolinamide. DFT calculations were used to help rationalise the effect of directing groups on the C?H palladation steps which were found experimentally to be irreversible. The substituted picolinamide directing groups were also examined on acyclic amine scaffolds and in many cases increased yields and selectivity could be obtained using methylpicolinamides. For a selection of other amine scaffolds, the yield of C?H arylation could be improved significantly using 3-methylpicolinamide as the directing group and/or 3-methylpentan-3-ol as the solvent. (Figure presented.).

Reaction of N-fluoropyridinium fluoride with isonitriles and TMSN 3: A convenient one-pot synthesis of tetrazol-5-yl pyridines

Reaction of N-fluoropyridinium fluoride generated in situ with a series of isonitriles and TMSN3 led to the formation of the corresponding tetrazol-5-yl pyridines in good yields (37-84%). A similar reaction sequence for quinoline yielded the respective derivatives of 2-quinoline. The proposed reaction mechanism involves the intermediate formation of a highly reactive carbene species.

A case study of Pd?Pd intramolecular interaction in a benzothiazole based palladacycle; catalytic activity toward amide synthesisviaan isocyanide insertion pathway

An acetate bridge benzothiazolepalladacycle containing a rare metallophilic intramolecular Pd?Pd interaction was synthesized and thoroughly characterized. The synthesized benzothiazolepalladacycle directly anchored on SBA-15 to form an efficient heterogen

Iridium(III)-Catalyzed Regioselective Intermolecular Unactivated Secondary Csp3?H Bond Amidation

For the first time, a highly regioselective intermolecular sulfonylamidation unactivated secondary Csp3?H bond has been achieved using IrIIIcatalysts. The introduced N,N’-bichelating ligand plays a crucial role in enabling iridium–nitrene insertion into a secondary Csp3?H bond via an outer-sphere pathway. Mechanistic studies and density functional theory (DFT) calculations demonstrated that a two-electron concerted nitrene insertion was involved in this Csp3?H amidation process. This method tolerates a broad range of linear and branched-chain N-alkylamides, and provides efficient access to diverse γ-sulfonamido-substituted aliphatic amines.

Pd(ii)-Catalyzed gamma-C(sp3)-H alkynylation of amides: Selective functionalization of R chains of amides R1C(O)NHR

The gamma C(sp3)-H bond alkynylation of R chains of amides R1C(O)NHR, a fundamental class of synthetic substrates, has not been accomplished to date. Here, the first example of palladium(ii)-catalyzed alkynylation of an unactivated gamma C(sp3)-H bond of alkyl amides (cyclic, linear, and amino acids) is reported. The kinetic experiment shows that the rate of the reaction depends on the coupling partners and the amides. Late-stage diversification of alkynylated amides was developed by utilizing amine and alkyne functionalities.

Expedient Synthesis of Bridged Bicyclic Nitrogen Scaffolds via Orthogonal Tandem Catalysis

Bridged nitrogen bicyclic skeletons have been accessed via unprecedented site- and diastereoselective orthogonal tandem catalysis from readily accessible reactants in a step economic manner. Directed Pd-catalyzed γ-C(sp3)-H olefination of aminocyclohexane with gem-dibromoalkenes, followed by a consecutive intramolecular Cu-catalyzed amidation of the 1-bromo-1-alkenylated product delivers the interesting normorphan skeleton. The tandem protocol can be applied on substituted aminocyclohexanes and aminoheterocycles, easily providing access to the corresponding substituted, aza- and oxa-analogues. The Cu catalyst of the Ullmann-Goldberg reaction additionally avoids off-cycle Pd catalyst scavenging by alkenylated reaction product. The picolinamide directing group stabilizes the enamine of the 7-alkylidenenormorphan, allowing further product post functionalizations. Without Cu catalyst, regio- and diastereoselective Pd-catalyzed γ-C(sp3)-H olefination is achieved.

Catalytic direct amidations in: Tert -butyl acetate using B(OCH2CF3)3

Catalytic direct amidation reactions have been the focus of considerable recent research effort, due to the widespread use of amide formation processes in pharmaceutical synthesis. However, the vast majority of catalytic amidations are performed in non-polar solvents (aromatic hydrocarbons, ethers) which are typically undesirable from a sustainability perspective, and are often poor at solubilising polar carboxylic acid and amine substrates. As a consequence, most catalytic amidation protocols are unsuccessful when applied to polar and/or functionalised substrates of the kind commonly used in medicinal chemistry. In this paper we report a practical and useful catalytic direct amidation reaction using tert-butyl acetate as the reaction solvent. The use of an ester solvent offers improvements in terms of safety and sustainability, but also leads to an improved reaction scope with regard to polar substrates and less nucleophilic anilines, both of which are important components of amides used in medicinal chemistry. An amidation reaction was scaled up to 100 mmol and proceeded with excellent yield and efficiency, with a measured process mass intensity of 8.

Polycyclic Azetidines and Pyrrolidines via Palladium-Catalyzed Intramolecular Amination of Unactivated C(sp3)-H Bonds

A novel strategy to construct complex polycyclic nitrogen-containing heterocycles from aliphatic amines via picolinamide-assisted palladium-catalyzed C-H bond activation reaction was reported. The reaction exhibits broad substrate scope for the synthesis of various azabicyclic scaffolds, including azetidines and tropane-class alkaloids. Application of this method to naturally occurring (-)-cis-myrtanylamine, an unprecedented type of carbon-carbon bond activation, in which the electron-pair involved initiates an intramolecular "SN2-like" displacement of a cyclopalladium-fragment from a tertiary center, is described.

Copper-catalyzed intermolecular amidation and imidation of unactivated alkanes

We report a set of rare copper-catalyzed reactions of alkanes with simple amides, sulfonamides, and imides (i.e., benzamides, tosylamides, carbamates, and phthalimide) to form the corresponding N-alkyl products. The reactions lead to functionalization at secondary C-H bonds over tertiary C-H bonds and even occur at primary C-H bonds. [(phen)Cu(phth)] (1-phth) and [(phen)Cu(phth)2] (1-phth2), which are potential intermediates in the reaction, have been isolated and fully characterized. The stoichiometric reactions of 1-phth and 1-phth2 with alkanes, alkyl radicals, and radical probes were investigated to elucidate the mechanism of the amidation. The catalytic and stoichiometric reactions require both copper and tBuOOtBu for the generation of N-alkyl product. Neither 1-phth nor 1-phth2 reacted with excess cyclohexane at 100 C without tBuOOtBu. However, the reactions of 1-phth and 1-phth2 with tBuOOtBu afforded N-cyclohexylphthalimide (Cy-phth), N-methylphthalimide, and tert-butoxycyclohexane (Cy-OtBu) in approximate ratios of 70:20:30, respectively. Reactions with radical traps support the intermediacy of a tert-butoxy radical, which forms an alkyl radical intermediate. The intermediacy of an alkyl radical was evidenced by the catalytic reaction of cyclohexane with benzamide in the presence of CBr4, which formed exclusively bromocyclohexane. Furthermore, stoichiometric reactions of [(phen)Cu(phth)2] with tBuOOtBu and (Ph(Me)2CO) 2 at 100 C without cyclohexane afforded N-methylphthalimide (Me-phth) from β-Me scission of the alkoxy radicals to form a methyl radical. Separate reactions of cyclohexane and d12-cyclohexane with benzamide showed that the turnover-limiting step in the catalytic reaction is the C-H cleavage of cyclohexane by a tert-butoxy radical. These mechanistic data imply that the tert-butoxy radical reacts with the C-H bonds of alkanes, and the subsequent alkyl radical combines with 1-phth2 to form the corresponding N-alkyl imide product.