Transition metal-free synthesis of primary amides from aldehydes and hydroxylamine hydrochloride

Primary aromatic amides can be synthesized from aldehydes and hydroxylamine hydrochloride in the presence of Cs₂CO₃. Various aromatic aldehydes (include some heteroaromatic aldehydes) are able to generate the corresponding aromatic amides in moderate to excellent yields.     

Convenient metal-free direct oxidative amidation of aldehyde using dibromoisocyanuric acid under mild conditions

A facile method for the direct synthesis of amides from aldehydes is described. Amide bonds were synthesized by an oxidative amidation in the presence of dibromoisocyanuric acid (DBI). Treatment of aromatic and aliphatic aldehydes with dibromoisocyanuric acid generated acyl bromide intermediates, which were employed to react with a variety of secondary and primary amines to give amides. Through this reaction method, various amides were synthesized directly from aldehydes under mild conditions in high yields and short times. This facile and efficient procedure provides potential strategy for the direct synthesis of amides from aldehydes.     

Aerobic oxidation of N-alkylamides catalyzed by N-hydroxyphthalimide under mild conditions. Polar and enthalpic effects

The oxidation of N-alkylamides by O(2), catalyzed by N-hydroxyphthalimide (NHPI) and Co(II) salt, leads under mild conditions to carbonyl derivatives (aldehydes, ketones, carboxylic acids, imides) whose distribution depends on the nature of the alkyl group and on the reaction conditions. Primary N-benzylamides lead to imides and aromatic aldehydes at room temperature without any appreciable amount of carboxylic acids, while under the same conditions nonbenzylic derivatives give carboxylic acids and imides with no trace of aldehydes, even at very low conversion. These results are explained through hydrogen abstraction by the phthalimide-N-oxyl (PINO) radical, whose reactivity with benzyl derivatives is governed by polar effects, so that benzylamides are much more reactive than the corresponding aldehydes. The enthalpic effect is, however, dominant with nonbenzylic amides, making the corresponding aldehydes much more reactive than the starting amides. The importance of the bond dissociation energy (BDE) of the O-H bond in NHPI is emphasized.     

Tf<Subscript>2</Subscript>O-TMDS combination for the direct reductive transformation of secondary amides to aldimines,aldehydes, and/or amines

The direct partial reduction of highly stable secondary amides to more reactive aldimines and aldehydes is a challenging yet highly demanding transformation. In this context, only three methods have been reported. We report herein an improved version of the Charette’s method. Our protocol consists of activation of secondary amides with triflic anhydride/2-fluoropyridine, and partial reduction of the resulting intermediates with 1,1,3,3-tetramethyldisiloxane (TMDS), which delivered aldimines or aldehydes upon acidic hydrolysis. Aromatic amides were reduced to the corresponding aldimines in 85%–100% NMR yields, and yields (NMR) from aliphatic amides were 72%–86%. Acidic hydrolysis of the aldimine intermediates afforded, in one-pot, the corresponding aldehydes in 80%–96% yields. A simple protocol was established to isolate labile aldimines in pure form in 92%–96% yields. The improved method gave generally higher yields as compared to the known ones, and features the use of cheaper and more atom-economical TMDS as a chemoselective reducing agent. In addition, a convenient extraction protocol has been established to allow the isolation of amines, which constitutes a mild method for the N-deacylation of amides, another highly desirable transformation. The extended method retains the advantages of the original method of Charette in terms of mild conditions, good functional group tolerance, and excellent chemoselectivity.     

Mild and selective hydrozirconation of amides to aldehydes using Cp2Zr(H)Cl: scope and mechanistic insight

An investigation of the use of Cp2Zr(H)Cl (Schwartz's reagent) to reduce a variety of amides to the corresponding aldehydes under very mild reaction conditions and in high yields is reported. A range of tertiary amides, including Weinreb's amides, can be converted directly to the corresponding aldehydes with remarkable chemoselectivity. Primary and secondary amides proved to be viable substrates for reduction as well, although the yields were somewhat diminished as compared to the corresponding tertiary amides. Results from NMR experiments suggested the presence of a stable, 18-electron zirconacycle intermediate that presumably affords the aldehyde upon water or silica gel workup. A series of competition experiments revealed a preference of the reagent for substrates in which the lone pair of the nitrogen is electron releasing and thus more delocalized across the amide bond by resonance. This trend accounts for the observed excellent selectivity for tertiary amides versus esters. Experiments regarding the solvent dependence of the reaction suggested a kinetic profile similar to that postulated for the hydrozirconation of alkenes and alkynes. Addition of p-anisidine to the reaction intermediate resulted in the formation of the corresponding imine mimicking the addition of water that forms the aldehyde.     

Cannizzaro-type disproportionation of aromatic aldehydes to amides and alcohols by using either a stoichiometric amount or a catalytic amount of lanthanide compounds

Aromatic aldehydes can be directly converted to the corresponding amides and alcohols in good to excellent yields by the treatment of aromatic aldehydes with lithium amide LiN(SiMe3)2 in the presence of catalytic lanthanide chlorides LnCl3 or by the treatment of aromatic aldehydes with a stoichiometric amount of lanthanide amides [(Me3Si)2N]3Ln(mu-Cl)Li(THF)3 at ambient temperature. The effects of solvents, substitutents on the phenyl ring, and lanthanide metals on the reaction have been examined. The mechanism of the disproportionation reaction was proposed based on the experimental results.     

Metal-free one-pot oxidative amination of aldehydes to amides

Metal-free oxidative amination of aromatic aldehydes in the presence of TBHP provides convenient access to amides in 85-99% under mild reaction conditions within 5 h. This method avoids free carboxylic acid intermediates and integrates aldehyde oxidation and amide bond formation, which are usually accomplished separately, into a single operation. Proline-derived amides can be prepared in excellent yields without noticeable racemization.     

A FACILE SYNTHESIS OF HETEROCYCLE SUBSTITUTED CHALCONE AND 5-NITROFURANYL OLEFIN DERIVATIVES

Reaction of heterocycle substituted telluronium salts with aroma-tic aldehydes under mild conditions gave corresponding chalcones.In thepresence of dibutyl telluride,2-bromomethyl-5-nitrofuran condensed easilywith aromatic aldehydes in THF to afford corresponding olefin derivativesas one-pot reaction.     

Efficient method for the reduction of carbonyl compounds by triethylsilane catalyzed by PdCl2

The versatility of the palladium(II) chloride and triethylsilane system has been tested in the reduction of aromatic carbonyl compounds. The reaction takes place under mild conditions. This facile and efficient method affords high yields for the reduction of aldehydes and ketones to the corresponding alkanes.     

Palladium oxide nanoparticles supported on graphene oxide: A convenient heterogeneous catalyst for reduction of various carbonyl compounds using triethylsilane

Palladium oxide nanoparticles supported on graphene oxide ‐ triethylsilane was found to be an effective reductive system for a broad range of reduction processes, including the reduction of various carbonyl compounds such as aromatic aldehydes to their corresponding alcohols or methyl arene compounds, aromatic ketones to their respective alcohols or saturated compounds, aromatic acyl chlorides to their reduced compounds. The desired products were obtained in good to excellent yields under mild conditions. The heterogeneous environmentally friendly catalyst can be easily separated from the reaction mixture through a simple filtration, facilitating purification of the prepared compounds.     

Synthesis of functional derivatives of aryl trichlorovinyl (trichloroallyl) ketones via consecutive transformations of the carbonyl group

An efficient procedure have been developed for the selective reduction of the carbonyl group in phenyl trichlorovinyl ketone and aryl trichloroallyl ketones by the action of NaBH₄ in propan-2-ol to obtain the corresponding alcohols. The hydroxy group in the latter was converted into amino by the Ritter reaction. Treatment of the alcohols and amines with 5-phenylisoxazole-3-carbonyl chloride and 4,5-dichloroisothiazole-3-carbonyl chloride gave the corresponding esters and amides, and condensation of the amines with aromatic aldehydes afforded Schiff bases.     

Cu-catalyzed reduction of azaarenes and nitroaromatics with diboronic acid as reductant

A ligand-free copper-catalyzed reduction of azaarenes with diboronic acid as reductant in an aprotic solvent under mild conditions has been developed. Most interestingly, the nitroazaarenes could be reduced exclusively to give the corresponding amines without touching the azaarene moieties. Furthermore, the reductive amination of aromatic nitro compounds and aromatic aldehydes has also been realized. A series of hydrogenated azaarenes and secondary amines were obtained with good functional group tolerance.     

Reduction of N,N‐Dimethylcarboxamides to Aldehydes by Sodium Hydride–Iodide Composite

A new and concise protocol for selective reduction of N,N‐dimethylamides into aldehydes was established using sodium hydride (NaH) in the presence of sodium iodide (NaI) under mild reaction conditions. The present protocol with the NaH‐NaI composite allows for reduction of not only aromatic and heteroaromatic but also aliphatic N,N‐dimethylamides with wide substituent compatibility. Retention of α‐chirality in the reduction of α‐enantioriched amides was accomplished. Use of sodium deuteride (NaD) offers a new step‐economical alternative to prepare deuterated aldehydes with high deuterium incorporation rate. The NaH‐NaI composite exhibits unique chemoselectivity for reduction of N,N‐dimethylamides over ketones.     

Highly anti-selective catalytic aldol reactions of amides with aldehydes

Barium phenoxide-catalyzed, highly anti-selective direct-type aldol reactions of amides with aldehydes have been developed. In the presence of a slight excess amount of an amide, the desired reactions proceeded smoothly under mild conditions, and a wide range of aromatic, heterocyclic, alpha,beta-unsaturated aldehydes were applicable to afford the desired adducts in high yields with high anti-selectivities. A catalytic, enantioselective reaction of an amide with an aldehyde using a chiral ligand is also described.     

Synthesis of amides through the Cannizzaro-type reaction catalyzed by lanthanide chlorides

Amidation of aldehydes with lithium amides through the LnCl₃-catalyzed Cannizzaro-type reactions afforded a variety of amides in high yields. The electronic and steric effects on the reaction were investigated. The features of the economical catalysts, high yields, tolerance of a wide range of lithium amides and aromatic aldehydes make this methodology an easy and valid contribution to the direct synthesis of amides from aldehydes.     

Direct Oxidation of N‐Benzylamides to Aldehydes or Ketones by N‐Bromosuccinimide

A simple and efficient approach for the one‐pot transformation of N‐benzylamides to aldehydes or ketones under mild conditions was reported. All the 20 substrates gave moderate to excellent oxidative yields under the optimized conditions. Our study may provide a new approach for the one‐pot synthesis of aldehydes or ketones from the corresponding amides.     

2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate as an efficient coupling reagent for the amidation and phenylhydrazation of carboxylic acids at room temperature

The synthesis of amides and phenylhydrazides from the reaction of corresponding carboxylic acids with primary aliphatic, aromatic amines or phenylhydrazine in the presence of triethylamine or diisopropylethyl amine as a base using 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) proceeds smoothly under mild conditions to afford the corresponding amides or phenylhydrazides in good to high yields in ethyl acetate at room temperature.     

nBu4NI-catalyzed oxidative amidation of aldehydes with tertiary amines

An efficient oxidative coupling protocol for amide formation has been developed. Various tertiary amines and aromatic aldehydes were oxidized to their corresponding tertiary amides in moderate to good yields in the presence of a simple nBu₄NI-catalyst.     

Reduction of Aromatic Aldehydes,Ketones with Acyloxy Substituent at the Ortho-position by NaBH4 in the Presence of Waters

n unusual reduction of some aromatic aldehydes, ketones by sodium borohydride was discovered. In a THF/H₂O or DMSO/H₂O solvent system the aromatic aldehydes, ketones with acyloxy substituent on the ortho-position to the carbonyl group can be reduced to the corresponding alkyl phenols. This unusual reduction is applicable also to the corresponding alcohols of all the above aldehydes, ketones. A putative mechanism was suggested. In addition to the above aldehydes, ketones, benzyl alcohols, certain 4-acyloxybenzyl esters(probably also the 2-substituted analogues) such as 4-benzoyloxybenzyl benzoate was also found to be reduced to methylphenol by this unusual reduction.     

Reduction of Aromatic Aldehydes and Ketones with Acyloxy Substituent at the Orthoposition by NaBH4 in the Presence of Waters*

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