Practical one-pot preparation of ketones from aryl and alkyl bromides with aldehydes and DIH via Grignard reagents

Various diaryl ketones, alkyl aryl ketones, and dialkyl ketones were efficiently prepared in good yields by the reactions of the Grignard reagents derived from aryl or alkyl bromides, followed by the reactions with aromatic or aliphatic aldehydes and the subsequent treatment with 1,3-diiodo-5,5-dimethylhydantoin and K₂CO₃, in a one-pot method. The same treatment of aromatic bromides bearing electron-withdrawing groups, such as ester, nitrile, ketone, and nitro groups with i-PrMgCl·LiCl or PhMgCl instead of Mg, also provided the corresponding diaryl and alkyl aryl ketones in good yields. The above methods are simple and practical transition-metal-free methods for the preparation of various diaryl ketones and alkyl aryl ketones bearing electron-rich aromatic groups and electron-deficient aromatic groups, as well as dialkyl ketones.     

One-pot conversion of aromatic bromides and aromatics into aromatic nitriles via aryllithiums and their DMF adduct

Various aromatic bromides and iodides were smoothly converted into the corresponding aromatic nitriles in good to moderate yields by the treatment with n-butyllithium and subsequently DMF, followed by treatment with molecular iodine in aq NH₃. The same treatment of typical aromatics and heteroaromatics with n-butyllithium and subsequently DMF, followed by treatment with molecular iodine in aq NH₃ also provided the corresponding aromatic nitriles in good yields. Moreover, the same treatment of aromatic bromides and aromatics with half amount of DIH (1,3-diiodo-5,5-dimethylhydantoin) instead of molecular iodine worked effectively to give the corresponding aromatic nitriles, respectively, in good yields. These reactions are novel and environmentally benign one-pot methods for the preparation of aromatic nitriles from aromatic bromides and aromatics, respectively, through the formation of aryllithiums and their DMF adducts.     

Facile preparation of aromatic esters from aromatic bromides with ethyl formate or DMF and molecular iodine via aryllithium

Various aromatic bromides were treated with n-BuLi and subsequently with ethyl formate, followed by the reaction with ethanol and molecular iodine in the presence of K₂CO₃ to provide the corresponding aromatic ethyl esters in good yields. Moreover, aromatic bromides could be transformed into the corresponding aromatic methyl esters in good yields by the treatment with n-BuLi and subsequently with DMF, followed by the reaction with methanol, molecular iodine, and K₂CO₃. Some aromatics could be also converted into the corresponding aromatic esters in good yields by the treatment with n-BuLi, and subsequently with ethyl formate or DMF, followed by the reaction with molecular iodine and K₂CO₃. The present reactions offer a novel route for the transition-metal-free, carbon-monoxide-free, and therefore environmentally benign one-pot conversion of aromatic bromides and aromatics into aromatic esters.     

Practical one-pot conversion of aryl bromides and β-bromostyrenes into aromatic nitriles and cinnamonitriles

Various aryl bromides were efficiently converted into the corresponding aromatic nitriles in good yields by the treatment with Mg turnings and subsequently DMF, followed by treatment with molecular iodine and aq NH₃. The same treatment of aryl bromides, which are weakly reactive to Mg turnings, with ⁱPrMgCl·LiCl and subsequently DMF, followed by the treatment with molecular iodine and aq NH₃ also afforded the corresponding aromatic nitriles in good yields. On the other hand, when N-formylpiperidine was used instead of DMF, p-substituted β-bromostyrenes were converted into the corresponding p-substituted cinnamonitriles, i.e., α,β-unsaturated nitriles, in good to moderate yields by the same procedure. The reactions were carried out by means of a simple experimental procedure and did not require any toxic metal cyanides or expensive rare metals. Therefore, the present reactions are practical and environmentally benign one-pot methods for the preparation of aromatic nitriles, cinnamonitriles, and aliphatic nitriles from aryl bromides, β-bromostyrenes, and alkyl bromides, respectively, through the formation of Grignard reagents and their DMF or N-formylpiperidine adducts.     

Pd(0)‐Catalyzed Tandem One‐Pot Reaction of Biphenyl Ketones/Aldehydes to the Corresponding Di‐substituted Aryl Olefins

Synthesis of di‐substituted aryl olefins via a Pd(0)‐catalyzed cross‐coupling reaction of biphenyl ketones/aldehydes, tosylhydrazide, and aryl bromides (or benzyl halides) was developed. This methodology was achieved by one‐pot two‐step reactions involving the preparation of N ‐tosylhydrazones by reacting tosylhydrazide with biphenyl ketones/aldehydes, followed by coupling with aryl bromides (or benzyl halides) in the presence of Pd(PPh₃ )₄ and lithium t ‐butoxide to produce various di‐substituted aryl olefins in moderate to good yields.     

Transformation of aromatic bromides into aromatic nitriles via formations of grignard reagents and their DMF adducts

Various aromatic bromides were efficiently transformed into the corresponding aromatic nitriles in good yields via the formations of Grignard reagents and subsequently N,N-dimethyl formamide (DMF) adducts, followed by treatment with molecular iodine (I₂) in aq NH₃ at room temperature. The present reaction is an easy and practical method for the preparation of aromatic nitriles from aromatic bromides with less toxic reagents, such as Mg, DMF, I₂, and aq NH₃.     

Generation of Aryl and Heteroaryl Magnesium Reagents in Toluene by Br/Mg or Cl/Mg Exchange

The alkylmagnesium alkoxide sBuMgOR?LiOR (R=2‐ethylhexyl), which was prepared as a 1.5 m solution in toluene, undergoes very fast Br/Mg exchange with aryl and heteroaryl bromides, producing aryl and heteroaryl magnesium alkoxides (ArMgOR?LiOR) in toluene. These Grignard reagents react with a broad range of electrophiles, including aldehydes, ketones, allyl bromides, acyl chlorides, epoxides, and aziridines, in good yields. Remarkably, the related reagent sBu₂Mg?2 LiOR (R=2‐ethylhexyl) undergoes Cl/Mg exchange with various electron‐rich aryl chlorides in toluene, producing diorganomagnesium species of type Ar₂Mg?2 LiOR, which react well with aldehydes and allyl bromides.     

Transformation of aromatic bromides into aromatic nitriles with n-BuLi,pivalonitrile, and iodine under metal cyanide-free conditions

Various aromatic nitriles could be obtained in good yields by the treatment of aryl bromides with n-butyllithium and then pivalonitrile, followed by the treatment with molecular iodine at 70 °C, without metal cyanides under transition-metal-free conditions. The present reaction proceeds through the radical β-elimination of imino-nitrogen-centered radicals formed from the reactions of imines and N-iodoimines under warming conditions. © 2019 Elsevier Science. All rights reserved.     

Palladium-catalyzed coupling reactions of (ArCH2)Ti(O-i-Pr)3 with aromatic or heteroaromatic bromides

Three benzyltitanium compounds of (ArCH₂)Ti(O-i-Pr)₃ (Ar = Ph (1a), 4-MeOC₆H₄ (1b), 4-FC₆H₄ (1c)) were prepared and used as benzyl nucleophiles for coupling reactions with aromatic or heteroaromatic bromides. The simple catalytic system of 1 mol % Pd(OAc)₂ and 2 mol % PCy₃ worked efficiently for a wide variety of aromatic bromides, producing diarylmethanes in good to excellent yields of up to 96%. Coupling reactions of hindered aromatic bromides or aromatic bromides containing electron-withdrawing substituents were slower over longer reaction times of 3–6 h. Reactions of heteroaromatic bromides of bromopyridines, bromofurans, or bromothiophenes with benzyl reagents of 1a or 1b required either longer reaction times of 12–24 h or a higher reaction temperature of 80 °C, producing pyridyl-, furyl-, and thienyl-arylmethanes in moderate yields.     

Aromatic bromination of aldehydes and ketones using 1,3-di-n-butylimidazolium tribromide [BBIm]Br3 ionic liquids under solvent-free conditions

An environmentally benign and efficient process for the preparation of monobromo derivatives of aryl aldehydes and ketones was developed by simple and practical reactions of aryl aldehydes or ketones with 1,3-di-n-butylimidazolium tribromide ([BBIm]Br₃), as a brominating reagent under solvent-free conditions in very high yields. The process has several advantages: high conversions, short reaction time, mild reaction conditions, simple workup with good to quantitative yields and re-usable ionic liquid.     

Facile one-pot preparation of 5-aryltetrazoles and 3-arylisoxazoles from aryl bromides

The successive treatment of aryl bromides with n-BuLi, DMF, hydroxylamine hydrochloride, and finally diphenylphosphoryl azide provided efficiently the corresponding 5-aryltetrazoles in good to moderate yields. Similarly, the successive treatment of aryl bromides with n-BuLi, DMF, hydroxylamine hydrochloride, and finally diethyl acetylenedicarboxylate and Oxone^® provided efficiently the corresponding diethyl 3-arylisoxazole-4,5-dicarboxylates in good to moderate yields. Aromatic aldoximes are the key intermediates in both reactions, and 5-aryltetrazoles and 3-arylisoxazoles could be obtained from aryl bromides in one pot under transition-metal-free conditions.     

Access to substituted trifluoromethyl ketones using the versatile synthetic intermediate (E)-1,1-dimethyl-2-(1,1,1-trifluoropropan-2-ylidene)hydrazine

The N,N-dimethylhydrazone of 1,1,1-trifluoroacetone, (E)-1,1-dimethyl-2-(1,1,1-trifluoropropan-2-ylidene)hydrazine, has been shown to undergo a diverse set of reactions following deprotonation with n-butyl-lithium; including alkylation, addition to ketones and aldehydes, as well as palladium-catalyzed cross-couplings with aryl bromides. Mild hydrolysis of the N,N-dimethylhydrazone products from these transformations affords the corresponding trifluoromethyl ketones in good to excellent yields.     

Palladium(0) nanoparticle-catalyzed sp C-H activation: a convenient route to alkyl-aryl ketones by direct acylation of aryl bromides and iodides with aldehydes

Palladium(0) nanoparticles efficiently catalyze aliphatic aldehyde C-H functionalization by aryl halides to produce alkyl-aryl ketones in good yields. A wide range of substituted aryl and hetero-aryl bromides/iodides and open-chain aldehydes of varied chain length participated in this reaction.     

Palladium‐catalyzed direct arylation of polyfluoroarene and facile synthesis of liquid crystal compounds

A convenient approach has been developed to prepare polyfluorobiphenyl by Pd(OAc)₂/PCy₃‐catalyzed direct arylation of polyfluoroarenes with aromatic halides in the presence of Cs₂CO₃ as base and toluene as solvent. In most cases, the desired arylated products of aromatic bromides were obtained in good to excellent yield at 80°C, and aryl chlorides also gave modest to good yields of arylated products at 110°C. According to this efficient C―C bondforming method, polyfluorobiphenyl liquid crystal compounds were prepared by Pd‐catalyzed direct arylation reactions of polyfluoroarenes with long alkyl chain substituted aryl bromides in 62–96% yield. Copyright © 2014 John Wiley & Sons, Ltd.     

Gold(I)-catalyzed direct C-H arylation of pyrazine and pyridine with aryl bromides

An efficient procedure for the direct C-H arylation of electron-poor aromatics such as pyrazine and pyridine with aryl bomides is described. In the presence of catalytic amount of Cy₃PAuCl and with the use of t-BuOK as base, pyrazine undergoes the direct C-H arylation with aryl bromides at 100 °C, and the yields of the arylated products depend on the nature of aryl bromides. In the cases of electron-rich aryl bromides used, the arylated pyrazines can be obtained in good to high yields. For electron-poor aryl bromides, the addition of AgBF₄ is the crucial point to accelerate the coupling reaction to give the arylated products in moderate yields. Pyridine also reacts with electron-rich aryl bromides catalyzed by Cy₃PAuCl to give a mixture of arylated regioisomers in moderate yield. However, in order to realize the direct C-H arylation of pyridine with electron-poor aryl bromides, the addition of silver salt as additive and a milder reaction temperature (60 °C) are required.     

Mannich-type reactions of aromatic aldehydes, anilines, and methyl ketones in fluorous biphase systems created by rare earth (III) perfluorooctane sulfonates catalysts in fluorous media

Rare earth (III) perfluorooctane sulfonates (RE(OPf)₃) catalyze the three-component Mannich-type reactions of different ketones with various aromatic aldehydes and aromatic amines in fluorous media to give various β-arylamino ketones in good yields. By simple separation of the fluorous phase containing only catalyst, reaction can be repeated several times.     

Practical one-pot transformation of electron-rich aromatics into aromatic nitriles with molecular iodine and aq NH3 using Vilsmeier–Haack reaction

Various electron-rich aromatics could be efficiently transformed into the corresponding aromatic nitriles in good to moderate yields by treatment with DMF and POCl₃, followed by the reaction with molecular iodine or 1,3-diiodo-5,5-dimethylhydantoin (DIH) in aq NH₃. Some of less reactive aromatics, such as anisole, 1,2-dimethoxybenzene, 1,4-dimethoxybenzene, and mesityrene, could be also transformed into the corresponding aromatic nitriles in good to moderate yields using N-methylformanilide and O(POCl₂)₂, followed by the reaction with molecular iodine in aq NH₃. Moreover, propiophenone derivatives could be successfully transformed into the corresponding β-chlorocinnamonitriles by the reaction with DMF and POCl₃, followed by the reaction with molecular iodine and aq NH₃. These reactions are novel metal-free one-pot methods for the preparation of aromatic nitriles from electron-rich aromatics and β-chlorocinnamonitriles from propiophenones.     

Sulfamic acid as a reusable and green catalyst for efficient and simple synthesis of 2-substituted-2,3-dihydroquinazolin-4(1H)-ones in water or methanol

A series of 2,3-dihydroquinazolin-4（1H）-ones have been synthesized in good to excellent yields through direct cyclocondensation of anthranilamide and aryl aldehydes or ketones in water or methanol under mild conditions.The reaction was efficiently promoted by 10 mol%sulfamic acid（SA,H₂NSO₃H） and the catalyst could be recovered easily after the reactions and reused without evident loss of reactivity.     

One-pot synthesis of 1,5-diketones catalyzed by barium isopropoxide

A tandem cross-coupling reaction of aryl methyl ketones with aromatic aldehydes has been accomplished employing barium isopropoxide as a catalyst, in which barium enolates are generated and then three consecutive reactions (aldol reaction/β-elimination/conjugate addition) occur; this one-pot procedure is a convenient method to obtain symmetrical 1,5-diketones in good yields. In some cases, addition of iso-propanol is effective in improving the chemical yield.     

Palladium-catalyzed cross-coupling of cyclopropylmethyl N-tosylhydrazones with aromatic bromides: an easy access to multisubstituted 1,3-butadienes

Direct synthesis of 1,1-disubstitued 1,3-butadienes has been efficiently realized from the cross-coupling of cyclopropylmethyl N-tosylhydrazones with aromatic bromides by means of PdCl₂(MeCN)₂ as catalyst. 1,1,4-Trisubstitued 1,3-butadiene derivatives were obtained in up to 70% yields through a one-pot procedure catalyzed by Pd(OAc)₂ in the presence of excessive amount of aromatic bromides. The present methodology provides an easy and efficient route to multisubstituted 1,3-butadienes.