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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.

Hypervalent iodine(III) compounds containing iodine-nitrogen bonds are very attractive amination reagents in organic synthesis. Heteroaromatic (aryl)iodonium imides containing a iodine-nitrogen bond and a hypervalent iodine(III) atom were prepared from heteroarenes, bis(sulfon)imides and (diacetoxyiodo)arenes under mild conditions. These compounds were stable under air and in organic solvents, and could be easily purified by precipitation. X-ray crystal structure analysis indicated that the structure of N-pivaloyl indolyl(phenyl)iodonium bis(tosyl)imides and N-pivaloyl indolyl(2-butoxyphenyl)iodonium bis(tosyl)imides was a dimer with a T-shaped geometry at the iodine atom linked to an indole group and a bis(tosyl)imide by a monomer unit. Moreover, the use of substituted iodoarenes facilitated the purification of some of the heteroaromatic (aryl)iodonium imides.

A novel one-pot, two-step preparation of 5-aryltetrazoles from aromatic aldehydes and alkylhydrazines is presented.

A variety of ethylarenes were converted into the corresponding primary aromatic amides in good yields via treatment with N-bromosuccinimide in the presence of a catalytic amount of 2,2′-azobis(isobutyronitrile) in a mixture of ethyl acetate and water, acetonitrile and water, or chloroform and water, followed by reaction with molecular iodine and aq NH3 in one pot. It was found that aryl α-bromomethyl ketones and/or aryl methyl ketones were formed at the first reaction step and their iodoform-type reaction occurred at the second reaction step to provide primary aromatic amides. The present reaction is a useful and practical transition-metal-free method for the preparation of primary aromatic amides from ethylarenes.

On the basis of a study of the O-phenylation of 3-phenyl-2-propyn-1-ol with diphenyliodonium triflate and t-BuONa, a variety of 4-aryl-3-iodo-2H-benzopyrans were prepared in good to moderate yields in one pot from the reaction of 3-aryl-2-propyn-1-ols with diaryliodonium triflates and t-BuONa, followed by the treatment with N-iodosuccinimide and BF3·OEt2, under transition-metal-free and mild conditions. The formed 4-phenyl-3-iodo-2H-benzopyran was converted into 4-phenyl-2H-benzopyran derivatives through C–C bond formations at the 3-position by Pd-catalyzed coupling reactions and into coumarin with oxidants.

An oxidative bromoetherification involving a bromine transfer from alkyl bromides upon reacting them with aldehydes in a Grignard reaction with a concurrent oxidation of bromide was developed to provide substituted tetrahydrofurans in high yields. This reaction, which proceeds through two types of bromine transfer, was promoted by the addition of a Brønsted acid. Mechanistic studies suggested that a magnesium Lewis acid activates hypobromate, which is generated in situ from the reaction of bromide and Oxone to improve the electrophilicity of the bromonium ion (Br(+) ) for the oxidative bromoetherification of alkenyl alcohols. Furthermore, the magnesium Lewis acid catalyzed oxidative bromoetherification of an alkenyl alcohol proceeded to provide a cyclization product in 92 % yield.

N , N -Diisopropylarylmethylamines were smoothly converted into the corresponding N -isopropylarylmethylamines by the reaction with molecular iodine in the presence of Na 2 CO 3 in chloroform at 60 °C. Other related tertiary amines were also transformed into the corresponding secondary amines by the reaction with molecular iodine under the same reaction conditions.

The title reaction proceeds via the oxidative umpolung of bromide using alkali metal bromide and an inorganic oxidant.

Unsymmetrical diaryl ethers were efficiently obtained in good yields by the reactions of aryl(4-methoxyphenyl)iodonium tosylates­ with phenols, and aryl(2,4-dimethoxyphenyl)iodonium tosylates­ with phenols, in the presence of potassium carbonate in acetonitrile, respectively. The latter iodonium tosylates provided the corresponding unsymmetrical diaryl ethers in good yields with high regioselectivities, together with the quantitative formation of 1-iodo-2,4-dimethoxybenzene.

Various [(diacetoxy)iodo]arenes bearing 4-methylphenyl, phenyl, 4-nitrophenyl, 3-nitrophenyl, 4-cyanophenyl, 4-bromophenyl, 4-methoxycarbonyphenyl, 3,5-bis(trifluoromethyl)phenyl, and 4-(N,N,N-trimethylammonium)methylphenyl groups were efficiently prepared by the treatment of iodoarenes with m-chloroperoxybenzoic acid in acetic acid. The great advantage of the present method is the easy preparation and isolation of [(diacetoxy)-­iodo]arenes bearing electron-withdrawing groups, such as 4-nitro, 4-cyano, 4-methoxycarbonyl, and 3,5-bis(trifluoromethyl) groups, on the aromatic ring.

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.

The Swern oxidation of various benzylic and allylic alcohols, primary alcohols, and secondary alcohols with two ion-supported methyl sulfoxides A-1 ( C 6 ) and B-1 ( C 10 ) , and oxalyl chloride in the presence of triethylamine in dichloromethane, followed by simple diethyl ether extraction of the reaction mixture, gave the corresponding aldehydes and ketones, respectively, in good yields with high purity. Similarly, the Corey–Kim oxidation of various benzylic and allylic alcohols, primary alcohols, and secondary alcohols with two ion-supported methyl sulfides A-2 ( C 6 ) and B-2 ( C 10 ), and N -chlorosuccinimide in the presence of triethylamine in dichloromethane, followed by simple diethyl ether extraction of the reaction mixture, furnished the corresponding aldehydes and ketones, respectively, in good yields with high purity. Both reactions did not produce any unpleasant odor at all. In the Swern oxidation, ion-supported methyl sulfides were recovered in high yields and could be re-oxidized to produce ion-supported methyl sulfoxides A-1 ( C 6 ) and B-1 ( C 10 ), for reuse in the same oxidation. In the Corey–Kim oxidation, ion-supported methyl sulfides A-2 ( C 6 ) and B-2 ( C 10 ) were recovered in high yields and could be also reused for the same oxidation.

Various electron-rich aromatics could be efficiently transformed into the corresponding aromatic nitriles in good to moderate yields by treatment with DMF and POCl 3 , followed by the reaction with molecular iodine or 1,3-diiodo-5,5-dimethylhydantoin (DIH) in aq NH 3 . 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(POCl 2 ) 2 , followed by the reaction with molecular iodine in aq NH 3 . Moreover, propiophenone derivatives could be successfully transformed into the corresponding β-chlorocinnamonitriles by the reaction with DMF and POCl 3 , followed by the reaction with molecular iodine and aq NH 3 . These reactions are novel metal-free one-pot methods for the preparation of aromatic nitriles from electron-rich aromatics and β-chlorocinnamonitriles from propiophenones.

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 K 2 CO 3 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 K 2 CO 3 . 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 K 2 CO 3 . 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.

The oxidation of secondary alcohols and primary alcohols with novel ion-supported (diacetoxyiodo)benzenes (IS-DIB) in the presence of a catalytic amount of 2,2,6,6-tetramethylpiperidine-1-oxy radical (TEMPO) in dichloromethane at room temperature proceeded efficiently to provide the corresponding ketones and aldehydes, respectively, in good yields with high purity. Isolation of the product was easily accomplished by simple diethyl ether extraction of the reaction mixture and subsequent removal of the solvent from the extract. Moreover, ion-supported iodobenzenes, which were co-products derived from IS-DIB in the present oxidation, were recovered in good yields and could be re-oxidized to IS-DIB for reuse in the same oxidation.

Various N-tosyl arylimines reacted with methyl vinyl ketone and ethyl vinyl ketone in the presence of ion-supported Ph3P A and B to give adducts, N-(2′-methylene-3′-oxo-1′-arylbutyl)-4-methylbenzenesulfonamides and N-(2′-methylene-3′-oxo-1′-arylpentyl)-4-methylbenzenesulfonamides, respectively, in good yields with high purity by simple diethyl ether extraction of the reaction mixture. Moreover, ion-supported Ph3P A and B could be repeatedly used for the same reaction to provide the corresponding adducts while maintaining good yields with high purity.

Aromatic ketones were efficiently prepared in good yields by the reactions of aryl bromides with n-BuLi, followed by the reactions with aromatic aldehydes or aliphatic aldehydes and the subsequent treatment with molecular iodine and K2CO3, in a one-pot method. The same treatment of arenes, instead of aromatic bromides, also provided the corresponding aromatic ketones in good yields. Using these methods, various diaryl ketones and alkyl aryl ketones bearing electron-rich aromatics and electron-deficient aromatics could be prepared efficiently by a simple, transition-metal-free, and therefore environmentally benign experimental procedure.

Various esters were efficiently converted into the corresponding nitriles in good yields by the treatment with sodium diisobutyl-tert-butoxyaluminium hydride (SDBBA-H), followed by treatment with molecular iodine in aq ammonia. The present one-pot method is very efficient and practical for the conversion of various aromatic and aliphatic esters into the corresponding nitriles.

The oxidative intramolecular bromo-amination of various N-alkenyl sulfonamides and N-alkenoxyl sulfonamides via umpolung of alkali metal bromides occurred exo-selectively to generate cyclic bromoamides in high yields with good diastereoselectivities. This method provided the desired products without elaborating the stoichiometric amount of corresponding organic waste.

Treatment of alkylbenzenes with (diacetoxyiodo)benzene in the presence of catalytic amounts of p-toluenesulfonamide or p-nitrobenzenesulfonamide, and molecular iodine in 1,2-dichloroethane at 60 °C gave the corresponding (α-acetoxy)alkylbenzenes in good to moderate yields. The present reaction is a simple method for the introduction of an acetoxy group to the benzylic position of alkylbenzenes.

Alkyl aryl ketones and dialkyl ketones could be converted intothe corresponding α-tosyloxy ketones by the reaction with MCPBAand P-toluenesulfonic acid monohydrate(PTSA˙H 2 O) in the presence of a catalytic amountof molecular iodine (I 2 ) in a mixture of acetonitrileand 2,2,2-trifluoroethanol, although the yields were dependent onthe ketones (method A). The same conversion of alkyl aryl ketonesand dialkyl ketones into the corresponding α--tosyloxyketones could be smoothly carried out by the reaction with MCPBAand PTSA˙H 2 O in the presence of catalytic amountsof -iodine and TERT-butylbenzenein a mixture of acetonitrile and 2,2,2-trifluoroethanol (methodB). In those reactions, P-iodotolueneand 4- TERT-butyl-1-iodobenzene were formedat first in method A and method B, respectively, and then they wereconverted into P-[(hydroxy)(tosyloxy)]iodotolueneand 4- TERT-butyl-1-[(hydroxy)(tosyloxy)iodo]benzeneby the reaction with MCPBA and PTSA˙H 2 O. P-[(Hydroxy)(tosyloxy)]iodotolueneand 4- TERT-butyl-1-[(hydroxy)-(tosyloxy)iodo]benzeneworked as an α-tosyloxylation reagent of ketones.

Various N , N -dimethyl amides, N -methoxy- N -methyl amides, and isopropyl esters were smoothly transformed into the corresponding nitriles in good to moderate yields by the treatment with diisobutylaluminium hydride, followed by treatment with molecular iodine in aq ammonia. The present reactions are novel one-pot and practical methods for the transformation of N , N -disubstituted amides and isopropyl esters into nitriles, through the formation of hemiaminal O -AlBu 2 and hemiacetal O -AlBu 2 , respectively.

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.

The utility of hydroxylamines as nitrogen nucleophiles was investigated in the iridium-catalyzed regio- and enantioselective allylic substitution. Allylic substitution with hydroxylamines proceeded with good enantioselectivities by using the iridium-complex of bis(oxazolinyl)pyridine ligand. The good regio- and enantioselectivities were also achieved in the reaction with alkylamines, p-anisidine, and 4-methoxyphenol.

The transesterification of an equimolar mixture of carboxylic esters and primary (1°), secondary (2°), and tertiary (3°) alcohols in hydrocarbon solvents was promoted with high efficiency by a lanthanum(III) complex, which was prepared in situ from lanthanum(III) isopropoxide (1 mol %) and 2-(2-methoxyethoxy)ethanol (2 mol %). The present La(III) catalyst was highly effective for the chemoselective transesterification in the presence of competitive 1°- and 2°-amines. Remarkably, esters were obtained in good to excellent yields as colorless materials without an inconvenient workup procedure.

Treatment of p-alkylbenzenesulfonic acids with mCPBA and molecular iodine gave p-alkyliodobenzenes in good to moderate yields via electrophilic ipso-substitution by the iodonium species (I+) formed. This desulfonyloxyiodination was promoted by the addition of a catalytic amount of iodoarenes, such as o-iodobenzoic acid. The same treatment of dimethylbenzenesulfonic acids and trimethylbenzenesulfonic acids with mCPBA and molecular iodine proceeded smoothly both in the absence and in the presence of o-iodobenzoic acid to provide the corresponding monoiodo-dimethylbenzene and diiodo-dimethylbenzene, and diiodo-trimethylbenzene and triiodo-trimethylbenzene, in good to moderate yields, respectively. On the other hand, the same desulfonyloxyiodination of benzenesulfonic acid and p-chlorobenzenesulfonic acid with mCPBA and molecular iodine proceeded only in the presence of o-iodobenzoic acid to generate iodobenzene and p-chloroiodobenzene, respectively, in moderate yields.

Electron-deficient nitrogen-containing heteroaromatics, such as quinoline, isoquinoline, and pyridine, were treated with benzoyl peroxide in dioxane, tetrahydropyran, tetrahydrofuran, diethyl ether, and dipropyl ether at 80 °C to form alkylated nitrogen-containing heteroaromatics in good yields under transition-metal-free conditions. This method was successfully applied to the preparation of lariat aza-crown ethers using 18-crown-6 or 15-crown-5 with quinoline and isoquinoline in the presence of benzoyl peroxide in good yields under irradiation conditions with a Hg lamp.

The reaction tolerates variously substituted arylmethyl ketones as well as hetarylmethyl ketones and is performed using alkyl nitriles, benzonitrile as well as succinonitrile as the reaction partner.

Various methylarenes are treated with 1,3-dibromo-5,5-dimethylhydantoin or N-bromosuccinimide and a catalytic amount of 2,2′-azobis(isobutyronitrile) in acetonitrile, carbon tetrachloride, or methyl tert-butyl ether, and then reacted with benzoic acid, p-toluenethiol, sodium p-toluenesulfinate, aqueous dimethylamine, and succinimide (formed from N-bromosuccinimide) to provide the corresponding arylmethyl benzoates, arylmethyl p-tolyl thioethers, arylmethyl p-tolyl sulfones, N-arylmethyl-N,N-dimethylamines, and N-(arylmethyl)succinimides in good yields, respectively. The reactions involve one-pot, transition-metal-free functionalizations to form C–O, C–S or C–N bonds at the benzylic positions of the methylarenes.

Electron-rich arenes bearing methyl or methoxy groups on the aromatic ring were treated with dichloromethyl methyl ether and ZnBr2, and then with molecular iodine and aq. ammonia to give the corresponding aromatic nitriles in good yields. Using this method, febuxostat was efficiently prepared from 4-bromophenol in four steps. The method can be used for the preparation of aromatic nitriles from arenes in one pot under metal-cyanide-free conditions.

A regioselective Csp2–H dual functionalization of indoles, which underlies bromo-amination via the 1,3-migration of imide groups on indolyl(phenyl)iodonium imides as novel imide-combined hypervalent iodines(III), has been developed to provide 2-bis(sulfonyl)amino-3-bromo-indoles under the metal-free conditions.

The synthetic utility of this one-pot procedure is demonstrated in the preparation of the xanthine oxidase inhibitor febuxostat (X).

A one-pot transition metal-free method for the preparation of 2-arylbenzofuran derivatives of type (III) or (VI) is presented.

Stepwise oxidation of methylarenes with a mixture of hydrogen peroxide and concentrated HBr followed by oxidation with iodine in the presence of ammonia offers a facile synthesis of the corresponding nitriles.

On the basis of studies of the transformation of benzylic bromides into the corresponding aromatic aldehydes by treatment with N-methylmorpholine N-oxide, various methylarenes were treated either with DBDMH in the presence of AIBN in acetonitrile at reflux (Method A) or with NBS in CCl4 under irradiation with a tungsten lamp at 30 °C (Method B), followed by treatment with N-methylmorpholine N-oxide to provide aromatic aldehydes in good yields. These methods could be adopted in one-pot transformations of methylarenes into aromatic aldehydes under conditions free of less toxic reagents and transition metals.

A regioselective C(sp(2))-H dual functionalization of indoles, which underlies bromo-amination via the 1,3-migration of imide groups on indolyl(phenyl)iodonium imides as novel imide-combined hypervalent iodines(III), has been developed to provide 2-bis(sulfonyl)amino-3-bromo-indoles under the metal-free conditions.

A bromide-catalyzed oxidation of alcohols was developed which proceeded in the presence of an alkali metal bromide and an oxidant under mild conditions. The reaction involved an organic-molecule-free oxidation using KBr and Oxone and a Bronsted acid assisted oxidation using KBr and aqueous H2O2 solution to provide a broad range of carbonyl compounds in high yields. Moreover, the bromide-catalyzed oxidation of primary alcohols enabled the divergent synthesis of carboxylic acids and aldehydes under both reaction conditions in the presence of TEMPO. A possible catalytic mechanism was suggested on the basis of various mechanistic studies.

The oxidative debenzylation of N-benzyl amides and O-benzyl ethers was promoted with high efficiency by a bromo radical formed through the oxidation of bromide from alkali metal bromide under mild conditions. This reaction provided the corresponding amides from N-benzyl amides and carbonyl compounds from O-benzyl ethers in high yields.

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 (I 2 ) in aq NH 3 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, I 2 , and aq NH 3 .

A simple and practical one-pot method for the highly regioselective synthesis of 3,5-disubstituted pyrazoles [e.g. (III), (V), and (VII)], isoxazoles [e.g. (XII), (XIV), and (XV)] from easily available compounds is presented.

The oxidative debenzylation of N-benzyl amides and O-benzyl ethers was promoted with high efficiency by a bromo radical formed through the oxidation of bromide from alkali metal bromide under mild conditions. This reaction provided the corresponding amides from N-benzyl amides and carbonyl compounds from O-benzyl ethers in high yields.

A variety of aromatic and aliphatic carboxylic acids were smoothly converted into the corresponding nitriles in good yields in a one-pot procedure by treatment with ethyl iodide/K2CO3/18-crown-6, followed by sodium diisobutyl-tert-butoxyaluminium hydride (SDBBA-H), and finally treatment with molecular iodine or 1,3-diiodo-5,5-dimethylhydantoin (DIH), and aqueous ammonia. This method is useful for the conversion of various aromatic and aliphatic carboxylic acids into the corresponding nitriles in a one-pot procedure.

Two cyanide-free and transition-metal-free one-pot procedures are presented for the synthesis of aromatic nitriles from methylarenes using NBS or 1,3-dibromo-5,5-dimethylhydantoin as the oxidant.