Tert-butyl Nitrite Research Articles

Tert-Butyl Nitrite Mediated Synthesis of Fluorinated O-Alkyloxime Ether Derivatives.

A tert-butyl nitrite (TBN)-mediated synthesis of fluorinated O-alkyloxime ether derivatives with bromodifluoroalkyl reagents as the fluorine sources has been developed. A variety of halodifluorinated compounds were found compatible, delivering the desired products in moderate to excellent yields. This transformation features a simple operation, can be done in air, and found to involve radicals. This protocol represents a straightforward approach to access various fluorinated O-alkyloxime ether derivatives.

Palladium-Catalyzed One-Pot Stereospecific Synthesis of 2-Deoxy Aryl C-Glycosides from Glycals and Anilines in the Presence of tert-Butyl Nitrite

The palladium-catalyzed one-pot synthesis of 2,3-deoxy-3-keto aryl C-glycosides is achieved from glycals and anilines in the presence of tert-butyl nitrite and aqueous HBF4 under mild conditions. This one-pot method stereospecifically provides α- and β-aryl glycosides (≥19:1 by NMR) in good yields at room temperature. The configuration at the C-3 position in the glycal determines the anomeric selectivity (i.e., α or β) of the desired products.

Dual Roles of tert-Butyl Nitrite in the Transition Metal- and External Oxidant-Free Trifluoromethyloximation of Alkenes.

By employing tert-butyl nitrite as both nitrogen source and oxidant, the trifluoromethyloximation of alkenes proceeds smoothly in a free-radical process. The developed difunctionalization reaction enables practical and efficient synthesis of a wide range of α-CF3 ketoximes in moderate yields with excellent regioselectivity. This method features the use of readily available and stable alkenes as substrates and inexpensive CF3 SO2 Na as a CF3 reagent, no involvement of transition metals or external oxidant, and room-temperature conditions. Moreover, a scale-up of the reaction, further transformation of the products into various valuable CF3 -containing compounds, and removal of the trifluoromethyl group are readily achieved.

Metal‐Free Aerobic Oxidative C–O Coupling of C(sp3)–H with Carboxylic Acids Catalyzed by DDQ andtert‐Butyl Nitrite

The formation of the C–O bond is one of the hot topics in the area of C(sp3)–H bond functionalization. A metal‐free oxidative cross‐coupling between benzylic C(sp3)–H bond and carboxylic acids has been developed. The reactions were performed with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) as the catalyst,tert‐butyl nitrite (TBN) as the co‐catalyst, and molecular oxygen as the terminal oxidant. A variety of diarylmethanes could be successfully coupled with various carboxylic acids to obtain diarylmethanol esters in good to excellent yields. In addition, 2‐benzylbenzoic acids could be converted into phthalides in moderate yields through an intramolecular oxidative cyclization.

Copper‐catalyzed C‐H Bis‐nitration of 1‐Naphthylamide Derivatives with tert‐Butyl Nitrite as Nitro Source

AbstractA simple and atom‐economical protocol for bis‐nitration of 1‐naphthylamides was firstly discovered with tert‐butyl nitrite (TBN) as nitro source and catalyzed by Cu(OAc)2. Assisted by picolinamide direction, the C2,4‐H bis‐nitration could be achieved with excess amount of TBN at 50°C in HOAc. A radical pathway and single electron transfer process might be involved in the bis‐nitration process.

Tunable Functionalization of Saturated C-C and C-H Bonds of N,N'-Diarylpiperazines Enabled by tert-Butyl Nitrite (TBN) and NaNO2 Systems.

A tunable functionalization of saturated C-C and C-H bonds of N,N'-diarylpiperazine derivatives was realized by tert-butyl nitrite (TBN) and NaNO2 systems, respectively. When TBN was employed as the oxidant, C-C bond cleavage occurred smoothly, providing a series of formamides in good yields. In the presence of NaNO2, C-H oxidation was achieved, resulting in efficient synthesis of nitroalkenes. The mechanistic study shows that a mixed mechanism is involved in these reactions, in which a generated enamine might be the key intermediate.

Tert-Butyl Nitrite Mediated Synthesis of 1,2,4-Oxadiazol-5(4 H)-ones from Terminal Aryl Alkenes.

tert-Butyl nitrite (TBN) mediated synthesis of 3-aryl-1,2,4-oxadiazol-5(4 H)-ones has been accomplished using terminal aryl alkenes via a biradical reaction intermediate. Three consecutive sp2 C-H bond functionalizations of styrenes afforded 3-phenyl-1,2,4-oxadiazol-5(4 H)-ones via the formation of new C═N, C═O, C-O, and two C-N bonds. Both of the N atoms originate from TBN, while the carbonyl oxygen is from the water (moisture) the other oxygen from the N═O part of the TBN.

Synthesis of 3-Acyl-isoxazoles and Δ2-Isoxazolines from Methyl Ketones, Alkynes or Alkenes, and tert-Butyl Nitrite via a Csp3-H Radical Functionalization/Cycloaddition Cascade.

A novel metal-free tandem Csp3-H bond functionalization of ketones and 1,3-dipolar cycloaddition has been developed. An efficient approach to a variety of oxazole and isoxazoline derivatives is demonstrated using the 1,3-dipolar cycloaddition of alkynes and alkenes to nitrile oxides generated by reactions of methyl ketones with tert-butyl nitrite. This new protocol provides access to a variety of isoxazolines with diverse functionalities. An isoxazole generated in this way was found to have significant antifungal activity.

Synthesis of 4-Oxoisoxazoline N-Oxides via Pd-Catalyzed Cyclization of Propargylic Alcohols with tert-Butyl Nitrite.

A cyclization of propargylic alcohols with tert-butyl nitrite at room temperature in air was achieved using Pd(OAc)2 as catalyst. The first reported 4-oxoisoxazoline N-oxides could be directly accessed from a range of multisubstituted propargylic alcohols in moderate to excellent yields under mild conditions. Density functional theory calculations indicated that the reaction proceeds through a palladium-catalyzed NO2 addition that efficiently generates a ketoxime radical, which eventually produces 4-oxoisoxazoline N-oxide.

Metal‐Free Oxidative Annulation/Cyclization of 1,6‐Enynes for the Synthesis of 4‐Carbonylquinolines

AbstractHerein we report on the development of a metal‐free oxidative annulation reaction of 1,6‐enynes, leading to 4‐carbonylquinolines by using dioxygen as a green sustainable oxidant. Key advances include the use of readily available tert‐butyl nitrite (TBN) to promote radical annulation of 1,6‐enynes and easy‐to‐handle reaction conditions. Preliminary mechanistic studies including radical capture reactions and isotope labelling experiments are also conducted.magnified image

Nitration-Peroxidation of Alkenes: A Selective Approach to β-Peroxyl Nitroalkanes.

Nitration-peroxidation of alkenes for the synthesis of β-peroxyl nitroalkanes has been developed by using tert-butyl nitrite and tert-butyl hydroperoxide. The method presents a new and selective difunctionalization of alkenes to introduce a nitro group and a peroxyl group across the double bonds of alkenes under mild conditions. A radical reaction pathway is proposed by experimental and theoretical studies.

Multiple-functionalizations of terminal alkynes with sodium sulfinates and tert-butyl nitrite: facile synthesis of 2H-azirines.

A new, catalyst-free tandem annulation route to 2,2-disulfonyl-2H-azirines via multiple-functionalizations of terminal alkynes with sodium sulfinates and tert-butyl nitrite is described. The use of sodium sulfinates and tert-butyl nitrite enables the formation of sulfonyl and NO radicals to selectively initiate and terminate the tandem annulation protocol, constituting a straightforward, conceptually different method to existing 2H-azirine synthesis techniques that currently require multiple steps by prior activation of the common starting materials.

Synthesis of α-trifluoromethyl ethanone oximes via the three-component reaction of aryl-substituted ethylenes, tert-butyl nitrite, and the Langlois reagent

A three-component reaction of aryl-substituted ethylenes, tert-butyl nitrite, and the Langlois reagent to synthesize a-trifluoromethyl ethanone oximes was developed.

Tert-Butyl nitrite promoted transamidation of secondary amides under metal and catalyst free conditions.

A mild and efficient method is demonstrated for the transamidation of secondary amides with various amines including primary, secondary, cyclic and acyclic amines in the presence of tert-butyl nitrite. The reaction proceeds through the N-nitrosamide intermediate and provides the transamidation products in good to excellent yields at room temperature. Moreover, the developed methodology does not require any catalyst or additives.

A three-component approach to isoxazolines and isoxazoles under metal-free conditions.

A 1,3-dipolar cycloaddition of 2-methylquinoline, tert-butyl nitrite (TBN) and alkynes or alkenes for the synthesis of biheteroaryls containing both isoxazoline/isoxazole and quinoline motifs has been developed. In this protocol, TBN serves as a convenient N-O source to convert 2-methylquinoline into intermediate nitrile oxides in situ.

Silver-catalyzed nitration/annulation of 2-alkynylanilines for a tunable synthesis of nitrated indoles and indazole-2-oxides

Two new types of silver-catalyzed nitration–annulations of 2-alkynylanilines with tert-butyl nitrite (TBN) were reported, leading to the selective formation of a variety of nitrated indoles and indazole-2-oxides.

Intramolecular nitration-aminocarbonylation of unactivated olefins: metal-free synthesis of γ-lactams.

Disclosed herein is a novel, metal-free synthesis of γ-lactams through the radical-mediated nitration-aminocarbonylation of unactivated olefins. The reaction is initiated by a nitro radical generated from the homolysis of tert-butyl nitrite. The intramolecular cyanamide serves as the aminocarbonylating reagent. This protocol offers an environment-benign method to produce the synthetically valuable nitromethyl substituted γ-lactams.

Visible-Light-Induced Aerobic Oxidation of Benzylic C(sp3)–H of Alkylarenes Promoted by DDQ, tert-Butyl Nitrite, and Acetic Acid

A visible-light photocatalytic aerobic oxidation of benzylic C(sp3)–H bonds proceeded in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, tert-butyl nitrite, and acetic acid. Advantages of this aerobic oxidation method include its relatively mild conditions, the use of visible-light irradiation instead of conventional thermal methods, the use of a low catalyst loading, and the ability to oxidize a range of alkyl­arenes, including xanthenes, thioxanthenes, and 9,10-dihydroacridines, to the corresponding ketones in excellent yields.

Regioselective Nitration of N-Alkyl Anilines using tert-Butyl Nitrite under Mild Condition.

Regioselective ring nitration of N-alkyl anilines is reported using tert-butyl nitrite. The reactions proceed efficiently with a wide range of substrates providing synthetically useful N-nitroso N-alkyl nitroanilines in excellent yields which can be easily converted into N-alkyl phenylenediamines and N-alkyl nitroanilines using Zn-AcOH and HCl/MeOH, respectively.

Water-controlled nitro-oximation of alkenes under catalyst-free conditions

A convenient and precise nitration and oximation of alkenes with tert-butyl nitrite has been reported, yielding α-nitro ketoximes in satisfactory yields with broad substrate generality and excellent stereoselectivity under mild conditions. Experiments indicate that tert-butyl nitrite serves as both NO and NO2 sources and water plays a key role in this difunctionalization reaction.