Tert-butyl Nitrite Research Articles

Examining the effect of common nitrosating agents on chitosan using a glucosamine oligosaccharide model system

Chitosan has received substantial attention as a biomaterial due to its unique properties. It has become increasingly common to derivatize chitosan to produce nitric oxide (NO)-releasing materials that exert various therapeutic effects through the action of NO. It is generally the case that these NO-releasing polymers are prepared by exposure to high-pressure NO or nitrosating agents like nitrous acid (HNO2) or alkyl nitrites (RONO). In our study, mass spectrometry and spectroscopic methods demonstrate that both monomeric and oligomeric glucosamine experience chemical alteration after exposure to HNO2-based nitrosating conditions from the literature. In polymeric chitosan, HNO2-based nitrosating conditions were found to induce degradation through the formation of 2,5-anhydro-d-mannose and oligosaccharides. In contrast, the RONO tert-butyl nitrite and high-pressure NO were not found to significantly degrade or otherwise alter the structure of glucosamine or its oligomers, supporting the suitability of these approaches.

Tert‐Butyl Nitrite Mediated Different Functionalizations of Internal Alkenes: Paths to Furoxans and Nitroalkenes

Abstracttert‐Butyl nitrite (TBN) reacts differently with various internal alkenes leading to interesting and useful products. Synthesis of 1,2,5‐oxadiazole‐N‐oxides (furoxans) has been achieved from internal alkenes using tert‐butyl nitrite (TBN), quinoline and K2S2O8. Under an identical reaction condition α,β‐unsaturated carboxylic acids and cyclic and acyclic internal alkenes both afforded nitroalkenes as the sole product via decarboxylative and direct nitration path respectively.magnified image

Tuning Regioselectivity of Wacker Oxidation in One Catalytic System: Small Change Makes Big Step.

A regioselectivity switchable aerobic Wacker-Tsuji oxidation has been developed using catalytic tert-butyl nitrite as a simple organic redox cocatalyst. By solely switching the solvent, either substituted aldehydes or ketones could be prepared under mild aerobic conditions in good yields, respectively. A mechanistic explanation for the selectivity control is proposed.

Recently Applications of tert-butyl Nitrite in Organic Synthesis-Part I

Recently Applications of tert-butyl Nitrite in Organic Synthesis-Part I

Tert-Butyl Nitrite Promoted Oxidative Intermolecular Sulfonamination of Alkynes to Synthesize Substituted Sulfonyl Pyrroles from the Alkynylamines and Sulfinic Acids.

tert-Butyl nitrite promoted oxidative intermolecular sulfonamination of alkynes to synthesize substituted sulfonyl pyrroles from the alkynylamines and sulfinic acids via tandem addition/cyclization was developed. This reaction is performed well by employing tert-butyl nitrite as the oxidant, and various substituted sulfonyl pyrroles are formed in moderate to good yields with no requirement of metal catalysis.

AcOH-catalyzed aza-Michael addition/N-nitrosation: An efficient approach to CF2HCH2-containing N-nitrosoamines

A simple and highly efficient protocol for the AcOH-catalyzed three-component reaction among nitroalkenes, difluoroethylamine and tert-butyl nitrite through cascade aza-Michael addition/N-nitrosation has been developed. A range of CF2HCH2-containing N-nitrosoamines were obtained in good to excellent yields. This approach features easily available cheap materials, without using additional organic solvents, simple operation under room temperature, gram scalable preparation and functionally diverse products.

Cobalt-Catalyzed C-H Nitration of Indoles by Employing a Removable Directing Group.

A mild and efficient C(sp2 )-H nitration of 3-substituted indoles, by using the economical and non-toxic cobalt nitrate hexahydrate [Co(NO3 )2 ⋅6 H2 O] as a catalyst and tert-butyl nitrite (TBN) as the nitro source, is reported. This approach provides a unique methodology involving a site-selective C-N bond formation for preparation of C-2 substituted nitro indoles. Utilization of the tBoc as the removable directing group enhances the synthetic utility of the method.

Saccharin: a cheap and mild acidic agent for the synthesis of azo dyes via telescoped dediazotization

Abstract Green synthesis methods are considered as a safer alternative to the conventional synthetic processes due to their eco-friendly nature, cost-effectiveness, and easy handling. In the present study, an eco-friendly and sustainable method for the synthesis of stable arenediazonium has been developed using saccharin as a cheap and mild acidic agent and tert-butyl nitrite as a diazotization reagent for the first time. These stable intermediates were used in the azo coupling reaction with 4-hydroxybenzaldehyde via telescoped dediazotization. The current method has advantages such as reduced waste by avoiding solvent for the purification of intermediate in diazotization step, cost-effectiveness, simple experimental procedure, good yield of azo dyes, metal-free waste, and environmentally benign conditions. An interesting aspect of this study is the recovery of saccharin from the reaction, which could be reused.

DDQ-Catalyzed Direct C(sp3)–H Amination of Alkylheteroarenes: Synthesis of Biheteroarenes under Aerobic and Metal-Free Conditions

A strategy for oxidative Csp3–H/N–H cross-coupling is presented. This reaction successfully utilizes 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and tert-butyl nitrite (TBN) as co-catalysts to construct the biomedical applicable biheteroarenes under aerobic conditions. Notably, this amination reaction is successful with a wide range of alkylheteroarenes and could be used as a functionalization tactic for pharmaceutical research and other areas. Furthermore, preliminary mechanistic studies indicate that the C–N bond formation proceeds through the nucleophilic attack of azole to the carbon cation.

Renaissance of Sandmeyer-Type Reactions: Conversion of Aromatic C-N Bonds into C-X Bonds (X = B, Sn, P, or CF3).

The Sandmeyer reaction represents an important organic transformation that converts an arylamine to an aryl halide using Cu(I) halide via a diazonium salt intermediate. The reaction was first reported by Sandmeyer in 1884, and a number of named reactions closely related to it have been developed and widely applied in organic synthesis throughout the 20th century. These include the Pschorr reaction for the synthesis of biaryl tricycles, the Gomberg-Bachmann reaction for biaryl formations, the Balz-Schiemann reaction for C-F bond formations, and the Meerwein reaction for arylation of α,β-unsaturated carbonyl compounds. However, all these reactions were discovered before 1940. In 1977, Doyle and co-workers reported an organic phase diazotization process, and Kikukawa and Matsuda used aryldiazonium salts in transition metal-catalyzed cross-coupling reactions. However, completely new processes involving diazonium salts have been seldom reported since then, although aryldiazonium salts are widely utilized in modern organic synthesis. In the past few years, diazonium salt chemistry has been revisited and become a fast-growing research topic. Several novel transformations based on diazonium salts have been developed and have been practiced in organic synthesis. In 2010, we reported a direct conversion of arylamines to pinacol boronates through the reaction of in situ generated aryl diazonium salts with B2pin2. This new strategy is under metal-free conditions and thus completely avoids contamination by transition metals in the boron products. From readily available arylamines various functionalized arylboronates, some of which are difficult to access by other methods, can be easily obtained with this reaction. Mechanistic investigations indicate the reaction likely follows a radical mechanism, which is similar to traditional Sandmeyer-type reactions. Subsequently, modified reaction conditions for this transformation appeared in the literature, which include light-induced reactions, aqueous-phase diazotization methods, and reactions with aryltriazenes as the arene diazonium salt surrogates. In addition to the borylation, we have also demonstrated the corresponding stannylation and phosphorylation of arylamines with similar Sandmeyer-type approaches. The stannylation of arylamines was achieved by the reaction of in situ generated diazonium salts with a distannane reagent, while phosphorylation is the reaction of arylamines with trimethyl phosphite in the presence of tert-butyl nitrite (t-BuONO). With the sequential borylation and stannylation approaches, the aromatic compounds bearing two amino groups are easily converted into trimethylstannyl arylboronates, which can be further used in consecutive Stille and Suzuki-Miyaura cross-couplings. Finally, direct conversion of the amino group of arylamines to the trifluoromethyl group has been developed through aryl diazonium salts almost simultaneously by several groups. These reactions represent a novel strategy to achieve trifluoromethylation of aromatic compounds. These developments show the revivification of this age-old chemistry, and this Account will summarize the Sandmeyer reaction-related transformations that have been developed since 2010.

Three Sequential C-N Bond Formations: tert-Butyl Nitrite as a N1 Synthon in a Three Component Reaction Leading to Imidazo[1,2-a]quinolines and Imidazo[2,1-a]isoquinolines.

tert-Butyl nitrite serves the dual role of an oxidant as well as a N1 synthon in a multicomponent reaction involving quinolines, isoquinolines, and styrenes. Herein, two sp2 C-H functionalizations of styrenes and one sp2 C-H functionalization of quinolines and isoquinolines lead to the formation of fused quinolines and isoquinolines via three sequential C-N bond formations.

TBN as a metal-free reagent initiated sp3 C–H functionalization of glycine esters: Synthesis of quinoline-2-carboxylate esters

As a metal-free reagent, tert-butylnitrite (TBN) initiated aerobic sp3 C–H bond oxidation of glycine esters was achieved, providing a series of quinoline-2-carboxylates in good yields. The mechanistic investigation revealed that in the presence of molecular oxygen, TBN derived radicals were involved in the C–H bond oxidation and the terminal aromatization.

In situ generation of nitrile oxides from copper carbene and tert-butyl nitrite: synthesis of fully substituted isoxazoles.

Herein, we present a novel [3 + 2] cycloaddition reaction of β-keto esters with nitrile oxides, which were generated in situ from copper carbene and tert-butyl nitrite. This three-component reaction provides new methodology for the direct synthesis of fully substituted isoxazole derivatives, featuring mild reaction conditions, readily accessible starting materials and simple operation. The experimental studies and DFT calculations suggest that the reaction starts with the generation of the key intermediate nitrile oxides, followed by a [3 + 2] cycloaddition reaction of β-keto esters to give the final isoxazole products.

Tert-Butyl nitrite mediated nitrogen transfer reactions: synthesis of benzotriazoles and azides at room temperature.

A conversion of o-phenylenediamines into benzotriazoles was achieved at room temperature using tert-butyl nitrite. The optimized conditions are also well suited for the transformation of sulfonyl and acyl hydrazines into corresponding azides. This protocol does not require any catalyst or acidic medium. The desired products were obtained in excellent yields in a short span of time.

Biodegradable crosslinked polyesters derived from thiomalic acid and S-nitrosothiol analogues for nitric oxide release.

Crosslinked polyesters with Young's moduli similar to that of certain soft biological tissues were prepared via bulk polycondensation of thiomalic acid and 1,8-octanediol alone, and with citric or maleic acid. The copolymers were converted to nitric oxide (NO)-releasing S-nitrosothiol (RSNO) analogues by reaction with tert-butyl nitrite. Additional conjugation steps were avoided by inclusion of the thiolated monomer during the polycondensation to permit thiol conversion to RSNOs. NO release at physiological pH and temperature (pH 7.4, 37 °C) was determined by chemiluminescence-based NO detection. The average total NO content for poly(thiomalic-co-maleic acid-co-1,8-octanediol), poly(thiomalic-co-citric acid-co-1,8-octanediol), and poly(thiomalic acid-co-1,8-octanediol) was 130 ± 39 μmol g-1, 200 ± 35 μmol g-1, and 130 ± 11 μmol g-1, respectively. The antibacterial properties of the S-nitrosated analogues were confirmed against Escherichia coli and Staphylococcus aureus. The hydrolytic degradation products were analyzed by time-of-flight mass spectrometry after a 10-week study to investigate their composition. Tensile mechanical tests were performed on the non-nitrosated polymers as well as their S-nitrosated derivatives and suggested that the materials have appropriate Young's moduli and elongation values for biomedical applications.

Synthesis of 2-aminobenzophenones through acylation of anilines with α-oxocarboxylic acids assisted by tert-butyl nitrite.

In this paper, a regioselective, efficient and convenient synthesis of 2-aminobenzophenones through acylation of anilines with α-oxocarboxylic acids assisted by tert-butyl nitrite is presented. Interestingly, tert-butyl nitrite acts as not only an efficient and mild nitrosation reagent, but also a sustainable oxidant required in the Pd(ii)-catalyzed decarboxylative acylation. Meanwhile, the NO unit turned out to be an easily introduced and readily removable directing group for the regioselective acylation.

Saccharin and tert-Butyl Nitrite: Cheap and Efficient Reagents for the Synthesis of 1,2,3-Benzotriazine-4-(3H)-ones from 2-Aminobenzamides under Metal-Free Conditions

A mild and eco-friendly protocol for the synthesis of 1,2,3-benzotriazine-4-(3H)-ones is described using saccharin as a cheap and efficient catalyst and tert-butyl nitrite as a diazotization reagent for the first time. The current method has advantages such as cost effectiveness, energy efficiency, and simple experimental procedure, good yield of the desired product, and metal-free and environmentally benign conditions.

Tert-Butyl Nitrite (TBN) as a Versatile Reagent in Organic Synthesis

tert-Butyl nitrite (TBN) is an important metal-free reagent that is widely applied in various organic transformations. Besides its traditional applications in nitrosation and diazotization, its ability to activate molecular oxygen to enable the initiation of radical reactions, including nitration, oximation, oxidation, and so on, has attracted extensively attention in the past decade. This review highlights recent advances in this field to promote further exploration of this versatile compound.1 Introduction2 Reactions Involving TBN2.1 Nitrosation2.2 Oximation2.3 Diazotization2.4 Nitration2.5 Oxidation2.6 Other Reactions3 Conclusion and Perspective

Tert-Butyl nitrite induced radical dimerization of primary thioamides and selenoamides at room temperature

A simple and efficient method for the dimerization of primary thioamides into 1,2,4-thiadiazoles using tert-butyl nitrite is described. The optimized condition was also found to be suitable for the dimerization of benzoselenoamides into 1,2,4-selenadiazoles. All the reactions proceed smoothly at room temperature and gave the desired products in excellent yields in a short span of time.

One-Pot Synthesis of Quinoxalinones via Tandem Nitrosation/Cyclization of N-Aryl Cyanoacetamides.

A new one-pot strategy for the synthesis of quinoxalin-2-ones from the tandem nitrosation/cyclization reaction of N-aryl cyanoacetamides with tert-butyl nitrite has been developed. The dehydrogenative N-incorporation is achieved through a sequence of nitrosation, tautomerization, and cyclization, affording quinoxalin-2-ones in moderate to good yields with good functional group tolerance.