Formation Of Nitrile Oxides Research Articles

Cascade Rearrangement: Nitro Group-Participating Syntheses of 1,2,5-Thiadiazoles and 1,2,4-Thiadiazolones.

A trifluoroacetic anhydride-mediated cascade process for the synthesis of thiadiazole derivatives is described. 1,2,5-Thiadiazoles and 1,2,4-thiadiazolones could be obtained by variation of the reaction conditions. A group of functionalized thiadiazole derivatives were synthesized in moderate to good yields from nitro-group-containing N-tert-butanesulfinamides. The reactions involved in this tandem process are a Pummerer-like rearrangement of the tert-butanesulfinamide unit, a nitrile oxide formation via nitro group rearrangement, addition of oxygenated nucleophiles, and an N-S bond forming cyclization followed by concomitant elimination.

Catalyst-Free Formation of Nitrile Oxides and Their Further Transformations to Diverse Heterocycles.

The formation of nitrile oxides with diazocarbonyl compounds by nitrosyl transfer from tert-butyl nitrite under mild conditions and without the use of a catalyst or an additive is reported. This transformation is broadly applicable to the synthesis of furoxans by dimerization and isoxazoles and isoxazolines by cycloaddition. This methodology is also applied for the millimole-scale synthesis of two biologically active compounds. The formation of the nitrile oxide from a diazoacetamide is stable and confirmed experimentally.

Does electrophilic activation of nitroalkanes in polyphosphoric acid involve formation of nitrile oxides?

The mechanistic rationale involving activation of nitroalkanes towards interaction with nucleophilic reagents in the presence of polyphosphoric acid (PPA) was re-evaluated. Could nitrile oxide moieties be formed during this process? This experiment demonstrates that at least in some cases this could happen, as generated nitrile oxides were successfully intercepted as adducts of [3 + 2] cycloadditions.

Postsynthetic Modification of Metal-Organic Frameworks through Nitrile Oxide-Alkyne Cycloaddition.

Postsynthetic modification of metal-organic frameworks is an important method to tailor their properties. We report on the nitrile oxide-alkyne cycloaddition (NOAC) as a modification tool, a reaction requiring neither strained alkynes nor a catalyst. This is demonstrated with the reaction of nitrile oxides with PEPEP-PIZOF-15 and -19 at room temperature. PIZOF-15 and -19 are porous Zr-based MOFs (BET surface areas 1740 and 960 m2 g-1, respectively) consisting of two mutually interpenetrating UiO-type frameworks with linkers of the type -O2C[PE-P(R1,R2)-EP]CO2- (P, phenylene; E, ethynylene; R1 and R2, side chains at the central benzene ring with R1 = R2 = OCH2C≡CH or R1 = OCH2C≡CH and R2 = O(CH2CH2O)3Me). Their syntheses, using benzoic acid as a modulator, and their characterization are reported herein. The propargyloxy (OCH2C≡CH) side chains contain the ethyne moieties needed for NOAC. Formation of nitrile oxides through oxidation of oximes in aqueous ethanolic solution in the presence of PEPEP-PIZOF-15 and -19 resulted in the reaction of 96-100% of the ethyne moieties to give isoxazoles. Thereby the framework was preserved. The type of nitrile oxide RCNO was greatly varied with R being isopentyl, tolyl, 2-pyridyl, and pentafluorophenyl. A detailed NMR spectroscopic investigation showed the formation of the 3,5-disubstituted isoxazole to be clearly favored (≥96%) over that of the constitutional isomeric 3,4-disubstituted isoxazole, except for one example.

Pd Catalysis in Cyanide-Free Synthesis of Nitriles from Haloarenes via Isoxazolines.

A method to obtain aryl nitriles from the corresponding halides by Pd catalysis, in the absence of any cyanide source, is reported. The reaction of an aryl halide, ethyl nitroacetate, and an olefin readily delivers an aromatic nitrile. A variety of aryl iodides/bromides have been converted into the corresponding cyanoarenes in fair to excellent yields. The reaction likely involves the following steps: (a) Pd-catalyzed α-arylation of ethyl nitroacetate; (b) nitrile oxide formation;

ChemInform Abstract: An Improved Procedure for the Preparation of β‐Thiohydroximates for Glucosinolate Synthesis.

AbstractA new coupling method for the formation of β‐thiohydroximate bonds involves in situ generation of an oximyl chloride from the corresponding oxime and inexpensive chlorine bleach followed by base‐mediated formation of nitrile oxides which react with thioglucopyranose (II).

Synthesis of isoxazoles by hypervalent iodine-induced cycloaddition of nitrile oxides to alkynes

Treatment of oximes with hypervalent iodine leads to substituted isoxazoles via rapid formation of nitrile oxides. Reaction with terminal alkynes led to a series of 3,5-disubstituted isoxazoles with complete regioselectivity and high yield, in a procedure mild enough to prepare a range of nucleoside and peptide conjugates. Exceptionally high reaction rates were found for the formation of 3,4,5-trisubstituted isoxazoles from a cyclic alkyne.

ChemInform Abstract: Enhanced Rate of Intramolecular Nitrile Oxide Cycloaddition and Rapid Synthesis of Isoxazoles and Isoxazolines.

An enhanced rate of intramolecular nitrile oxide cycloaddition and hence a rapid synthesis of isoxazoles and isoxazolines is described. Formation of nitrile oxides from oximes using only 1 or 2 Eq (equivalents) of aqueous sodium hypochlorite solution is also described.

Magtrieve™ (CrO 2) and MnO 2 mediated oxidation of aldoximes: studying the reaction course

Magtrieve™ (CrO 2) and MnO 2 mediated oxidation of aldoximes to nitrile oxides were studied in details. In presence of external radical source, TEMPO, these reagents did not furnish nitrile oxides, instead favoured deoximation to aldehydes. A common trend of deoximation was established from electronically tuned aldoximes, which is: aliphatic>aromatic>aldoximes with strong electron-withdrawing group, though the extent of deoximation was less in case of CrO 2. Above effects were not observed with chloramine-T and diacetoxyiodobenzene, reagents known to produce nitrile oxides via hydroximoyl halide or equivalent ionic intermediates. A putative reaction mechanism is proposed for MO 2 (M=Cr, Mn) mediated oxidation of aldoximes through formation of a nitroso-oxime tautomeric pair. Formation of nitrile oxide is possibly occurred from the oxime tautomer via a σ-type iminoxy radical intermediate. The deoximation process, dominating in presence of external radical environment, is explained following decomposition of the nitroso tautomer.

ChemInform Abstract: One-Pot Synthesis of Five-Membered Cyclic Thioethers or Ethers via Intramolecular Nitrile Oxide-Olefin Cycloaddition (INOC) or Intramolecular Alkoxycarbonyl Nitronate-Olefin Cycloaddition (IAOC) by the Use of Methyl Chloroformate.

Abstract Reaction of β-nitrostyrenes 1 with allyl mercaptan 2 in the presence of triethylamine generated unsaturated nitro sulfides 3 and then the solution was treated with methyl chloroformate (MCF) and was refluxed to obtain [3.3.0]bicyclic products trans-6 and cis-6 in one-pot. The rations of trans-6:cis-6 were from 1.1:1 to 1.8:1 and the mechanism of the formation 6 is proposed to proceed through the formation of nitrile oxides 5 to undergo intramolecular nitrile oxide-olefin cycloaddition (INOC). Nitronates 16, prepared from 1 with allyl alcohol and base, can be converted into methoxycarbonyl nitronates 22 by treating the solution with methyl chloroformate and calytic amount of 4-dimethylaminopyridine (DMAP) in the presence of different amounts of triethylamine. Intermediates 22 can either undergo intramolecular alkoxycarbonyl nitronate-olefin cycloaddition (IAOC) to generate highly stereoselective product trans-14 or undergo INOC to yield trans-14 and cis-14. The application of this improved methodology to synthesize different heterocyclic products 10, 26, and 27 is reported.

Enhanced rate of intramolecular nitrile oxide cycloaddition and rapid synthesis of isoxazoles and isoxazolines

AbstractAn enhanced rate of intramolecular nitrile oxide cycloaddition and hence a rapid synthesis of isoxazoles and isoxazolines is described. Formation of nitrile oxides from oximes using only 1 or 2 Eq (equivalents) of aqueous sodium hypochlorite solution is also described.Graphical abstract[IMAGE]

Nucleoside and nucleotide analogues by catalyst free Huisgen nitrile oxide–alkyne1,3-dipolar cycloaddition

An efficient, catalyst free, 1,3-dipolar cycloaddition strategy to conjugate nucleosides and nucleotides with isoxazoles under atmospheric conditions and in an aqueous environment is reported. The protocol involves chloramine-T as a practical reagent to induce in situ nitrile oxide formation and the alkyne partner is attached to the sugar residue or the nucleobase. The reactions are regiospecific, fast and high yielding.

Preparation of a Spiroisoxazolinopiperidinylbenzamide-Based Scaffold

A route to spiroisoxazolinopiperidinylbenzamides has been developed. N-Boc-4-piperidone underwent a Wittig olefination and Boc-deprotection followed by a nucleophilic substitution reaction with 4-fluoro-3-nitrobenzoic acid to yield the starting scaffold 3 in excellent yields. Diversification of the acid with primary amines, followed nitrile oxide formation in situ (aryl oximes treated with bleach) and subsequent 1,3-dipolar cycloaddition to the exomethylene moiety delivered the spiroisoxazolinopiperdines. Reduction of the arylnitro group followed by acylation with acid chlorides or reductive amination with aldehydes yielded the spiroisoxazolinopiperidinylbenzamide library.

Synthesis and biological activity of 2-(4,5-dihydroisoxazol-5-yl)-1,3,4-oxadiazoles

Acid hydrazides were coupled with acrylic acid derivatives and cyclodehydration gave 1,3,4-oxadiazoles. Lastly, in-situ nitrile oxide formation from aryl oximes treated with sodium hypochlorite, and subsequent 1,3-dipolar cycloaddition to the exomethylene moiety delivered 2-(4,5-dihydroisoxazol-5-yl)-1,3,4-oxadiazoles. This library was evaluated in a high-throughput screen at Dow AgroSciences. Several compounds were active against fungal pathogens and pest insects.

Formation of Isoxazole Derivatives via Nitrile Oxide Using Ammonium Cerium Nitrate (CAN): A Novel One‐Pot Synthesis of 3‐Acetyl‐ and 3‐Benzoylisoxazole Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Formation of isoxazole derivatives via nitrile oxide using ammonium cerium nitrate (CAN): a novel one-pot synthesis of 3-acetyl- and 3-benzoylisoxazole derivatives

The reactions of alkenes and alkynes with ammonium cerium(IV) nitrate ((NH 4) 2Ce(NO 3) 6, CAN(IV)) in acetone under reflux gave the corresponding 3-acetyl-4,5-dihydroisoxazole and 3-acetylisoxazole derivatives. In the case of acetophenone, 3-benzoyl-4,5-dihydroisoxazole and 3-benzoylisoxazole derivatives were obtained. Reaction of acetone with CAN(IV) afforded the corresponding furoxan (3,4-diacetyl-1,2,5-oxadiazole 2-oxide) as the dimer of nitrile oxide. Moreover, it was found that yields of isoxazole derivatives were improved using ammonium cerium(III) nitrate tetrahydrate ((NH 4) 2Ce(NO 3) 5·4H 2O, CAN(III))-formic acid. The reaction mechanisms based on nitration and formation of nitrile oxide mediated by CAN(IV) or CAN(III) from acetone or acetophenone are also proposed.

Reaction of Benzohydroximinoyl Chlorides and β‐(Trifluoromethyl)acetylenic Esters: Synthesis of Regioisomeric (Trifluoromethyl)isoxazolecarboxylate Esters and Oxime Addition Products.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Reaction of benzohydroximinoyl chlorides and β‐(trifluoromethyl)‐acetylenic esters: Synthesis of regioisomeric (trifluoromethyl)‐isoxazolecarboxylate esters and oxime addition products

AbstractThe triethylamine induced reaction of benzohydroximinoyl chlorides, precursors of nitrile oxides, with β‐trifluoromethylacetylenic esters gives rise to three products: 5‐trifluoromethyl‐4‐isoxozolecarboxylate esters, regioisomeric 4‐trifluoromethyl‐5‐isoxazolecarboxylate esters and an unexpected oxime 1,4‐addition adduct. Product distribution is rationalized in terms of two competing reaction modes, either 1,4 addition of the oxime anion to the acetylenic ester or formation of the nitrile oxide followed by 1,3‐dipolar cycloaddi‐tion. Anionic 1,4‐addition of the oximinoyl chloride to the acetylenic ester is preferred at low temperatures, while nitrile oxide formation followed by cycloaddition is preferred at temperatures above 0 °C. Regioisomeric products from addition of nitrile oxides to various perfluoroalkylacetylenes are compared and assigned by 13C NMR.

A SIMPLE AND EFFICIENT METHOD FOR THE SYNTHESIS OF NITRILE OXIDE FROM ALDOXIME USING TRICHLOROISOCYANURIC ACID

Treatment of the aldoxime derived from vanilin with trichloroisocyanuric acid in the presence of olefins as dipolarophiles caused the formation of nitrile oxides and subsequent 1,3-dipolar cycloaddition forming the corresponding isoxazoline derivatives in good yields.

One-pot synthesis of five-membered cyclic thioethers or ethers via intramolecular nitrile oxide-olefin cycloaddition (INOC) or intramolecular alkoxycarbonyl nitronate-olefin cycloaddition (IAOC) by the use of methyl chloroformate

Reaction of β-nitrostyrenes 1 with allyl mercaptan 2 in the presence of triethylamine generated unsaturated nitro sulfides 3 and then the solution was treated with methyl chloroformate (MCF) and was refluxed to obtain [3.3.0]bicyclic products trans- 6 and cis- 6 in one-pot. The rations of trans- 6: cis- 6 were from 1.1:1 to 1.8:1 and the mechanism of the formation 6 is proposed to proceed through the formation of nitrile oxides 5 to undergo intramolecular nitrile oxide-olefin cycloaddition (INOC). Nitronates 16, prepared from 1 with allyl alcohol and base, can be converted into methoxycarbonyl nitronates 22 by treating the solution with methyl chloroformate and calytic amount of 4-dimethylaminopyridine (DMAP) in the presence of different amounts of triethylamine. Intermediates 22 can either undergo intramolecular alkoxycarbonyl nitronate-olefin cycloaddition (IAOC) to generate highly stereoselective product trans- 14 or undergo INOC to yield trans- 14 and cis- 14. The application of this improved methodology to synthesize different heterocyclic products 10, 26, and 27 is reported.