Phosphorylinitrile oxides. 7. Quantum chemical study of the dimerization of nitrile oxides

A semiempirical MNDO calculation was carried out for the singlet potential energy surface for the dimerization of acetonitrile oxide leading to dimethylfuroxane. The dimerization of nitrile oxides proceeds by a two-step mechanism. The rate-limiting step is formation of a dinitrosoethylene intermediate. A semiempirical AMI calculation was carried out to study the effect of phosphoryl substituents on formation of the transition state of the rate-limiting step in the dimerization of dimethoxyphosphorylnitrile oxide. Independently of the initial orientation of the two phosphorylnitrile oxide molecules, a gauche-oriented dimerica species is formed in the first step in the dimerization. There is hardly any specific effect ofthe phosphoryl substituents in the first step of phosphorylnitrile oxide dimerization.Communication 6, see ref. [1].Kazan State Technological University, 420015 Kazan, and Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432 Chernogolovka. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1269–1273, September, 1994. Original article submitted August 5, 1994.     

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

The 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.     

[3 + 2] Cycloaddition of nitrile oxides to dichloropropenes and 1,3-dichlorobut-2-ene: A regioselectivity issue

The reaction of nitrile oxides with 2,3-dichloroprop-1-ene, 1,3-dichloroprop-1-ene, and 1,3-dichlorobut-2-ene leads to 5-(chloromethyl)isoxazoles, 4-(chloromethyl)isoxazoles, or to mixtures of both regioisomers. The direction of cycloaddition and reactivity of substrate is determined by the steric hindrance at the terminal carbon atom of the alkene double bond. It has been found that the isomeric products of cycloaddition of nitrile oxides to 1,3-dichloropropene have significantly different dehydrochlorination capabilities. The experimental data on the regioselectivity of cycloaddition and the relative reactivity of substrates are in agreement with the results of quantum chemical calculations.     

Nitrile oxides cycloadditions to cinnamaldehyde. Facile dehydrogenation of 4-formyl-4,5-dihydroisoxazoles

Nitrile oxides (1) react with cinnamaldehyde (2) at the ethylenic double bond to give 4-formyl-4,5-dihydro-isoxazoles (3) as the predominant regioisomers (¹H nmr). These primary cycloadducts easily dehydrogenate to the corresponding isoxazoles (4). In the presence of an excess of nitrile oxide (1), either the aldehydes (3) and (4) undergo further cycloaddition at the C?O bond yielding the bis-cycloadducts (5) and (6), respectively.     

Reactivity of Pt- and Pd-bound nitriles towards nitrile oxides and nitrones: substitution vs. cycloaddition

Reactions of the nitrone CH3CH=N(CH3)O and the nitrile oxide CH3C[triple bond]NO with the nitrile complexes trans-[MCl2(N[triple bond]CCH3)2] (M = Pt, 1; Pd, 2) were investigated by theoretical methods at B3LYP and, for some processes, CCSD(T) levels of theory. The mechanisms of substitutions and cycloadditions were studied in detail. The former occur via a concerted asynchronous mechanism of dissociative type. The calculations of the metal-ligand bond energies in the starting complexes and substitution products and the analysis of structural features of the transition states indicate that the M-N bond dissociation (rather than M-O bond formation) is the step, which controls the reactivity of and in substitutions. The different chemical behaviours of the Pt and Pd complexes towards the 1,3-dipoles were investigated. The exclusive isolation of cycloaddition rather than substitution products in any solvents in the case of is both kinetically and thermodynamically controlled.The switch of the reaction mode from cycloaddition to substitution for 2 in CH2Cl2 solution is caused by the significantly lower Pd-N bond energy in comparison with the Pt-N bond energy, consistent with the higher lability of the Pd complexes. The different chemical behaviour of 2 in CH3CN and CH2Cl2 solvents is accounted for by the great excess of acetonitrile in the CH3CN solution rather than a different solvation character. The relative variation of Wiberg bond indices along the reaction path is proposed as a quantitative criterion for the classification of the reaction mechanism.     

Synthèses de 1,2,4-triazolo[4,3-d][1,4]diazépines et de 1,2,4-oxadiazolo[4,5-d][1,4]diazépines par cycloaddition dipolaire-1,3

We report here a one-step synthesis of the 4,5,6,7-tetrahydro-1H- 1,2,4,-triazolo[4,3-d][1,4]diazepine, 4-6, and 1,2,4-oxadiazolo[4,5-d][1,4]-diazepine, 7-10, by 1,3-dipolar cycloaddition of nitrile imines and nitrile oxides with 2,3-dihydro-H-1,4-diazepine, 1. In all cases these cycloaddition are peri- and regioselectives (the C ? N bond is sole affected) and occures with high yields. Structure and conformations of cycloadducts have been assigned by means of nmr analysis     

One step regioselective synthesis of 5-aminoisoxazoles from nitrile oxides and alpha-cyanoenamines

The 1,3-dipolar cycloaddition of nitrile oxides to 1-cyanoenamines gives 5-aminoisoxazoles regioselectively. Moderate to good yields could be obtained depending on the method used to generate the nitrile oxides. The intermediate isoxazolines could not be isolated.     

A convenient synthesis of 5-(1,2,4-oxadiazol-5-yl)pyrimidine-2,4(1H,3H)-diones

The synthesis of 5-heteroaryl-substituted uracil derivatives is presented. The 1,3-dipolar cycloaddition reaction was applied for the construction of a heterocyclic ring. The nitrile oxides were obtained from the appropriate 4-substituted benzaldoximes using N-chlorosuccinimide (NCS) under basic conditions. [2+3] Cycloaddition of nitrile oxides with 5-cyanouracil as a dipolarophile gave the corresponding 5-(3-substituited-1,2,4-oxadiazol-5-yl)uracils in satisfactory yields under mild conditions. 5-Substituted uracils having an additional heterocyclic ring were obtained as a result of the [2+3] cycloaddition of 5-cyanouracil to nitrile oxides generated from thiophene-2-carbaldehyde and 5-formyluracil derivatives.     

Study on the 1,3-dipolar cycloaddition reaction of 4-ethoxy-1,1,1-trifluoro-3-buten-2-one with nitrile oxides

1,3-Dipolar cycloaddition (1,3-DC) reaction of 4-ethoxy-1,1,1-trifluoro-3-buten-2-one 1 with nitrile oxides was studied. It was found that besides its CC participating in the formation of isoxazole rings, trifluoromethyl activated CO also underwent 1,3-DC reaction with nitrile oxides to afford 1,4,2-dioxazole rings. Single crystal diffraction analysis also evidenced the diheterocyclic configuration.     

Regio- and stereoselective (3 + 2)-cycloaddition of nitrile oxides and nitrones to <Emphasis Type="Italic">N</Emphasis>-vinylindole

1,3-Dipolar cycloaddition of nitrile oxides and nitrones to N-vinylindole proceeds regioselectively at the exocyclic multiple bond to form 5-indolyl-substituted isoxazolines and isoxazolidines in good yields.     

N-aryltrifluoroacetimidoylphosphonates

By reaction of N-aryltrifluoroacetimidoyl chlorides with trialkyl phosphites the corresponding N-aryltrifluoroacetimidoylphosphonates CF₃C(=NAr)P(O)(OR)₂ existing as dynamic equilibrium mixture of Z,Eisomers [Z/E ～ (7–12):1] were prepared. By ¹⁹F NMR spectroscopy kinetic and activation parameters of Z-E isomerization were evaluated. Reaction of imidoylphosphonates with O-or S-centered nucleophiles leads to the products of addition to C=N bond whereas cycloaddition with of nitrile oxide gives previously unknown phosphorylated oxadiazolines.     

3,3′-diaryl-5-morpholino-4,5,4′,5′-tetrahydro-4,5′-spirobi[isoxazoles]. Synthesis by cycloaddition reactions and substituent effect on the cycloaddition kinetics

3-Aryl-4-methylene-5-morpholino-4,5-dihydroisoxazoles 1a-e were synthesized; fifteen different 3,3′-diaryl-5-morpholino-4,5,4′,5′-tetrahydro-4,5′-spirobi[isoxazoles] 3 were obtained by their reaction with some stable aryl nitrile oxides. The spiro-derivatives were characterized by their nmr spectra. Kinetic measurements showed that substituents on the nitrile oxide have a weak effect on the cycloaddition rate (Hammett 'p = ca 0.3), while substituents on the dipolarophile have no effect at all.     

1,3-Dipolare Cycloadditionen von Nitrilium-Betainen mit 4,4-Dimethyl-2-phenyl-2-thiazolin-5-thion

1,3-Dipolar cycloadditions of Nitrilium Betaines with 4,4-Dimethyl-2-phenyl-2-thiazolin-5-thione Benzonitrile ylides, imines, and oxides undergo smooth 1,3-dipolar cycloaddition reactions with the exocyclic, C,S-double bond of 4,4-dimethyl-2-phenyl-2-thiazolin-5-thione ( 1 ), yielding heterocyclic spiro-compounds. The structure of the cycloadducts 5c, 5c ′, and 3f (Fig.) have been established by x-ray structure analysis. With the benzonitrile ylides, the two regioisomeric cycloaddition modes have been observed, depending on the substituents of the ylide-C-atom. It is questionable, whether the reaction of 1 and the oxazaphosphol 8 (Schemes 8 and 13) proceeds via the corresponding nitrile ylide as an intermediate.     

Microwave Accelerated Cycloaddition Reactions of Nitrile Oxides and Allylic Alcohols

The application of microwaves in promoting the cycloaddition reactions of allyl alcohols with nitrile oxides using a domestic microwave oven and a focused monomode microwave reactor have demonstrated that not only was the reaction time substantially reduced, but also the reaction yields were significantly improved over the conventional stirred reactions. Microwave irradiation alters the regioselectivity of the cycloaddition reaction which favors the non‐hydrogen‐bond directed cycloadduct, isoxazoline 4 .     

Cycloaddition reactions of 1,2-diazepines with nitrile oxides. synthesis of 1,2,9-triaza-8-oxabicyclo-[5.3.0]-3,5,9-decatriene derivatives

A new heterocyclic system, 1,2,9-triaza-8-oxabicyclo-[5.3.0]-3,5,9-decatriene 4, has been synthesized by regiospecific 1,3-dipolar cycloaddition of nitrile oxides to the imine double bond of 1,2-diazepines. Bis-adduct 5a is obtained in only trace amounts showing that the imine double bond is more reactive than the Δ⁴-olefinic bond.     

Syntheses with nitrile oxides. 2. Reaction of aromatic nitrile oxides with bis(trimethylsilylcarbodiimide)

The reaction of aromatic nitrile oxides with bis(trimethylsilylcarbodiimide) gives 5-amino-3-aryl-1,2,4-oxadiazoles.For previous communication, see [1].N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117334 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 10, pp. 2430–2432, October, 1992.     

锗苯与腈氧化物1,3偶极环加成反应理论研究

采用密度泛函理论(DFT)方法在B3LYP/6-311G**水平研究了锗苯与腈氧化物的1,3偶极环加成反应的微观机理、势能剖面,考察取代基和四氢呋喃溶剂对反应势能剖面的影响.计算结果表明,所研究反应均以协同但非同步的方式进行,且总是Ge—O键先于C—C键形成.锗苯分子中Ge原子上的给电子和吸电子取代基均有利于反应的进行,而腈氧化物C原子上的2,4,6-三甲苯基取代基在热力学上对反应很不利.四氢呋喃溶剂对所研究反应的势能剖面影响不大.     

4,5-Dihydroisoxazole and 4,5-dihydro-1,2,4-oxadiazole derivatives from cycloaddition reactions of nitrile oxides to alkyl N-(diphenylmethylene)-α,β-dehydroamino acids

The alkyl N-(diphenylmethylene)-α,β-dehydroamino acids 1 have been submitted to 1,3-dipolar cycloadditions with nitrile oxides. The reactivity of these compounds depends on the type and on the stereochemistry of the β-substituents. With the unsubstituted terms 1a,b the reaction occurs on the C,C double bond, providing a good method for the synthesis of the 4,5-dihydroisoxazole derivatives 3a,b,c and for the gem-functionalized 4,5-dihydroisoxazoles amino carboxylic ester 5. The β-substituted compounds 1c,d,e , inert to 1,1-dimethylethylnitrile oxide, undergo the reaction to the N,C double bond, thus giving with 2a,b the 4,5-dihydro-1,2,4-oxadiazole derivatives 4. All the reactions occur with high site- and regioselectivity.     

Cycloaddition of Nitrile Oxides to Graphene: a Theoretical and Experimental Approach

Density functional theory (DFT) studies of the interaction between graphene sheets and nitrile oxides have proved the feasibility of the reaction through 1,3-dipolar cycloaddition. The viability of the approach has been also confirmed experimentally through the cycloaddition of few-layer exfoliated graphene and nitrile oxides containing functional organic groups with different electronic nature. The cycloaddition reaction has been successfully achieved in one-pot from the corresponding oximes under microwave (MW) irradiation. The successful formation of the isoxazoline ring has been confirmed by Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS).     

The site-selectivity of cycloadditions of nitrile oxides to β-aminocinnamonitriles. A remarkable solvent dependence

Cycloadditions of nitrile oxides to N-mono and unsubstituted β-aminocinnamonitriles are remarkably affected by the hydrogen acceptor ability of the solvent. Addition to C ? N bond predominates in non and weak hydrogen bond acceptor solvents because of the assistance of favourable hydrogen bonding effects. In strong hydrogen bond acceptor solvents the assistance is fully relieved and the regular addition to C ? C bond becomes prevalent.