The 2:1 cycloadducts from [3 + 2] 1,3-dipolar cycloaddition of nitrile oxide and vinylacetic acid. Synthesis and liquid crystal behaviour

Abstract

2012The 2:1 cycloadducts from [3+2] 1,3-dipolar cycloaddition of nitrile oxide and vinylacetic acid. Synthesis and liquid crystal behaviour LIQUID CRYSTALS, ABINGDON, v. 39, n. 2,pp. 175-184, FEB, 2012 http://www.producao.usp.br/handle/BDPI/42740 This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden.The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae, and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand, or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material. Four liquid crystals (LC) 3,7a-bis(4-alkyloxyphenyl)-7,7a-dihydro-6H-isoxazolo[2,3-d][1,2,4]oxadiazol-6-yl)acetic acid (7a-d) were synthesised and the mesomorphic behaviour reported. The LCs were characterised as 2:1 bisadducts, which were obtained from a double [3 + 2] 1,3-dipolar cycloaddition. In the first step, the cycloaddition of 4-alkyloxyphenylnitrile oxide (4a-d) and vinylacetic acid (5) gave the initial unobserved 1:1 cycloadducts 2-[3-(4-alkyloxyphenyl)-4,5-dihydroisoxazol-5-yl]acetic acid (6a-d). In the second step, the addition of a second equivalent of 4 to 6 yielded the 2:1 bisadducts 7a-d without any traces of 6. All compounds 7a-d were unstable during the transition from the mesophase to the isotropic state upon first heating as evidenced by the large peaks in the differential scanning calorimetry traces. Due to the chemical instability of the compounds upon heating, the transition temperature related to the smectic C to smectic A transitions was acquired by means of an image processing method. X-Ray diffraction experiments were also used to analyse the liquid-crystalline phases. A theoretical calculation was performed using density functional theory (DFT) methods at the PBE1PBE/6-311+G(2d,p) level (with solvent effect) in order to get information about the energetic profile of the 2:1 cycloaddition. DFT studies revealed that the cycloaddition process is controlled by the HOMO (dipolarophile) -LUMO (1,3-dipole) , and that the double [3 + 2] 1,3-dipolar cycloaddition reaction is quite possible.

Nitrile Oxide, Alkenes, Dipolar Cycloaddition, Isomerization and Metathesis Involved in the Syntheses of 2-Isoxazolines

“…An interesting report came from Tavares et al in 2011. They used double 1,3-DP cycloaddition for the syntheses of liquid crystals, namely 3,7a-bis(4-alkyloxyphenyl)-7,7a-dihydro-6 H -isoxazolo [2,3- d ][1,2,4]oxadiazol-6-yl)acetic acid derivatives— Scheme 84 [ 91 ]. In the first step of this synthetic route, the 1,3-DP cycloaddition of 4-alkyloxyphenylnitrile oxide to vinylacetic acid gave the initial but unobserved 3,5-disubstituted 2-isoxazolines (1:1 cycloadducts), namely 2-[3-(4-alkyloxyphenyl)-4,5-dihydroisoxazol-5-yl]acetic acid derivatives.…”

The 1,3-Dipolar Cycloaddition of Nitrile Oxide to Vinylacetic Acid: Computational Study of Transition States Selectivity, Solvent Effects, and Bicyclo Formation

“…However, the cycloadduct 3 was not observed experimentally and only the bisadduct 4 was obtained. 17 One possible explanation is the higher thermodynamic stability of the bisadduct, compared to cycloadduct, in addition to the slight difference in activation barriers ( Figure 5). …”

“…This reaction produces a bicyclo, which is experimentally observed. 17 The three DFT functionals produce approximately the same free energies and electronic energies for the TS2, except for TS2_β-anti-HB.…”

“…17 To better understand this reaction, the mechanism of the 13DC between vinylacetic acid (1) and benzonitrile oxide (2) (Scheme 1) was studied using different DFT functionals and post Hartree-Fock calculations. Considering the large use of B3LYP functional to describe cycloaddition reactions and taking into account PBE1PBE, 44 and CAM-B3LYP 45 hybrid functionals together with the 6-311+G(2d,p) basis set The solvent effects were included with CPCM 51,52 and PCM 53 formalisms together with three solvents with a different dielectric constant, i.e., THF (ε = 7.43), ACN (ε = 35.69) and FORM (ε = 108.94), with the aim of evaluating the possible changes in the reaction energetic profile with the increase of dielectric constant of the environment.…”

“…1 These reactions are stereospecific, regiospecific and diasteroselective 2,3 and have been applied to organic synthesis, 4 materials chemistry, 5,6 drug discovery, 7,8 and, most recently, have also been employed to modify carbon materials, such as fullerene, 9 carbon nanotubes, 10 and graphene. 11,12 The cycloaddition of nitrile oxides to olefins, in particular, has considerable interest for obtaining isoxazoline rings, 13 substrates of many products with biological activity [14][15][16] and organic molecules with technological interest, such as liquid crystal materials 17 and organic semiconductors. 18 From the pioneering work of Huisgen,19,20 who postulated the concerted reaction mechanism of cycloaddition reactions, this kind of reaction has been widely studied, both theoretically and experimentally.…”