Synthesis and reactions of benzotriazolyl epoxides

Substituted vinylbenzotriazoles were efficiently converted to benzotriazolyl epoxides by dimethyldioxirane. The behavior of these epoxides toward nucleophiles and strong bases was investigated.


Introduction
A recent study demonstrated the dimethyldioxirane (DMD) conversion of 1alkylbenzotriazoles into 3-alkylbenzotriazole 1-oxides. 1We now report the efficient and almost quantitative low temperature epoxidation of vinylbenzotriazoles by dimethyldioxirane together with some reactions of the epoxides formed.Compounds 1a-d reacted with DMD exclusively at the C=C bond to give epoxides, but not at the N-3 atom of the benzotriazole ring.This can be explained by the relative energies of the two MO's localized mainly on the C=C bond and on the N-3 atom.
According to a study of the electronic structure of 1-vinyl-1H-benzotriazoles, 10 the energy of the MO of the C=C bond is higher than that of those localized on N-3.The order of these two MOs here is reversed compared to that of 1-allylbenzotriazole, which is oxidized to the 3-N-oxides. 1 The stereochemistry of the olefins was preserved during oxidations below 0 o C: trans-olefins 1c and 1d gave trans-epoxides 2c and 2d, respectively.The trans-stereochemistry of the epoxides 2c and 2d was deduced from the vicinal coupling constant (1.5 Hz or less) that is in agreement with the literature data for J values (0−1.7 Hz) for 1-aryl-2-phenyl epoxides. 11In the 1 H NMR spectrum of 2c, the α-H (with respect to Bt) appeared as a doublet at δ 5.44 with a coupling constant of 1.2 Hz, while the β-H appeared as a doublet of quartets at δ 4.24 (J = 1.2 and 5.4 Hz), and the methyl group appeared as a doublet at δ 1.60 (J = 5.4 Hz).In the 1 H NMR spectrum of 2d, two epoxide protons were observed at δ 5.11 and 5.69 ppm as doublets with a coupling constant of 1.5 Hz.
A mixture of the cis (40%) and trans (60%) isomers of 1d reacted with 1.5 equiv of DMD to give three isolated products: the trans-epoxide 2d (52%), the cis-epoxide 4 (28%) and the 1,3dioxolane 5 (1.4%) (Scheme 1).The cis-stereochemistry of 4 was confirmed by the 1 H NMR spectrum, in which two doublets of integral intensity of 1H were observed at δ 5.82 (J = 2.6 Hz) and 4.58 (J = 2.6 Hz).In the 1 H NMR spectrum of 5, two methyl groups appeared as singlets at δ 1.83 and 1.88; the dioxolane protons appeared as doublets at δ 6.40 and 6.61 with a coupling constant of 6.1 Hz.The trans-stereochemistry of 5 was assigned by comparing the 1 H NMR spectrum to literature data. 12The coupling constant is slightly smaller than that of a similar type of dioxolane (J = 8.5 Hz) 12 due to the presence of the electron-withdrawing benzotriazole group.Since Eisch and Galle 13 reported the deprotonation of α-heterosubstituted epoxides, oxiranyllithium compounds have become important synthetic intermediates.Phenylsulphonyl 14 and benzothiazolyl 15 groups were used to stabilize the oxiranyl anion successfully in the functionalization of epoxides.Here we report the generation of oxiranyllithium species stabilized by a benzotriazole group and their reactions.
Treatment of the simplest benzotriazolyl epoxide 2a with LDA at −78 ºC, followed by the addition of MeI failed to give any coupling product.When Me 3 SiCl was used at −116 ºC, the anion generated in situ from 2a by LDA, was captured to give the expected product 6 in 30% isolated yield.This proved the formation of an oxiranyllithium species that is stabilized by benzotriazole.Treatment of epoxide 2d with fresh LDA at -116 ºC, followed by the immediate addition of electrophile PhCH 2 Br, afforded epoxide 8 in 51% yield along with the rearranged product 11 (Scheme 2).The generation of oxiranyllithium 7 from 2d by LDA is very fast at -116 o C, which is stable at and below this temperature for about 5 to 20 minutes.As the temperature goes above -110 o C, the anion starts to undergo rearrangement to give compound 11, which is the major product when the LDA is not freshly prepared.The rearrangement product 11 was the only product, when 2d was treated with LDA at −116 ºC, and allowed to warm up to 20 ºC.The oxiranyllithium 7 reacts with a strong electrophile p-toluoyl chloride to give coupling product 9 in 56% yield; it also reacts with a hindered ketone, benzophenone, to give oxiranyl alcohol 10 in 52% yield, as shown in Table 2.

Experimental Section
General Procedures.Melting points were determined on a MEL-TEMP ® capillary melting point apparatus equipped with a Fluke 51 digital thermometer, and are uncorrected. 1H and 13 C NMR spectra were recorded at 300 MHz and 75 MHz respectively in CDCl 3 and referenced to Me 4 Si for the 1 H spectra and CDCl 3 for the 13 C spectra.Tetrahydrofuran was distilled under nitrogen from sodium-benzophenone immediately before use.All reactions with moisture-sensitive compounds were carried out in dry argon atmosphere.Substituted 1-(1-ethenyl)benzotriazoles were prepared according to previously reported procedures. 18Dimethyldioxirane solutions were prepared as described previously. 8,9neral procedure for the oxidation of vinylbenzotriazoles 1a-d Vinylbenzotriazole 1 was placed in a dry flask, dissolved in 1.5 M equivalent of DMD solution in dichloromethane and kept at −20 o C. The reaction was monitored by TLC.The removal of the solvent afforded the product in quantitative yield.

General procedure for the lithiation of 2-(benzotriazol-1-yl)oxiranes (2a and 2d)
Oxirane 2 (1.5 mmol) was placed in an oven dried flask under argon, dissolved in dry THF (10 mL), dry diethyl ether (10 mL) was added as a co-solvent, and the reaction mixture was cooled to -116 o C with stirring.To this, 1.1 equiv of LDA (fresh) was added dropwise, and immediately after, an electrophile (1.65 mmol) was added dropwise.The reaction mixture was allowed to warm up to room temperature and quenched with water.The reaction mixture was extracted with CH 2 Cl 2 , dried over MgSO 4 , and concentrated to give a brown oil, which was purified by column chromatography on silica gel using diethyl ether and pentane.

Table 2 .
The coupling reactions of oxiranyllithium 7 from 2d with electrophiles We next examined the possible replacement of the benzotriazole group in epoxides 2 by nucleophiles, which could be activated by an α-oxygen atom.The reaction of Grignard reagent PhCH 2 MgCl with 2a or 2d at −30 to −18 ºC gave complex mixtures.When trisubstituted epoxide 8 was treated with PhCH 2 MgCl or with organozinc reagent PhCH 2 ZnCl in THF and diethyl ether, the starting material was recovered unreacted.
on heating neat in 3 N sulfuric acid solution at 70 o C for 3 h (Scheme 2).Epoxide 9 survived under these conditions, but decomposed when refluxed in THF with 30% HclO 4 for 24 h.4Issue