A new and efficient approach to isoxazolines. First synthesis of 3-aryl-5-dichloromethyl-2-isoxazolines

Abstract

a b s t r a c tAn efficient synthetic method for 3-aryl-5-dichloromethyl-2-isoxazolines has been established. Reactions between anhydrous chloral and acetophenones in hot acetic acid lead to 1-aryl-4,4,4-trichloro-3-hydroxybutan-1-ones (chloralacetophenones), which provided 1-aryl-4,4-dichlorobut-3-en-1-ones (2,2-dichlorovinylacetophenones) by dehydration and subsequent electrochemical reduction. These b,g-unsaturated enones reacted with hydroxylamine yielding oxime intermediates whose treatment with aqueous sodium hydroxide gave novel 3-aryl-5-dichloromethyl-2-isoxazolines in fair to high yields. The molecular structure of a member of this family of compounds, 5-dichoromethy1-3-(4-methoxyphenyl)-2-isoxazoline, was determined by X-ray crystallography.

A Simple, Efficient One‐Pot Synthesis of 2‐Isoxazoline Derivatives and their Antimicrobial Activity

“…This is presumably to avoid the competing oxidative side reactions, if the nitrile oxide was generated oxidatively from the aldoxime. In this aim, a suitable dipole is represented by the nitrile oxide, which has been reacted with vinyl derivatives of sulfides, sulfoxides, and sulfones (2)(3)(4)(5)(6) that are prepared according the previous report [15,16]. All the titled compounds have been performed in a single step onepot synthesis (Scheme 1).…”

“…All the titled compounds have been performed in a single step onepot synthesis (Scheme 1). The nitrile oxide 1a-d, derived in situ from araldehyde bromoxime by treatment with triethylamine, was added to the desired vinyl sulfide (2)(3)(4)(5)(6) for the formation of 2-isoxazolines derivatives (7 a-d to 11 a-d ) and showed higher yields. The higher conversions of 2-isoxazoline derivatives are observed without the formation of any by-products even though at 20-to 35-h reaction time ( Table 1).…”

“…2‐Isoxazolines derivatives are an important class of heterocyclic compounds, and their chemical properties have been studied over the years . They are versatile scaffolds for the synthesis of a wide variety of complex natural products and important pharmacophore in therapeutic chemistry . 2‐Isoxazolines are also known to exhibit interesting biological activities such as antifungal , antibacterial , anti‐convulsant , anti‐inflammatory , antiviral , analgesic , and anti‐HIV activities .…”

A novel synthetic approach to Pyrazolooxazines. One‐pot synthesis of Pyrazolo[5,1‐c][1,4]oxazine derivatives from 2,2‐dichlorovinylacetophenones

“…For some years we have been working in developing new synthetic approaches to six‐ and five‐membered heterocyclic compounds starting from chloral derivatives. For example, imidazo‐pyrazolones [22], oxadiazolines [23], triazoles [24], pyrimidines [25], isoxazolines [26], pyrazolines [27], thiazolines [28], oxazolines [29], etc. In connection with this line of research we report here a new, general and efficient method for preparing still almost unknown pyrazolooxazines based on 2,2‐dichlorovinylacetophenones, which are readily available chloral derivatives [30] capable to react efficiently with commercial 2‐hydroxyethylhydrazine.…”

Copper-Catalyzed Dichloromethylazidation of Alkenes Using BrCCl2H as a Stoichiometric Dichloromethylating Reagent

“…Among all known polyhalogenated functional groups, the dichloromethyl unit (CCl 2 H) plays an irreplaceable key role in numerous bioactive natural molecules (see Figure ). As a result, the development of efficient methods for facile incorporation of the dichloromethyl group into organic molecules has attracted increasing attention in the past several decades. The traditional method toward the incorporation of dichloromethyl groups into organic compounds is deoxychlorination of aldehydes; highly acidic agents, which are corrosive or moisture-sensitive, are normally required in such reactions .…”