The Infra-red Spectra of Complex Molecules.

The discovery of important roles of C-nitroso compounds in various biological metabolic processes has generated a renewed interest in the general chemical properties of nitrosoalkanes (R–N=O; R =alkyl) and nitrosoarenes (ArNO; Ar =aryl), two important subsets of this general class of compounds. For example, the identification of the nitrosobenzene adduct of hemoglobin as a product of nitrobenzene poisoning1,2 and the realization that some amine-containing drugs may be metabolized to nitroso derivatives3–6 led to an increased desire to study the fundamental biochemical properties of this fascinating class of C-nitroso compounds. To this end, many studies have been reported on the fundamental chemistry of C-nitroso compounds under conditions that either stabilize the C-nitroso functionality or enhance their reactivity toward isomerization or reactivity with substrates.

A major difficulty in C-nitroso chemistry, however, is that the high reactivity of these compounds necessarily imposes constraints upon the methods employed for their preparation, particularly with regard to the yield of the desired product. For example, the ease of oxidation of the desired nitroso compound (if oxidation of a suitable precursor is the chosen synthetic route) to its nitro derivative can significantly reduce the yield of the nitroso product. Similarly, the ease of isomerization of R2C(H)NO compounds to the corresponding oximes R2C=NOH can restrict the choice of solvent for the preparation of primary and secondary nitrosoalkanes. A further consideration to be borne in mind is the possibility of reaction of the C-nitroso compound with the starting material and/or preparative reagents. There is, however, a considerable variety of synthetic routes available for the high-yield preparations of C-nitroso compounds (monomers or dimers; Figure 1), some of which have been in regular use for well over 100 years.




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Figure 1



Some earlier reviews of this area have been published. Book chapters by Sandler and Karo (in 1986)7 and by Williams (in 1988)8 present the most detail to date on the experimental techniques for preparations of C-nitroso compounds. Other useful earlier reviews are those by Touster,9 Boyer,10 Metzger and Meier,11 Seidenfaden,12 and Katritzky et al.13

Given the renewed interest in the study of the biological and environmental consequences of C-nitroso compound formation, it is not surprising that many new and/or improved procedures for the preparations of these compounds have been developed over the last two decades. In this review, we present a comprehensive review of the synthetic procedures for the preparation of C-nitroso compounds and place these procedures in proper historical context. We also include a small number of routes to the production of C-nitroso compounds that may have preparative possibilities or which require improved workup methods. We indicate, when known, whether the method of preparation is applicable to all types of C-nitroso compounds or only to separate classes such as nitrosoarenes, nitrosoalkanes, nitrosohomocycles, or nitrosoheterocycles. Nitrosoalkenes are considered in a separate section. The coordination chemistry of C-nitroso compounds with metals has been reviewed recently.6,14

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Preparations of C-Nitroso Compounds

A new method is presented for 1,3-difluorination and 1,3-oxyfluorination reactions. The process is based on iodonium mediated opening of 1,1-disubstituted cyclopropanes. The reaction proceeds with high chemo- and regioselectivity under mild reaction conditions typically at room temperature in a couple of hours. The reaction probably occurs via electrophilic ring-opening of cyclopropanes.

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Fluorinative ring-opening of cyclopropanes by hypervalent iodine reagents. An efficient method for 1,3-oxyfluorination and 1,3-difluorination

The preparation methods and reactions of isoxazoles are described and systematized on the basis of analysis of the literature published from 2005 to present. In the discussion of synthesis, major attention is focused on the most efficient approaches: condensation of hydroxylamine with 1,3-dielectrophiles and reactions of nitrile oxides with alkenes and alkynes. Five-membered ring opening reactions leading to acyclic functionalized or other heterocyclic compounds are considered. The transformations of isoxazole derivatives that occur without ring cleavage to form fused heterocyclic systems, as well as reactions that lead to the introduction of C-substituents into isoxazoles, are considered. Data on the biological activity of some isoxazole derivatives are reported. The bibliography includes 439 references.

http://iopscience.iop.org/article/10.1070/RCR4503/pdf

Recent advances in isoxazole chemistry

This review is devoted to the scientific achievements of the departments of organic chemistry in higher schools of Russia within the past decade.

Modern Trends of Organic Chemistry in Russian Universities

Nitrosation of gem-dichloro(alkyl)cyclopropanes with the complex NOCl·2SO3 gave regioisomeric alkyl-5-chloroisoxazoles in high yields; a similar reaction with 1,2-bis(gem-dichlorocyclopropyl)ethane afforded the corresponding bis(5-chloroisoxazoles). The reactivities of gem-dichlorobicyclo[n.1.0]alkanes depend on their spatial structures, sharply decreasing with an increase in the number of the methylene units in the bicyclic molecule.

gem-dichloro(alkyl)cyclopropanes in reactions with NOCl·2SO3: Synthesis of alkyl-5-chloroisoxazoles

Reactions of potassium dihaloiodates with arylcyclopropanes and polycyclic compounds containing a cyclopropane fragment characterized by different degrees of strain lead to formation of mixed 1,3-halogenation products. If iodohalogenation should give rise to products having a iodine atom in the benzylic position, 1,3-dichloro or 1,3-dibromo derivatives are formed. Iodohalogenation of exo-tricyclo[3.2.1.02,4]octane is stereoselective and is accompanied by Wagner-Meerwein rearrangement.

Reactions of cyclopropanes with potassium dihaloiodates

Nitrosation with complex NOCl·2SO3 of gem-dichloroarylcyclopropanes containing acceptor substituents in the aromatic ring proceeded chemo- and regioselectively affording 3-aryl-5-chloroisoxazoles in high yields. The presence of donor substituents complicated the reaction by the occurrence of competing processes.

Transformations of gem-dichloroarylcyclopropanes in the reaction with NOCl·2SO3. Synthesis of 3-aryl-5-chloroisoxazoles

The reaction of phenylcyclopropanes substituted in the three-membered ring with nitrosyl chloride activated with sulfur(IV, VI) oxides provided in good yield substituted 5-phenylisoxazolines as a mixture of structural isomers.

Δ2-isoxazolines from arylcyclopropanes: III. Phenylcyclopropanes substituted in three-membered ring in reaction with nitrosyl chloride activated with oxides of sulfur(IV, VI)

A new method for the synthesis of thiocyanato- and isothiocyanatoalkyl phenyl sulfides by the reaction of unsaturated compounds with ethyl benzenesulfenate and trimethylsilyl isothiocyanate has been suggested. Regio- and stereoselectivity of the reaction was studied, having taken alkenes, dienes, and alkynes as examples.

A. Yu. Gavrilova

Papers

gem-dichloro(alkyl)cyclopropanes in reactions with NOCl·2SO3: Synthesis of alkyl-5-chloroisoxazoles

Reactions of cyclopropanes with potassium dihaloiodates

Transformations of gem-dichloroarylcyclopropanes in the reaction with NOCl·2SO3. Synthesis of 3-aryl-5-chloroisoxazoles

Δ2-isoxazolines from arylcyclopropanes: III. Phenylcyclopropanes substituted in three-membered ring in reaction with nitrosyl chloride activated with oxides of sulfur(IV, VI)

Reaction of unsaturated compounds with ethyl benzenesulfenate and trimethylsilyl isothiocyanate