Acyl C-Nitroso Compounds

C-Acyl nitroso compounds are highly reactive species and no examples of stable and isolable C-acyl nitroso compounds have been reported. Charge-reversal and neutraHzation-reionization mass spectrometry experiments provided the first spectroscopic evidence for the existence of acyl nitroso compounds in the gas phase [30,... 

Scheme 7.3 Alternative methods of C-acyl nitroso compound formation.

Scheme 7.4 Nucleophilic substitution of a C-acyl nitroso compound with nitroxyl formation.

Extensive structure-activity relationships for the oxidative formation of C-acyl nitroso compounds or the release of NO or HNO from C-acyl nitroso compounds do not exist. However, the -R group of the cycloadducts of acyl nitroso compounds and 9, 10-dimethylanthracene (4, Scheme 7.3) appears to strongly influence the rate that these compounds undergo retro-Diels-Alder reactions to produce acyl nitroso compounds. 

In general, C-acyl nitroso compounds-9,10-dimethylanthracene cycloadducts derived from hydroxamic acids (-R = alkyl, aryl, ti/2 = 4.1 h for -R = -Ph at 60°C) decompose more slowly than those derived from N-hydroxycarbamates or N-hydroxyureas [11, 13, 14]. Further addition of alkyl groups to the N atom of N-hydroxyurea-derived cycloadducts produces a further increase in the rate of the retro-Diels-Alder reaction of these cycloadducts [36]. These general trends suggest the possibility of the development of acyl nitroso compound-9, 10-dimethylanthracene cycloadducts as a general class of HNO or NO donors with varied release profiles. 

Acyl nitroso compounds (3, Scheme 7.2) contain a nitroso group (-N=0) directly attached to a carbonyl carbon. Oxidation of an N-acyl hydroxylamine derivative provides the most direct method for the preparation of acyl C-nitroso compounds [10]. Treatment of hydroxamic acids, N-hydroxy carbamates or N-hydroxyureas with sodium periodate or tetra-alkyl ammonium periodate salts results in the formation of the corresponding acyl nitroso species (Scheme 7.2) [11-14]. Other oxidants including the Dess-Martin periodinane and both ruthenium (II) and iridium (I) based species efficiently convert N-acyl hydroxylamines to the corresponding acyl nitroso compounds [15-18]. The Swern oxidation also provides a useful alternative procedure for the oxidative preparation of acyl nitroso species [19]. Horseradish peroxidase (HRP) catalyzed oxidation of N-hydroxyurea with hydrogen peroxide forms an acyl nitroso species, which can be trapped with 1, 3-cyclohexanone, giving evidence of the formation of these species with enzymatic oxidants [20]. 

Acyl nitroso compounds react with 1, 3-dienes as N-O heterodienophiles to produce cycloadducts, which have found use in the total synthesis of a number of nitrogen-containing natural products [21]. The cycloadducts of acyl nitroso compounds and 9,10-dimethylanthracene (4, Scheme 7.3) undergo thermal decomposition through retro-Diels-Alder reactions to produce acyl nitroso compounds under non-oxidative conditions and at relatively mild temperatures (40-100°C) [11-14]. Decomposition of these compounds provides a particularly clean method for the formation of acyl nitroso compounds. Photolysis or thermolysis of 3, 5-diphenyl-l, 2, 4-oxadiazole-4-oxide (5) generates the aromatic acyl nitroso compound (6) and ben-zonitrile (Scheme 7.3) [22, 23]. Other reactions that generate acyl nitroso compounds include the treatment of 5 with a nitrile oxide [24], the addition of N-methyl morpholine N-oxide to nitrile oxides and the decomposition of N, O-diacylated or alkylated N-hydroxyarylsulfonamides [25-29]. 

N, O-Diacylated or O-alkylated N-hydroxysulfonamides release nitroxyl (HNO) upon hydrolysis or metabolic dealkylation, as determined by gas chromatographic identification of nitrous oxide in the reaction headspace [27-29, 38]. Scheme 7.5 depicts the decomposition of a representative compound (7) to a C-acyl nitroso species that hydrolyzes to yield HNO. Either hydrolysis or metabolism removes the O-acyl or O-alkyl group to give an N-hydroxy species that rapidly decomposes to give a sulfinic acid and an acyl nitroso species. This C-acyl nitroso species (8) hydrolyzes to the carboxylic acid and HNO (Scheme 7.5). These compounds demonstrate the ability to relax smooth muscle preparations in vitro and also inhibit aldehyde dehydrogenase, similar to other HNO donors [27, 29]. 

The oxidation of A-acyl-A-arylhydroxylamines with lead tetraacetate is very rapid even at very low temperatures. The product obtained is the corresponding aromatic nitroso compound. The most favorable reaction conditions involve propionic acid or ethanol-acetic acid as a solvent and reaction times of less than 10 sec at temperatures of —20°C or lower [87]. The use of ethanol-acetic acid is particularly recommended for several reasons. First, since the product is best isolated by steam distillation, the solvent assists in steamdistilling rapidly. The ethanol in the distillate helps minimize clogging of the condenser and also solubilizes small quantities of impurities that may be entrained. 

C.iii. Nitroso-Type Compounds. Nitroso compounds (R—N=0) show reactivity as dienophiles in Diels-Alder reactions, giving heterocyclic rings. In Kibayashi s synthesis of fasicularin, " for example, hydroxamic acid 180 was treated with tetrapropylammonium periodate in the presence of 9,10-dimethyl-anthracene to give transient acylnitroso compound 181, and the resultant Diels Alder product 182 was formed in 84% yield. In this particular example, the Diels-Alder adduct essentially "protected" the acyl nitroso unit, which was used in a subsequent reaction. 

We review in this chapter the nature of the photodecomposition pathways of several of the major products of atmospheric oxidation of the hydrocarbons, namely, the acyclic aldehydes in section IX-B the aldehydes containing additional functional groups in section IX-C the acyclic ketones in section IX-D the cyclic ketones in section IX-E the ketones containing additional functional groups in section IX-F the acyl halides and carbonyl halides in section IX-G nitrous acid, the alkyl nitrites, the nitroalkanes, and the nitroso-compounds in section IX-H nitric acid and the alkyl nitrates in section IX-I the peroxyacyl nitrates in section IX-J the alkyl hydroperoxides in section IX-K and some oxygenates derived from the aromatic hydrocarbons in section IX-L. 

The diimines (229) differ considerably in thermal stability. The sulfonyl compounds (226) and (229a) are stable crystalline compounds which rearrange at elevated temperatures. The acyl derivatives (229b and c) and the dianion formed by demesylation of (226) undergo retrocyclization below -15 °C at a rate equal to or faster than loss of N2O from N- nitroso intermediates. 

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