N,O-Diacylation

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]. 

Acylation of -ones and -diones appears to occur mainly at oxygen, but in the fused pyridazino[4,5-6]quinoline (312) the O-acyl derivative (313) was formed via an N.O-diacyl derivative (72BSF1588). Reduced derivatives, however, are acylated at nitrogen. 

Zur Herstellung von N.O-Diacyl-hydroxylaminen durch Oxidation von N-Acyl-hydroxylaminen (Hydroxamsauren) mit Kaliumjodid/Jod s. 

Free radicals may be generated by oxidation, reduction, or by homolytic cleavage of one or more covalent bonds, such as C—C bonds e.g. dimers of triarylmethyl radicals), N—N bonds e.g. tetrasubstituted hydrazines), O—O bonds e.g. hydroperoxides, dialkyl and diacyl peroxides, peroxycarboxylic esters), C—N bonds e.g. dialkyl azo compounds), and N—O bonds (as in the thermolysis of nitrogen pentoxide O2N— O—NO2). Two typical examples, which have been investigated in different solvents, are given in Eqs. (5-56) and (5-57) cf. also reaction (5-39a) in Section 5.3.2. 

N-tert.-Butyl-N,0-diacyl- E5, 782 (N.O-Diacylier.) O-(l-Carboxy-alkyl)- X/l, 1190 N-(Chlor-aryl)- IV/lc, 594... 

The reaction of 11 with tosyl chlorides gave imino ether (36). The reduction of 36 yielded 9-deoxo-9a-aza-9a-homo-EM A (37). The synthesis of its N-, O-acyl, and A,0-diacyl azalide derivatives, their 11, 12-cyclic carbonates, and their in vitro antimicrobial activities were studied, but 9a-N monoacyl (acetyl, propionyl) compounds exhibited in vitro activity 10 to 50 times lower than that of 37 [26]. 

Acylation. Reaction conditions employed to acylate an aminophenol (using acetic anhydride in alkaU or pyridine, acetyl chloride and pyridine in toluene, or ketene in ethanol) usually lead to involvement of the amino function. If an excess of reagent is used, however, especially with 2-aminophenol, 0,A/-diacylated products are formed. Aminophenol carboxylates (0-acylated aminophenols) normally are prepared by the reduction of the corresponding nitrophenyl carboxylates, which is of particular importance with the 4-aminophenol derivatives. A migration of the acyl group from the O to the N position is known to occur for some 2- and 4-aminophenol acylated products. Whereas ethyl 4-aminophenyl carbonate is relatively stable in dilute acid, the 2-derivative has been shown to rearrange slowly to give ethyl 2-hydroxyphenyl carbamate [35580-89-3] (26). 

The low condensation of diacyl chloride and bis-orf/zo-aminophenol gave a polyhydroxy amide that was submitted to a thermal dehydration.185 187 The two functions of an aminophenol could be acylated, and the question of chemose-lective acylation has been discussed.188 The problem is not O-acylation versus N-acylation because the N-acylated product is tire more stable isomer, but the question is how to control N-monoacylation versus diacylation that could reduce the molecular weight. It has been shown that the condensation in the presence of inorganic salt (LiCl) in NMP gives selectively the N-monoacylated... 

Other pyrimidine substrates to be converted to A, A -dinitro derivatives by loss of N-substituents include the diacyl compounds 503 and 504, and the di-(/ftt-butyl) compound 505 <2000JOC1200>. In the case of the disulfamic acid derivative 506, O-nitration also occurred, to give the trinitro derivative 507 <2000RCB1082>. 

Other compound classes in the synthesis of which chiral 3-carbon synthons were used include sphingosine chains (32), 3-amino-2-azetidinones (33), (3,y-unsaturated-a-amino acids 34), fluorinated macrocyclic bis(indolyl) maleimides35, fluorocyclopropyl alcohols (36), l-O-phosphocholine-2-O-acyl-octadecanes and l-Ophosphocholine-2-N-acyl-octadecane (37) diacyl glycerols 38-42) and analogs of fragments of leukotriene-B4 43). 

N-Diacyl-hydroxylamine sind Tautomere zu O -Acyl-hydroximsauren [Carbonsaure-(acyloximide)] (s. S. 829f.) ... 

Substituierte 0,N-Diacyl-hydroxylamine erhalt man durch direkte Acylierung von Hy-droxylaminen mit Carbonsaure-chloriden in Gegenwart von Pyridin oder mit Carbonsau-re-anhydriden in Gegenwart von Natrium-acetat[vgl. Bd. X/l, S. 1237 (1971)]. In der Regel erfolgt zuerst N- und im zweiten Schritt O-Acylierung. Eine Ausnahme bildet N-tert.-Butyl-hydroxylamin (s. S. 775). 

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