Nitrosation, of enols

Nitrones = -V-alkylidene amine N-oxides, 153 Nitrosyl chloride diazotization with, 312-313 nitrite esters from, 286 nitrosation of enol ethers, 268 Nocardicinic acid, 3-amino- (ANA 1,1-dimethylethyl ester synthesis, 161... 

Katritzky reported that oxime 12, formed by nitrosation of enol 11, reacted with benzyl bromide in the presence of K2CO3 in DMF at room temperature to form oxazole 4 in 43% yield. Since benzyloxime 16 formed by the reaction of diketone 3 and o-benzylhydroxyamine didn t form oxazole 4 in the presence of K2CO3 in DMF, even under forcing conditions (heating at 60 °C), he proposed the following for its formation. The reaction of oxime 12 with benzyl bromide formed nitrone 13, which could also exist as resonance structure 14, followed by cyclization and loss of HO, afforded oxazole 4. Alkyl halides could also used as electrophiles to react with 1,2-diketone nitrones to form oxazoles (17 18). 

Although nitrosation of (l-dicarbonyl compounds becomes increasingly more facile upon successive replacement of the a alkyl groups with perfluoroalkyl groups because of the increased ionization of the perfluorinated enolate (equation 7), the stability of the nitrosodiketone tautomers decreases Thus, 1,1,1-trifluoro pentane-2,4-dione and 1,1,1,5,5,5-hexafluoropentane 2,4 dione mtrosate much faster than penta-2,4 dione but yield ketoximes, which decompose upon workup... 

These seemingly anomalous results suggest that the formation and fragmentation of a-amino nitrite esters could be playing a central role in the nitrosation of aminopyrine. The characterization of both fast and slow reactions, as well as the identification of two pH optima, imply that more than one kinetically significant pathway is involved in the overall transformation. The mechanism of Fig. 5a could well be the first order component the kinetic studies show to be operative under some conditions. It is noteworthy that this pathway also leads directly in its final step to the keto-enol derivative IV, which Mirvish et al. have identified as a by-product of aminopyrine nitrosation. 

Base-catalysed nitrosation of acetone by t-butyl nitrite to give l-hydroxyimino-2-oxopropane [H3C-C(=0)-CH=N0H] has been studied by ab initio methods.89 Using a sodium enolate route, the cation participates to give Z-isomer, whereas a naked enolate calculation results in the -product being favoured. 

Nitrosation of the enol of 60 in acid solution and tautomerisation of the nitroso compound 61 gives the oxime 62. Hydrolysis of the oxime 62 gives the diketone 63. 

Fig. 12.9. Nitrosation of malonic acid diethyl ester. The mechanism of the acid-catalyzed enolization malonic ester malonic ester enol (E) and the mechanism of the actual nitrozation (E -> A) is shown here.

The nitrosation uses the same intermediate (NO+) used in the diazotization and is really very like the nitrosation of the enol we described on p. 000. There it tautomerized to an oxime—it can t do that here. Make sure you can draw a mechanism forthis reaction and explain why the NO group goes in that position. 

Indirect replacement of the a-hydrogen atom of carboxylic esters by the nitroso group is remarkable. This procedure uses ketene 0-alkyl O -silyl acetals (1), generated from carboxylic esters, which are treated with nitric oxide or isopentyl nitrite in the presence of titanium(IV) chloride. In the absence of an a-hydrogen a-nitroso esters (2) are obtained. a-Nitroso esters with an a-hydrogen undergo isomerization to oximes of a-keto esters (3 equation 1). Similarly, silyl enol ethers of aldehydes or ketones can be used instead of the carbonyl compound itself for nitrosation. Thus, treatment of enol ether (4) with nitro-syl chloride gives the a-nitroso aldehyde (5 equation 2), which is quite stable at 0 C, but dimerizes at room temperature. 

Avoidance by choice of oxygenated starting materials Oxidation through Lithiation and Ort/ro-Lithiation Hydroxylation of Pyridines by ortho-Lithiation Synthesis of Atpenin B Introducing OH by Nucleophilic Substitution Part II - Oxidation of Enols and Enolates Direct Oxidation without Formation of a Specific Enol Selenium dioxide Nitrosation with nitrites Nitrosation with stable nitroso compounds Indirect Oxidation with Formation of a Specific Enol Enone Formation Pd(II) oxidation ofsilyl enol ethers Bromination of enols in enone formation Sulfur and selenium compounds in enone formation Asymmetric Synthesis of Cannabispirenones... 

Unsatnrated 0-silylated oximes or nnsaturated hydrazones, in particular those with a silylated oxygen at C-3 as well, take part in cycloadditions, with loss of the iV-snbstituent (see also 8.14.1.1) giving 3-hydroxypyridines. ° The starting 1-azadienes are easily available via a-nitrosation of a ketone, then oxime and enol 0-silylations. 

The nitrosation of j5-phosphinoylacetaldehydes (with KNO2-ACOH) occurs at the carbon a to phosphoryl, to provide a system of dimeric nitroso-enol in equilibrium with... 

The keto-enol equilibrium constant of benzoylacetone in water is perturbed in the presence of -cyclodextrin, from a value of 0.62 to 5, and also in sodium dodec-yl sulfate micelles, in both cases by preferential binding of the enol tautomer. Thermodynamic parameters from temperature studies of the equilibrium give more information about the structures of the complexes for example, the enol penetrates further into the cavity of the cyclodextrin, as confirmed by H NMR spectroscopy. Nitrosation of benzoylacetone is slowed in the presence of the cyclodextrin, consistent with a protective effect arising from the strong binding to the enol. 

Carbons adjacent to a Z group (as defined on p. 548) can be nitrosated with nitrous acid or alkyl nitrites. The initial product is the C-nitroso compound, but these are stable only when there is no tautomerizable hydrogen. When there is, the product is the more stable oxime. The situation is analogous to that with azo compounds and hydrazones (12-7). The mechanism is similar to that in 12-7 R—H —> R + N=0 — R—N=0. The attacking species is either NO or a carrier of it. When the substrate is a simple ketone, the mechanism goes through the enol (as in halogenation 12-4) ... 

Reactions of Halogenation and Nitrosation Nitrones with protons in the a-alkyl group can occur in tautomeric nitrone-hydroxylamine equilibrium (Scheme 2.117) similar to keto-enol and imine-enamine tautomerisms. 

There appears to be little reported work on S-nitrosation reactions of simple thioke-tones. Thiocamphor when treated with /50-amyl nitrite in fact gives the oxime58 (formerly called a isonitroso compounds), presumably via the tautomeric form of the thione, i.e. the enethiol. In this respect the reaction is very similar to the reactions of ketones59 which give oximes or C-nitroso compounds via the enol intermediates60. 

Evidence is that the reaction, in the presence of X" (Br, Cl , or SCN ) was first order in ketone and in H , but zero order in HN02 and X. 159 Furthermore, the rate of the nitrosation was about the same as that for enolization of the same ketones. The species NOX is formed by HONO + X + FT - HOX + H20. In the cases of F.,CCOCH2COCF3 and malon-onitrile the nitrosation went entirely through the enolate ion rather than the enol.16,1... 

The minor products frequendy formed in deaminations may result from such side reactions as reaction of the intermediate cation with nucleophiles, for example, acetate or chloride ions,49,30 present in low concentration. Nitrite ions can give rise to nitrite esters or ni-troalkanes 50,51 the former are probably hydrolyzed prior to or during processing of the products.52 Some alkenes have been reported to react with nitrous acid or related nitrosating agents.19,58 Enol ethers would be expected to be more nucleophilic than simple alkenes, and it has been found that D-glucal reacts with nitrous acid under the conditions of deamination.54... 

Styrenes, enolates, and dienoates 337 can be nitrosated using (tetraphenyl-porphyrin)cobalt(II) 326a as the catalyst (entry 17). Under these conditions oximes 345 were isolated in 31-94% yield. The mechanistic details of this reaction remain to be elucidated [397]. 

The treatment of cyclic enol ethers with alkyl nitrites or with nitrosyl chloride gave oximino macrolides in almost quantitative yield [100] [102], The furan derivatives are inert to hydrolytic nitrosation [100]. 

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