Carbonyl compounds oxime synthesis

In a prostaglandin synthesis a carbonyl group was protected as an oxime in which the hydroxyl group was protected against Collins oxidation by the phenylthiome-thyl-group. The phenylthiomethyl group is readily removed to give an oxime that is then cleaved to the carbonyl compound. ... 

The mechanism of the original Knorr pyrrole synthesis entails in situ reduction of the oxime moiety to an amine, condensation with the second carbonyl compound, and cyclization with loss of a second molecule of water to give a pyrrole for example, 10 + 11 to 12. Several studies have demonstrated that different pathways and pyrrole products obtain depending on the substrates. 

One of the most important routes to isoxazole and isoxazoline rings involving the formation of the 1—5 and 2—3 bonds involves the condensation of hydroxylamine with a,/8-unsaturated carbonyl compounds. This method was previously widely used, but it is now of no preparative value, though it has been recently applied to determine the configuration of oximes. " The only new modification of this synthesis is the use of the acetals (27) of a,/8-acetylenic aldehydes for preparation of 5-substituted isoxazoles (28)... 

OxiddQon of oximes to rutro compounds with w-CPBA has been applied to the synthesis of dialkyl l-nitroalkanephosphonates fEq 2 63, which are useful reagents for d carbonyl compounds to nitroalkenes... 

As discussed in Chapter 6, nitro compounds are converted into amines, oximes, or carbonyl compounds. They serve as usefid starting materials for the preparation of various heterocyclic compounds. Especially, five-membered nitrogen heterocycles, such as pyrroles, indoles, ind pyrrolidines, are frequently prepared from nitro compounds. Syntheses of heterocyclic compounds using nitro compounds are described partially in Chapters 4, 6 and 9. This chapter focuses on synthesis of hetero-aromadcs fmainly pyrroles ind indolesi ind saturated nitrogen heterocycles such as pyrrolidines ind their derivadves. 

Reductive alkylations have been carried out successfully with compounds that are not carbonyls or amines, but which are transformed during the hydrogenation to suitable functions. Azides, azo, hydrazo, nitro and nitroso compounds, oximes, pyridines, and hydroxylamines serve as amines phenols, acetals, ketals, or hydrazones serve as carbonyls 6,7,8,9,12,17,24,41,42,58). Alkylations using masked functions have been successful at times when use of unmasked functions have failed (2). In a synthesis leading to methoxatin, a key... 

Azirines (three-membered cyclic imines) are related to aziridines by a single redox step, and these reagents can therefore function as precursors to aziridines by way of addition reactions. The addition of carbon nucleophiles has been known for some time [52], but has recently undergone a renaissance, attracting the interest of several research groups. The cyclization of 2-(0-tosyl)oximino carbonyl compounds - the Neber reaction [53] - is the oldest known azirine synthesis, and asymmetric variants have been reported. Zwanenburg et ah, for example, prepared nonracemic chiral azirines from oximes of 3-ketoesters, using cinchona alkaloids as catalysts (Scheme 4.37) [54]. 

Nitro compounds are versatile precursors for diverse functionalities. Their conversion into carbonyl compounds by the Nef reaction and into amines by reduction are the most widely used processes in organic synthesis using nitro compounds. In addition, dehydration of primary nitro compounds leads to nitrile oxides, a class of reactive 1,3-dipolar reagents. Nitro compounds are also good precursors for various nitrogen derivatives such as nitriles, oximes, hydroxylamines, and imines. These transformations of nitro compounds are well established and are used routinely in organic synthesis. 

This protocol could be extended to a range of different ,/i-unsaturated carbonyl compounds and either activated or deactivated aryl iodides [22], An application of related Heck chemistry to the synthesis of methylated resveratrol (3,4, 5-trihydroxy-( )-stilbene) is shown in Scheme 6.4 [23]. The phytoalexin resveratrol exhibits a variety of interesting biological and therapeutic properties, among them activity against several human cancer cell lines. Botella and Najera have shown that the trimethyl ether of resveratrol (Scheme 6.4) can be rapidly prepared by microwave-assisted Heck reaction of the appropriate aryl iodide and styrene derivatives, using the same oxime-derived palladacycle as indicated in Scheme 6.3. 

The resulting radicals R efficiently alkylate BENAs (495) at the (3-C atom to give silyl derivatives of oximes (496) in good yields. The latter readily undergo deoximation in the presence of 1 M hydrochloric acid to give the corresponding carbonyl compounds (494). Thus, a convenient procedure was developed for the synthesis of carbonyl compounds (494) from secondary AN (493) through the intermediate terminal BENA (495) (527). 

The Ponzio reaction provides a useful route to gem-dinitro compounds and involves treating oximes with a solution of nitrogen dioxide or its dimer in diethyl ether or a chlorinated solvent. The Ponzio reaction works best for aromatic oximes where the synthesis of many substituted aryldinitromethanes have been reported. Compound (56), an isomer of TNT, is formed from the reaction of dinitrogen tetroxide with the oxime of benzaldehyde (55) followed by mononitration of the aromatic ring with mixed acid. Yields are usually much lower for aliphatic aldoximes and ketoximes. " The parent carbonyl compound of the oxime is usually the major by-product in these reactions. 

The final synthetic analogues we consider are the trioxolanes prepared by Vennerstrom and coworkers. These are prepared by a very efficient co-ozonolysis procedure from oxime 90 and a carbonyl compound 91 (Scheme 37A). This provides the 1,2,4-trioxolane in yields of greater than 50%. Further studies on 4-substituted cyclohexanones (e.g. 92) revealed that this reaction proceeds with very good cisitrans selectivity to produce the ester 93, which was derivatized to produce a clinical candidate OZ 277 (6) as shown. The chemistry for the synthesis of this compound has been scaled up beyond 30 kg (Scheme 37B). 

Imines and Carbonyl Compounds. Simple 2-alkyl(aryl)-5-(4//)-oxazolones like 191 can react with aldehydes, ketones, imines, and oximes to afford the corresponding unsaturated analogues 192 (Scheme 7.58). In some cases, this procedure is especially advantageous over the classical one-pot synthesis.The chemistry of unsaturated 5(4//)-oxazolones like 192 will be discussed in detail in Section 7.4. 

Corsaro, U. Chiacchio, V Pistara, Regeneration of Carbonyl Compounds from the Corresponding Oximes, Synthesis 2001, 1903-1931. 

The synthesis consists in forming the oxime by reaction of a carbonyl compound ( aldehyde or ketone ) with hydroxylamine followed by reaction with an isocyanate... 

Reduction in acid solution of nitroalkenes prepared from carbonyl compounds and nitroalkanes has been employed for the synthesis of oximes and carbonyl compounds [30-32] with a longer carbon chain. 

For decades oximes and hydrazones have been used for the derivatization of carbonyl compounds and are mainly applied for carbonyl group characterization in analytical procedures. However, they can also be applied as viable protecting groups in complex reaction schemes. For instance in the synthesis of ery-thronolide A a carbonyl group had to be converted to an oxime to allow the selective removal of the remaining isopropylidene protecting group without side reactions. The reconversion of the oxime to the carbonyl compound proceeds by A -nitrosation (Scheme 92). The previously attempted removal of the... 

Up until the end of the 1980s, radical carbonylation chemistry was rarely considered to be a viable synthetic method for the preparation of carbonyl compounds. In recent years, however, a dramatic change has occurred in this picture [3]. Nowadays, carbon monoxide has gained widespread acceptance in free radical chemistry as a valuable Cl synthon [4]. Indeed, many radical methods can allow for the incorporation of carbon monoxide directly into the carbonyl portion of aldehydes, ketones, esters, amides, etc. Radical carboxylation chemistry which relies on iodine atom transfer carbonylation is an even more recent development. In terms of indirect methods, the recent emergence of a series of sulfonyl oxime ethers has provided a new and powerful radical acylation methodology and clearly demonstrates the ongoing vitality of modem free radical methods for the synthesis of carbonyl compounds. 

Table 1.5 Average contents of carbonyl compounds identified in Cbardonnay and Cabernet Sauvignon wines before and after MLF operated by two different Oenococcus oeni bacterial strains, n.f. = not found. Amounts expressed as internal standard o-chlorobenzaldehyde (I.S.). Quantified on basis of 1 of 2 synlanti oxime peaks. Amounts calculated as 1-heptanol (I.S.) in the GC/MS analysis performed without synthesis of the PFBOA-derivafives.

Figure 1.19 Mass spectra of acetaldehyde PFB-oxime (a), diacetyl mono PFB-oxime (b), acetoin PFB-oxime derivative (c), and o-chlorobenzaldehyde PFB-oxime (d) recorded in the GC/MS analysis of standard solution performed in positive ion chemical ionization mode using methane as reagent gas (reagent gas flow 1 mL/min ion source temperature 200 °C). Flamini et al., (2005) Monitoring of the principal carbonyl compounds involved in malolactic fermentation of wine by synthesis of 0-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine derivatives and solid-phase-microextraction positive-ion-chemical-ionization mass spectrometry analysis, Journal of Mass Spectrometry, 40, p. 1561. Copyright John Wiley Sons, Ltd. Reproduced with permission...

DMF is recommended as diluent in the Ullmann synthesis of diaryls from aryl halides and as solvent for the Beckmann rearrangement of steroidal enone oximes. The Willgerodt-Kindler reaction (a carbonyl compound with a secondary amine and sulfur to give a thioamide) can be carried out in good yield at 50-60 if DMF is... 

The Bucherer-Bergs synthesis is of general application to carbonyl compounds, employing potassium cyanide and ammonium carbonate.1,4 Carbonyl derivatives such as semicarbazones, thiosemicarbazones, oximes, azines, phenylhydrazones, imidazolidines, and azomethines also are readily converted directly to the corresponding hydantoins 44 The extent to which the reaction occurs appears unrelated to the hydrolytic stability of the starting material. The proposed mechanism is given in Scheme 1. 

One of the classical methods for the synthesis of pyrazines involves dimerization of an a-amino carbonyl compound and subsequent aromatization. Oximes have often been used as the latent functionality to generate the amine by a variety of reductive processes. 3-Oxo-2-oximinobutanoic esters or the amides (146), which are formed by nitrosation of acetoacetic acid derivatives, are reduced by catalytic hydrogenation <82CPB3424, 91JHC1731> or titanium(III)-induced reduction <88H(27)il23> to give the tetrasubstituted pyrazines (147) (Equation (17)). 

A regioselective synthesis of alkylpyrazines (155) starts with condensation of a-oximino carbonyl compounds with allylamines (Scheme 38). The imine intermediates are isomerized in the presence of potassium r-butoxide to the corresponding 1-hydroxy-1,4-diazahexatrienes. Thermal cyclization-aromatization to pyrazines is best performed after 0-acylation of the oximes with methyl chloro-formate <91JOC2605>. 

Alternatively, carbonyl compounds can be converted to gew-dichlorides through formation of oximes followed by chlorination (Fig. 17). This method has already been used for the synthesis of 2,2-dichlorononane [14]. 

The hydroxyimino group attached to carbon (C=NOH) may be converted into an amino group by way of the intermediate hydroxyamino or imino group. The reduction of oximes can be conducted so as to yield (1) a synthesis of amines from carbonyl compounds, (2) introduction of amino groups into a compound containing active methylene groups (by way of the isonitroso compounds obtained by nitrosation), or (3) production of amines from the adducts of nitrogen oxides or nitrosyl chloride to olefins. 

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