Substitution oximes

For oximes, the word oxime is placed after the name of the aldehyde or ketone. If the carbonyl group is not the principal group, use the prefix hydroxyimino-. Compounds with the group Z = N—OR are named by a prefix alkyloxyimino- as oxime O-ethers or as O-substituted oximes. Compounds with the group r C=N(0)R are named by adding A-oxide after the name of the alkylideneaminc compound. For amine oxides, add the word oxide after the name of the base, with locants. For example, C5H5N—O is named pyridine A-oxide or pyridine 1-oxide. 

Electrophilic nitrosation of the carbanion generated from the reaction of an organic base with a strong organic acid, such as a-hydrohexafluoroisobutyronitnle [2], a hydrohexafluoroisobutyric acid or its acid chloride [2], or a hydrotetra fluoroethanesulfonyl fluoride [4], yields the corresponding a-nitroso compound as the major product (equations 2 and 3) The a-hydrohexafluoroisobutyric acid or acid chloride reacts with excess trifluoroacetyl nitrite in dimethylformamide to afford the O substituted oxime [3] (equation 4)... 

As we found that furan and thiophene substituted oximes can be used as substrates for the INOC reactions (Eq. 5) [29b] similarly, furan substituted nitro alkane 134 is also a good substrate for INOC reactions (Eq. 13) [40]. The furfuryl derivative 134, prepared via Michael addition of furfuryl alcohol to 4-methoxy- -nitrostyrene, was subsequently transformed without isolation of the intermediate nitrile oxide 135 to the triheterocyclic isoxazoline 136 as a 5 1 mixture of isomers in high yield. 

I. reactions of BENA with C-nucleophiles Russian researchers performed comprehensive studies on C,C-coupling reactions of terminal BENAs A with anions of nitro compounds (516, 517). This process enables one to assemble 3-substituted oximes from two different AN ((441) and 442). It should be noted that compound (442) must have the methyl group at the a-C atom necessary for generation of terminal BENA. Both nitroalkanes should be prepared for C,C-coupling, that is, AN (441) is transformed into the anion C by the reaction with DBU, while AN (442) is successively transformed into BENA A and nitrosoalkene B. The C,C-coupling reaction B + C is shown in Scheme 3.238. 

An efficient procedure for the synthesis of 5-aminoisoxazoles starting from BENAs (Scheme 3.242) was described in Section 3.5.4.2.2.1. An analogous approach to the synthesis of aminooxazoles can be successfully used in the case of silyl derivatives of a-cyano-substituted oximes (476a,b) (Scheme 3.255). 

Only in one case (498), a- chloro-substituted oxime was isolated as the only product of silylation of secondary -functionalized AN. 

A convenient procedure for catalytic carbonylation of bromooxazines (520) giving rise to previously unknown methoxycarbonylmethyl-substituted oxazines (525) in good yields (538) deserves note, all the more because this is the first example of catalytic C,C-coupling reactions of ethers of a-halo substituted oximes. 

The presence of a substituted oxime in the amide side chain at the C-3 position is the important criteria for cephalosporinase inhibitory activity. 

FIGURE 5.19 Approaches for synthesis of protected peptides using acid-sensitive protectors. For (A) the last residue is incorporated as the Cbz-derivative. (B) The chain is assembled on a substituted oxime resin,44 starting at the penultimate residue. The chain is then detached from the resin by displacement by the carboxy-terminal residue of the target peptide, which may be a free (terf-butylammonium salt) or carboxy-substituted residue. (C) An alternative for producing acids by use of the oxime resin is transesterfication of the peptide with A-hydroxypiperidine, followed by reduction to remove the piperidino substituent. 

An oximine (i.e., a substituted oxime) analogue of alprenoxime was examined in an attempt to overcome the problem of low stability in aqueous solution. To this end, the methoxime analogue of alprenolol (11.74, R = Me) was prepared and evaluated [109]. Stability in solution was greatly improved at neutral pH. Topical administration to rabbits produced a decrease in intraocular pressure that had the same onset and intensity as that produced by alprenolol, but that lasted longer. Alprenolol was, indeed, formed in eye tissues as a metabolite, with the peak concentration reached 30 min after topical administration of the methoxime. 

O-Substituted oxime derivatives are synthetically useful in a wide variety of transformations. Hoffman and Butani have observed that reaction of a series of aldehydes and ketones with the potassium salt of Af,0-bis(trimethylsilyl)hydroxylamine 4a or 4b (a rapid equilibrium between 4a and its Af,N-bis(silylated) isomer 4b probably exists in solution) gave high yields of the corresponding oximate anion 5, formed via the Peterson-type reaction, together with the silyl ether 6. Anion 5 could be protonated to the oxime 7 or trapped in situ with a variety of electrophiles to give 0-substituted oxime derivatives (Scheme 6). 

In some cases 0-substituted oximes reacted with azomethine ylides. Thus, reaction of 0-substituted oxime (NC)2C=NOTs 139 with azomethine yhde derived from aziridine 140 afforded imidazoline 141 in 44% yield (equation 61). Addition of lithium derivative of silylated alkyne to oxime ethers 142 leads to 4-ethynyl-Af-hydroxy-2-imidazolines 143 in 49-72% yields (equation 62) . 

Indole oximes are widely used in the synthesis of a-, /3- and y-carbolines. Synthesis of a-carbolines 302 was easily realized from 0-2,4-dinitrophenyl-substituted oximes 301... 

Electrophilic C-amination with 0-substituted hydroxylamines, oximes and O-substituted oximes... 

III. ELECTROPHILIC C-AMINATION WITH OXIMES AND O-SUBSTITUTED OXIMES... 

Alternatively, oximes may be converted to O-substituted oximes (typically O-tosyl oximes) making the rearrangement much easier. Sometimes, these oxime derivatives rearrange spontaneously under the condition of their formation and cannot be isolated. Usually, O -tosyl ketoximes rearrange smoothly with exclusive anti migration. Relative to the acid-promoted Beckmann rearrangement, the rearrangement of O -tosyl oximes is much milder and specific. 

FIGURE 39. Calculated gas-phase acidities (AG(gas, 29s k>) of substituted oxime acids... 

An oxidized stage of isohexide nitrates, wherein the remaining hydroxyl group is transformed into the ketone, gives rise to a number of derivatives 161, such as oximes, semicarbazones, acyclic and cyclic acetals, and hydra-zones.154 Among them, 3-amino-2-hydroxypropyl-substituted oxime ethers... 

In the case of unsymmetrically substituted oximes (e.g. Ar -C(=NOH)-Ar2) the structure of the oxime (syn or anti) may be deduced by hydrolysis of the anilide and characterisation of the isolated carboxylic acid and amine. Thus if the products are Ar1-C02H and Ar2NH2, the hydroxyl group in the oxime must of necessity be anti to the group Ar2 owing to the trans intramolecular rearrangement step specified in the formulation above. Illustrative details for the... 

Eplivanserin contains three stereogenic units. In addition to the E-config-ured alkene double bond there is a Z-configured substituted oxime. The single bond between both double bonds has partial double bond character. The formula shown below represents the s-trans isomer. This means that it represents an antiperiplanar conformation. 

As part of such investigations, ortho-substituted oxime intermediates were found to be active, and this led to an examination of their precursor ortho-substituted ketones, again within the context of simple aryl systems like that present in practolol and its para-substituent [132]. This gradual accumulation of SAR data further demonstrates propranolol s key role as a pioneer drug during ABDD, as well as practolol s key role as an early offspring that prompted so much interest in... 

Cheng, Q., Zhang, W., Tagami, Y., and Oritani, T. 2001. Microwave-induced 1,3-dipolar intramolecular cycloadditions of iV-substituted oximes, nitrones, and azomethine ylides for the chiral synthesis of functionalized nitrogen heterocycles. Journal of Chemical Society Perkin Transactions, 1 452-56. 

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