Formation of Oximes

A method for protecting ketones and aldehydes is the formation of oximes, but sometimes further protection of the oximes is required. For this purpose, the oximes can be protected as allyl ethers. The oxime ethers ean be eleaved with triethylammonium formate in boiling dioxane[444]. The allyl ether of oximes is eleaved under mild conditions without attaeking the aeetal group in 677. 

An example of the electrophilic reactivity of the C-4 atom is the easy formation of oxime and phenylhydrazone derivatives (422). It has been reported, however, that 2 pheny -A-2-thiazoline-4-one does not react with phenylhydrazine (397). 

The formation of oxime and rearrangement to caprolactam are conventional. The rearrangement produces 1.5 kg of the total 2.4 kg by-product ammonium sulfate per kilogram of caprolactam. Purification is accompHshed by vacuum distillation. A similar caprolactam process is offered by Inventa (11). 

The formation of oximes, hydrazones, and related imine derivatives is usually catalyzed by both general acids and general bases. General base catalysis of dehydration of the tetrahedral intermediate involves nitrogen deprotonation concerted with elimination of hydroxide ion. ... 

All attempts to isolate primary and secondary nitroso compounds result only in the formation of oximes. Tertiary nitroso compounds, however, are stable. Explain. 

It has been shown that the rate of formation of oximes is at a maximum at a pH that depends on the substrate but is usually 4, and that the rate decreases as the pH is either raised or lowered from this point. We have previously seen (p. 425) that bell-shaped curves like this are often caused by changes in the rate-determining step. In this case, at low pH values step 2 is rapid (because it is acid catalyzed), and step 1... 

It is much more common not to be able to isolate any intermediates at all, but this does not necessarily mean that none are formed, merely that they may be too labile or transient to permit of their isolation. Their occurrence may then often be inferred from physical, particularly spectroscopic, measurements made on the system. Thus in the formation of oximes from a number of carbonyl compounds by reaction with hydroxylamine (p. 219),... 

In carbonyl addition reactions, a commonly occurring and important mechanistic step is the transfer of a proton from one site to another in a reactive intermediate (proton switch). If the proton switch occurs sufficiently rapidly compared with the rate of collapse of the intermediate to reactants, the overall reaction may be facilitated by trapping of the unstable intermediate by the proton switch (Jencks, 1976). For example, in the formation of oximes from the reaction of benzaldehyde with O-methylhydroxylamine shown in (87H89) (Sayer and Jencks, 1973 Rosenberg et al., 1974), the first unstable intermediate (It) on the reaction pathway is converted by a proton switch (88) to the intermediate (I2) which has less tendency than It to... 

The transformation of A-oxides (150a,b) into butyrolactone derivatives (151a,b), accompanied by the formation of oximes (152) as by-products, is yet another example (331) (Scheme 3.122). 

Transformations on the keto group of benzo[c]thieno[3,2-/][l,2]thiazepin-4(9H)-one 313 and isomeric benzo[c]thieno[3,4-/][l,2]thiazepin-10(5H)-one (not depicted in the Scheme) include reduction with sodium borohydride to afford alcohol 314 and formation of oximes (Scheme 67, Section 3.3.1.2 (1997JHC1191, 1998PHA130)). The later can be further O-alkylated to 2-aminoethyl 315 (2003FES1, 1996AP352). Similarly, substituted 2-aminoethyl ethers 316 were synthesized using two alternative routes (2000JHC389). 

The last species is Ph2C=N—OPh, where its enthalpy of formation does not appear in our table of enthalpies of formation of oxime ethers. The N—O bond dissociation energy, i.e. roughly the enthalpy of reaction 53, has been measured and the enthalpy of formation of PhO" is quite reliably known, e.g. see Reference 81. 

Intermolecular or intramolecular 1,4-addition of hydroxylamines as well as N- and 0-alkylhydroxylamines 39 to activated carbon-carbon double bonds (e.g. 40, equation 27) is widely used for preparation of both A-substituted, and A,A-disubstituted hydroxylamines. The addition proceeds regiospecifically. The most commonly utilized activating groups are ester , carboxyl , suRone , ketone and 2-pyridyl . Depending on reaction conditions, addition of hydroxylamines to a,/ -unsaturated ketones can be accompanied by formation of oximes . 

Reaction of hydroxylamine as well as O- and A-substituted hydroxylamines with aldehydes 63 results in formation of oximes and/or oxyiminium salts of type 64 (equation 42). Subsequent reaction with carbon, nitrogen, oxygen or phosphorous nucleophiles provides A-substituted hydroxylamines of type 65. 

The second example was the pyruvate decarboxylase catalyzed formation of (ll )-l-hydroxy-l-phenyl-2-propanone (PAC) with benzaldehyde as substrate (Fig. 5 a) [64]. This second reaction shows one potential limitation of this method. Some compounds are too volatile for direct measurement by MALDl mass spectrometry or they do not ionize directly due to their nonpolar character. In this case, these compounds have to be derivatized prior to their measurement in order to reduce their volatihty and to introduce ionizable functions. This is, however, often very easy using well estabhshed quantitative reactions, e.g., formation of oximes from aldehydes and sugars (Fig. 5b). 

Treatment of sodium and potassium nitronates with alkyl halides typically results in the formation of oximes and carbonyl compounds by cleavage of the N—O bond (11). In one case, however, reaction of w-butyl bromide with the potassium salt of nitro ester 191 does afford the -butyl nitronate (192, Eq. 2.14) (154). 

Problem 15.30 Explain why formation of oximes and other ammonia derivatives requires slightly acidic media (pH = 3.5) for maximum rate while basic or more highly acid conditions lower the rate. ... 

The nitrosation of aliphatic carbon atoms, particularly of carbon atoms activated by adjacent carbonyl, carboxyl, nitrile, or nitro groups, has been reviewed in great detail [2]. Judging from this review, with few exceptions, nitrosation of active methylene compounds leads to the formation of oximes (unfortunately termed isonitroso compounds in the older literature). The few exceptional cases cited in which true nitroso compounds (or their dimers) were formed involved tertiary carbon atoms in which no hydrogen atoms were available to permit tautomerism to the oxime or involved a reaction which was carried out under neither acidic nor basic conditions. 

This compound may be used to form oximes of aldehydes and ketones without alkali because the aqueous solution has a pH of about 5 at which the maximum rate of formation of oximes occurs. It is prepared conveniently from the chloride as follows ... 

The production of aldehyde groups through periodate oxidation and subsequent formation of oxime groups is being used as a basis for an anionic initiation of grafting with titanium chloride as catalyst according to a process claimed by Asahi Chemical Industries Company (135). With this method styrene was grafted onto viscose rayon. Also bi- and tri-valent vanadium salts can be used as initiators. 

The formation of oximes and hydroximic acids from hydroxylamine, and of, say, ethylnitrolic acid, CH3.C(N02)N0H, from dibromonitroethane, CH3.CBr2(N02), and hydroxylamine, observed by V. Meyer ... 

The reaction of ketone 243 with hydroxyamine resulted in the formation of oxime 244. Treatment of this oxime with polyphosphoric acid induced the Beckmann rearrangement of oxime 244 to form lactam 245 without detectable formation of isomeric lactam (Scheme 43) <1997JHG921>. Other examples of the Beckmann rearrangement of pyran and thiane derivatives have been reported <2004BML5907, 2004TL1051, 2005JOC10132>. 

Oximes can be formed by the iV-hydroxylation of imines and primary amines. Imines have been suggested as intermediates in the formation of oximes from primary amines (Figure 7.6). 

Formation of Oximes - Carbonyl functional groups can be transformed into an oxime derivative by alcoholic hydroxylamine chlorohydrate and monitored by the liberation of HC1. 

Finally, several groups have reported irreversible chemistries that work selectively in the presence of proteins or even whole cells. These include the Huisgen cycloaddition recently improved by Sharpless and others,1146-481 chemical ligation,1491 the formation of oximes or hydrazones and the Staudinger ligation.1501... 

Other imino derivatives arise, as by-products or in side reactions, on heterocyclization. Thus, the treatment of cinnamoyltropolones 75 with hy-droxylamine (Scheme 19) yields, in the case of the 5-nitro derivative, the corresponding isoxazolotroponeoxime (89JHC371). The formation of oximes and several hydrazones from 3-acetyltropolone or its derivatives has also been mentioned (Section II,A,3,c). Moreover, an azine was obtained in addition to quinoxalotropone 213 (Section II,B,2,c) a tropone immonium salt was isolated after an extremely complex diene reaction of an 6-amino-2-azaazuIene (93CB441). 

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