Other Cyclic Hydroxylamines

While numerous nitrones react with olefins to form isoxazolidines (l-oxa-2-azacyclo-pentanes) by a formally simple [3 + 2] cycloaddition reaction, there have been few calorimetric investigations of this process. Among these is the reaction of some -substituted 

A-diphenyl nitrones (p-XC6H4CHN(0)Ph, X = NO2, Cl, H, Me and MeO) with N-phenylmaleimide to form 2,3,6-triaryl derivatives of l-oxa-2,6-diazabicyclo[3.3.0]octane-5,7-dione. No enthalpy of formation data are available for A-phenylmaleimide or for maleimide itself. However, it is available for the corresponding A-methyhnaleimide along with some other imides. The gas phase enthalpy of hydrogenation of this species (derived as the difference between its enthalpy of formation and that of N-methylsucc-inimide ) is 133.7 2.2 kJmoC. This value is essentially the same as for ethylene (derived as the difference between its enthalpy of formation and that of ethane) of 136.3 0.4 kJmoH. Therefore, let us assume the reaction of the above parent nitrone with ethylene to form the diphenylated isoxazolidine, shown in equation 12, has very much the same exothermicity as with A-phenylmaleimide, namely ca 82 kJmol . If so, the enthalpy of formation of 2,3-diphenylisoxazolidine would be 233 kJmol . Now, is this value plausible  

Let us assume that the 2- and 3-dephenylation reactions to form the parent heterocycle isoxazolidine have the same enthalpies as those of isopropylbenzene and dimethylani-line, 108.7 and 118.6 kJmol , respectively. Therefore, the enthalpy of formation of isoxazolidine is predicted to be ca 6 kJmoL. Consider the reaction in eqnation 13. 

If this reaction is assumed to be thermoneutral (neglecting the effects of heteroatoms on conformation and on ring strain), the predicted enthalpy of formation of isoxazolidine is 11.6 kJmoC. Admitting that it may be simplistic, as well as simple, to have assnmed thermoneutrality, we take these two predicted values of 6 and 11.6 kJ moH to be in satisfactory agreement and choose an average value of 9 kJmol for the enthalpy of formation of isoxazolidine. 

Very different enthalpies of addition are found for the acylnitrone PhC(0)CHN(0)Ph. Instead of the above exothermicity of ca 82 kJmoH for the addition of PhCHN(0)Ph and its substituted derivatives to a maleimide, the acylated nitrone adds to a variety of norbomenes with an average exothermicity of ca 120 kJmoL, some 38 kJmoH more favorable. This suggests about 40 kJmol destabilization arises from the presence of the adjacent acyl and nitrone groups. No enthalpy of formation data are available for any acylnitrone. To simulate the mutual destabilizing effect of the acyl and nitrone 

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Titanous ions are known to reduce nitro groups to amines and also other kinds of N—O bonds to N—H. Reduction of the cyclic hydroxylamine de-... 

Isoxazolidines display properties consistent with their cyclic hydroxylamine structures. Thus, isoxazolidines behave as nucleophiles and thus can be N-alkylated or N-acylated. Isoxazolidines are also strong bases (p5.05) and undergo other reactions such as hydrogenolysis, oxidation, thermolysis, photolysis, and decomposition by bases. 

Early attempts to extend the halolactonization procedure to yield lactams gave cyclic imidates instead, but several approaches favor lactam products. These include working with silyl imidates, imidate esters or oxazolines, using sulfonylcarbamates or other acidic amides or by using hydroxyl-amine derivatives with increased nucleophilicity due to the a-effect. Lactams can also be favored as a consequence of steric requirements. In a few cases, amines can be cyclized to cyclic amines many lead references are given in a recent report on cyclic hydroxylamines such as (64). Veiy recent work has provided a fairly general iodolactamization procedure from unsaturated amides, trimethylsilyl triflate and iodine (Scheme 89). ... 

Oxaziridines can be regarded as a special category of cyclic hydroxylamines. Activated compounds of this type, such as the IV-benzenesulfonyl derivative (46) and the salt (47), are very easily reduced. They are proving to be useful in synthesis as oxygen-transfer reagents to alkenes, thiols and other nucleophiles. 

Revised structures have been proposed for tyriverdin (241), the precursor of Tyrian Purple, and for other indole pigments. The nitroxide radical (242 R = H) reacts with bromine to yield a mixture of the cyclic hydroxylamines... 

The progress of the reaction was followed by monitoring the decrease in formaldehyde concentration with time. Previous studies used the hydroxylamine hydrochloride method of analysis (5 -55), but this was avoided in the current study as it requires tedious pH titrations. Instead, a colorimetric method was used that was first developed by Nash (55), involving formation of 3,5-diacetyl-1,4-dihydrolutidine, by reaction of formaldehyde with ammonia and acetyl acetone at neutral pH. The cyclic product absorbs at 412 nm with a molar extinction coefficient of 8,000 (55). Other colorimetric methods cannot be used as they all involve very strongly acidic or basic media (55), which would force the phenol-formaldehyde reaction to completion. 

In a continuing study(20), these experiments were applied to five fulvic and humic samples. In addition, the DEPT pulse sequence was used. This technique allows for a further discrimination between singly and doubly protonated nuclei. They found that all five samples react in the same manner. Reaction products of hydroxylamine with esters were observed. Other resonances discovered were attributable to the tautomeric forms of the nitrosophenol and monooxime derivatives of quinones. Thus, this study provides indirect evidence for the presence of quinones in humic material and also suggests the possible presence of cyclic... 

Decomposition products of the surprisingly unstable aminyloxide 222 are 2-methyl-2-nitrosopropane and hydroxylamine 22J183. The extraordinarily easy decomposition of 222 is caused by the formation of the energetically favorable dimethyl allyl radical by a-scission, which then adds further starting radical 222 giving 223. On the other hand the cyclic aminyloxide 224 is very stable. 

Chain-breaking acceptor (CB-A) antioxidants, on the other hand, act by oxidizing alkyl radicals in a stoichiometric reaction and hence are only effective under oxygen-deficient conditions (reaction lOd). Antioxidants with structures based on benzofuranone derivatives (lactones) and hydroxylamines, as well as on quinones and stable free radicals, are good examples of CB-A antioxidants (91-96). Hindered amine derivatives [often referred to as hindered amine stabilizers (HAS) eg, AOs 25-27, Table 3 also function by a chain-breaking mechanism and, through their transformation products, are able to trap both R. and ROO in a cyclical regenerative mechanism (50,55,62,94,97-100) for simplified reaction mechanism, see Scheme 11. 

Other types of cyclic compounds can sometimes be generated in the oximeforming reaction if the carbonyl is sufficiently close to the ester/acid moiety. Reaction of 1.107 (prepared by literature methods) with hydroxylamine, for example, gave isoxazolidine 1.108 via reaction of the initially formed oxime with... 

The ketone moiety of a cyclic keto-ester need not be in conjugation with the carboxyl moiety. This allows other methods for introduction of the amine group. Conversion of R-7.127 (resolved from the racemic material with brucine) to its oxime (7.128) was accomplished by treatment with hydroxylamine and pyridine.20... 

Takeo and Lei showed that it was indeed possible to use our methods for a-ketoacid and hydroxylamine synthesis to prepare several cyclic peptide namral products [34, 35]. No post-cyclization manipulatimis other than purification were required. The ability to perform the cyclization on unprotected side chains may... 

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