Oximes structural effects

Structural effects on reactivity and properties of oximes and hydroxamic acids... 

Examples of the application of correlation analysis to oxime and hydroxamic acid pK data sets are considered below. In the best of all possible worlds all data sets have a sufficient number of substituents and cover a wide enough range of substituent electronic demand, steric effect and intermolecular forces to provide a clear reliable description of the kind and magnitude of structural effects on the property of interest. In the real world this is often not the case. We will therefore try to show how the maximum amount of information can be extracted from small data sets. 

One brief report concerns the isolation, and characterization by i.r. spectroscopy and X-ray analysis, of a most unusual metabolite from the microorganism Gymnodinium breve (responsible for the red tide effect), and which has been shown to possess the E,E) form of the oxime structure (1). ... 

Later on, the structural effects of the alkenyl group of terpenoid ketone (5-alken-2-ones) oximes on the formation of pyrroles and N-vinylpyrroles as well as on prototropic isomerization of the alkenyl substituent have been studied [209]. 

The structures of these molecules show the effects of intramolecular electrostatic interactions. Two examples are the lone pair—lone pair repulsion that is an important determinant of hydroxylamine and oxime conformations, and the intramolecular hydrogen bonding in hydroxamic acids that promotes the near-planarities of their —C(=0)—NO frameworks. 

The intimate relationship between NMR parameters such as chemical shifts and spin-spin coupling constants and molecular geometry is particularly evident for derivatives with rigid frameworks. Therefore, structural and conformational effects are treated first as a separate topic and then in conjunction with specific compounds. As data on hydroxylamines, oximes and hydroxamic acids are not as extensive as those for other types of systems containing nitrogen or oxygen, comparisons with their respective parameters or effects have also been included wherever they are considered relevant. 

An extensive analysis of the effect of lone pairs on the nitrogen atom on spin-spin coupling constants is reviewed in the context of a description of molecular electronic structure. Several oximes are analyzed in studies of these effects and their relevance for structural determination has been pointed out. 

On the condition that two subsets have a structural feature whose parameterization is essentially the same, they can be combined into a single data set. As an example consider set 0X13, anfi-Ak—iyw-X—C=NOH, where Ak is either Me or Et. The electrical effects of these groups for Me and Et, respectively, are a , —.01, —,Q ad, —.14, —.12 ae, —.030, —. 036 the values of the steric parameter v are. 52 and. 56. A significant difference is found only in the polarizability parameter a, where the values for Me and Et are. 046 and. 093, respectively. Combination of oxime pXa values for Ak = Me or Et results in set 0X13 the best correlation was with the LDR equation. As only three substituent types are present in this data set and is 0.33, this data set cannot be considered as proof of anything. The only acceptable conclusion is that it is in accord with the combination of the two subsets. 

In the search of antidotes for these cholinesterase inhibitors, oximates as well as hydrox-ylamines and hydroxamates have become paramount, since these are 100- or greater-fold more reactive under mild conditions than the common base, hydroxide Structures of commonly studied oximes including pyridinium aldoximes are given in Scheme 4. The pyridinium moiety confers advantages of solubility as well as in lowering the oxime pTsTa. thus effecting higher reactivity under milder conditions of pH. 

At both these times, thigh muscle contained a higher concentration of 2-PAM I than abdominal muscle, but a lower concentration of III. Dogs and rabbits appear, therefore, to tolerate repeated daily intravenous doses of 2-PAM I at 30 mg/kg or of III at 10 mg/kg during a period of 6-8 wk when the dally doses are suspended during each weekend. Because in this and the other studies reviewed the animals were killed at or soon after the end of the period of administration of an oxime, there has been no opportunity to judge whether repeated administration of an oxime may initiate some alteration in normal structure or function that will result eventually in a definite lesion. No truly chronic study of the toxicity of an oxime has been found. Thus, possible cryptic toxic effects of this type of compound have never been assessed. 

EFFECT OF STRUCTURE AND RING SUBSTITUTION ON THE HYDROGEN BOND IN OXIMES... 

Carbamate Insecticides. These are structurally optimized derivatives of the unique plant alkaloid physostigmine [57-47-6], a cholinergic drug isolated in 1864 from Physostigma venenosum (see Alkaloids) (17,24,35—39). The carbamates maybe considered synthetic derivatives of the synaptic neurotransmitter acetylcholine, with very low turnover numbers. The N,N-dimethylcarbamates of heterocyclic enols (36) and the N-methylcarbamates of a variety of substituted phenols (35) with a wide range of insecticidal activity were described in 1954 (35). The latter are the most widely used carbamate insecticides, and the N-methylcarbamates of oximes have subsequently been found to be effective systemic insecticides. 

Alkyl-2-phenylpyrrole are readily formed, according to Scheme 5, under atmospheric pressure as well (50-70°C, 5-10 hr, equimolar amount or slight excess of KOH relative to oxime, excess of DMSO). Table XV illustrates the effects of the reaction temperature and time as well as of the structure of ketoximes on the composition and the yield of end products. 

Benzoquinone oximes (30) exhibit sidedness the structures exhibit anomalous 1H-NMR coupling constants (J21 can exceed by 0.6 Hz), and its additions show a syn selectivity.49 The apparent stereoelectronic effect is concluded to be primarily steric in origin. 

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