Azines addition

Many of the reactions of SmCp 2 and Sm(Cp )2(THF)2 with olefins and other unsaturated substrates had no precedents in organometallic chemistry indicating that these reductants could reduce unsaturated systems in nonstandard ways. To explore this issue further, Evans (Evans and Drummond, 1989) examined reactions of Sm(Cp )2(THF)2 pyridazine and ben-zaldehyde azine. Addition of 1 equivalent of pyridazine to a solution of Sm(Cp )2(THF)2 in toluene produces [(Cp )2(THF)Sm]2[/x, 7 -(pyraz)2] in a 98% yield (eq. (126)). The reduction leading to coupling of the pyridazine... 

A large variety of newer poly(ether imide)s has been described. Included among these are perfluorinated polymers (96), poly(ester ether imide)s (97), poly(ether imide)s derived from A/,Ar-diamino-l,4,5,8-naphthalenetetracarboxyHcbisimide (98), and poly(arylene ether imide ketone)s (99). In addition, many other heterocyHc groups have been introduced into polyether systems, eg, poly(pyrazole ether)s (100) and poly(aryl ether phenylquinoxaLine)s (101) poly(aryl ether oxazole)s with trifluoromethyl groups (102) and polyethers with other heterolinkages, eg, poly(arylether azine)s (103). 

Hexafluoroacetone azine accepts nucleophiles (ROH, RSH, R NH) in positions 1 and 2 to yield hydrazones [27] Phosphites give open-chain products via a skeletal rearrangement [22] Radical addition reactions are also reported [22] Treatment of tnfluoropyruvates with tosylhydrazine and phosphorus oxychlo-ride-pyndme yields tnfluoromethyl-substituted diazo compounds [24] (equation 3)... 

The scope of heteroaryne or elimination-addition type of substitution in aromatic azines seems likely to be limited by its requirement for a relatively unactivated leaving group, for an adjacent ionizable substituent or hydrogen atom, and for a very strong base. However, reaction via the heteroaryne mechanism may occur more frequently than is presently appreciated. For example, it has been recently shown that in the reaction of 4-chloropyridine with lithium piperidide, at least a small amount of aryne substitution accompanies direct displacement. The ratio of 4- to 3-substitution was 996 4 and, therefore, there was 0.8% or more pyridyne participation. Heteroarynes are undoubtedly subject to orientation and steric effects which frequently lead to the overwhelming predominance of... 

There are conflicting generalizations in the heterocyclic literature as to the relative reactivity of a- and y-positions in azines toward nucleophiles. Variations in the relative reactivity are attributed in this and subsequent sections to specific factors operating in addition to activation by azine-nitrogen. Another possible source of variation may be a decrease in selectivity with increasing reactivity of one or both reagents, an effect established in electrophilic aromatic... 

In spite of the extensive kinetic work of Chapman and co-workers, much remains to be done on the reactivity of azines with nucleophiles. The data available on substitution by alkoxide ions are especially meager. The missing information on alkoxide reactions should give a better picture of the activation of different ring-positions than is possible with the data on aminations. The latter include the effects shown in 235, 276, and 277 in addition to activation by the azine-nitrogens. 

Covalent addition of solvent or of nucleophile prior to substitution will alter the reactivity characteristics of the substrate. Covalent addition of nucleophile after substitution will affect the kinetics in a way similar to the formation of 389. Covalent hydration and additions are especially likely to occur in bicyclic azines. (cf. Section IV,B,3,b).ii>i o>i i i4... 

From the qualitative indications of preparative organic chemistry, it is clear that additional ring-nitrogens in bicyclic azines increase... 

Three comparisons of para vs. ortho activation by an additional ring-nitrogen are possible from the available data and all show the former to be more effective, as found for the nitronaphthalenes above and for monocyclic azines (Section III). In piperidino-dechlorination of chloroquinazolines (Table XV, lines 3 and 4), the 4-isomer (405) reacts 6,500-fold faster than the 2-chloro compound (400) due entirely to a 4.1 kcal decrease in the dS being the same for both. However,... 

Specific alterations of the relative reactivity due to hydrogen bonding in the transition state or to a cyclic transition state or to electrostatic attraction in quaternary compounds or protonated azines are included below (cf. also Sections II, B, 3 II, B, 5 II, C and II, F). A-Protonation is often reflected in an increase in JS and therefore the relative reactivity can vary with the significance of JS in controlling the reaction rate. Variation can also result from rate determination by the second stage of the SjjAr2 mechanism or from the intervention of thermodynamic control of product formation. Variation in the rate and in the reactivity pattern of polyazanaph-thalenes will result when nucleophilic substitution [Eq. (10)] occurs only on a covalent adduct (408) of the substrate rather than on its aromatic form (400). This covalent addition is prevented by any 4-... 

An illustrative example of the Michael reaction is that of the thiirene dioxide 19b with either hydroxylamine or hydrazine to give desoxybenzoin oxime (87) and desoxybenzoin azine (88), respectively, in good yields6 (see equation 29). The results were interpreted in terms of an initial nucleophilic addition to the a, j8-unsaturated sulfone system, followed by loss of sulfur dioxide and tautomerization. Interestingly, the treatment of the corresponding thiirene oxide (18a) with hydroxylamine also afforded 86 (as well as the dioxime of benzoin), albeit in a lower yield, but apparently via the same mechanistic pathway6. 

The alkaline sodium sulphite solution may be replaced by saturated amtnonlum sulphite solution prepared as follows. Pass sulphur dioxide into a mixture of 1 part of concentrated ammonia solution (sp. gr. 0-88) and two parts of crushed ice in a freezing mixture imtil the liquid smells strongly of sulphur dioxide, and then neutralise with ammonia solution. This solution slowly deposits ammonium sulphite crystals and contains about 0-25 g. of SOj per ml. Use 60 ml. of this ice-cold ammonium sulphite solution to which 8 ml. of concentrated ammonia solution are added. After the addition of the solution of p-nitrophenyldiazonium chloride, allow the mixture to stand for 1 hour in a freezing mixture, filter oft the yellow precipitate of ammonium p-nitrophenyUiydrazine disulphonate, heat it on a water bath with 20 ml. of concentrated hydrochloric acid at 70-80° for 7 minutes, cool the blood-red solution, and dissolve the resulting precipitate of p-nitrophenylhydr-azine hydrochloride and ammonium salts in water, and isolate the base as above. 

Azines have been prepared by initial condensation of diethoxyphosphinyIhydrazine anions with aldehydes or ketones (Scheme 9). Phosphoryl azides undergo 1,3-dipolar cycloaddition to 2-tetralone enamines to give triazolines, possibly en route to amidines. A full paper on the addition of diethyl dibromophosphoramidate to alkenes(leading to the synthesis of 2-bromoalkylamines) has appeared. ... 

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