Nitrogen relative reactivity

Sulfonate Esters. Sucrose sulfonates are valuable intermediates for the synthesis of epoxides and derivatives containing halogens, nitrogen, and sulfur. In addition, the sulfonation reaction has been used to determine the relative reactivity of the hydroxyl groups in sucrose. The general order of reactivity in sucrose toward the esterification reaction is OH-6 OH-6 > OH-1 > HO-2. 

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... 

It is postulated that hydrogen-bonded cyclic transition states such as 62 or the analogous one involving H0CH2CH20 will be found to increase relative reactivity adjacent to the azine-nitrogen in aprotic solvents cf. also Sections II,E,2,e and II,F. 

The effect of hydrogen bonding to nuclear substituents in transition states is reviewed in Sections I,D, 2,b, and II, E. Relative reactivity at different ring-positions is postulated to be alterable by hydrogen bonding of an azine-nitrogen to the solvent or to the reagent (Section II, B, 3 and III,B). However, there appears to be no kinetic data relevant to this postulate. 

Halopyridines undergo self-quaternization on standing while the less reactive 2-halo isomers do not. However, more is involved here than the relative reactivity at the ring-positions. The reaction rate will depend on the relative riucleophilicity of the attack-ing pyridine-nitrogens (4-chloropyridine is more basic) and on the much lower steric hindrance at the 4-position. Related to this self-quatemization are the reactions of pyridine and picolines as nucleophiles with 4-chloro- and 2-chloro-3-nitropyridines. The 4-isomer (289) is. again the more reactive by 10-30-fold (Table VII, p. 276). 

In Scheme IV, intranuclejar activation is depicted. Kinetic studies with ionic nucleophiles show a variable relationship between the rates of reaction ortho and para to an azine-nitrogen (348 vs. 353 or 349) or nitro group due to entropy effects the energy of activation is expected on further study to be consistently lower for the para-position. The relative reactivity of 2- and 4-substituted bicyclic azines... 

Isodesmic reactions 2 and 3 were calculated as a measure of the relative ease of formation of the aza-epoxides, in order to obtain some insight as to the effect of nitrogen atom on metabolic activation of aza-PAHs. It was presumed that formation of the epoxides is not as relevant as carbocation formation in determining the relative reactivities of Phe, BhQ and BfQ, because almost no energy differences were observed for the isodesmic reactions involving these compounds. 

Figure 16.3 Relative reactivity of basic and non-basic nitrogen compounds in the hydrocracker environment.

The gas-phase reactivity of various terpenes has been measured. Stephens and Scott were the first to include two terpenes (pinene and a-phel-landrene) with their study of the relative reactivity of various hydrocar ns. Both monoterpenes showed the high reactivity predicted by their olefinic structure. Conversion of nitric oxide to nitrogen dioxide in e presence of isoprene is at a rate intermediate between those for ethylene and trans-2-butene, and Japar et al, reported rate constants for the a-pinene and terpinolene-ozone reactions. Grimsrud et a/. measured the rate con-... 

This reaction apparently proceeds by way of the normal phosphonate condensation product, the diazoalkylidene, which then spontaneously loses nitrogen to form the transient alkylidene car-bene. Careful work showed that, after statistical corrections were applied, the reactivity of a C-H bond toward insertion was approximately 0.003 for primary C-H bonds (methyl), 1.0 for secondary C-H bonds (methylene), 7.5 for benzylic (methylene) C-H bonds and 18.6 for tertiary C-H bonds. These relative reactivities are very similar to those previously observed for intramolecular C-H insertion by an alkylidene carbenoid generated from a vinyl bromide27. It was shown subsequently that the alkylidene carbene insertion reaction proceeds with retention of absolute configuration28. Using this approach, (l )-3-dimethyl-3-phenyl-l-cyclopentene and (i )-4-methyl-4-phenyl-2-cyclohexcnonc were prepared in high enantiomeric purity. 

The reactivity of aromatic molecules in fluorination reactions with trifluoromethyl hypofluorite has been studied in detail, and in the case of aniline derivatives the effect of the substituent on nitrogen on the relative reactivity and ortho/para ratio in various aprotic nonpolar, aprotic polar and protic solvents has been determined.5... 

Imidazo[4,5-b pyridines. Methyl chloride reacts with 78 at the nitrogen atom of the pyridine ring, but with 79 at the unsubstituted imidazole nitrogen atom.183 The Former result is surprising because it does not fit a prediction based on a consideration of the relative reactivities of pyridine and 1-methylimidazole.44... 

Although MO calculations do give an indication of the relative reactivity of the a- and /3-positions, no satisfactory explanation has been proposed for the relatively unreactive character of the nitrogen atom. In all theoretical calculations, the charge density on the nitrogen atom is considerably higher than on the carbon atoms. This anomaly may only be explained when we have more detailed information on the mechanism of pyrrole substitution reactions. 

Reaction with Nitrogen Nucleophiles. The acid-catalyzed reaction of primary, secondary, and tertiary amines with ethyleneimine yields asymmetrically substituted ethylenediamines (71). Steric effects dominate basicity in the relative reactivity of various amines in the ring-opening reaction with ethyleneimine (72). The use of carbon dioxide as catalyst in the aminoethylation of aliphatic amines, for which a patent application has been filed (73), has two advantages. First, the corrosive salts produced when mineral acids are used as catalysts (74,75) are no longer formed, and second, the reaction proceeds with good yields under atmospheric pressure. 

On the other hand, it seems less likely that the relative reactivities of n-nucleophiles should be independent of the reactivity of a carbocation. At least when they act as bases, there is little or no evidence that changes in structure of n-nucleophiles lead to changes in intrinsic barrier.301 One might expect therefore that carbocations of different reactivities reacting with a structurally related group of nitrogen or oxygen nucleophiles would show different slopes of plots of log k versus log K. 

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