Nucleophilic reagents, reactivity

Isopentenyl pyrophosphate and dimethylallyl pyrophosphate are structurally sim liar—both contain a double bond and a pyrophosphate ester unit—but the chemical reactivity expressed by each is different The principal site of reaction m dimethylallyl pyrophosphate is the carbon that bears the pyrophosphate group Pyrophosphate is a reasonably good leaving group m nucleophilic substitution reactions especially when as in dimethylallyl pyrophosphate it is located at an allylic carbon Isopentenyl pyrophosphate on the other hand does not have its leaving group attached to an allylic carbon and is far less reactive than dimethylallyl pyrophosphate toward nucleophilic reagents The principal site of reaction m isopentenyl pyrophosphate is the carbon-carbon double bond which like the double bonds of simple alkenes is reactive toward electrophiles... 

Acrylamide, C H NO, is an interesting difiinctional monomer containing a reactive electron-deficient double bond and an amide group, and it undergoes reactions typical of those two functionalities. It exhibits both weak acidic and basic properties. The electron withdrawing carboxamide group activates the double bond, which consequendy reacts readily with nucleophilic reagents, eg, by addition. 

Substitution Reactions on Side Chains. Because the benzyl carbon is the most reactive site on the propanoid side chain, many substitution reactions occur at this position. Typically, substitution reactions occur by attack of a nucleophilic reagent on a benzyl carbon present in the form of a carbonium ion or a methine group in a quinonemethide stmeture. In a reversal of the ether cleavage reactions described, benzyl alcohols and ethers may be transformed to alkyl or aryl ethers by acid-catalyzed etherifications or transetherifications with alcohol or phenol. The conversion of a benzyl alcohol or ether to a sulfonic acid group is among the most important side chain modification reactions because it is essential to the solubilization of lignin in the sulfite pulping process (17). 

Tiichloiomethanesulfenyl chloiide can be reduced to thiophosgene by metals in the presence of acid and by various other reducing agents. The sulfur-bonded chlorine of trichloromethanesulfenyl chloride is most easily displaced by nucleophilic reagents, but under some conditions, the carbon-bound chlorines are also reactive (54). 

Reaction with vatious nucleophilic reagents provides several types of dyes. Those with simple chromophores include the hernicyanine iodide [16384-23-9] (20) in which one of the terminal nitrogens is nonheterocyclic enamine triearbocyanine iodide [16384-24-0] (21) useful as a laser dye and the merocyanine [32634-47-2] (22). More complex polynuclear dyes from reagents with more than one reactive site include the trinuclear BAB (Basic-Acidic-Basic) dye [66037-42-1] (23) containing basic-acidic-basic heterocycles. Indolizinium quaternary salts (24), derived from reaction of diphenylcyclopropenone [886-38-4] and 4-picoline [108-89-4] provide trimethine dyes such as (25), which absorb near 950 nm in the infrared (23). 

In this section three main aspects will be considered. Firstly, the basic strengths of the principal heterocyclic systems under review and the effects of structural modification on this parameter will be discussed. For reference some pK values are collected in Table 3. Secondly, the position of protonation in these carbon-protonating systems will be considered. Thirdly, the reactivity aspects of protonation are mentioned. Protonation yields in most cases highly reactive electrophilic species. Under conditions in which both protonated and non-protonated base co-exist, polymerization frequently occurs. Further ipso protonation of substituted derivatives may induce rearrangement, and also the protonated heterocycles are found to be subject to ring-opening attack by nucleophilic reagents. 

The reactivities of the substrate and the nucleophilic reagent change vyhen fluorine atoms are introduced into their structures This perturbation becomes more impor tant when the number of atoms of this element increases A striking example is the reactivity of alkyl halides S l and mechanisms operate when few fluorine atoms are incorporated in the aliphatic chain, but perfluoroalkyl halides are usually resistant to these classical processes However, formal substitution at carbon can arise from other mecharasms For example nucleophilic attack at chlorine, bromine, or iodine (halogenophilic reaction, occurring either by a direct electron-pair transfer or by two successive one-electron transfers) gives carbanions These intermediates can then decompose to carbenes or olefins, which react further (see equations 15 and 47) Single-electron transfer (SET) from the nucleophile to the halide can produce intermediate radicals that react by an SrnI process (see equation 57) When these chain mechanisms can occur, they allow reactions that were previously unknown Perfluoroalkylation, which used to be very rare, can now be accomplished by new methods (see for example equations 48-56, 65-70, 79, 107-108, 110, 113-135, 138-141, and 145-146)... 

The most striking chemical property of epoxides is their far- greater reactivity toward nucleophilic reagents compared with that of simple ethers. Epoxides react rapidly with nucleophiles under conditions in which other ethers are inert. This enhanced reactivity results from the angle strain of epoxides. Reactions that open the ring relieve this strain. 

In addition to having typical A -oxide reactions, quinazoline 3-oxide also shows the same reactivity as quinazoline toward nucleophilic reagents, but the reaction goes a step further by eliminating water as shown in reaction 2d. Oxidation with hydrogen peroxide... 

Efforts to establish a theoretical explanation of the reactivity of nucleophilic reagents have centered on correlations with intrinsic electron-donor properties which are the fundamental basis of nucleophilicity. According to Edwards and Pearson, in general, such properties include basicity, polarizability, and the presence of unshared electron pairs on the atom adjacent to the nucleophilic atom of the reagent. When only the first two of these properties are operative, Eq. (8), which was proposed by Edwards, has proved successful in... 

The reactivity of a nucleophilic reagent may also depend on stereochemical conformation, degree of solvation and hydrogen-bonding,... 

A more proper comparison regarding Vl-group nucleophilic reagents would be between the pairs PhO and PhS , and MeO" and MeS. However, both phenoxide and alkylsulfide ions are more basic than phenylsulfide ion, and their reactions are less amenable to study in alcoholic solution. For dilute solutions of phenoxide in methanol the equilibrium (9) shifts nearly half-way toward the right if a stoichiometric excess of phenol is not present. If phenoxide ion is less reactive... 

The effect of other substituents and of the nucleophilic reagent on ortho vs. para reactivity in nitrobenzene derivatives has been discussed... 

Other types of leaving groups and of nucleophilic reagents also show greater reactivity at the 4-position 2,4-dichloropyrimidine with alcoholic potassium thiocyanate (to 304) and with chemical monodehalogenation (zinc and ammonia or ammonium chloride), 2,4- lj, 3fi )-pyrimidinedithione with ammonia or... 

Naphthyridines are (just as pyridines) characterized as 7r-deficient systems. Introduction of an electron-withdrawing group such as the nitro group further depletes the ring of its 7r-electrons and lowers its electron density. On account of this low electron density, nitronaphthyridines show a high reactivity to nucleophilic reagents and low reactivity to electrophiles several characterictic examples of this behavior are shown in this chapter. 

Quinoxalines undergo facile addition reactions with nucleophilic reagents. The reaction of quinoxaline with allylmagnesium bromide gives, after hydrolysis of the initial adduct, 86% of 2,3-diallyl-l,2,3,4-tetrahydroquinoxaline. Quinoxaline is more reactive to this nucleophile than related aza-heterocyclic compounds, and the observed order of reactivity is pyridine < quinoline isoquinoline < phenan-thridine acridine < quinoxaline. ... 

Nevertheless the 2-position of selenazoles appears to be somewhat less reactive than the 2-position of thiazoles toward nucleophilic reagents. However, this conclusion needs further confirmation as a result of the difficulties in the preparation of suitably substituted... 

The nucleophilic substitution reactions are still more limited in scope owing to the instability of the isoxazole ring toward nucleophilic reagents. Homolytic reactions appear to be unknown though some of the reactions being studied are possibly of this type. Besides those reactions which are characteristic of the reactivity of the isoxazole nucleus itself, we shall consider in this section some substitution reactions in the side chain organomagnesium synthesis in the isoxazole series, condensation reactions of the methyl groups of methyl-isoxazoles, and finally some miscellaneous reactions. 

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