Addition Reactions with Nucleophilic Reagents

Pyrylinm salts nsually add nucleophiles at a carbon adjacent to the oxygen, and such reactions are analogous with those of 0-protonated carbonyl compounds. 

The degree of snsceptibility of pyrylinm salts to nucleophilic attack varies widely pyrylinm cation itself is even attacked by water at 0 °C, whereas 2,4,6-trimethylpyrylium is stable in water at 100 °C. Hydroxide anion, however, adds very readily to C-2 in all cases. 

The reaction of 2-methyl-4,6-diphenylpyrylinm is typical the immediate 2-hydroxy-2H-pyran, which is a cyclic enol hemiacetal, is in eqnilibrium with a dominant concentration of the acyclic tautomer, reached probably via a proton-catalysed process, since methoxide adducts remain cyclic. Treatment of such acyclic unsaturated diketones with acid regenerates the original pyrylinm salt (11.3.1). 

With pyryliums carrying a-alkyl groups, more vigorous alkaline treatment leads to an alternative closure, producing arenes, for example reaction of 2,4,6-trimethylpyrylium with warm alkali causes a subsequent cyclising aldol condensation of the acyclic intermediate to give 3,5-dimethylphenol. ° 

The reaction of a secondary amine cannot, of course, lead to a pyridine, however in pyrylinms carrying an a-methyl, ring closure to an arene can occnr, this time via an enamine.  

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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. ... 

It has long been known that a, l -unsaturated sulfones resemble a, l -unsaturated ketones and aldehydes in undergoing addition reactions with nucleophilic reagents. These reactions are initiated by nucleophilic attack at the carbon jS to the sulfone group ... 

Due to the presence of carbonyl, aldehyde or ketone radicals, sugars are capable of addition reactions with nucleophilic reagents such as phenylhydrazine (C6H5-NH-NH2). The addition of three phenylhydrazine molecules to an aldose (Figure 3.12) leads to the formation of osazone, a crystallized product with specific physicochemical characteristics, especially its melting point. This makes it possible to identify the corresponding sugar. 

In Chapter 11 we continue our focus on organic molecules with electron-rich functional groups by examining alkynes, compounds that contain a carbon-carbon triple bond. Like alkenes, alkynes are nucleophiles with easily broken n bonds, and as such, they undergo addition reactions with electrophilic reagents. 

The Michael-type addition reaction of nucleophilic reagents with chirally modified a,jff-substituted carbonyl compounds constitutes the established methodology for the preparation of y9-substituted carbonyl compounds. The disadvantage of this type of asymmetric Michael reaction is the loading and disloading process of the chiral auxiliary on the Michael acceptor. However, this type of the reaction has been well documented to give the adduct with a high level of diastereoselectivity [83, 84]. 

The answer is B. Aldehydes can undergo nucleophilic addition reaction with Grignard reagents. The major product here is 3-pentanol which is a five carbon alcohol. 

In reactions with nucleophilic reagents diacetylene behaves as acetylene activated with acceptor group that is common to conjugated polyynes. Therefore, the nucleophilic addition of amines, alcohols, and thiols occurs to its terminal position and leads to the formation of the corresponding l-heteroalk-l-en-3-ynes readily involved in diverse cyclization reactions. 

Consequently, aldehydes and ketones undergo nucleophilic addition reactions with Grignard reagents (Section 17.3). 

From a number of the reactions to be recorded the substitution products arise from decomposition of initial addition products. From other reactions with nucleophilic reagents, pyridine and its derivatives provide addition rather than substitution products. This is especially so when the group which would be replaced is hydride ion. Because addition compounds may be intermediates in nucleophilic processes generally (p. 218), no attempt is made here to classify separately nucleophilic additions and substitutions. 

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. 

Both acetylenedicarboxylic acid and its ester undergo Michael addition reactions with a variety of nucleophilic reagents. An example is... 

The reduction of carbonyl compounds by reaction with hydride reagents (H -) and the Grignard addition by reaction with organomagnesium halides (R - +MgBr) are examples of nucleophilic carbonyl addition reactions. What analogous product do you think might result from reaction of cyanide ion with a ketone ... 

Nitriles are similar in some respects to carboxylic acids and are prepared either by SN2 reaction of an alkyl halide with cyanide ion or by dehydration of an amide. Nitriles undergo nucleophilic addition to the polar C=N bond in the same way that carbonyl compounds do. The most important reactions of nitriles are their hydrolysis to carboxylic acids, reduction to primary amines, and reaction with organometallic reagents to yield ketones. 

Perhaps the most characteristic property of the carbon-carbon double bond is its ability readily to undergo addition reactions with a wide range of reagent types. It will be useful to consider addition reactions in terms of several categories (a) electrophilic additions (b) nucleophilic additions (c) radical additions (d) carbene additions (e) Diels-Alder cycloadditions and (f) 1,3-dipolar additions. 

Both overt carbanions and organometallic compounds, such as Grignard reagents, are powerful nucleophiles as we have seen in their addition reactions with C=0 (p. 221 et seq.) they tend therefore to promote an SN2 pathway in their displacement reactions. Particularly useful carbanions, in preparative terms, are those derived from CH2(C02Et)2, (3-ketoesters, l,3-( 3-)diketones, e.g. (55), a-cyanoesters, nitroalkanes, etc.—the so-called reactive methylenes ... 

Li and co-workers also reported a highly efficient conjugate addition reaction with arylsilanes as nucleophilic reagents. The reaction of 2-cyclohexenone with 4 equiv. of either diphenyldichlorosilane or phenylmethyldichlorosilane in water generated the conjugate addition product in 97% and 95% yields, respectively (Scheme 55).143 An excess of sodium fluoride additive was important in this reaction. 

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