Carbonyl compound , acidity electrophilicity

Although the reaction of ketones and other carbonyl compounds with electrophiles such as bromine leads to substitution rather than addition, the mechanism of the reaction is closely related to electrophilic additions to alkenes. An enol, enolate, or enolate equivalent derived from the carbonyl compound is the nucleophile, and the electrophilic attack by the halogen is analogous to that on alkenes. The reaction is completed by restoration of the carbonyl bond, rather than by addition of a nucleophile. The acid- and base-catalyzed halogenation of ketones, which is discussed briefly in Section 6.4 of Part A, provide the most-studied examples of the reaction from a mechanistic perspective. 

Another type of sp -hybridized S-oxido functionahzed organolithium compounds has been easily prepared from chloroacetic acid (149). After a double deprotonation with lithium diisopropylamide in THF at —78°C, a DTBB catalyzed (5%) hthiation in the presence of different carbonyl compounds as electrophiles at the same temperature followed by final hydrolysis afforded the expected S-hydroxy acids 151. The corresponding intermediate 150 was probably involved in the process (Scheme 54)" . 

The use of carbon dioxide as electrophile afforded directly the thiolactone 367 in 72% yield. Finally, compounds 366, derived from the use of a carbonyl compound as electrophile, were easily cyclized under acidic conditions (85% H3PO4, toluene reflux) to yield the corresponding thioisochromans 368 in 85-97% yield. 

Carbonyl compounds C=0 have two major resonance structures, R.2C=0 <—> R2C-6. In the second resonance structure, C is electron-deficient, so carbonyl compounds are good electrophiles. Carbonyl groups with a-hydrogen atoms are relatively acidic compounds, because the carbanions produced upon removal of the H are stabilized by resonance with the carbonyl group 0=CR-CR2 <—> 0-CR=CR2. The enolate anions that are thereby obtained are nucleophilic at the a-carbon and on O. Under basic conditions, then, carbonyl compounds are electrophilic at the carbonyl carbon and nucleophilic at the a-carbons (if they have H atoms attached). All the chemistry of carbonyl compounds is dominated by this dichotomy. 

An a,/3-unsaturated carbonyl compound is electrophilic at the /3- and carbonyl carbons. It is nucleophilic at the a-carbon after a nucleophile has added to the /3-carbon to make an enolate. It is not acidic at the a-carbon. 

The carbocation that is formed upon protonation of a carbonyl compound can lose H+ from the a-carbon to give an enol. Enols are good nucleophiles. Thus, under acidic conditions, carbonyl compounds are electrophilic at the carbonyl C and nucleophilic at the a-carbon and on oxygen, just like they are under basic conditions. Resonance-stabilized carbonyl compounds such as amides and esters are much less prone to enolize under acidic conditions than less stable carbonyl compounds such as ketones, aldehydes, and acyl chlorides in fact, esters and amides rarely undergo reactions at the a-carbon under acidic conditions. 

Under both acidic and basic conditions, a carbonyl compound is electrophilic at the carbonyl carbon and nucleophilic at the a-carbon. Similarly, under both acidic and basic conditions, an a,/3-unsaturated carbonyl compound is electrophilic at the carbonyl and /3-carbons and nucleophilic at the a-carbon after a nucleophile has already added to the /3-carbon. Carbonyl mechanisms differ under acidic and basic conditions only in the protonation and deprotonation steps under acidic conditions, nucleophilic addition is always preceded by protonation of the electrophile and followed by deprotonation of the nucleophile. 

Review. Seebach and Corey have published a general paper on the preparation and metalation of 1,3-dithianes and examples of the reaction of 2-lithio-l,3-dithianes with electrophilic reagents (alkyl halides, carbonyl compounds, acids, and oxides). The value of these sulfur-stabilized anionic reagents is that they are equivalent to acyl anions (a), in which the normal polarity of the carbonyl group is reversed (reversible umpolung). 

The carbocation that is formed upon protonation of a carbonyl compound can lose H+ from the a-carbon to give an enol. Enols are good nucleophiles. Thus, under acidic conditions, carbonyl compounds are electrophilic at the carbonyl C... 

Arsenic.—Carbanions of the type Ph2As(0)CHR and Ph2AsCHCH2R are obtainable by deprotonation of the conjugate acids with LiNPr and by addition of RLi to Ph2AsCH=CH2 respectively. They react with electrophiles such as carbonyl compounds or alkyl halides to give the expected products, e.g. Ph2As(0)CHRE (E = group derived from electrophile), and the arsenic moiety can subsequently be replaced by Br or by a nucleophilic moiety. In the case of products obtained from carbonyl compounds as electrophiles, the products derived from brominolysis are bromoalkenes. ° ... 

The Mukaiyama aldol reaction is a highly selective cross aldol condensation using a silyl enol ether as nucleophile and a Lewis acid-coordinated carbonyl compound as electrophile. 

Recently, different a-lithioenamines 75 have been prepared by chlorine-lithium exchange from the corresponding chloroenamines 74 and reacted with electrophiles to give functionalized enamines 76. A mixture of lithium and a catalytic amount of DTBB was used as the lithiating reagent (Scheme 2.12) [67]. The process can be performed either step-by-step (lithiation-reaction with the electrophile) at -90 °C or under Barbier-reaction conditions at -40 °C. In the case of using carbonyl compounds as electrophiles, after acidic hydrolysis, a-hydroxyketones were obtained, intermediates 74 acting in this case as acyl anion equivalents [41]. 

Masked lithium homoenolates of type XII are of interest in synthetic organic chemistry and can be considered as three-carbon homologating reagents with umpolung reactivity [122]. The lithiation of the jS-chloro orthoester 147 with lithium in the presence of a catalytic amount of DTBB, under Barbier-reaction conditions, and using carbonyl compounds as electrophiles, followed by acidic hydrolysis, led to lactones 149 as reaction products, the masked lithium homoenolate 148 bang proposed as a reaction intermediate (Scheme 2.20) [123]. 

The diminished rr electron density m the double bond makes a p unsaturated aide hydes and ketones less reactive than alkenes toward electrophilic addition Electrophilic reagents—bromine and peroxy acids for example—react more slowly with the carbon-carbon double bond of a p unsaturated carbonyl compounds than with simple alkenes... 

In general, the xanthenes are synthesized by the reaction of two moles of a nucleophilic / -substituted phenol (10) with an electrophilic carbonyl compound (11), the reaction occurring most readily with an acid catalyst at temperatures of 100—200°C. 

Electrophilic Reactions. Perfluoroepoxides are quite resistant to electrophilic attack. However, they react readily with Lewis acids, for example SbF, to give ring-opened carbonyl compounds (20—22) (eq. 2). 

Another important feature of the Nef reaction is the possible use of a CH-NO2 function as an umpoled carbonyl function. A proton at a carbon a to a nitro group is acidic, and can be abstracted by base. The resulting anionic species has a nucleophilic carbon, and can react at that position with electrophiles. In contrast the carbon center of a carbonyl group is electrophilic, and thus reactive towards nucleophiles. 1,4-Diketones 4 can for example be prepared from a-acidic nitro compounds by a Michael additionfNef reaction sequence " ... 

Judging from the following electrostatic potential maps, which kind of carbonyl compound has the more electrophilic carbonyl carbon atom, a ketone or an acid chloride Which has the more nucleophilic carbonyl oxygen atom Explain. 

Note the key difference between the base-catalyzed and acid-catalyzed reactions. The base-catalyzed reaction takes place rapidly because water is converted into hydroxide ion, a much better nucleophile. The acid-catalvzed reaction takes place rapidly because the carbonyl compound is converted by protonation into a much better electrophile. 

Carbonyl compounds are in a rapid equilibrium with called keto-enol tautomerism. Although enol tautomers to only a small extent at equilibrium and can t usually be they nevertheless contain a highly nucleophilic double electrophiles. For example, aldehydes and ketones are at the a position by reaction with Cl2, Br2, or I2 in Alpha bromination of carboxylic acids can be similarly... 

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