Carbonyl compounds reactivities

Additional gas-phase reactivity data, such as gas-phase acidities of alcohols [41], proton affinities of alcohols and ethers [41], and proton affinities of carbonyl compounds [42] could equally well be described by similar equations. 

Synthesis Since a-halo-carbonyl compounds are very reactive electrophiles, we can use a short cut ... 

The selective intermolecular addition of two different ketones or aldehydes can sometimes be achieved without protection of the enol, because different carbonyl compounds behave differently. For example, attempts to condense acetaldehyde with benzophenone fail. Only self-condensation of acetaldehyde is observed, because the carbonyl group of benzophenone is not sufficiently electrophilic. With acetone instead of benzophenone only fi-hydroxyketones are formed in good yield, if the aldehyde is slowly added to the basic ketone solution. Aldols are not produced. This result can be generalized in the following way aldehydes have more reactive carbonyl groups than ketones, but enolates from ketones have a more nucleophilic carbon atom than enolates from aldehydes (G. Wittig, 1968). 

The most commonly used protected derivatives of aldehydes and ketones are 1,3-dioxolanes and 1,3-oxathiolanes. They are obtained from the carbonyl compounds and 1,2-ethanediol or 2-mercaptoethanol, respectively, in aprotic solvents and in the presence of catalysts, e.g. BF, (L.F. Fieser, 1954 G.E. Wilson, Jr., 1968), and water scavengers, e.g. orthoesters (P. Doyle. 1965). Acid-catalyzed exchange dioxolanation with dioxolanes of low boiling ketones, e.g. acetone, which are distilled during the reaction, can also be applied (H. J. Dauben, Jr., 1954). Selective monoketalization of diketones is often used with good success (C. Mercier, 1973). Even from diketones with two keto groups of very similar reactivity monoketals may be obtained by repeated acid-catalyzed equilibration (W.S. Johnson, 1962 A.G. Hortmann, 1969). Most aldehydes are easily converted into acetals. The ketalization of ketones is more difficult for sterical reasons and often requires long reaction times at elevated temperatures. a, -Unsaturated ketones react more slowly than saturated ketones. 2-Mercaptoethanol is more reactive than 1,2-ethanediol (J. Romo, 1951 C. Djerassi, 1952 G.E. Wilson, Jr., 1968). 

Diene carboxylates can be prepared by the reaction of alkenyl halides with acrylates[34]. For example, pellitorine (30) is prepared by the reaction of I-heptenyl iodide (29) with an acrylate[35]. Enol triflates are reactive pseudo-halides derived from carbonyl compounds, and are utilized extensively for novel transformations. The 3,5-dien-3-ol triflate 31 derived from a 4,5-unsaturated 3-keto steroid is converted into the triene 32 by the reaction of methyl acrylate[36]. 

The reactivity of 2-methylselenazole toward carbonyl compounds is the same as its thiazoie homolog. Reaction of 2,4-dimethylselenazole with benzaldehyde in the presence of anhydrous zinc chloride as catalyst gives 4-methyl-2-styrylselenazoie [m.p. 74-75 C (19)] (Scheme 43). 

It is well known that in nitrogen-containing heterocyclic compounds the reactivity of alkyl groups is enhanced. In the thiazole series, alkyl groups in the 2-position are reactive towards carbonyl compounds and condensations may be realized. 

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... 

Ethyl acetoacetate behaves similarly to diethyl malonate in its reactivity toward a p unsaturated carbonyl compounds Give the structure of the product of the following reaction sequence... 

The sonochemistry of solutes dissolved in organic Hquids also remains largely unexplored. The sonochemistry of metal carbonyl compounds is an exception (57). Detailed studies of these systems led to important mechanistic understandings of the nature of sonochemistry. A variety of unusual reactivity patterns have been observed during ultrasonic irradiation, including multiple ligand dissociation, novel metal cluster formation, and the initiation of homogeneous catalysis at low ambient temperature (57). 

Addition to Carbonyl Compounds. Unlike Grignard and alkykitliium compounds, trialkylboranes are inert to carbonyl compounds. The air-catalyzed addition to formaldehyde is exceptional (373). Alkylborates are more reactive and can transfer alkyl groups to acyl halides. The reaction provides a highly chemoselective method for the synthesis of ketones (374). 

Six-membered heterocycles with two heteroatoms are prepared by reaction of diketene with a substrate containing a C—O or C—N multiple bond. With carbonyl compounds diketene reacts in the presence of acids to give l,3-dioxin-4-ones. The best known is 2,2,6-trimethyl-4H-l,3-dioxin-4-one [5394-63-8] (15), the so-called diketene—acetone adduct, often used as a diketene replacement that is safer to handle and to transport, albeit somewhat less reactive than diketene itself (103,104), forming acetylketene upon heating. 

Mesityl Oxide. Mesityl oxide (MSO) (4-metliyl-3-penten-2-one) is an oily colorless liquid with an unpleasant odor. It exhibits the versatiUty and unusual reactivity associated with conjugated a,P unsaturated carbonyl compounds (172). On standing ia air, mesityl oxide slowly forms bis(3,5,5-trimethyl-l,2-dioxolanyl)-3-peroxide (173). 

Methacryhc acid and its ester derivatives are Ctfjy -unsaturated carbonyl compounds and exhibit the reactivity typical of this class of compounds, ie, Michael and Michael-type conjugate addition reactions and a variety of cycloaddition and related reactions. Although less reactive than the corresponding acrylates as the result of the electron-donating effect and the steric hindrance of the a-methyl group, methacrylates readily undergo a wide variety of reactions and are valuable intermediates in many synthetic procedures. 

The dipolar ion can react in several ways according to the solvent and the stmcture of the olefin. In inert solvents, if the carbonyl compound is highly reactive (eg, an aldehyde), the dipolar ion can be added to the carbonyl fragment to give the normal ozonide or 1,2,4-trioxolane (7) for example, 1,1-and 1,2-dialkylethylenes react in this manner. Tri- or tetraalkyl-substituted olefins produce a smaH, if any, yield of an ozonide when the ozonolysis is... 

Methoxydimethylsulfonium and Trimethylsulfoxonium Salts. Alkylating agents react with DMSO at the oxygen. For example, methyl iodide gives methoxydimethylsulfonium iodide (10) as the initial product. The alkoxysulfonium salts are quite reactive and, upon continued heating, either decompose to give carbonyl compounds or rearrange to the more stable trimethylsulfoxonium salts, eg, (11) (eq. 21) (52) ... 

AH ahphatic aldehydes and most ketones react to form cyanohydrins. The lower reactivity of ketones, relative to aldehydes, is attributed to a combination of electron-donating effects and increased steric hindrance of the second alkyl group in the ketones. The magnitude of the equiUbrium constants for the addition of hydrogen cyanide to a carbonyl group is a measure of the stabiUty of the cyanohydrin relative to the carbonyl compound plus hydrogen cyanide ... 

In the diaziridine field many compounds are known bearing N-YL, A/-alkyl and A-acyl groups, but here no dramatic changes in reactivity are caused by A-substituents. N-Aryldiaziridines are underrepresented. The ring carbon is in the oxidation state of a carbonyl compound or, in the diaziridinones (5) and the diaziridinimines (6) that of carbonic acid. In single cases, diaziridine carbon bears chlorine or fluorine. 

Derivatives of carbonyl compounds that have been used as protective groups in synthetic schemes are described in this chapter some of the more important protective groups are listed in Reactivity Chart 5. ... 

Chapters 1 and 2. Most C—H bonds are very weakly acidic and have no tendency to ionize spontaneously to form carbanions. Reactions that involve carbanion intermediates are therefore usually carried out in the presence of a base which can generate the reactive carbanion intermediate. Base-catalyzed condensation reactions of carbonyl compounds provide many examples of this type of reaction. The reaction between acetophenone and benzaldehyde, which was considered in Section 4.2, for example, requires a basic catalyst to proceed, and the kinetics of the reaction show that the rate is proportional to the catalyst concentration. This is because the neutral acetophenone molecule is not nucleophihc and does not react with benzaldehyde. The much more nucleophilic enolate (carbanion) formed by deprotonation is the reactive nucleophile. 

The study of the chemistry of carbonyl compounds has shown that they can act as carbon nucleophiles in the presence of acid catalysts as well as bases. The nucleophilic reactivity of carbonyl compounds in acidic solution is due to the presence of the enol tautomer. Enolization in acidic solution is catalyzed by O-protonation. Subsequent deprotonation at carbon gives the enol ... 

The reactions of the specific classes of carbonyl compounds are related by the decisive importance of tetrahedral intermediates, and differences in reactivity can often be traced to structural features present in the tetrahedral intermediates. 

Three-dimensional potential energy diagrams of the type discussed in connection with the variable E2 transition state theory for elimination reactions can be used to consider structural effects on the reactivity of carbonyl compounds and the tetrahedral intermediates involved in carbonyl-group reactions. Many of these reactions involve the formation or breaking of two separate bonds. This is the case in the first stage of acetal hydrolysis, which involves both a proton transfer and breaking of a C—O bond. The overall reaction might take place in several ways. There are two mechanistic extremes ... 

The mechanistic pattern established by study of hydration and alcohol addition reactions of ketones and aldehydes is followed in a number of other reactions of carbonyl compounds. Reactions at carbonyl centers usually involve a series of addition and elimination steps proceeding through tetrahedral intermediates. These steps can be either acid-catalyzed or base-catalyzed. The rate and products of the reaction are determined by the reactivity of these tetrahedral intermediates. 

Because the imine is much more basic than the carbonyl compound, it is more extensively protonated at any given pH than is the aldehyde. The protonated imine is also more reactive as an electrophile than the neutral aldehyde. There are four possible electrophiles in the system ... 

Organolithium and organomagnesium reagents are highly reactive toward most carbonyl compounds. With aldehydes and ketones, the tetrahedral adduct is stable, and alcohols are isolated after protonation of the adduct, which is an alkoxide ion. 

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