Carbonyl compounds base-catalyzed condensation

Such copolymers of oxygen have been prepared from styrene, a-methylstyrene, indene, ketenes, butadiene, isoprene, l,l-diphen5iethylene, methyl methacrjiate, methyl acrylate, acrylonitrile, and vinyl chloride (44,66,109). 1,3-Dienes, such as butadiene, yield randomly distributed 1,2- and 1,4-copolymers. Oxygen pressure and olefin stmcture are important factors in these reactions for example, other products, eg, carbonyl compounds, epoxides, etc, can form at low oxygen pressures. Polymers possessing dialkyl peroxide moieties in the polymer backbone have also been prepared by base-catalyzed condensations of di(hydroxy-/ f2 -alkyl) peroxides with dibasic acid chlorides or bis(chloroformates) (110). 

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. 

TABLE 16.1 Base Catalyzed Condensations Showing the Active Components and the Carbonyl Compounds... 

The base-catalyzed condensation of azides with activated methylene compounds is a well-established route to IJT-triazoles. In particular, it is the best route to triazoles bearing a 5-amino or hydroxy substituent and an aryl or carbonyl-containing function in the 4-position. The addition is regiospecific. The reaction is a stepwise one, since anomerism of glycosyl azides has been observed in their reaction with activated methylene compounds, indicating the presence of an intermediate. The mechanism can be envisaged as a nucleophilic attack by the car-banion on the terminal nitrogen of the azide, followed by cyclization to a... 

The high-molecular-weight products formed by the condensation of phenols with carbonyl compounds (especially with formaldehyde) are known as phenolic resins. They are mixtures of structurally nonuniform compounds that are initially soluble and fusible but which can become crosslinked (cured) by subsequent reactions. One distinguishes between acid- and base-catalyzed condensations, since they lead to different end products the properties of the condensation polymer are also affected by the mole ratio of phenol to formaldehyde. 

The second pattern in Scheme 13 is based upon nucleophilic addition to an a,/3-unsaturated carbonyl compound and has been developed where the nitrogen substituent X is arenesulfonyl. Base-catalyzed condensation of N- (p-toluenesulfonyl)glycine with a,(3 -unsaturated ketones gives intermediate 1-p-toluenesulfonyldihydropyrroles which can be aromatized by base-catalyzed elimination of the p -toluenesulfinate anion (equation 116) (65JCS4389). 

A common side reaction during Oppenauer oxidations consists of the base-catalyzed condensation of the carbonyl compound, resulting from the oxidation, with the carbonyl compound used as oxidant. Sometimes, advantage is taken from this side reaction for synthetic purposes. For example, oxidation of primary alcohols with an aluminium alkoxide and acetone results in the formation of an intermediate aldehyde that condenses with acetone, resulting in a synthetically useful formation of an enone.59... 

In 2007, Wiles et al. (2007c) demonstrated the ability to employ solid-supported catalysts in series within an EOF-based microreactor. As summarized in Scheme 39, the model reaction sequence involved combining a previously investigated acid-catalyzed deprotection with a base-catalyzed condensation reaction to enable the synthesis of a,(3-unsaturated carbonyl compounds from dimethyl acetals. 

The employment of activated cyanomethylene compounds (e.g., malononitrile) for condensation with -amino carbonyl derivatives (e.g., the protected aminoacetaldehyde 184) provides 2-aminopyrroles 185 (Scheme 101) <2004OL2857>. In a comparable fashion, the condensation of -mercapto carbonyl compounds with malononitrile derivatives provides 2-aminothiophenes (Scheme 102) <1979LA328>. Similarly, 2-aminofuran-3-nitriles can be obtained by base-catalyzed condensation of -hydroxy ketones with malononitrile < 1966GB 1002>. 

Further kinetic evidence for the importance of enols comes from work on the base-catalyzed condensations of carbonyl-containing compounds. There are a number of such reactions characteristic of aldehydes, ketones, carboxylic acids, esters, amides, etc. Of these the most elementary appear to be the aldol condensations, which are prototypes of the others. These reactions can be represented by the equation... 

Treatment of methyl phenyl sulfoxide with diethylaminosulfur trifluoride (DAST), in the presence of antimony trichloride provides 159 in quantitative yield (66). The reaction proceeds in good yield with dialkyl sulfoxides and alkyl aryl sulfoxides (163). Reoxidation of the a-fluorosulfide (165) to the corresponding sulfoxide (161), followed by pyrolysis, provides a direct synthesis of fluoroolefins (65). The reaction is believed to proceed by a Pummerer-type mechanism (l.e., a fluoro-Pummerer reaction, Scheme 48). Similarly, Umemoto (67) reported that N-fluorocollidine (167) converted sulfides to ot-fluorosulfides (170) presumably via an S-fluorosulfonium cation species 168 (Scheme 49). The synthetically challenging fluorovinyl ether nucleosides (175) and (176) were prepared using the fluoro-Pummerer reaction (Scheme 50) (60) the (E)-isomer (175) could be isomerized to 176 under photolytic conditions. Finch and co-workers (69) converted 160 to the sulfoximine 178 and demonstrated the utility of this compound as a mild fluoromethylene synthon (Scheme 51). Base-catalyzed condensation 178 with a carbonyl compound gave 179 which afforded... 

Condensation of urea with carbonyl compounds A rapid and efficient MW-assisted synthesis of hydantoins and thiohydantoins was described by Muccioli et al. [117]. The most straightforward conditions for synthesis of phenytoin are the base-catalyzed condensation using benzil and urea, known as the Biltz synthesis (Eq. 33). MW activation of the Biltz synthesis of phenytoin improved both yield and reaction time. The first step consists in MW activation of the reaction of benzil with (thio)urea the second includes the conversion of the resulting 2-(thio)hydantoin to hydantoin using hydrogen peroxide. When reactions were performed at the same temperature under both reaction conditions, yields were by far better under the action of MW and emphasized the evident specific MW effects. These are perfectly expected when one considers the polar TS involved in the first step (nucleophilic addition of neutral NH2 group on carbonyl moiety). 

Aldol Reaction (Condensation) [24] Traditionally, it is the acid- or base-catalyzed condensation of one carbonyl compound with the enolate/enol of another, which may or may not be the same, to generate a P-hydroxy carbonyl compound— an aldol. The method is composed of self-condensation, polycondensation, generation of regioisomeric enols/enolates, and dehydration of the aldol followed by Michael addition, q.v. The development of methods for the preparation and use of preformed enolates or enol derivatives that dictate specific caibon-caibon bond formation have revolutionized the coupling of carbonyl compounds (Fig. 6.6) ... 

Siegrist Reaction. Double bonds can be synthesized by a variety of base-catalyzed condensations between an active methylene compound and a carbonyl group. Meier et al. [895, 896] used a base-catalyzed self-coupling of the Schiff bases of various p-methylbenzaldehydes to prepare PPV. 

Linear polymers can be obtained by the base-catalyzed condensation of compounds possessing active methylene groups with compounds possessing carbonyl groups. An example is shown in Eq. (1-2) (20-23). Anhydrous ethanol, dioxane, dimethylformamide, and dimethyl sulfoxide were suitable solvents. Low molecular weight polymers were obtained that had predominately aldehydic termination. The insolubility and infusibility of the polymer shown in Eq. (1-2) led to the belief that it was not linear (33). Cross-linking... 

The usual base or acid catalyzed aldol addition or ester condensation reactions can only be applied as a useful synthetic reaction, if both carbonyl components are identical. Otherwise complicated mixtures of products are formed. If two different aldehydes or esters are to be combined, it is essential that one of the components is transformed quantitatively into an enol whereas the other component remains as a carbonyl compound in the reaction mixture. 

Polymerization of olefins such as styrene is promoted by acid or base or sodium catalysts, and polyethylene is made with homogeneous peroxides. Condensation polymerization is catalyzed by acid-type catalysts such as metal oxides and sulfonic acids. Addition polymerization is used mainly for olefins, diolefins, and some carbonyl compounds. For these processes, initiators are coordination compounds such as Ziegler-type catalysts, of which halides of transition metals Ti, V, Mo, and W are important examples. 

The mechanistic pathway of the ordinary Friedlander synthesis is not rigorously known. Two steps are formulated. In a first step a condensation reaction, catalyzed by acid or base, takes place, that can lead to formation of two different types of products (a) an imine (Schiff base) 4, or (b) an o ,/3-unsaturated carbonyl compound 5 ... 

Another advantage of this method is that no catalyst is needed for the addition reaction this means that the base-catalyzed polymerization of the electrophilic olefin (i.e., a,j8-unsaturated ketones, esters, etc.) is not normally a factor to contend with, as it is in the usual base-catalyzed reactions of the Michael typCi It also means that the carbonyl compound is not subject to aldol condensation which often is the predominant reaction in base-catalyzed reactions. An unsaturated aldehyde can be used only in a Michael addition reaction when the enamine method is employed. 

The Knoevenagel condensation is a cross-aldol condensation of a carbonyl compound with an active methylene compound leading to C-C bond formation (Scheme 7). This reaction has wide application in the synthesis of fine chemicals and is classically catalyzed by bases in solution (146,147). 

Condensations with carbonyl compounds phenol-formaldehyde resins. Acid or base catalyzes electrophilic substitution of carbonyl compounds in ortho and para positions of phenols to form phenol alcohols (Lederer-Manasse reaction). 

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