Aryl aldehydes, aldol condensation

Classical Aldol. Aldol reaction is an important reaction for creating carbon-carbon bonds. The condensation reactions of active methylene compounds such as acetophenone or cyclohexanone with aryl aldehydes under basic or acidic conditions gave good yields of aldols along with the dehydration compounds in water.237 The presence of surfactants led mainly to the dehydration reactions. The most common solvents for aldol reactions are ethanol, aqueous ethanol, and water.238 The two-phase system, aqueous sodium hydroxide-ether, has been found to be excellent for the condensation reactions of reactive aliphatic aldehydes.239... 

The catalysed alkylation of l//,4//-pyrazol-5-ones is solvent dependent. In benzene, bis-alkylation occurs at the 4-position whereas, in a carbon disulphide benzene mixture, O-alkylation is observed, although the major product (4, Scheme 5.22) results from nucleophilic attack by the pyrazolone on the carbon disulphide, followed by alkylation of the dithiolate dianion [92]. The catalysed reaction of 2-thiono-3-aryl-thiazolidin-4-ones with alkylating agents under soliddiquid two-phase conditions results in alkylation at the 5-position (60-80%) [93]. The aldol condensation of the thiazolidinones with aryl aldehydes is also catalysed by quaternary ammonium salts. 

The aryl aldehyde (10 mmol) and the methyl ketone (10 mmol) are stirred at room temperature with aqueous NaOH (0.02 M, 100 ml) and CTMA-Br (50 mg, 1.37 mmol). When the reaction is complete, as shown by TLC analysis, the mixture is extracted with E20 n-C6H14 (1 1, 3 x 35 ml). The dried (MgS04) extracts are evaporated to yield the aldol condensation product [e.g. from MeCOPh 74% with PhCHO 78%, 4-MeOC6H4CHO 95%, 4-ClC6H4CHO 90%, 4-Me2NC6H4CHO. PhCHO and Me2CO produce (PhCH=CH)2CO (89%)]. 

C-7 methyl substituents on the 7-methylpyrazino[2,3-( ][l,2,6]thiadiazine 88 undergo aldol condensation reactions with aryl aldehydes to give the 7-styryl compounds 89 as shown in Scheme 12. It is interesting to note that the 6-methyl analogues 90 do not react, a consequence of the lower acidity of the 6-methyl group <2003HCA139>. 

Enanantioselective aldol reactions. Divalent tin enolates of aldehydes and aryl ketones generated with tin(II) triflate undergo aldol condensation with aldehydes to form aldols.2 The reaction is highly enantioselective if conducted in the presence of chiral diamines derived from (S)-proline, such as l.3... 

Earlier syntheses of arylquinolizidine alkaloids mainly utilized the pelletierine condensation to construct the basic skeleton, 4-aryl-2-quinolizidinone (11) (Scheme 1). Two mechanistic pathways, involving (a) initial aldol condensation of pelletierine (8) with an aromatic aldehyde followed by intramolecular Michael-type addition of the resulting enone 9 (6, 7) and (b) a Mannich-type reaction through 10 (8, 9), were proposed without any experimental evidence. Preparation and cyclization studies of the intermediate 9, however, gave conclusive evidence to show that the pelletierine condensation proceeded through pathway a (10). 

Since simple aliphatic aldehydes readily undergo aldol condensation under basic conditions, their intermolecular a-arylation is not successful. However, the intramolecular reaction is possible (Eq. 20) [59]. It is interesting that an unusual cyclization product via cleavage of the aldehyde C-H bond is observed in addition to the normal a-arylation product. Other examples of this kind of arylation are described in Sect. 3.3. 

The use of a relatively soluble base such as CS2CO3 allows good product yield. No products are formed via carbopalladation. Therefore the reaction is considered to occur on a dienolate anion generated from the enal to give an aryl(7r-allyl)palladium intermediate. The regioselectivity seems to be determined in the reductive elimination of the product. Treatment of aliphatic aldehydes with aryl bromides brings about aldol condensation followed by y-aryla-tion to afford 2 1 coupling products (Eq. 27). Note that y-arylation products are also produced in the arylation of a tin-masked dienolate [65,66]. 

The aldol condensation of ketones with aryl aldehydes to form a,p-unsaturated derivatives is called the Claisen-Schmidt reaction ° . ... 

Boric acid catalyzes the self-condensation of aldehydes and ketones to produce a,/l-unsaturated enones [6]. The yields are much higher than those reported with other acidic or basic catalysts. Under similar conditions, aldehydes which are not readily susceptible to aldol condensation, dismutate to form esters (Tischenko reaction) [7]. A catalytic amount of boric acid-sulfuric acid mixture has been used to synthesize aryl esters in good yields (Eq. 3) [8] this reaction was unsuccessful when mineral acids or boric acid alone were used. 

When aliphatic nitro compounds are used instead of aldehydes or ketones, no reduction occurs, and the reaction has been referred to as a Tollens reaction (see 16-43). However, the classical condensation of an aliphatic nitro compound with an aldehyde or ketone is usually called the Henry reaction or the Kamlet reaction, and is essentially a nitro aldol reaction. A variety of conditions have been reported, including the use of a silica catalyst, Mg—A1 hydrotalcite, a tetraalkylam-monium hydroxide,proazaphosphatranes, " or an ionic liquid.A solvent free Henry reaction was reported in which a nitroalkane and an aldehyde were reacted on KOH powder. Potassium phosphate has been used with nitromethane and aryl aldehydes. The Henry reaction has been done using ZnEt2 and 20%... 

An intramolecular analogue of the aforementioned reaction has been encountered during the Darzens condensation of a-bromo ketones with two equivalents of an aryl aldehyde (94TL9367). The intermediate a-keto oxiranes engage in aldol additions to the second aldehyde equivalent before cyclizing to the five-membered heterocyclic ring (Scheme 27). 

The a-arylation of aldehydes is also possible [57,58]. The choice of ligand and solvent is important (Eq. 15) [57]. In the case when a less bulky ligand or a more polar solvent is used, aldol condensation occurs at first, which is follwed by y-arylation to give a 1 2 coupling product. 

L-Pro was chosen as catalyst for the effective synthesis of flavanones from 2-hydro qracetophenones and aryl aldehydes. The transformation presumably occurs by the aldol condensation between both carbonyl... 

Purpose. We prepare the first of three intermediates on the synthetic pathway to our target molecule, a photochromic imine. A base-catalyzed aldol reaction is carried out in which an aromatic aldehyde is condensed with an aryl alkyl ketone. This addition reaction is followed by dehydration to form an a,p-unsaturated ketone this particular product is commonly called a chalcone. This intermediate is isolated and purified for use as the starting material in the next stage of the synthesis. You will carry out a semimicroscale reaction to gain experience at conducting larger-scale organic reactions. 

The classical aldol addition commonly uses a basic catalyst. However, the condensation reaction of various ketones with aryl aldehydes under basic conditions in water gave the expected aldol products along with the dehydration compounds. The presence of surfactants led mainly to dehydration products, whereas the use of a water/dioxane two-phase system gave good yields of aldol products with reactive aliphatic aldehydes. 

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