Methylene groups, activated aldol condensation

Another classic approach to thiophenes is that of Hinsberg, where an alpha-diketone and a sulfide with two methylene groups activated by carbalkoxy groups are reacted in the presence of sodium ethoxide in a double aldol condensation (Scheme 9.12). If the carbalkoxy groups are not desired in the final product, they can be hydrolyzed with NaOH acidification then gives the free di-acid, which can be decarboxylated thermally. 

Isatin (190) is a compound with interesting chemistry. It can be iV-acetylated with acetic anhydride, iV-methylated via its sodium or potassium salt and O-methylated via its silver salt. Oxidation of isatins with hydrogen peroxide in methanolic sodium methoxide yields methyl anthranilates (81AG(E)882>. In moist air, O-methylisatin (191) forms methylisatoid (192). Isatin forms normal carbonyl derivatives (193) with ketonic reagents such as hydroxylamine and phenylhydrazine and the reactive 3-carbonyl group also undergoes aldol condensation with active methylene compounds. Isatin forms a complex derivative, isamic acid (194), with ammonia (76JCS(P1)2004). 

KNOEVENAGEL OOEBNER STOBBE Condensation Base catalyzed aldol condensation of aldehydes or ketones with an activated methylene group of a malonic ester (Knoevenagel Doebner) or a succinic ester (Stobbe)... 

The reactive 3-carbonyl group in compounds of type (279) undergoes aldol condensation with active methylene compounds such reactions of isatin with indoxyl, oxindole (Section 3.3.2.5.4) and with thiophenes (Section 3.3.1.5.7.ii) have already been mentioned. These compounds also react with Grignard reagents and phosphorus halides as expected, e.g. isatin (279 Z = NH) with MeMgBr and PC13 yields (285) and (286), respectively. 

The reaction of homophthalic acids or anhydrides with citral in the presence of pyridine yields reduced pyran-2-ones by means of an aldol condensation involving the activated methylene group of the acid. Dehydration is followed by an acid-catalyzed rearrangement to the pyran-2-one (Scheme 201) <79H(12)253). 

Several a-btomo-a,/3-olefinic ketones and esters have been prepared by an interesting cleavage of S-acyl or )3-carbethoxy-a-ketolactones. It is unnecessary to isolate the bromolactone. Bromination and cleavage take place readily at 0-20° over-all yields are 60-85%. The /6-acyl and /6-catbethoxy-a-ketolactones are prepared by aldol-type condensations of aldehydes with the active methylene groups of ethyl )3-acetyl-pyruvate, CHjCOCHjCOCO CjHs, and ethyl oxalacetate,... 

A wide variety of reaction conditions have been proposed for the reaction of starch with aldehydes. Early studies entailed use of alkaline solutions, perhaps in order to gelatinize starch.1276 Because of the known behavior of aldehydes in alkaline media (Cannizzaro disproportionation and aldol condensations of aldehydes with active active a-methylene groups), this reaction has no simple outcome. However, a process of acetalation in alkaline solutions was subsequendy patented.1293 An exothermic reaction was observed within 3 4 min using an excess of formaldehyde. It was also reported that a,(3-unsaturated aldehydes reacted readily in slightly basic media.1294... 

Aldol-type condensation of an aromatic aldehyde with activated methylarene or phenylacetic acid is a useful reaction for preparing stilbene derivatives. Starting from para-substituted toluenes or para-substituted aromatic aldehydes, one can obtain 4,4 -disubstituted stilbenes. This reaction is relatively simple but has low yield. As an example, condensation of 2,4-dinitrotoluene and 4-nitrophenylacetic acid with aromatic aldehyde was studied [26]. The reaction involves carbanion addition to the carbonyl group. The carbanion is formed by the extraction of proton from the active methylene group of 2,4-dinitrotoluene by the base (usually, piperidine). The carbanion then adds to carbon atoms of the carbonyl group of the aldehyde. The reaction will therefore be facilitated by the ease of both the formation of the... 

The first step in the base-catalyzed condensation is the proton abstraction of active methylene groups with base catalysts, followed by attack of the anion on a carbonyl moiety. Elimination of water then produces the CMD double bond. Numerous heterogeneous catalysts have been reported to promote these condensations, including the rehydrated hydrotalcites described above for the Aldol reactions (41,51), vanadate apatite (52), and amine-functionalized silica (53). The merits of using these heterogeneous catalysts are the ease of product isolation and catalyst reusability, which is associated with elimination of the necessity to neutralize homogeneous bases such as NaOH and NaOMe. 

This reactive thiol ester is capable of tandergoing aldol-type (see Experiment [20]) condensations under physiological conditions. AcetylCoA is first carboxy-lated with the help of the enzyme, acetyl CoA-carboxylase, to yield a thioknalonyl derivative. The resulting intermediate possesses an activated methylene group... 

Purpose. This experiment explores the use of the interesting heterocyclic compound, rhodanine, as the source of an active (acidic) —CH2— group. (The methylene group contained in the thiazoHdinone ring system possesses the capacity to participate in base-catalyzed condensation reactions smular to those of the aldol reaction.) You will carry out a base-catalyzed condensation reaction with an aromatic aldehyde. You will examine the properties of this condensation product, which has the capacity to function as an intermediate in a number of synthetic pathways. Indeed, one of these routes yields the important class of aromatic amino acids, the phenylalanines. 

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