Condensation reactions diethyl malonate

When the reactant is of the form ZCH2Z, aldehydes react much better than ketones and few successful reactions with ketones have been reported. However, it is possible to get good yields of alkene from the condensation of diethyl malonate, CH2(COOEt)2, with ketones, as well as with aldehydes, if the reaction is run with TiCU and pyridine in THF. In reactions with ZCH2Z, the catalyst is most often a secondary amine (piperidine is the most common), though many other catalysts have been used. When the catalyst is pyridine (to which piperidine may or may not be added) the reaction is known as the Doebner modification of the Knoevenagel reaction. Alkoxides are also common catalysts. 

Knoevenagel condensation of diethyl malonate or related compounds with a,fi-unsaturated aldehydes and ketones results in diene esters (equation 40)78. This condensation reaction has been used to extend the polyene chain length of vitamin A related compounds (equations 4179 and 4280). 

A patent describes the synthesis of the useful penicillin side-chain 3-thienylmalonic acid through the reaction of sodium sulphide with (1), which was prepared by the AlCl3-catalysed addition of chloroacetyl chloride to acetylene followed by condensation with diethyl malonate. ... 

Hydroxycoumarin is an important intermediate for many reactions, and a recent one-step synthesis is of interest. 2-Acetoxybenzoyl chloride (191) was condensed with diethyl malonate in the presence of magnesium hydroxide to give the coumarin. ... 

Quinoxaline-2-carboxaldehyde has been converted into the 2-carboxylic acid by oxidation with potassium permanganate in acetone and reduced to the 2-hydroxymethyl compound by treatment with formalin and potassium hydroxide. It also undergoes other typical reactions of aromatic aldehydes such as benzoin formation on reaction with potassium cyanide - and condensation reactions with malonic acid and its diethyl ester and Schiff base formation. Acid-catalyzed reaction of quinoxaline-2-carboxaldehyde with ethylene glycol gives the cyclic acetal the diethylacetal has been prepared by reaction of 2-dibromomethylquinoxaline with sodium ethoxide. " An indirect preparation of the oxime 11 is achieved by treatment of 2-nitromethyl-quinoxaline (10) with diazomethane followed by thermolysis of the resulting nitronic ester. 

In 450 cc of methanol is added 47 grams of sodium metal and the mixture allowed to completely react to form a methanol solution of sodium methoxide. The methanol solution of sodium methoxide is then cooled to 60°C and 68 grams of thiourea which has been thoroughly dried is added with stirring until a uniform solution is formed. Thereafter, 157 grams of diethyl allyl-(1-methylbutyl)malonate is added to the solution of the sodio derivative of thiourea at a temperature of 55°C and the condensation reaction mixture maintained at the said temperature for 24 hours. Methyl alcohol is removed under vacuum during the course of the reaction while maintaining a temperature of 55°C. 

The Knoevenagel reaction is a carbonyl condensation reaction of an ester with an aldehyde or ketone to yield an a,j8-unsaturated product. Show the mechanism of the Knoevenagel reaction of diethyl malonate with benzaldchyde. 

Fluorenylamine, 40,5 Formaldehyde, reaction with diethyl malonate to form diethyl bis-(hydroxymethyl)malonate, 40,27 Formamide, condensation with 4,4-dimethoxy-2-butanone to give 4-methylpyrimidine, 43, 77 Formic acid, and hydrogen peroxide, with indcne, 41, 53... 

The interaction of l-(p-arsonophenyl)biguanide and ethyl acetoacetate failed to give the expected 2-(p-arsonophenylguanidino)-4-hydroxy-6-methylpyrimidine under a variety of conditions (408), as did the corresponding reaction with diethyl malonate. Condensation did occur, however, with acetylacetone (see Section VII J5) (see also ref. 590). 

Barbitone. (Barbital, veronal, 5 5-diethyl malonyl urea) The exclusion of water is also paramount in this step (use drying tubes, etc.). 30 kilos of dry urea and 76.5 kilos of the above malonate (dry diethyl diethyl malonate) are placed in the reaction vessel and stirred very well. To this mixture is added a solution of hot (75°) sodium ethylate (18 kilos of clean sodium metal in 270 liters of dry ethanol) and the mixture is brought to a boil with good stirring. The alcohol is removed with the boiling action (the reaction vessel is equipped with a slanted vapor condenser) and the mixture becomes more viscous. The alcohol (ethanol) is distilled out completely and the heat is then removed. The residue left behind should be a creamy white powder. 

Because a base-catalyzed reaction involves the abstraction of a proton by the catalyst, one approach to measurement of the total number of basic sites and also the base strength distribution is to use the reactions of molecules with various values (96-100). For instance, the basic site distribution in calcined MgAl hy-drotalcites was determined by Corma et al. (99), who used the Knoevenagel condensation (Scheme 7) between benzaldehyde and methylene active compounds with various pKa values, i.e., ethyl cyanoacetate (pKa = 9), diethyl malonate (pKa = 13.3), and ethyl bromoacetate (pKa = 16.5). The authors found that this material has basic sites with pKa values up to 16.5, although most of the basic sites... 

Mettler and colleagues reported an alternative synthesis of malonate 16 in the same paper (Griffiths et al., 1991) in which they condensed cyclohexanone with ethyl cyano-acetate instead of diethyl malonate in the Knoevenagel reaction to give ethyl cyano(cyclohexylidene)-acetate (18). In the presence of a catalytic amount of sodium cyanide, the Michael addition of HCN to cyanoacetate 18 proceeded in good yield at room temperature to generate the dicyanoester 19. Intermediate 19 was selectively converted to malonate 16 with pressurized HCI treatment in ethanol (Scheme 16.4). 

The acetic anhydride-induced cyclodehydration of the symmetrical diamide 411, derived from the tetrahydro-benzothiophene / -amino ester 410 and diethyl malonate, afforded the thieno[2,3-r7 [h3]oxazine derivative 413 rather than the expected bis-oxazine 412 (Scheme 78). The reaction probably takes place through sequential cyclizations, in which the pyridine ring of 413 is produced by condensation of the exocyclic double bond of the enamine tautomeric form of the 1,3-oxazine moiety and the mixed anhydride formed by the carboxylic group and acetic anhydride <2003PS245>. 

The condensation of 5-acetyl derivative 404 instead of the corresponding 5-formyl compound, with ethyl acetoace-tate, ethyl benzoylacetate, and diethyl acetone-1,3-dicarboxylate, by heating in the absence of base gave the respective 6-acylpyrido[2,3-4]pyrimidin-7(8//)-ones 406. The reaction of 404 with diethyl malonate afforded the 6-carboxylate 407 <2005RCB784>. Reaction of 405 with triethyl phosphonoacetate yielded 408 <2001W02001070741>. 

Nine hundred and twenty-five milliliters of absolute ethanol (Note 1) is placed in a 2-1. three-necked round-bottomed flask, fitted with a mercury or glycerin-sealed stirrer (Note 2), dropping funnel, and reflux condenser. To this is added 46 g. (2 gram atoms) 2 of freshly cut sodium, a few pieces at a time and at such a rate that the reaction proceeds rapidly but the solvent does not reflux too vigorously. When most of the sodium has dissolved, a calcium chloride drying tube is fitted to the top of the condenser and 320 g. (2 moles) of redistilled diethyl malonate is added from the dropping funnel. Then 205 g. (2 moles) of 3-chlorocyclopentene (p. 42) (Note 3) is added at such a rate that a gentle reflux is maintained. Towards the end of the addition, it is desirable to test the reaction mixture with pH test paper, and the addition should be stopped if the solution becomes acidic. 

The reflux condenser is replaced by a Claisen distillation head, and the reaction mixture is distilled until the temperature of the vapor reaches 140°. The residue is transferred to a smaller flask and fractionated through a 30-cm. column packed with glass helices. A low-boiling fraction containing ethylidene diacetate and diethyl malonate is collected first, followed by 79-89.5 g. (68-77%) of diethyl ethylidenemalonate b.p. 102-106°/10 mm. %>5 1.4394 (Note 1). 

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