Rhodanines, condensation with aldehydes

In 1884, Nencki (70), studying the properties of rhodaninic acid, confirmed the formula proposed by Libermann and Lange (39) and noted its ability to condense with aldehydes. 

The condensation of rhodanine (42) with aldehydes is an important reaction closely related to the Er-lenmeyer azalactone synthesis (equation 22) the resulting condensation products are particularly useful intermediates for the preparation of various functionalized arylacetic acids and derivatives via standard manipulations of the nitrile (43), which is available as illustrated in Scheme 11. Similarly, aldehydes... 

In 1886, Ginsburg and Bondzynski (71) and Berlinerblau (72) developed the reaction of rhodanine with aldehydes, but proposed a chain formula for the condensation product. 

During a relatively long period, the condensation of rhodanines with aldehydes was developed, especially by Andreasch s group (78-87). Finally, Holmberg (88, 89) described the best method to obtain rhodanines the condensation of ammonium dithiocarbamate with a sodium or potassium salt of an a-chloro acid. 

Benzo[6]thiophene aldehydes have been condensed with a variety of active methylene compounds, including cyclic511, 644 and open-chain645-647 ketones, aliphatic aldehydes,90 benzyl cyanides,93-436 malononitrile,487 rhodanine,144,648 hippuric acid,477 barbituric acid,487 diethyl malonate,487 and malonic acid (Section VI,M). Aliphatic nitro compounds condense smoothly with most benzo[6]-thiophene aldehydes03,141,337,343, 556,640,650 (except 5-hydroxy- and... 

Selenophene-2-aldehyde takes part in the Hantzsch synthesis [Eq. (I)]108 and reacts readily with ammonia, aromatic amines and diamines,109 hippuric, barbituric, and malonic acids, malononitrile,70 and rhodanine.109 /3-(Selenien-2-yl)acrylic acid has been obtained from selenophene-2-aldehyde by the Perkin reaction and by Knoevenagel condensation with malonic acid.70 Esters of /9-(selenien-2-yl)acrylic acid are easily formed by condensation of the aldehyde... 

Nitriles are also formed in excellent yields by the decarboxylation and dehydration of oximino acids with warm acetic anhydride. A good route for obtaining the starting materials consists in the condensation of aldehydes with rhodanine followed by cleavage of the product with alkali and treatment with hydroxylamine. 

Homologation of aromatic aldehydes to arylpropanoic acid derivatives, including arylalanines, via condensation with thiazolidone 2 (rhodanine 3)... 

Condensed 1,3f4-Thiadiazoles. - Triazolof3,4-b][1,3,4Jthiadiazoles and thiadiazolines are prepared by cyclisation of 3-mercapto-4-amino-1,2,3-triazoles with substituted alkyl carboxylic acids or treatment with HCl followed by reflux with aldehydes. Thiazolo[4,3-b]M,3,4Ithiadiazoles (368 R=Me,Ph,H,R =Ar) result from treatment of acyl rhodanines (367) with PCl. Further reactions of the former have been reported. Imidazo [2,3-b][1,3,4]-... 

Heating the first-obtained product in a strong acid leads to the hydrolysis of the ester. The resulting (3-ketoacid loses carbon dioxide under reaction conditions the acetal hydrolyses also reveal the free aldehyde (106-6). Aldol condensation of this last intermediate in the presence of a base with readily available rhodanine (106-7) links the two fragments. The double bond in the first-formed product is then reduced catalytically to afford darglitazone (106-8) [117]. 

Yields in each step are in the range of 80% to 97%. The facile preparation of rhodanine in large quantity has been described along with improved directions for each step. Aliphatic, aromatic, and heterocyclic aldehydes undergo the initial condensation however, only products from the last two series are frequently carried to the final step, for example, 3,4-dimethoxyphenylacetonitrile (90% over-all), 2-ftiranaceto-... 

This reaction was initially reported by Granacher in 1922. It is the preparation of thionic acid by the treatment of Aldol Condensation product from an aldehyde and rhodanine with a base (e.g., NaOH). Therefore, this reaction is known as the Granacher synthesis or Granacher reaction." The prepared thionic acid in this reaction can be further converted into a variety of derivatives under different conditions. For example, it can be transformed into a-thiol acid under a basic sodium amalgam reduction, whereas aliphatic acid is formed under an acidic zinc amalgam reduction. In addition, when the thionic acid is treated with ammonia, a-keto acid is generated, and the thionic acid can be converted into af-carboxyl oxime in reaction with hydroxylamine, from which either cy-amino acid or aliphatic nitrile forms via the treatment of sodium amalgam reduction or acetic anhydride, respectively. 

Along with the attempts to reduce environmental pollution and economic problems, solvent-free reactions, as a characteristic of green chemistry, are preferred by the scientific community. The solvent-free condensation of an equimolar mixture of aldehyde (1) with 2,4-thiazolidinedione/rhodanine (124) in the presence of nano-ZnO involving the Knoevenagel condensation reaction has been documented (Scheme 9.39) (Suresh and Sandhu 2012). After completion of the reaction, the reaction mass was cooled and stirred with ethanol. This was followed by centrifugation... 

Carotenoid aldehydes form intensely coloured condensation products with the rhodanine reagent (No. 222) after drying, which serve for identification. As little as 0.02—0.03 g retinal can be seen as an orange-red spot [150]. Blue to deep violet complexes, depending on the compound, are yielded with the indandione reagent (No. 138). The sensitivity is similar and they also fluoresce orange in UV light [133] (Fig. b, Plate II). 

EXPERIMENT 18 The Perkin Reaction Condensation of Rhodanine with an Aromatic Aldehyde 289... 

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. 

ILs have attracted extensive research interest in recent years as environmentally benign solvents of their favorable properties. Liu and cowoikers prepared a basic IL, which was soluble in water and thus they used it for the synthesis of some interesting rhodanines. In their work, a basic functionahzed IL, 1-butyl-3-methylimidazolium hydroxide ([bmim][OH]), catalyzed the Knoevenagel condensation of rhodanine with aromatic aldehydes (Scheme 9.20). It proceeded smoothly in water to afford the 5-benzyUdene thodanine derivatives in high yields at room temperature. 

Condensation of 73 and related aldehyde 271 with acetoacetate and NH3 afforded 1,4-dihydropyridines 272 [157]. Reaction of 73 with rhodanine followed by basic hydrolysis of 273 led to a-mercapto-p-(5-trifluoromethyl-2-furyl)acrylic acid 274 [158],... 

The conversion of an aldehyde to an amino acid containing two more carbon atoms can be effected in at least three other ways. These involve condensation of the aldehyde with hydantoin and its derivatives, with diketopiperazine, or with rhodanine. Since these methods have been... 

At least two other methods are available for preparing arylacetic acids from aromatic aldehydes. One involves the condensation of the aldehyde with rhodanine, and the other involves the formation of the... 

A wide range of condensation products of type (268) and (269), derived from aldehydes and rhodanine or 5-oxothiazolidine-2-thione, has been produced by conventional methods, with a view to determining their antimicrobial activities. Bromomalonaldehyde tetraethylacetal reacts at the active 5-methylene group of 3-substituted rhodanines, yielding products of structure (270). ... 

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