Thioamides primary amines

Hydrazono derivatives of a thiocarbonyl-1,2,4-triazole have been converted with primary amines into the corresponding thioamides 1-1681... 

Thioamides of secondary amines are deprotonated with isopropyhnagnesium to give (Z)-enolates. Thioamides of primary amines react with two equivalents of /-PrMgBr to afford dianions that have been shown to have the (Z)-configuration. These magnesium species are versatile intermediates in stereoselective aldol reaction (equation 50, Table 5 ... 

The products obtained after treatment of thioamides with magnesium bromide diiso-propylamide (BMDA) and subsequent aldol condensation are presented in equation 111. The difference in the stereochemistry between thioamides of secondary amines and primary amines should be noted (Table 15). Although, in each case, the metallation leads to... 

In 1996 we performed a classical U-4CR of primary amines, aldehydes and isocyanides, but instead of using carboxylic acids we employed thiocarboxylic acids [17]. The reaction leads highly chemoselectively to a-aminoacyl thioamides and no trace of a-aminothioacyl amides is found. This finding is not noteworthy per se and... 

In contrast, the reaction of thionoesters bearing a /Tcarbonyl group with primary amines does not lead to thioamides, but instead to a-oxo ami-noketene acetals, arising from elimination of H2S rather than ROH [71]. 

The Kindler modification of the Willgerodt reaction uses sulfur and dry amines, ammonia, primary amines or secondary amines, which leads to the formation of thioamides (conversion of thioamides to amides cf Section 2.3.1.7). This reaction can also be extended to aldehydes, hydrocarbons and heterocyclic ketones. Due to the usually low to moderate yields this reaction has not found general application. 

Nucleophilic attack of ammonia or of a primary or secondary amine on an O-alkyl thiocarboxylate (2) provides a formally straightforward approach to thioamides and a number of examples have been reported (equation l). - However, some limitations should be noted. Thus, there is a tendency of esters (2) to rearrange to their 5-alkyl isomers on heating (cf. Volume 6, Chapter 2.5) and these yield amides with amines rather than thioamides. Besides, excess primary amine will lead to amidine formation, or the tetrahedral intermediate of the substitution reaction may break down to an imidate rather than a thioamide (cf. Volume 6, Chapter 2.7). These unwanted side reactions are favoured in polar, protic solvents such as ethanol. In contrast, THF has proven to be particularly useful in the synthesis of tertiary thioamides according to equation (1). For improved reactivity in the preparation of V-aryl derivatives and milder reaction conditions, it is advantageous to employ the amine in the form of its Mg salt. ... 

A microwave-assisted Willgerodt-Kindler reaction was developed to synthesize a-aryl thioacetamides 16 from aromatic ketones, morpholine, and elemental sulfur (Eq. 3) [13]. The reaction is carried out without solvents and completes within 4 min. The reaction can also be used for aldehydes. The reaction temperature and times are dependent on the substituents in the aldehydes and amines [13,14]. The use of secondary cyclic amines gives the corresponding thioamides in good to high yields. In the primary amine reaction, higher reaction temperatures are necessary. Primary thioamides are formed by... 

The Ugi four- or five-component condensation using CS2 and COS leading to thioamides has been reported [52]. Isocyanides and CS2 are added to a reaction mixture of primary amines and aldehydes, and the stirring is maintained for... 

Reduction of iV-arylimino- 1,2,3-dithiazoles 89, prepared from dithiazolium chloride and primary amines, using lithium aluminum hydride furnishes the iV-aryldithioxamides 90 (Eq. 31) [53]. The reaction is carried out for 15 min at room temperature, and the yields of 90 are moderate. It should be noted that the thioamide moiety, which is easily reduced with lithium aluminum hydride, remains in the products. 

A Pinner reaction between the primary amine (403) and the thioimidate (404) (from the thioamide and iodomethane) gave xylamidine (405) (Scheme 5.94.). Base catalysed reaction between 2-chloropropionitrile and 3-methoxyphenol followed by lithium aluminium hydride reduction provided the amine (403). Xylamidine is a powerful 5HT2 receptor antagonist, and has some value in pharmacological research [551],... 

The Hantzsch synthesis has been used to generate pyrroles, thiazoles and dihydropyridine derivatives. Pyrroles (3) are generated from the reaction of P-ketoesters with ammonia, ammonia derivatives or primary amines, and a-haloketones (path A). Thiazoles (5) are generated from the reaction between a-haloketones and thiourea or thioamide derivatives (path B). Dihydropyridines (7) are generated from the reaction of aldehydes with p-ketoesters and ammonia or ammonia derivatives, or enamines derived from the reaction of ketones or P-ketoesters with amines (path C). Dihydropyridines can be readily converted to the corresponding pyridine derivatives and so this reaction is often termed the Hantzsch pyridine synthesis. 

Synthesis of Amines, Amides, Ureas, Thioamides, and Thioureas. The Fukuyama-Mitsunobu reaction is the best method to synthesize secondary amines from primary amines, avoiding formation of undesired tertiary amines and/or the quaternary ammonium salts (eq 1). ... 

T. B. Nguyen, L. Ermolenko, A. Al-Mourabit, Org. Lett. 2012, 14, 4274-4277. Efficient and selective multicomponent oxidative coupling of two different aliphatic primary amines into thioamides by elemental sulfur. 

The Kindler variation, - which promises to be more useful than the original Willgerodt procedure, consists in heating the ketone with approximately equimolecular amounts of sulfur and a dry amine instead of aqueous ammonium polysulfide. A thioamide is formed as the principal product and on hydrolysis with acid or alkali affords the carboxylic acid, usually in good yield. Generally a secondary aliphatic amine but sometimes a primary amine or even anhydrous ammonia is used the development of a method for the electrolytic reduction of the thioamides to amines extended the usefulness of the reaction as a new route to the synthesis of many important nitrogen bases. Early descriptions of this... 

Cinchona-based primary amine catalysis in the asymmetric functionalization of carbonyl compounds has been reviewed and their modularly designed thioamide 0 derivatives have been applied successfully to direct cross-aldol reactions between aldehydes and ketones, reactions of activated carbonyl compounds (isatins) with acetylphosphonate as the enol precursor, and C( 1) functionalization of 1,3-dicarbonyl compounds by aldehydes and ketones. Cross-aldol addition to C(3) of isatins by the methyl group of 4-aryl-tra 5 -cf, -unsaturated methyl ketones has also been promoted... 

Cyanopyridazines add ammonia, primary and secondary amines and hydroxylamine to give amidines or amidoximes. Substituted amides, thioamides and carboximidates can be also prepared. With hydrazine, 3-pyridazinylcarbohydrazide imide is formed and addition of methylmagnesium iodide with subsequent hydrolysis of the imine affords the corresponding pyridazinyl methyl ketone. 

Thioamides can be synthesized by reacting thioazolides with primary or secondary amines in cyclohexane, THF, or CH2CI2, or without solvent at 20-50 °C.[164Mi6S]... 

Acyl hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. Reaction of acyl hydrazides 149 with imidoylbenzotriazoles 148 in the presence of catalytic amounts of acetic acid under microwave irradiation afforded 3,4,5-trisubstituted triazoles 150 <06JOC9051>. Treatment of A-substituted acetamides with oxalyl chloride generated imidoyl chlorides, which reacted readily with aryl hydrazides to give 3-aryl-5-methyl-4-substituted[ 1,2,4]triazoles <06SC2217>. 5-Methyl triazoles could be further functionalized through a-lithiation and subsequent reaction with electrophiles. ( )-A -(Ethoxymethylene)hydrazinecarboxylic acid methyl ester 152 was applied to the one-pot synthesis of 4-substituted-2,4-dihydro-3//-1,2,4-triazolin-3-ones 153 from readily available primary alkyl and aryl amines 151 <06TL6743>. An efficient synthesis of substituted 1,2,4-triazoles involved condensation of benzoylhydrazides with thioamides under microwave irradiation <06JCR293>. 

The three component condensations of aldehydes, amines and elemental sulfur using 1-methyl-2-pyrrolidone as solvent employing microwave flash heating 100-180 °C for 2-20 min give the corresponding primary, secondary and tertiary thioamides (Scheme 6).23... 

With primary and secondary amines, the aminolysis of a trifluoromethyl group to a carbonitrile group is not possible nevertheless, under these reaction conditions, analogs of carboxylic acids, c.g. amidines,51,52 amides29,53 - 55 or thioamides,56 are formed. 

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