Thioamides amines

Natrium-trithio-dihydrido-borat Amin, (Thioamid) 14... 

Ketone Formula Aryl Group Amine Thioamide Formed Yield Refer-. ences... 

A further improvement is embodied in the Klndler variation of the Willgerodt reaction this consists in heating the ketone with approximately equal amounts of sulphur and a dry amine instead of aqueous ammonium polysulphide. The principal product is a thioamide, and hydrolysis with acid or alkali affords the carboxylic acid, usually in good yield. 

It has been tentatively suggested that one mechanism underlies the Willgerodt reaction and the Kindler modification of it. A labile intermediate is first formed which has a carbon—carbon bond in the side chain. The scheme is indicated below it postulates a series of steps involving the addition of ammonia or amine (R = H or alkyl), elimination of water, re addition and eUmination of ammonia or amine until the unsaturation appears at the end of the chain then an irreversible oxidation between sulphur and the nitrogen compound may occur to produce a thioamide. 

In catalytic hydrogenation, a compound is reduced with molecular hydrogen in the presence of a catalyst. This reaction has found appHcations in many areas of chemistry including the preparation of amines. Nitro, nitroso, hydroxylamino, azoxy, azo, and hydrazo compounds can all be reduced to amines by catalytic hydrogenation under the right conditions. Nitriles, amides, thioamides, and oximes can also be hydrogenated to give amines (1). Some examples of these reactions foUow ... 

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. 

Me3Si)2NH, Me3SiCl, Pyr, 20°, 5 min, 100% yield. ROH is a carbohydrate. Hexamethyldisilazane (HMDS) is one of the most common sily-lating agents and readily silylates alcohols, acids, amines, thiols, phenols, hydroxamic acids, amides, thioamides, sulfonamides, phosphoric amides, phosphites, hydrazines, and enolizable ketones. It works best in the presence of a catalyst such as X-NH-Y, where at least one of the group X or Y is electron-withdrawing. ... 

Next the product is acylated with bromoacetyl chloride and the glycine equivalent is constructed in place by a Gabriel amine synthesis (phthalamide anion followed by hydrazine) subsequent to which cyclization to benzodiazepine occurs. The synthesis of the tranquilizer quazepam (88) is finished by thioamide conversion with phosphorus pentasulfide. ... 

The necessary condition to assure thioamidation of PAN is the use of basic catalysts, and, in particular, of amines facilitating the formation of the mercapto anion in the reaction medium. 

There are amines such as A-methylnitroamine, that are too weakly nucleophilic to be able to form covalent adducts with arenediazonium ions. The products of the latter appear to be those of salts ArNJ N(N02)CH3, as found by Baranchik et al. (1957). Amides also appear not to be sufficiently nucleophilic, but thioamides are, as is shown by the reaction of A-phenylthiourea in the presence of NaOH (Scheme 13-12 Nesynov et al., 1970). First a (probably homolytic) phenylation-de-diazoniation takes place, followed by A-coupling. Selenourea also reacts a mixture of products is formed, which indicates a reaction of the same type as with thiourea (Nesynov and Aldokhina, 1976). 

Bei der Reduktion von Aldehyden und Ketonen werden neben den Alkoholen auch Di- und Polysulfane er-halten (s. S. 276), mit aromatischen Nitrilen im UberschuB5, mit Oxiranen (S. 422) und mit Thiiranen (S. 449) werden Thioamide, Dihydroxy-disulfane oder Polysulfane gebildet. Mit Thiolen entstehen Borsaure-trithioester, die mit Aldehyden und Ketonen Thioacetale ergeben6. Prim. Nitro-alkane Iiefern Nitrile, sek. Ketone und Oxime (S. 472), Nitro-aromaten die entspreehenden Amine (S. 478). Oxime konnen selektiv zu Hydroxylaminen Oder weiter zu Aminen reduziert werden (S. 375). 

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]... 

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

The reaction of alcohols with CO was catalyzed by Pd compounds, iodides and/or bromides, and amides (or thioamides). Thus, MeOH was carbonylated in the presence of Pd acetate, NiCl2, tV-methylpyrrolidone, Mel, and Lil to give HOAc. AcOH is prepared by the reaction of MeOH with CO in the presence of a catalyst system comprising a Pd compound, an ionic Br or I compound other than HBr or HI, a sulfone or sulfoxide, and, in some cases, a Ni compound and a phosphine oxide or a phosphinic acid.60 Palladium(II) salts catalyze the carbonylation of methyl iodide in methanol to methyl acetate in the presence of an excess of iodide, even without amine or phosphine co-ligands platinum(II) salts are less effective.61 A novel Pd11 complex (13) is a highly efficient catalyst for the carbonylation of organic alcohols and alkenes to carboxylic acids/esters.62... 

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>. 

Another frequently used multicomponent reaction is the Kindler thioamide synthesis (the condensation of an aldehyde, an amine, and sulfur). The Kappe group has described a microwave-assisted protocol utilizing a diverse selection of 13 aldehyde and 12 amine precursors in the construction of a representative 34-member library of substituted thioamides (Scheme 6.114) [226]. The three-component con-... 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

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... 

Carboxylic acid, amine and O/7-dicihyl dithiophosphoric acid (3 equiv.) have been refluxed in toluene. This one-pot reaction yields the corresponding secondary or tertiary thioamides (Scheme ll).32... 

Dihydro-2//-l,3,5-thiadiazines substituted at the 2 and 5 positions have been synthesized by treatment of TV-substituted tV,VV-fc(l//-l,2,3-benzotriazol-l-ylme-thyl)amines with thioamides and zinc bromide in dry CH2C12 (Scheme 27).54... 

Glycoamidines have been readily prepared by a mercury-promoted reaction of the corresponding thioamides with amines.69 TV-Boc protected amidines have been prepared from /V-(Boc) thioamides by treatment with base and mercury(II) chloride (Scheme 34).70... 

An asymmetric synthesis of phosphonylated thiazolines has been described. The phosphonodithioacetate 46 was aminated with a chiral amino alcohol 47 to give the phosphonylated thioamide 48 in good yield. This was then cyclised using a Mitsunobu procedure to give the chiral thiazoline phosphonate 49 in good yields under mild conditions. Homer-Wadsworth-Emmons reaction of these phosphonylated thiazolines gave chiral vinylic thiazolines 50 <00S1143>. 

Addition to thioamides.s Alkyl- or aryllithiums add to the carbon-sulfur bond of aromatic thioamides to give adducts that are hydrolyzed to unsymmetrical ketones. Reduction of the adducts with LiAlHj before hydrolysis provides a-alkylated amines. 

Most reactive metabolites produced by CYP metabolic activation are electrophilic in nature, which means that they can react easily with the nucleophiles present in the protein side chains. Several functional groups are recurrent structural features in M Bis. These groups have been reviewed by Fontana et al. [26] and can be summarized as follows terminal (co or co — 1) acetylenes, olefins, furans and thiophenes, epoxides, dichloro- and trichloroethylenes, secondary amines, benzodioxoles (methylenediox-yphenyl, MDP), conjugated structures, hydrazines, isothiocyanates, thioamides, dithiocarbamates and, in general, Michael acceptors (Scheme 11.1). 

The formation of thioamides from amines (methylamine, dimethylamine and morpholine) and dithioester sulphines, prepared from dithio esters and peracids, is thought to proceed via the intermediates shown in equation 102325. 

The reaction of thioaldehydes, generated from phosphonium ylides and sulphur with secondary amines such as dimethylamine, leads to thioamides. If the thioaldehydes possess a a-hydrogen atom enamines are produced (equation 103)326. 

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