Thiobenzamides

When thioamides such as thiobenzamide are used directly, neither dioxane nor magnesium carbonate is necessary. Instead absolute alcohol with fused sodium acetate in the presence of piperidine is used (457). 

Thiobenzamide reacts also with a- or -naphthylbromomethylketone to give 2-phenyi-4-a- or /3-naphthylthiazoles (54),... 

Thiazole carboxylic acid hydrazides were prepared in a similar way (444, 445). Thus by refluxing thioacetamide or thiobenzamide with y-bromoaceto acetic ester arylhydrazones (83) for several hours in alcohol the 4-carboxythiazole derivatives (84) listed in Table II-ll were obtained (Scheme 36) (656). This reaction is presumed to proceed via dehydration of the intermediate, thiazoline-S-oxide. 

For example, (2-phenyl-4-thiazolyl) acetate (87), R = H, was obtained in good yield from thiobenzamide and ethyl-7-bromo acetoacetate (86) as in Scheme 38 (640). 

The reaction of N-methyl-(p-dimethylamino)thiobenzamide (99) with a number of a-haloketones and a-bromoheptaldehyde gave stable 4-hydroxythiazolinium salts (100), which could be subsequently dehydrated by methanolic hydrogen chloride to the thiazolium salts (101), (Scheme 44) (622). 

In a similar reaction, bromosuccinic acid and thiobenzamide in ethyl-acetate yielded an acyclic intermediate (229), Ri = Ph, R2 = CH2C02H, which by heating in water cyclizes to the thiazole (230), Rj = Ph and R2 = CH2C02H. (260). 

Although not fully characterized, 2-carbethoxy-4-hydroxythiazole (230a), R, = C02Et, R2 = H, apparently results from the reaction of chloroacetonitrile with ethyl thiooxamate (2), Ri = C02Et (417). a-Chlorothioacids (232) condensed with thiobenzamide in the presence of carbon disulfide (542) yield the corresponding 2-phenyl-4-hydroxy-thiazole (234). The same product was obtained from 233 (Scheme 121). 

Very few 4-aminothiazoles have been synthetized directly. The reaction of a-halonitriles with thioamides generally fails and only extensive decomposition results. However, the benzene sulfonic ester of mandelonit-rile reacts with thiobenzamide to give 2,5-diphenyl-4-aminothiazole (257), Ri = R2 = Ph, in 37% yield (Scheme 132) (417) Similarly, a-cyano-a-acetylthioacetamide condensed with a-chloroacetonitrile give 257, Ri = CH(CN)CH3 and R2 = H (804). 

Because of the structural requirements of the bielectrophile, fully aromatized heterocycles are usually not readily available by this procedure. The dithiocarbamate (159) reacted with oxalyl chloride to give the substituted thiazolidine-4,5-dione (160) (see Chapter 4.19), and the same reagent reacted with iV-alkylbenzamidine (161) at 100-140 °C to give the 1 -alkyl-2-phenylimidazole-4,5-dione (162) (see Chapter 4.08). Iminochlorides of oxalic acid also react with iV,iV-disubstituted thioureas in this case the 2-dialkylaminothiazolidine-2,4-dione bis-imides are obtained. Thiobenzamide generally forms linear adducts, but 2-thiazolines will form under suitable conditions (70TL3781). Phenyliminooxalic acid dichloride, prepared from oxalic acid, phosphorus pentachloride and aniline in benzene, likewise yielded thiazolidine derivatives on reaction with thioureas (71KGS471). 

This method is based on the procedure of Oxley, Partridge, and Short N-Phenylbenzamidine has also been prepared by heating aniline hydrochloride with benzonitrile or thiobenzamide ... 

Phenyl-5,6-dihydro-l//,7//-pyrido[3,2,l-//]quinazoline-7-one and 1,7-dione 179 (X = H2 and O) were prepared from tetrahydroquinolines 206 and 207 with A-(ethoxycarbonyl)thiobenzamide and PhCOCl, respectively (98EJM763). 

A ring-opening reaction of 1,3-diazetidines 1004 with thiobenzamide gave [l,3,4]thiadiazolo[2,3-c][l,2,4]triazine 1005 [89JCR(S)140] (Scheme 186). 

Thioamide2, Thiohydrazide3 und Thiolactame4 werden durch Lithiumalanat analog den entsprechenden Carbonsaure-Derivaten reduziert. Thiobenzamid ergibt z. B. mit einem Hydrid-OberschuB neben wenig Benzonitril 64% d.Th. Benzylamin2 ... 

The ligands N-[bis(isopropoxy)thiophosphoryI]thiobenzamide and N-[bis(isopro-poxy)thiophosphoryl]-N -phenylthiourea can be deprotonated with the acetylacetonate gold(III) derivative [Au(C6F5)2(acac)] [26] giving the corresponding pentafluorophenyl complexes with the ligand acting as a chelate one [192]. 

Thiobenzamides synthesized via the thioazolides N-thiobenzoylimidazole (A), JV-thio-benzoyl-2-methylimidazole (B) and A-thiobenzoylbenzimidazole (C) are listed in Table 4-5. 

Thiobenzamides can also be obtained by reaction of N-thiobenzoyl-1,2,4-triazole (D) or N-thiobenzoylbenzotriazole (E) and amines (in cyclohexane, CHC13, or acetone as solvents, at temperatures between 10 and 50 °C),[166] as indicated in Table 4-6. 

Thiazoles may be obtained starting from the imidazolicte of a-bromocarboxylic acids and thiobenzamide, as shown by the following example. 

This reaction has been studied in mote detail, and a study of the cyclization of thiobenzamide using DMSO as oxidant led to the following conclusions. There must be an oxygen donor oxidant present and it is essential to use a solvent of high polarity such as dimethyl formanide (DMF). An acid catalyst is essential and the counterion is also important HCl and HBr are good catalysts but sulfuric acid, methanesulfonic acid, and trifluoroacetic acid do not give... 

The thiobenzamide K-oxide 67 reacts in the presence of HCl without any oxidant present to give 3,5-diphenyl-... 

Manno et al. [43] observed the formation of superoxide during the oxidation of arylamines by rat liver microsomes. Noda et al. [44] demonstrated that microsomes are able to oxidize hydrazine into a free radical. In contrast, hepatic cytochrome P-450 apparently oxidizes paracetamol (4 -hydroxyacetanilide) to A-acetyl-p-benzoquinone imine by a two-electron mechanism [45]. Younes [46] proposed that superoxide mediated the microsomal S -oxidation of thiobenzamide. 

Homogeneous oxidation of substituted thiobenzamides and N,N -diphenylthiourea in aqueous AN/BU4 NOAc or in aqueous EtOH/Et4NOTs, mediated by the organotellurium species... 

The triple bond of the cyano group in benzonitrile is also affected by Sx anions thiobenzamide was formed in this case in a 40% yield [255,256]. An interesting example of a simultaneous introduction of both sulfur and carbon using a sacrificial carbon-sulfur cathode is the formation of 4-morpholino-a-thioxoethaneditioate from morpholine [264]. 

Griitzmacher, H.-F. Mechanisms of Mass Spectrometric Fragmentation Reactions. XXXII. The Loss of Ortho Halo Substituents From Substituted Thiobenzamide Ions. Org. Mass Spectrom. 1981, 16, 448-450. 

Oxidation with p-methoxyphenyltellurinic anhydride benzonitrile (typical procedure) Thiobenzamide (0.15 g, 1.0 mmol) is mixed with the anhydride (0.189 g, 0.356 mmol) in dry CH2CI2 (4 mL). The suspension is stirred at room temperature under N2 and becomes clear in 0.5 h. After evaporation of the solvent under vacuum, benzonitrile is separated from the residue by Ktigelrohr distillation (b.p. 122-123°C/100 torr 0.107 g (95%)). Si02 column chromatography of the residue (eluent benzene) gives red crystals of An2Tc2 (0.152 g). 

Sakamoto et al. reported an interesting example involving the solid-state photoreaction of AT-(a,p-unsaturated carbonyl)thiobenzamides 1 leading to thietane-fused p-lactam 2 (Scheme 2) [29-31]. 

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