Thioamides metalation

A partially reduced quinoline derivative with antiulcerative and antisecretory activities is isotiquimide (14). It may be synthesized by metallating (with n-BuLi) 4-methyl-5,6,7,8-tetrahy-droquinoline and condensing this with dimethylmethoxysilylisothiocyanate to produce the desired thioamide isotiquimide (14) [4],... 

In the Michael addition of achiral enolates and achiral Michael acceptors the basic general problem of simple diastereoselection (see Section D.1.5.1.3.2.), as described in Section 1.5.2.3.2. is applicable. Thus, the intermolecular 1,4-addition of achiral metal enolates to enones, a.jS-unsat-urated esters, and thioamides, results in the formation of racemic syn-1,2 and/or anti-3,4 adducts. 

Thioamides have been transformed into the corresponding nitriles. Treatment of primary thioamides by tellurium tetrachloride or selenium tetrachloride in combination with triethylamine affords nitriles.66 Treatment of primary amides and thioamides with l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) gives nitriles.67 Reactions of thioamides with metal carboxylates in organic solvents enables the selective preparation of nitriles, imides or amides depending on the substitution pattern of the starting material (Scheme 33).68... 

Iodides should not be used alone since the normal gland will escape from iodide blockade in 2-8 weeks. Chronic use in pregnancy is not recommended because it crosses placenta and cause fetal goitre. Iodide treatment results in high intrathyroidal iodide content that can delay the onset of thioamide therapy or delay the use for radioactive iodine therapy for weeks if not months. Adverse effects include Hodism which is rare and reversible. The clinical symptoms are acneiform rash, sialadenitis, mucous membrane ulceration, conjuctivitis, rhinor-rhoea, metallic taste and rarely anaphylactoid reaction. 

Extensive studies have been performed on the metallation of thioamides, sulfones and sulfoxides. 

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... 

Analogously, thioacid fluorides can be used for the preparation of thioamides,114 and (difluoromethylcnc)amines can be aminated by metal amides.115116 Reaction of acid fluorides with imines leads to acyliminium compounds116 which can be further utilized, e g. in cycloaddition reactions.117 " 1 9... 

Thioacetamide, MeC(=S)NH2 (taa), is isoelectronic with thiourea which it resembles by acting as a unidentate S-donor ligand. Thiobenzamide, PhC(=S)NH2 (tba), behaves similarly. Both thioamides form stable complexes with (b) class and borderline metals. Thioacetamide forms the tetrahedral complexes [MX2(taa)2] (M = Fe, Co, Zn X = Cl, Br, I, NCS).47,153-157 The v(M—S) frequency is rather low, ranging from 255 to 230cm, .14s The Mossbauer spectra of FeX2(taa)2 PC = Cl, Br) are consistent with a tetrahedral configuration.158... 

A,TV-Dimethyl-A -phenylthiourea has been shown to coordinate to Rh111 as an N—S bidentate involving four-membered chelate ring formation.154 N-Substituted thioamides also may bond in this manner.155 156 l-Amidino-2-thioureas (44) may behave either as N—S or as N—N bidentates, with this donor choice being dependent mainly on pH and the nature of the metal ion.157 As N—S donors they are known to stabilize lower oxidation states.158 As part of a study on Mo—S-containing complexes as models for redox-active molybdoenzymes, Dilworth et al. have shown that some p-(substituted)phenylhydrazines may coordinate as N—S bidentates in three different ways to one metal atom.159 The three diazenido, diazene and hydrazonido forms vary in their degree of deprotonation and therefore their anionic nature. 

The use of soft metal ions to direct the course of reactions of sulfur compounds has been utilised in the preparation of nitriles from thioamides. The first step involves the alkylation of the thioamide to give the iminothioester, which is then converted to the nitrile on treatment with mercury(n) salts (Fig. 4-41). 

N-Benzyl thioamides can be readily lithiated twice with BuLi, to yield benzylic organolithium derivatives. As illustrated by the examples (Scheme 5.23), the regioselectivity of this metalation is quite different than that of comparable amides. 

Ligands (53) and (54) (L) form the complexes FeL X2 (X = Cl. Br. or I). for which spectral data suggest square-pyramidal structures.241 I.IO-Phenanthroline-2-carbo-thioamide and its -phenyl-derivative form both mono- and bis-ligand complexes with iron(u). which exhibit temperature-dependent spin-equilibria. In the monoligand complexes the metal atom is believed to be six-co-ordinate.242... 

One of the most valuable methods for the preparation of A2-thiazolines is of this class. The reaction of 2-haloalkylamines (334) with thioamides, metal thiocyanates or carbon disulfide give 2-alkyl- or -aryl- (335), 2-amino- (336), and 2-mercapto- (337) A2-thiazolines, respectively (Scheme 218) (17CB804). A method derived from the last procedure leads to a convenient synthesis of 2-phenyl-A2-thiazolines (340) under very mild conditions and consists of the condensation between a-aminothiols (338) and thiobenzoylmercaptoacetic acid (339 Scheme 219) (74TL1863) (this method could be better classified under Type E, Section 4.19.3.2.5). 

Allylic Thioamides and Thiocarbamates by Metal-Catalyzed 3-Aza-l-Thia-Cope... 

Studies of metal ion promotion of the reactions of thiocarboxylic acids and anhydrides, thioamides " and a variety of other sulfur compounds have been carried out. The interested reader should consult the comprehensive review by Satchell. ... 

Thioamides (86) are readily reduced to amines (93) (Scheme 50). The reduction generally occurs more easily than with amides and can be achieved with a variety of reducing agents, e.g. metal-acid, sodium amalgam, lithium aluminium hydride or Raney nickel. 

In substrates where a halogen is located ortho to nitrogen, ring closure to benzimidazoles can be achieved by palladium(0)-catalysed or copper-catalysed sequences similar formation of benzothiazoles from orf/20-haloarylamine-thioamides, does not require a metal catalyst. ... 

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