Thioamides reversible

A limited series of amide replacements have been examined including thioamides (219) [163], reverse amides (220) [164], heterocycles (221) [164], ethers (222) [165], carbamates (223), (224) [165], ureas (225) [165] and ketones (226) [166] (see Table 6.19). In general, replacement of the amide results in a loss of binding affinity compared to AEA. In some cases, replacement of the amide results in increased stability with regard to hydrolysis by FAAH [164, 165]. 

Very interesting transformations were observed with dimedone 103b and arylidenethioacetamides 110 (88ZOR460). When the reaction was carried out at ambient temperature, Michael adducts 111 were formed. Compounds 111 can be converted on heating into hydrogenated pyridi-nethiones 112 (in ethanol) or to 2-aminopyran-3-thioamides 113 (in benzene). The formation of the latter ones was found to be reversible. Thus, 113 convert into 112 on heating in ethanol, and yield 2-amino-3-cyanopyr-ans 104 when heated with MN in benzene (Scheme 39). 

Subsequent studies on thioamide pyrans with application of the competitive reactions method contribute to our understanding of the mechanisms of heterocyclizations with cyanothioacetamide 114 (89ZOR1331). 2,6-Diaminothiopyrans 115, on heating in benzene, open their thiopyran ring reversibly forming intermediate 116, which can eliminate cyanothioacetamide 114 or malononitrile 27a with formation of UNs 30 or 117, respectively. The direction of the subsequent reaction with... 

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. 

Other results with unsaturated thioamides include a nice reversal [233] of the endo selectivity in favour of the exo adduct by adjustment (Table 4, entry 9) of the thermal conditions (-30 °C vs 80 °C). Unexpected dimerisa-tions of enethioamides (entries 10 and 11) were observed [234, 235]. Thiocarbonyl chemistry has already been used in fullerene chemistry Acyl thio-acrylamides react [236] with [60]fullerene to yield hetero-Diels-Adler products (Table 4, entry 12). 

It is interesting to note that, due to the reversible character of the cycloaddition, isomerization favoring the product which is thermodynamically more stable may occur and an appropriate side-chain substituent may participate. For example, the thiazolo [4,5-b] quinoxalines 55, formed in the reaction of quinoxalinium salts with thioamides under kinetically controlled conditions, are able to undergo two different isomerizations (Scheme 45). When compound 55 contains an aryl group at C-2 (R2 = aryl) and this compound is heated in an ethanolic solution, the thiazoloquinoxaline 57 is formed. In the case of R2 = CH3, the methyl group participates in the isomerization process, yielding pyrrolo [2,3-b]quinoxalin-2-thione 58 (Scheme 45) (85KGS396). 

Thioamides arise from hydrogen sulphide addition to ynamines and it is clear that the reverse process would be much more interesting owing to the easy availability of thioamides. 

Numerous photorearrangements and related transformations have been described in the period covered by this Report. Reversible interconversion of two rotational isomers of methyl thionitrite has been detected in an argon matrix at 12K, and the cis-form of iV-methylthioacetamide was generated photo-chemically, at low temperatures in inert-gas matrices, from the much more stable trans-thioamide. Triplet-sensitized Z,E-photoisomerizations of /3-styryl methyl sulphone and 3-(4-cyanostyryl) methyl sulphone have been examined, and various (Z)-P-styryl methyl sulphones (200) have been prepared by irradiation of the corresponding E-isomers (201). Z,E-Photoisomerization of 2-naphthylvinylenethioamide has been examined in... 

The most widely used synthesis of thioamides (86) involves thionation of the corresponding amides by heating with phosphorus pentasulfide in xylene (Hofmann, 1878) (Scheme 45). In the preparation of primary thioamides (87) by this procedure, care must be taken to avoid the decomposition of the product into the nitrile and hydrogen sulfide—the reverse of the earliest preparative route to thioamides (Gay Lussac, 1815) (Scheme 46). 

A special feature of secondary and tertiary thioamides is that they provide selectively only the Z-configurated enolates 2 (the previously reported E assignment of enolates of thioamides576- 578 should be corrected579, s8°) irrespective of reaction conditions, i.e., kinetic or thermodynamic variation of the temperatures from —78 to +65°C, order of addition (addition of a base to the thioamide or the reverse), type of bases, type of solvents580-582. 

Direct excitation (A > 240 nm) of thiiran is followed by intersystem crossing to the lowest excited state. This species is capable of undergoing reversible addition to alkenes, thereby inducing Z, -isomerization inefficient irreversible addition has also been observed. The carbonyl sulphide, Ph2=6—S, has been proposed as a possible intermediate in the photodecomposition of diphenyloxathiiran, which is itself formed by irradiation of thiobenzophenone -oxide at 77 An unexpected photoinduced fragmentation and solvent incorporation was observed on irradiation of A-(6,7-dimethoxy-2-methyl-3-quinazolinio)ethoxythio-formamidate (289) in ethanol to give photoproducts (290)—(292). The photoreactions of some A-isoquinolinio(thioamidates) have been compared with those... 

Thioamides exhibit a nucleophilic character that allows a reversed order of the two deprotonation and alkylation steps (Scheme 9.9). Addition of allyl halides to thioamides provided S-allyl thioimidate salts. Subsequent deprotonation by a variety of bases (notably t-BuOK or simple tertiary amines) led to transient keteneami-nothiocetals, which underwent in situ rearrangement to the awaited y-unsaturated thioamides [51-54]. 

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