Nitriles from thioamides

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). 

A reagent prepared in THF from P4Sio/Na2S (1 1) converts nitriles into thioamides at ambient temperature [165]. 

Another economic problem of glucosinolates is the burnt flavor of milk from cattle who have eaten the cruciferous weed Coronopus didy-mus. This is caused by benzyl methyl sulfide or benzyl mercaptan formed in the cow from the glucotropaeolin of the weed (110), presumably via the thiocyanate. Finally, ferrous ion catalyzes the nonenzymatic breakdown (H) of glucosinolates to nitriles and thioamides (111)-... 

Nitriles from carboxylic acid thioamides CSNHg CN... 

The reaction of dichlorocarbene with primary amides, amidines, thioamides, and aldoximes all yield the corresponding nitriles. N,N-Disubstituted ureas likewise yield the corresponding N,N-disubstituted amine nitrile. This reaction amounts to a dehydration in the case of primary amides, aldoximes, and N,N-disubstituted ureas the elements of hydrogen sulfide are lost from thioamides, and HCN from amidines. 

Nitriles from carboxylic acid amides and thioamides... 

Chloroform-sodium hydroxide benzyltriethylammonium chloride Nitriles from carboxylic acid thioamides s. 29, 456... 

Thiolactams react with Fe(CO)s in THF to give cyclic Schiff bases (H. Alper, unpublished). Nitriles are obtained from thioamides or amides (Alper and Edward, 1968). 

With the intention of preparing nitriles from primary thioamides, Fujita and his co-workers allowed several of the latter type of compounds to react with NN -dialkyl phenylpropiolamidines, and they obtained, besides the... 

Several examples exist for the conversion of 5-aminothiazoles into the corresponding thiazolopyrimidines. Shaw and Butler report the formation of aminothiazole thiocarboxyamide 27 from the thioamide 26 and carbon disulphide using Cook and Heilbron s procedure. Methylation of 27 gave carboxythioimidate 28 which then reacted with sodium hydroxide to give amino-nitrile 29, and with formic acid and acetic anhydride to give the thiazolopyrimidine 30. 

Simple isothiazole-4-carboxylic acids have been made from the corresponding nitriles, which are available in turn from the halogeno derivatives, or directly by the olefin route.5-Aminoiso-thiazole-4-esters and -nitriles are readily obtained by the thioamide route. The 4-acids behave normally and form acid chlorides, esters, amides, and hydrazides. In contrast to the 5-series... 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

In thioamidation the nitrile groups of PAN have a much higher reactivity than those of the corresponding model compounds. This fact is explained by the specific character of the polymeric nature of PAN and by the mutual influence of adjacent groups. As it is seen from the data presented in Fig. 4, the highest reaction rate and conversion level, as compared with low-molecular nitriles, is observed in the thioamidation of PAN. 

The oxidation of thioamides 63 with a wide variety of oxidizing agents is a well-employed method for the synthesis of 3,5-disubstituted-l,2,4-thiadiazoles 64 <1982AHC285>. However, this method is limited mainly to arylthioamides. The most common oxidizing agents tend to be halogens, hydrogen peroxide, dimethyl sulfoxide (DMSO), and nitrous acid. Yields from these reactions are variable and depend on the thioamide, oxidant, and conditions used (Equation 19). By-products such as nitriles and isothiocyanates are usually formed. 

Treatment of nitriles with gaseous hydrogen sulfide in the presence of anion exchange resin (Dowex 1X8, SH from) at room temperature affords the corresponding primary thioamides.27 Treatment of nitriles with 70% sodium hydrosulfide hydrate and magnesium chloride hexahydrate in DMF or methanol affords primary thioamides in high yields.28 Primary thioamides have been... 

Sandmeyer s valuable isatin synthesis involves the removal of sulphur from diphenylthiourea (I) (p. 169) with basic lead carbonate. Hydrogen cyanide is combined with the reactive diphenylcarbodiimide (II) so obtained, and the nitrile (III) produced is converted by means of hydrogen sulphide into tbe thioamide (IV). Concentrated sulphuric acid brings about ring closure and the product is the a-anil of isatin (V). Then, by hydrolysis with dilute sulphuric acid, aniline is removed ... 

Selected examples of the synthesis of thioamides from nitriles ... 

Secondary amides have the advantage over tertiary amides that they are relatively easy to remove. It is quite difficult to stop the addition products from aldehydes, ketones, amides, epoxides and nitriles cyclizing directly to give a variety of lactone derivatives (by attack of OH on the secondary amide) or lactam derivatives (by attack of the secondary amide on the new electrophihc centre). Thioamides behave similarly . 

More decisive evidence is provided by the interconvertibility of N-aryl-JV-arylamidinothioureas (28) and Hector s bases by oxidation-reduction.63, B4,67b The former compounds are accessible (as salts) (i) by the condensation of arylthioureas (24) with arylcyanamides (23),63 (ii) by the extrusion of sulfur from the recently described40,41 s-diaryldithioformamidine hydrobromidesB4a (22), (tit) by the oxidation of arylthioureas (24) with 0.5 moles of hydrogen peroxide in the presence of mineral acids,B4a and (iv) by the mild reduction of Hector s bases by hydrogen sulfide in acid media.B4a The first of these four reactions limitB the structure of the products to the three alternatives 25, 28, and 30. Of these, 25 is excluded by the non-identity of the product with authentic67 N-phenyl-i -phenylamidinothiourea (25 R = Ph). The monosulfide structure (30) is not reconciled as readily with the observedB4a hydrolytic fission of the products into diaryl-guanidines (29) and thiocyanic acid as is structure 28. Indeed, as in the case of thioamides and nitriles (see Section II, C, 1), the present condensation may involve the primary formation of an intermediate diimido-monosulfide (30) and its isomerization to 28. 

Other routes to 1,3-oxazines employ condensation reactions between /3-chloroketones and nitriles or between chloroalkyl amides and alkynes <69LA(723)ill) (Scheme 62). Thiazines are available through similar condensations between thioamides, aldehydes and acetylenes (74G849), and AH- 1,3-benzoxazines may be prepared from 2-hydroxybenzyl alcohols and nitriles in the presence of either perchloric or sulfuric acids (Schemes 63 and 64) (68MIP22700). 

Table 13.21) or from amides by treatment with Lawesson s reagent. Thioamides can also be prepared on cross-linked polystyrene by the addition of H2S to nitriles (Entry 5, Table 13.21), by thiocarbamoylation of resin-bound organolithium compounds (Entry 6), or by the acylation of amines with reactive thio acid derivatives (Entry 7, Table 13.21). 

Carbanions from hydrocarbons, nitriles, ketones, esters, TV./V-dialkyl acetamides and thioamides, and mono and dianions from (3-dicarbonyl compounds are some of the most common nucleophiles through which a new C-C bond can be formed. This C-C bond formation is also achieved by reaction with aromatic alkoxides. Among the nitrogen nucleophiles known to react are amide ions to form anilines however, the anions from aromatic amines, pyrroles, diazoles and triazoles, react with aromatic substrates to afford C-arylation. 

Hydrogen and carbon monoxide were lost from the latter to form the Fe" complexes (XCIV x=0). The appearance of an absorption assigned to indicated the formation of an unstable Fe—H intermediate. Carbonyla-tion of (XCIV X = 0) gave the red cis complex (XCIV x = 2) 344). Noncoordinate irnine groups were postulated for the product (XCV R =/)-MeOC6H4) from the reaction of Fe2(CO)9 and p-methoxythio-benzamide, which contrasts with the normal reaction of iron carbonyls with primary amides and thioamides, w hich proceed to nitriles 16). 

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