Isothiouronium salt

The sulfur atom of the thiocarbonyl group is a good nucleophile, and reaction between benzyl bromide and l-(2-thiazolyl)thiourea yields the isothiouronium salt (496). The sulfur atom may also be engaged in a chelate, as exemplified by the Cu chelate of 2-thioureido-4-methylthiazole (491). These chelates with metal ions were thoroughly studied in acidic, neutral, and alkaline media for 66 metal ions in order to define their analytical use. They are formed in the molar ratio of 1 2 for metal II compounds (498). 

Thiourea derivative of Hercosett (isothiouronium salt) Scheme 10.63 Build-up good for dichlorotriazine dyes. Dyes of other types gave good results up to about 2% applied depths... 

The conversion of S-alkyl isothiouronium salts into thioethers is aided by the addition of a phase-transfer catalyst (4.1.4.E) [30]. Similarly, a,co-dihaloalkanes are converted in a one-pot reaction into bis-sulphides (> 90%) via the isothiouronium salts (Scheme 4.3) [31]. 

Isosteric equivalence, 77, 149 benzene and thiophene, 52 carbon and nitrogen, 399 Isothiouronium salts, as source of thiols, 44 Isothipendyl, 430 Isoxazole synthesis, 126 Isoxsuprine, 69 Ivanov reagent, 92, 93... 

Before the synthesis of the pseudoureas was published, Bernthsen and Klinger [6] reported a pseudothiourea synthesis involving the reaction of thioureas with alkyl halides. This reaction was briefly reviewed by Dains [16] and Stieglitz [49, 50], and it found many commercial applications [51-53]. The preparation of isothiouronium salts by the direct action of thiourea and halogen acids on alcohols (primary, secondary, and tertiary) was reported by Stevens [8] and further developed by Johnson and Sprague [54, 55] (Eq. 25). 

The addition of iodine and an a-unsubstituted pyrrole to the S- (2-pyrrolyl)isothiouronium salts yields an unsymmetrical dipyrrolyl sulfide (Scheme 41) (70AJC1199). 

Aminopropanols, when reacted with cyanogen bromide, also afford 2-amino-(or imino)-dihydro-1,3-oxazines (Scheme 90) (64ZOB3427), and related thiazines are formed when allylic isothiouronium salts (207) are cyclized with trifluoroacetic acid and stannic chloride. The necessary starting materials are synthesized from aldehydes or ketones by the action of vinylmagnesium chloride and subsequent treatment of the product allyl alcohols (206) first with hydrogen chloride and then with a thiourea (Scheme 91) (77JHC717). 

Some strategies used for the preparation of support-bound thiols are listed in Table 8.1. Oxidative thiolation of lithiated polystyrene has been used to prepare polymeric thiophenol (Entry 1, Table 8.1). Polystyrene functionalized with 2-mercaptoethyl groups has been prepared by radical addition of thioacetic acid to cross-linked vinyl-polystyrene followed by hydrolysis of the intermediate thiol ester (Entry 2, Table 8.1). A more controllable introduction of thiol groups, suitable also for the selective transformation of support-bound substrates, is based on nucleophilic substitution with thiourea or potassium thioacetate. The resulting isothiouronium salts and thiol acetates can be saponified, preferably under reductive conditions, to yield thiols (Table 8.1). Thiol acetates have been saponified on insoluble supports with mercaptoethanol [1], propylamine [2], lithium aluminum hydride [3], sodium or lithium borohydride, alcoholates, or hydrochloric acid (Table 8.1). 

Related intramolecular aminomercurations of cyclic guanidine derivatives have been studied in some detail,2 0 but are primarily useful for the synthesis of bicyclic heterocycles (equations 127 and 128). Cy-clizations of allylic isothiouronium salts have also been reported (equation 129).260b,260e... 

A. Drop 1 g of sodium into 10 ml of methanol in a small flask provided with a small water condenser heat the mixture until all the sodium has dissolved. Cool, and add 1 g of the ester and 0.5 ml of water. Frequently the sodium salt of the acid will be deposited either at once or after boiling for a few minutes. If this occurs, filter off the solid at once, wash it with a little methanol and convert it into the p-bromophenacyl ester, p-nitrobenzyl ester or S-benzyl isothiouronium salt (for experimental details, see Section 9.6.15, p. 1261). If no solid separates, continue the boiling for 30-60 minutes, boil off the alcohol, allow to cool, render the product just neutral to phenolphthalein with dilute sulphuric or hydrochloric acid, convert the sodium salt present in solution into a crystalline derivative (Section 9.6.15, p. 1261) and determine its melting point. 

Thiols may be prepared from the corresponding alkyl halide by reaction with thiourea followed by treatment of the isothiouronium salt with base. 

The conversion of halogenopyrazines into pyrazinethiones is usually done either with sodium hydrogen sulfide solution or by initial treatment with thiourea and subsequent hydrolysis of the intermediate isothiouronium salt (frequently unisolated). A third method, involving treatment of the halogeno substrate with thiosulfate, has proven promising in some heterocyclic series but not so far in the pyrazines 2-chloropyrazine did so give 2(1 //)-pyrazinethionc but only in 20% yield.1358... 

The analysis of isothiouronium salts, which are conveniently formed by reacting alkyl halides with thiourea, provide a way to study alkyl halides . The H NMR spectrum of s-butylisothiouronium chloride and bromide exhibited enantiomeric discrimination in the presence of [Eu(tfc)3(fod)] The enantiomeric purity of several alkyl methyl phenyl sulfonium ions (73) under conditions of slow inversion was determined using either [Eu(tfc)3(fod)] or [Eu(tfc)4] It was possible to study the inversion barrier by variable-temperature studies in the presence of the shift reagent. 

Cyanomethyl isothiouronium salt, as acyclic intermediate in reaction of thiourea with o-halonitrile, 297 Cyanothiazoles, from dehydration of amides, 530, 531... 

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