Chloromethyl with thiourea

Some 2-(chloromethyl) derivatives of kojic acid form quaternary salts with tertiary aliphatic amines80-86 and with thiourea.83 Quaternary pyridin-ium salts (LXII) were obtained by Looker and Okamoto81 from LX and LXI in dry pyridine. Water-insoluble derivatives of kojic acid could be rendered water-soluble by these quaternizations. 

The reaction of chloromethyl aryl ethers with nucleophilic reagents has been described by Barber et al Thus, by reaction with thiourea, potassium thiocyanate, or sodium cyanide, there arc obtained aryloxyalkylisothiouronium salts, aryloxyalkyl thiocyanates, and aryloxyalkylacetonitriles, respectively. The reaction of chloromethyl aryl ethers with butyllithium leads to an aryloxycarbene which on reaction with olefins gives aryloxy-cyclopropanes. The ethers react with triphenylphosphine and a base to give phcnoxymethylene ylides which arc useful in con-... 

Alternatively, we prefer to prepare polymers containing the thiol functionally (15,25) by reacting chloromethylated resin with thiourea (25). The reaction of y-CI Cl with thiourea gives a supported isothiouromium chloride. The latter solid is reacted with hydroxyl groups to produce a thiol-containing polymer. 

Thermal degradation of chloromethyl-1,3,5-trioxanes 127 (Scheme 29) in the presence of catalytic amounts of montmorillonite clay generated a-chloroaldehydes which could be treated in situ with thiourea to afford 2-aminothi-azoles 128, or with ethylene glycol to yield the corresponding 2-chloromethyl-l,3-dioxolanes 129 <1994CL2039>. The acidic sites in montmorillonite clays may act as acid catalysts, though the details of the mechanism were not provided. 

The Nierenstein reaction has been applied in the synthesis of 4-(P-chloromethyl)-2-aminothiazole by Carroll and Smith in 1933. The a, P-dichloromethylethyl ketone 22 was prepared via the Nierenstein reaction of the corresponding chloropropionyl chloride 21. Reaction with thiourea yielded the cyclized product 23. The authors additionally prepared the same ketone using an alternative approach involving the addition of ethylene to chloroacetyl chloride with aluminium chloride as a condensing agent. 

Preparative Methods Me3SiCH2S02Cl is (1) formed in 58% isolated yield via reaction of (chloromethyl)trimethylsilane with thiourea in ethanol followed by concentration and chlorination in water, extraction, and distillation . (2) formed in 63% isolated yield by peracetic acid oxidation of (trimethylsi-lyl)methanethiol followed by treatment with phosphorus(V) chloride (3) formed in 84% yield through reaction of Me3-SiCH2Cl with magnesium followed by sequential reaction of the Grignard reagent with sulfur dioxide followed by chlorine and (4) formed in 53% yield through reaction of tetramethylsilane with sulfuryl chloride. ... 

Poly(vinylbenzyl mercaptan) has been described by several authors. The synthesis always follows the same path chloromethylation of polystyrene followed by reaction with thiourea and hydrolysis of the isothiuronium salt 1,53,55,63-65). The redox properties of a polymer obtained from chloromethylated styrene-divinylbenzene copolymers have been evaluated (3). Redox capacities givrai for mercaptyl resins were determined to be 2. W>-5.27 milliequivalents of iodine reduced per gram of (dry) resin in aqueous potassium iodide. The oxidized form of the resin could be easily reduced with 10% aqueous bisulfite fmr a complete redox cycle. Recently polyvinylbenzyl mercaptan resins were prepared directly by treating chloromethylat polystyrene with KSH in dimethyl formamide (66). 

The use of thioureas in the preparation of thietans has been reviewed. Thietans have been prepared by treatment of 1,3-dihalides with thiourea and base, or with hydrogen sulphide-aluminium chloride by treatment of disulphonate esters of 1,3-glycols with sodium sulphide and by treatment of 2-chloromethyl-3-phenyloxiran with sodium hydrosulphide. aa-Diphenyl-]8-propiothiolactone was obtained by cyclization of the bromomethyl ester of diphenylthiolacetic acid. ... 

The N,N-disubstituted thioureas (135) condensed with a-halocarbonyl compounds give 2-disubstituted aminothiazoies (136) but in lower yields (30 to 70%) (Scheme 65 and Table 11-20) (518). For example, N,N-dialkylthioureas condensed with chloroacetaldehyde or dibromoether lead to Ar,At-dialkyl-2-aminothiazoles in 136, Ri=R2 = methyl (342, 404, 436, 637), ethyl (343, 436), n-propyl (518), n-butyl (518), ally] (518), and benzyl (26, 29). When chloroacetone and dichloroacetone are the carbonyl reactants the corresponding 4-methyl (518) and 4-chloromethyl derivatives (572) were obtained. 

Another entry into the anti ulcer sweepstakes is etinfidine (50). It is synthesized by displacement of halide from 4-chloromethyl-5-methylimidazole (4 ) with substituted thiol The latter is itself made from thiourea analogue by an addition-elimination reaction with cysteamine 52. °... 

The 111.6 kg resultant precipitates of N"-[4-(chloromethyl)-4,5-dihydro-4-hydroxy-2-thiazolyl]-guanidine hydrochloride are collected, and washed with 50 L of acetone. In 500 ml of water are dissolved 111.6 kg of N"-[4-(chloromethyl)-4,5-dihydro-4-hydroxy-2-thiazolyl]-guanidine hydrochloride and 32.9 kg of thiourea. The solution is stirred for one hour at 50°C. N -[4-[[(Aminoiminomethyl)thio]methyl]-2-thiazolyl]-guanidine dihydrochloride is formed in the reaction mixture, and this reaction mixture containing this compound is directly used for the next process without isolation of the formed compound. 

Chloromethylated polystyrene-DVB (2.5 g) (1.23 meq/g) and 2 g of thiourea were refluxed with a mixture of THF ethanol (2 1) for 48 hr. The resin was then washed with water, followed by THF and benzene, to remove all excess soluble reagents and byproducts. The resin was then suspended in a 50 ml of benzene and 0.1 g of tetraheptylammonium chloride and 2 g of sodium hydroxyde in 10 ml of deionized and degassed water were added. The three-phase mixture was refluxed under N2 for 48 hr. After filtration, washings with THF, water, THF 6N HC1 (3 1), water, THF, acetone, methylene chloride, and finally methanol were carried out. The resulting resin was dried under vacuum. 

Vinylbenzyl chloride (VBC Dow Chemical) represents a functional monomer with electrophilic sites which can be post-reacted after polymerization with nucleophiles such as amines, thiols, thioethers and thiourea [28]. The chloromethyl group may also be reacted before polymerization to form a new monomer, which can itself then be polymerized. VBC is typically copolymerized with monomers such as butadiene, styrene, acrylic or methacrylic acid, acrylonitrile, acrylamide and a variety of acrylate and methacrylate monomers [29] or it can be homopoly-merized to form functionalized particles [30]. Typical properties of vinylbenzyl chloride monomers include a homopolymer Tg of 82 °C, a boiling point of 229 °C (at 1 atm), a water solubility of 0.073 g dm , and Q and e values of 1.06 and —0.45, respectively. 

Related reactions of thiolate anions with ort/zo-chloromethyl-phenyl(diphenyl)phosphine have provided a range of ort/ o-alkyl and aryl-thiomethylphenyl(diphenyl)phosphines. " The reactions of 2-amino-alkylphosphines with isocyanates and isothiocyanates have provided routes to new chiral phosphinoalkyl-urea and -thiourea ligands. Similarly, treatment of hydroxy- or amino-functional arylphosphines with isocyanides in the presence of a cyclooctadienepalladium(II) complex results in the formation of bidentate arylphosphino-carbene palladium complexes. New chiral phosphinoarylphosphoramidite ligands, e.g.,... 

Besides dihomooxacalix[4]arenes bearing carbonyl groups at their lower rims (28-32) reported before 2000 [26, 27], 9a has been used to prepare the inherently chiral triethyl ester 33 [28] and the tetra(2-pyridyl) 34 [29] derivatives. Depending on the reaction conditions (use of 80 % NaH instead of 95 % NaH and less reaction time), partial 0-alkylation of 9a with 2-(chloromethyl)pyridine hydrochloride was also achieved by Marcos and coworkers [29]. Five of the eight possible partially alkylated compounds 35 (mono-substituted 35b and di-substituted 35c-f) were obtained in the cone conformation. Recently, the same group reported the preparation of a series of bidentate urea (36-41) and thiourea (42) derivatives in a four step synthesis from the parent compound 9a [30, 31]. Their structure determination in solution by NMR spectroscopy (and in the solid state for compounds 38 and 41 by single crystal X-ray crystallography) indicated the cone conformation for all the compounds. The cone tetraethyl ester 43 was also described [11]. 

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