Isothioureas

Isothiourea Acrylaldehyde, hydrogen peroxide, nitric acid... 

Sulfur is reactive ia many forms. Mercaptides are alkylated to thioethers, and thioethers react further to give sulfonium salts, R2S" CH20S0 2-Suitable thiones also alkylate. Thioachdone (34) and thiourea (35) are examples the first gives the alkylmetcaptoacridine and the second gives the isothiourea. 

When an S-alkyl-A A -disubstituted isothiourea reacts with diketene in a boiling solvent, 2-imino-4-keto-3,4-dihydro-l,3-2i/-oxazine derivatives (45) are formed. Analogous compounds can be prepared from dialkylcarbodiimides and diketene. ... 

Amino-5-phenylthiomethoxyacetanilide in methanol solution is heated with N,N -bis-meth-oxycarbonyl-isothiourea-S-methyl ether with the addition of a catalytic amount of p-toluene-sulfonic acid for three hours with stirring under reflux. The mixture is then filtered hot and after cooling the febantel product crystallizes out. It is filtered off, rinsed with ether and dried under high vacuum to give the final product, melting at 129°C to 130°C. 

The reaction often works poorly unless an excess of the nucleophile is used because the product thiol can undergo a second S 2 reaction with alkyl halide to give a sulfide as a by-product. To circumvent this problem, thiourea, (NH2J2C=S, is often used as the nucleophile in the preparation of a thiol from an alkyl halide. The reaction occurs by displacement of the halide ion to yield an intermediate alkyl isothiourea salt, which is hydrolyzed by subsequent reaction with aqueous base. 

Cyclic isothioureas 168 were prepared simply by reaction of 1,3 diamines 167 and CS2 in EtOH under microwave irradiation at 140 °C with elimination of one molecule of H2S (Scheme 60). 

When cyanogen bromide was used instead of CS2, the corresponding guanidines 169 were obtained under analogous conditions [108]. Moreover, differently substituted guanidines 171 could be obtained in very good yields when the isothiourea 168 was alkylated with Mel under microwave irradiation and the product treated with a primary amine. An intramolecular version of this reaction was also described for the preparation of structure 172 present in several important natural products (Scheme 61). 

Figure 9.5 FITC reacts with amine-containing compounds to produce an isothiourea linkage.

Figure 9.14 TRITC reacts with amine-containing molecules to create an isothiourea linkage.

Figure 9.52 The isothiocyanate group of a TMT europium chelate can be used to label amine-containing proteins and other molecules to result in an isothiourea bond.

Figure 10.2 The isothiocyanate group of DTTA can react with amine-containing molecules to form isothiourea bonds.

Figure 20.16 FITC may be used to label amine groups on antibody molecules, forming isothiourea bonds.

Figure 23.6 The reaction of FITC with avidin produces a fluorescent probe via isothiourea bonds.

Figure 27.16 The homobifunctional crosslinker PDITC may be used to conjugate an enzyme to a 5 -diamine-modified oligonucleotide, creating isothiourea linkages.

Preparation of guanidine from thioureas has been carried out. There are many ways to synthesize guanidines. Converting thioures and isothiourea moieties into guanidine is one of the most popular methods. 

Iodoform Iodomethane Iron disulfide Isothiourea Ketones Lactonitrile Lead Acetone, lithium, mercury(II) oxide, mercury(I) chloride, silver nitrate Silver chlorite, sodium Water, powdered pyrites Acrylaldehyde, hydrogen peroxide, nitric acid Aldehydes, nitric acid, perchloric acid Oxidizing materials Ammonium nitrate, chlorine trifluoride, hydrogen peroxide, sodium azide and carbide, zirconium, oxidants... 

Fig. 10.7 Inhibitory potencies of N-alkyl-S-isothioureas towards three NOS isoforms. The inhibitory potencies are expressed as 1/Kj. N.T. means not tested.

Ruetten, H.,Thiemermann, C., Prevention of the expression of inducible nitric oxide synthase by aminoguanidine or aminoethyl-isothiourea in macrophages and in the rat, Biochem. Biophys. Res. Commun. 225 (1996), p. 525-530... 

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