Alkylthio groups

Thione or alkylthio groups have also been involved in nucleophilic substitutions with hydrazine, or amines, and by desulfurization using Raney nickel or aluminum amalgam. 

The alkylthio group is replaceable by nucleophiles. The positions 7 and 4 react under mild conditions in that order the 2-alkylthio functions require more drastic treatment. Conversion of l-methyl-4-methylthiopteridin-2-one (157) into the 4-methylamino derivative (158) can be achieved by stirring with methylamine at room temperature (equation 48). The reactivity of an alkylthio group can often be further enhanced by oxidation to the corresponding sulfoxide and sulfone. Thus, reaction of l,3-dimethyl-7-methylthiolumazine (160) with m-chloroperbenzoic acid yields 7-methylsulfinyl- (161) and 7-methylsulfonyl-l,3-dimethyllumazine (162 equation 49) (82UP21601). 4-Amino-2-methylthio-7-... 

Alkylthio groups are oxidized to sulfoxides by H2O2 and readily by various oxidizing reagents to sulfones, e.g. in the imidazole series. The SR group is replaced by hydrogen with Raney nickel, and dealkylation is possible, e.g. of 3-alkylthio-l,2-dithiolyliums to give... 

Alkylthio groups are replaced in nucleophilic substitutions. Such reactions are easy in cationic derivatives for example, in the 1,2-dithiolylium series (539), substituted cydopen-tadienyl ion gives fulvene derivatives (540) (66AHC(7)39). 2-Methylthio groups in... 

Hydroxy and mercapto substituents at the 3- and 5-positions can also exist in tautomeric forms (see Section 4.01.5.2) and can be alkylated at either the substituent or the ring nitrogen atom. 3-Methoxy groups are not replaced by nucleophiles, but both 3- and 5-alkylthio groups react readily, as does 3-methoxy-l,2-benzisothiazole. Alkylthio compounds can be oxidized to sulfoxides and sulfones, and the latter readily undergo nucleophilic replacement. All the hydroxy compounds react with phosphorus pentachloride to give the chloro derivatives. 

Figure 8.P31 gives the pH-rate profile for hydrolysis of thioesters A-D and shows a dependence on the nature of the substituents in the alkylthio group. Propose a mechanism which would account for the pH-rate profile of each compound. 

Alkylthio groups replace the fluorine atoms of pentafluorobenzene derivatives tvith relative ease, but selectivity is difficult to eontrol [27] (equation 17). 

Arylthio but not 2-arylthio groups in quinazolines can be replaced with hydroxide ion or alkylamines. 4-Alkylthio-2-alkyl (or aryl)-quinazolines are readily alkoxylated (65°, 1 hr, 80-90% yield) at the 4-position. Arylthio and alkylthio groups have been found to be poorer leaving groups than chloro in several azines. 

These pyridazines are subject to direct deactivation of the leaving group. It would appear from the conditions used in its reactions with ammonia (115°) and methylamine (50°) that 4-chloro-2-ethylthiopyrimidine (225) is somewhat deactivated (indirect). In various aminations of pyrimidines, the effect of an alkylthio group seems to be very mildly deactivating, like that of methyl groups. However, these surmises from the conditions used are not as reliable as the direct qualitative comparison described above and the kinetic data. 

Substitution at the SiH moiety has been carried out with alkylthio groups, such as MeS and i-PrS. Tn s(alkylthio)silanes, (RSlsSiH, are radical-based reducing agents which can effect the reduction of bromides, iodides, xanthates, phenylselenides, and isocyanides in toluene, using AIBN as the initiator at 85... 

Similar to the above-mentioned alkoxy, alkylthio groups are also excellent peripheral substitutes. In 2003, Cook [58] determined the crystal structure of substituted Pc complexes PbnPc(HT)s (58) with eight hexylthio groups attached to the... 

Dimeric iminoboranes with two alkylthio groups, (XVI), result when an excess of alkylthiol is used. 

In comparison with the hydroboration and diborafion reactions, thioboration reactions are relatively limited. In 1993, Suzuki and co-workers reported the Pd(0)-catalyzed addition of 9-(alkylthio)-9-BBN (BBN = borabicyclo [3.3.1] nonane) derivatives to terminal alkynes to produce (alkylthio)boranes, which are known as versatile reagents to introduce alkylthio groups into organic molecules [21], Experimental results indicate that the thioboration reactions, specific to terminal alkynes, are preferentially catalyzed by Pd(0) complexes, e.g. Pd(PPh3)4, producing (thioboryl)alkene products, in which the Z-isomers are dominant. A mechanism proposed by Suzuki and co-workers for the reactions involves an oxidative addition of the B-S bond to the Pd(0) complex, the insertion of an alkyne into the Pd-B or Pd-S bond, and the reductive elimination of the (thioboryl)alkene product. 

For the thioboration reactions of alkynes preferentially catalyzed by Pd(0) instead of Pt(0), the reaction mechanism involves a metathesis-like process. The reason for not having an oxidative addition step can be related to the electron richness of the alkylthio group, which prevents the oxidative addition of thioborane to the metal center. Because of the preference for having a metathesis-like process, Pd becomes a better candidate due to its relative less electron richness in comparison to Pt. 

Systems with one amino group and one alkylthio group as donors, commonly known as ketene /V,S-aminals, are sterically rather similar to the 1-ethyliden-amino analogs like 9 and 10 (R = Me). However, comparison of the C=C barrier in 10, where R = R = R2 = Me (14.8 kcal/mol Table 3), with that of 31 (7.4 kcal/mol Table 6) shows that the MeS group must be much more... 

The sulphur atoms in dithiobiuret can be successively alkylated. It is therefore possible to synthesise 1,5-disubstituted biguanides carrying unlike substituents by the stepwise alkylation and replacement of the alkylthio-groups of dithiobimet, as has been described (295) for Paludrine (XXVIII, R = p-ClCeH4). 

The 3-alkylthio groups in 1,2,4-thiadiazoles are difficult to replace. Thus, 3-alkylthio-l,2,4-thia-diazoles resist the action of aniline at 100°C, ammonia at 120°C, molten urea and ammonium acetate however, hydrazine attacks 3-methylthio-l,2,4-thiadiazole (142) forming 3-amino-1,2,4-triazole (143) (Equation (21)) <65AHC(5)119>. In contrast to 3-alkylthiogroups, 5-sulfonyl groups in... 

Alkylthio com ounds 16 (R = Ph) are oxidized by 30% hydrogen peroxide,or by potassium permanganate to the corresponding A -imidaz-olin-5-one sulfuryl chloride transforms disulfide 19 into 24. Alkylthio groups are not displaced by hydrazine ... 

Other Reactions The alkylthio group attached to the 3 (or 6) position of the piperazinedione can be eliminated or oxidized to the sulfone (73CB165), or displaced by a peroxide group. Some of the transformations are shown in Scheme 47. 

---