Sulfur nucleophiles, reaction

Displacement Reactions with Carbon, O.xygen. and Sulfur Nucleophiles... 

Reaction with Sulfur Nucleophiles, Because sulfai is highly nucleophilic, reactions of aziridines with sulfur nucleophiles generally proceed rapidly (111) and with good yields. The reaction of hydrogen sulfide [7783-06S-J with ethyleneimine yields cysteamine [60-23-1] (2-mercaptoethylamine) or bis(2-aminoethyl)sulfide [871-76-1] (2,112) depending on the molar ratio of the reactants. The use of NaHS for the synthesis of cysteamine has also been described (113). 

Reaction with Selenium Nucleophiles. The reactions of selenium nucleophiles are similar to those of the sulfur nucleophiles selenophosphates can be aminoaLkylated (135). A dihydroselenazine has been obtained by reaction of diethyl ketone, elementary selenium, and ethyleneimine (136). 

Using sulfur trioxide plus chlorine, or sulfur dioxide plus chlorine, sulfur monochloride yields thionyl chloride [7719-09-7] SOCI2. Various nucleophilic reactions can displace the chlorine atoms of sulfur monochloride ... 

Nitrogen nucleophiles used to diplace the 3 -acetoxy group include substituted pyridines, quinolines, pyrimidines, triazoles, pyrazoles, azide, and even aniline and methylaniline if the pH is controlled at 7.5. Sulfur nucleophiles include aLkylthiols, thiosulfate, thio and dithio acids, carbamates and carbonates, thioureas, thioamides, and most importandy, from a biological viewpoint, heterocycHc thiols. The yields of the displacement reactions vary widely. Two general approaches for improving 3 -acetoxy displacement have been reported. One approach involves initial, or in situ conversion of the acetoxy moiety to a more facile leaving group. The other approach utilizes Lewis or Brmnsted acid activation (87). 

In forcing conditions with excess of reagents the 5,8-bis derivative was obtained in the above cases, with hydrazine and with sulfur nucleophiles. Other authors have also observed selective reactions in the pyrido[2,3-[Pg.242]

Many other examples are known of non-selective reactions of halo groups in pyridopyridazines with amines, alkoxides, sulfur nucleophiles such as hydrosulfide and thiolate ions, or thiourea, hydrazine(s), cyanide ion and dimethyl sulfoxide, or on catalytic reduction. 

The action of sulfur nucleophiles like sodium bisulfite and thiophenols causes even pteridines that are unreactive towards water or alcohols to undergo covalent addition reactions. Thus, pteridin-7-one smoothly adds the named S-nucleophiles in a 1 1 ratio to C-6 (65JCS6930). Similarly, pteridin-4-one (73) yields adducts (74) in a 2 1 ratio at C-6 and C-7 exclusively (equation 14), as do 4-aminopteridine and lumazine with sodium bisulfite. Xanthopterin forms a 7,8-adduct and 7,8-dihydropterin can easily be converted to sodium 5,6,7,8-tetrahydropterin-6-sulfonate (66JCS(C)285), which leads to pterin-6-sulfonic acid on oxidation (59HCA1854). 

Data on reactions of sulfur nucleophiles with azoles are sparse. Oxazoles are transformed in low yield into the corresponding thiazoles over alumina with HiS at 350 °C (74AHC( 17)99). Sulfur nucleophiles such as SH or RS add to 1,3-dithiolylium salts at the 2-position... 

Very little is known about nucleophilic attack on an unsubstituted carbon atom of pyrazoles and their aromatic derivatives (pyrazolones, pyrazolium ions). The SwAr reaction of halogenopyrazoles will be discussed in Section 4.04.2.3.7. Sulfur nucleophiles do not attack the ring carbon atoms of pyrazolium salts but instead the substituent carbon linked to nitrogen with concomitant dequaternization (Section 4.04.2.3.lO(ii)). The ring opening of pyrazolium salts by hydroxide ion occurs only if carbon C-3 is unsubstituted the exact mechanism is unknown and perhaps involves an initial attack of OH on C-3. 

When 6-diazopenicillanates are irradiated in the presence of sulfur nucleophiles, predominantly 6/3-substitution products are obtained (77JOC2224). When BFs-EtiO is used to catalyze the reaction with nucleophiles, however, the products are primarily the 6a-isomers (78TL995). The use of rhodium or copper catalysis led primarily to ring-opened thiazepine products, presumably by way of the intermediate (56 Scheme 39) (80CC798). 

The biological activity of calicheamicin 4 (simplified structure) is based on the ability to damage DNA. At the reaction site, initially the distance between the triple bonds is diminished by an addition reaction of a sulfur nucleophile to the enone carbon-carbon double bond, whereupon the Bergman cyclization takes place leading to the benzenoid diradical 5, which is capable of cleaving double-stranded DNA." ... 

With Sulfur Nucleophiles N-Carboxy-protected aziridine-2-carboxylates react with thiols to give P-mercapto-ot-amino acid derivatives. The reaction is usually catalyzed by BF3 and the yields range from fair to excellent [15, 16, 108-111]. With N-unprotected 3-substituted aziridine-2-carboxylates, the ring-opening with thiols usually takes place with anti stereoselectivity, especially in the case of the C-3 aliphatic substituted substrates. In cases in which C-3 is aromatic, however, the stereoselectivity has been found to be a function of the substitution pattern on the aromatic ring 3-p-methoxy ph eri yl-su bs li In led aziridines 143a (Scheme 3.51) and... 

The reactions in this chapter are classified according to the attacking atom of the nucleophile in the order O, S, N, halogen, H, C. For a given nucleophile, reactions are classified by the substrate and leaving group, with alkyl substrates usually considered before acyl ones. Nucleophilic substitutions at a sulfur atom are treated at the end. 

Solutions containing the nucleophiles and/or HS dissolve elemental sulfur by reactions according to the following equations (nucleophilic degradation) ... 

B. Reactions with Oxygen and Sulfur Nucleophiles 1. Hydrolysis... 

The toxicity of 3-methylindole has been attributed to methyleneindolenine trapping of nitrogen and sulfur nucleophiles.57 60-62 Likewise, the ene-imine shown in Scheme 7.9 readily reacted with hydroquinone nucleophiles, resulting in head-to-tail products. Shown in Fig. 7.6 is the 13C-NMR spectrum of a 13C-labeled ene-imine generated by reductive activation. The presence of the methylene center of the ene-imine is apparent at 98 ppm, along with starting material at 58 ppm and an internal redox reaction product at 18 ppm. Thus, the reactive ene-imine actually builds up in solution and can be used as a synthetic reagent. 

Modifications of the substituent at Cg are conveniently accomplished using sulfur nucleophiles to displace the acetoxy moiety which is present in the fermentation products. Cefamandole (26) is such an agent. Reaction of 7-aminocephalosporanic acid with thiotetrazole 24 gave displacement product 25,... 

Plummer invented a process for the biodesulfurization of hydrocarbons [157], in which organic sulfur compounds contained in liquid hydrocarbons are converted to elemental sulfur. The reaction is carried out in the presence of a biocatalyst and hydrogen, by dissolving completely the liquid hydrocarbons in an organic solvent, such as a nucleophilic and/or electrophilic solvent(s). The nucleophilic solvent should have a pKa greater than 2, and the electrophilic solvent more negative than -2. Recommended nucleophilic solvents include -butylamine, diethylamine, butanediamine, ethylenimine, toluene, pyridine, aniline, and acetophenone. The electrophilic solvents could be methylethylketone, pyrrole, or benzaldehyde. 

Compound 874, as a representative of derivatives with an electron-withdrawing substituent at C-[1 of the vinyl group, is easily prepared by elimination of one benzotriazole from 2,2-/fo(benzotriazol-l-yl)ethyl methyl ketone 873. The stereoselective elimination catalyzed by NaOH gives exclusively the (E) isomer of derivative 874. Addition of nucleophiles to the double bond of vinyl ketone 874 followed by elimination of benzotriazole leads to a,P unsaturated ketones 875. Amines used as nucleophiles do not need any catalysis, but reactions with carbon and sulfur nucleophiles require addition of a base. The total effect is nucleophilic substitution of the benzotriazolyl group at the i-carbon of orji-iinsaturatcd ketone (Scheme 142) <1996SC3773>. 

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