Sulfuric acid Sulfur nucleophiles

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). 

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). 

Thiirane 1-oxide undergoes acid-catalyzed ring opening by ethanethiol to give ethyl 2-ethylthioethyl disulfide. Treatment of thiirane 1,1-dioxide with thiolate anions, sodium sulfide or thiourea gives /3-mercaptosulfinic acid derivatives (75S55). Thiiranium ions are attacked at carbon by most sulfur nucleophiles (79ACR282), but see Section 5.06.3.4.3 for exceptions. 

Experimental observations indicate that acid strength significantly affects the reaction rate. For example, sulfuric acid promotes nucleophilic substitution of alcohols by bromide, but acetic acid does not. How would a change in acid strength affect your calculated reaction energies ... 

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... 

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,... 

Much attention has been devoted to the acid- and nucleophile-catalyzed racemization of thiosulfinates. As a result of the extensive studies by Kice and his co-workers (112) and by Fava (281), it is clear now that the easy racemization of thiosulfinates caused by acids and bases (e.g., pyridine) is related to the scission of the sulfur-sulfur bond and the formation of sulfenic acid or its anion as an achiral intermediate. As expected, introduction of steric hindrance... 

The benzo[fc]thiophene sulfoxides, such as (142), generated from the parent benzo-thiophene on the H202-TFA-mediated oxidation, undergoes Michael-type nucleophilic addition of oxygen and sulfur nucleophiles in acidic media to produce 3-substituted benzo[fc]thiophenes (143). This method provides an easy two-step functionalization of 2-acylbenzo[fc]thiophene derivatives. ... 

Reactions with carbon, nitrogen and sulfur nucleophiles 214 Direct observation of nitrenium ions acid-base chemistry and singlet-triplet chemistry 227 Heteroarylnitrenium ions 238 Calculations 244... 

Oxidation of cyclo(Pro-Pro) with lead tetraacetate afforded the trans-diacetoxy compound (121) in 32% yield. These acetoxy groups could be displaced by sulfur nucleophiles. Thus, with ethanethiol and ZnCl2, it gave the c -3,6-bis(ethylthio) derivative (120) solvolysis by dilute aqueous acid followed by treatment with H2S/ZnCl2 gave the m-dithiol (73CB396), which can be directly oxidized to the episulfide. 

Other sulfur nucleophiles found to transform epoxides into olelins were thiourea, thioacetamide, thiobenzamide, xanthamide, and tbiu-barbituxic acid. Epoxides reduced in this manner included atillirnn... 

In the first step of the conversion catalyzed by pyruvate decarboxylase, a carbon atom from thiamine pyrophosphate adds to the carbonyl carbon of pyruvate. Decarboxylation produces the key reactive intermediate, hydroxyethyl thiamine pyrophosphate (HETPP). As shown in figure 13.5, the ionized ylid form of HETPP is resonance-stabilized by the existence of a form without charge separation. The next enzyme, dihydrolipoyltransacetylase, catalyzes the transfer of the two-carbon moiety to lipoic acid. A nucleophilic attack by HETPP on the sulfur atom attached to carbon 8 of oxidized lipoic acid displaces the electrons of the disulfide bond to the sulfur atom attached to carbon 6. The sulfur then picks up a proton from the environment as shown in figure 13.5. This simple displacement reaction is also an oxidation-reduction reaction, in which the attacking carbon atom is oxidized from the aldehyde level in HETPP to the carboxyl level in the lipoic acid derivative. The oxidized (disulfide) form of lipoic acid is converted to the reduced (mer-capto) form. The fact that the two-carbon moiety has become an acyl group is shown more clearly after dissocia-... 

Sulfur nucleophiles have not been widely used in ir-allylpalladium chemistry, principally due to their ability to interfere with the catalyst by coordination. This is a less serious concern for sulfinic acid and sulfinate salts than with sulfides, and as a result, several reports have appeared using RSO2H and RSO2-.211-219 Alkenes allylically functionalized with a leaving group, dienes214 and vinyl nitro con-pounds218 219 have all served as precursors for the required ir-allyl species in these reactions (equations 60 and 61). 

Both XLII and XLI 11 are p-hydroxybenzyl aryl ethers so is the polymerization product (XLIV) 21) of the quinonemethide (XXI) mentioned above. Such benzyl aryl ether bonds are not very rare in lignin and are easily attacked by acids or nucleophilic reagents containing sulfur. 

During interaction of the diazonium chloride, and the o-ethyl dithiocarbonate ( xan-thate ) solutions, care must be taken to ensure that the intermediate diazonium dithiocarbonate decomposes to 2-thiocresol as fast as it is formed [1]. This can be assured by presence of a trace of nickel in the solution to effect immediate catalytic decomposition. When the 2 solutions were mixed cold and then heated to effect decomposition, a violent explosion occurred [2]. Caution The experiments claimed to show catalysis by nickel appear to have been performed on diazotised anthranilic acid which is the only benzenediazonium system never known to give explosive intermediates with sulfur nucleophiles [3]. 

Whereas the triester reacts with a range of sulfur nucleophiles, the corresponding diester does not react with thionucleophiles under ambient conditions (Eq. 8), suggesting that the precursor, which is a diester, must be activated for conversion to MPT. This activation could involve the C3 hydroxyl group of the precursor, which is missing in the model, or Lewis acidic groups present in molybdopterin synthase. 

Among the various sulfur nucleophiles which are encountered in natural waters, most are Bronsted acids or bases, i.e., they can accept or lose a proton. The sulfhydryl functional group is a monoprotic Bronsted acid, while H2S and H2SO3 are diprotic Bronsted acids. The rate of displacement of halide from a given substrate in aqueous solution containing a nucleophilic Bronsted acid depends upon the relative concentrations among the different protonated forms of the acid (of which there are two for a monoprotic acid, three for a diprotic acid), as well as the respective rates of reaction of the different protonated... 

Table I. Pseudo first-order rate constants for Michael addition of sulfur Nucleophiles (5 mM) to aciylic acid and acrylonitrile in seawater medium (salinity 35 and reaction pH 8.3 0.2)...

The Michael addition mechanism, whereby sulfur nucleophiles react with organic molecules containing activated unsaturated bonds, is probably a major pathway for organosulfur formation in marine sediments. In reducing sediments, where environmental factors can result in incomplete oxidation of sulfide (e.g. intertidal sediments), bisulfide (HS ) as well as polysulfide ions (S 2 ) are probably the major sulnir nucleophiles. Kinetic studies of reactions of these nucleophiles with simple molecules containing activated unsaturated bonds (acrylic acid, acrylonitrile) indicate that polysulfide ions are more reactive than bisulfide. These results are in agreement with some previous studies (30) as well as frontier molecular orbital considerations. Studies on pH variation indicate that the speciation of reactants influences reaction rates. In seawater medium, which resembles pore water constitution, acrylic acid reacts with HS at a lower rate relative to acrylonitrile because of the reduced electrophilicity of the acrylate ion at seawater pH. 

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