Nucleophile carbon-based

Nucleophilic reactions at the carbon atoms of 1,3,4-thiadiazoles occur readily owing to the electron-deficient nature of this ring. Halo-substituted thiadiazoles are therefore highly activated and react with a wide range of nucleophiles. Carbon-based nucleophiles such as malonates have been used in the synthesis of 2-substituted thiadiazoles. When chlorothiadiazole 52 was treated with ethyl acetate in the presence of NaHMDS, the 2-phenyl-1,3,4-thiadiazol-5-ylacetic ester 53 was obtained (Equation 6) <20060L1447>. 

The preparation and properties of the dithiocarboxylic acids and their metal complexes have been reviewed several times.38"11 The formation of C—C bonds in the direct reaction of CS2 requires sufficiently nucleophilic carbon bases, directly or potentially accessible in the form of ambifunction-al phenoxides, organometalfic compounds, CH acidic compounds, enamines or ketimines. Carba-nions react with CS2 to give dithiocarboxylates. The preparation and purification of the adds is performed via their salts. Metal complexes are in general readily available. The bonding in these complexes is mostly of the type (27) but a bonding mode (28) is also found. Action of elemental sulfur upon heavy metal complexes of (29) aromatic dithiocarboxylic acids yields the perthio complexes (29) of these compounds. 

The nucleophilic carbon of ketomethylene compounds can react with anhydrobases of different species in a basic medium. This reaction presents a narrow similitude with -CHj attack. The resulting dye, neut-rodimethine cyanine either mesomethyl-substituted or not. varies with the nature of the anhydro base (Scheme 30) (53. 54). 

Another important feature of the Nef reaction is the possible use of a CH-NO2 function as an umpoled carbonyl function. A proton at a carbon a to a nitro group is acidic, and can be abstracted by base. The resulting anionic species has a nucleophilic carbon, and can react at that position with electrophiles. In contrast the carbon center of a carbonyl group is electrophilic, and thus reactive towards nucleophiles. 1,4-Diketones 4 can for example be prepared from a-acidic nitro compounds by a Michael additionfNef reaction sequence " ... 

Before beginning a detailed discussion of alkene reactions, let s review briefly some conclusions from the previous chapter. We said in Section 5.5 that alkenes behave as nucleophiles (Lewis bases) in polar reactions. The carbon-carbon double bond is electron-rich and can donate a pair of electrons to an electrophile (Lewis acid), for example, reaction of 2-methylpropene with HBr yields 2-bromo-2-methylpropane. A careful study of this and similar reactions by Christopher Ingold and others in the 1930s led to the generally accepted mechanism shown in Figure 6.7 for electrophilic addition reactions. 

We saw in the preceding chapter that the carbon-ha]ogen bond in an alkyl halide is polar and that the carbon atom is electron-poor. Thus, alkyl halides are electrophiles, and much of their chemistry involves polar reactions with nucleophiles and bases. Alkyl halides do one of two things when they react with a nucleophile/base, such as hydroxide ion either they undergo substitution of the X group by the nucleophile, or they undergo elimination of HX to yield an alkene. 

We said at the beginning of this chapter that two kinds of reactions can happen when a nucleophile/Lewis base reacts with an alkyl halide. The nucleophile can either substitute for the halide by reaction at carbon or cause elimination of HX by reaction at a neighboring hydrogen ... 

Highly stabilized phosphorus ylides are prepared from acetylenic esters, a carbon-based nucleophile, and triphenylphosphine in aqueous media.40 In acetone-water (2 1) solvent, the reaction proceeds via the conjugate addition of triphenylphosphine to dialkyl acetylenedicarboxy-lates the resulting vinyl triphenylphosphonium salts undergo Michael addition reaction with a carbon-nucleophile to give the corresponding highly stabilized phosphorus ylides. 

The chlorine atom of 43 may be displaced readily by carbon-based nucleophiles with predominant overall retention of configuration at the phosphorus atom, similar to that observed in pentacoordinated analogues [37, 38], In some reactions, unselective substitution was observed [39], This approach was successfully applied for the... 

Carbon-based radicals stabilized by oxygen, though electronically neutral, can exhibit nucleophilic reactivity. C-Glycoside synthesis based on anomeric... 

The voltammetric reduction of a series of dialkyl and arylalkyl disulfides has recently been studied in detail, in DMF/0.1 M TBAP at the glassy carbon electrode The ET kinetics was analyzed after addition of 1 equivalent of acetic acid to avoid father-son reactions, such as self-protonation or nucleophilic attack on the starting disulfide by the most reactive RS anion. Father-son reactions have the consequence of lowering the electron consumption from the expected two-electron stoichiometry. Addition of a suitable acid results in the protonation of active nucleophiles or bases. The peak potentials for the irreversible voltammetric reduction of disulfides are strongly dependent on the nature of the groups bonded to the sulfur atoms. Table 11 summarizes some relevant electrochemical data. These results indicate that the initial ET controls the electrode kinetics. In addition, the decrease of the normalized peak current and the corresponding increase of the peak width when v increases, point to a potential dependence of a, as discussed thoroughly in Section 2. 

There are several classes of alkaloids. Among these are purines such as xanthine and caffeine, ter-penes (Chapter 22), polyketides (Chapter 21), and alkaloids derived from amino acids. The basic amino acids ornithine, arginine, histidine, and lysine as well as the aromatic amino acids, anthranilate, and nicoti-nate are some of the starting materials.199 201 Robinson202 203 in 1917 recognized that many alkaloids are derived directly from aromatic amino acids. He proposed that alkaloids arise from Mannich reactions (Eq. 25-12) in which an amine and an aldehyde (probably through a Schiff base) react with a nucleophilic carbon such as that of an enolate anion. Many of the... 

The reaction proceeds well with unhindered secondary amines as both nucleophiles and bases. The yield of allylic amine formed depends upon how easily palladium hydride elimination occurs from the intermediate. In cases such as the phenylation of 2,4-pentadienoic acid, elimination is very facile and no allylic amines are formed with secondary amine nucleophiles, while phenylation of isoprene in the presence of piperidine gives 29% phenylated diene and 69% phenylated allylic amine (equation 30).84 Arylation occurs at the least-substituted and least-hindered terminal diene carbon and the amine attacks the least-hindered terminal ir-allyl carbon. If one of the terminal ir-allyl carbons is substituted with two methyl groups, however, then amine substitution takes place at this carbon. The reasons for this unexpected result are not clear but perhaps the intermediate reacts in a a- rather than a ir-form and the tertiary center is more accessible to the nucleophile. Primary amines have been used in this reaction also, but yields are only low to moderate.85 A cyclic version occurs with o-iodoaniline and isoprene.85... 

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