Ambident anion

The preparation of a series of transition metal complexes (Co. Ni. Pd. Pt, Ir. Au. Cu. Ag) with ambident anion (70) and phosphines as ligands has been reported recently (885). According to the infrared and NMR spectra the thiazoline-2-thione anion is bounded through the exocyclic sulfur atom to the metal. The copper and silver complexes have been found to be dimeric. 

Mercury and tin in complexes (68 or 69) (Scheme 32 (154 mav behave as electrophilic centers (155. 156). Under basic conditions, the reactive species is an ambident anion (70) (Scheme 33). 

Since the exocyclic sulfur is more reactive in the ambident anion than in A-4-thiazoIine-2-thione. greater nucleophilic reactivity is to be expected. Thus a large variety of thioethers were prepared in good yields starting from alkylhalides (e.g.. Scheme 38 (54, 91, 111, 166-179). lactones (54, 160), aryl halides (54, 152. 180, 181), acyl chlorides (54. 149, 182-184). halothiazoles (54, 185-190), a-haloesters (149. 152. 177. 191-194), cyanuric chloride (151). fV.N-dimethylthiocarbamoyl chloride (151, 152. 195. 196), /3-chloroethyl ester of acrylic acid (197), (3-dimethylaminoethyl chloride (152). l,4-dichloro-2-butyne (152), 1,4-dichloro-2-butene (152), and 2-chloro-propionitrile (152). A general... 

Class (2) reactions are performed in the presence of dilute to concentrated aqueous sodium hydroxide, powdered potassium hydroxide, or, at elevated temperatures, soHd potassium carbonate, depending on the acidity of the substrate. Alkylations are possible in the presence of concentrated NaOH and a PT catalyst for substrates with conventional pX values up to - 23. This includes many C—H acidic compounds such as fiuorene, phenylacetylene, simple ketones, phenylacetonittile. Furthermore, alkylations of N—H, O—H, S—H, and P—H bonds, and ambident anions are weU known. Other basic phase-transfer reactions are hydrolyses, saponifications, isomerizations, H/D exchange, Michael-type additions, aldol, Darzens, and similar... 

Hydroxyindole (181) represents a well known example of a compound in which the hydroxyl group is to the ring heteroatom. The equilibrium mixture again contains mainly the carbonyl form (182), indoxyl. Deprotonation gives a reactive ambident anion which can be methylated either on oxygen or C-2 (Scheme 73). Indoxyl is easily oxidized to indigo (184), which may be formed by dimerization of the radical (183) produced by electron loss from the anion. 

In addition to reaction sequences of type (66) -> (67), electrophilic reagents can attack at either one of the ring nitrogen atoms in the mesomeric anions formed by proton loss e.g. 70 71 or 72 see Section 4.02.1.3.6). Here we have an ambident anion, and for unsymmetrical cases the composition of the reaction product (71) + (72) is dictated by steric and electronic factors. 

Azolinones are protonated on oxygen in strongly acidic media. O-Alkylation of 2-azolinones can be effected with diazomethane thiazolinone (486) forms (487). Frequently O- and iV-alkylation occur together, especially in basic media where proton loss gives an ambident anion. 

Sometimes compounds which exist predominantly in the hydroxyl form give products of N-methylation with diazomethane, for example 3-hydroxy-5-phenylisothiazole (63AHCi2)245) of course, the ambident anion (493) is an intermediate. 3-Hydroxypyrazoles, under rather severe conditions, can be converted into 3-chloropyrazoles with POCI3 <66AHQ6)347). 

NH form e.g. 505). Most 4- and 5-hydroxy compounds of types (500) and (502) exist largely in these non-aromatic azolinone forms, although the hydroxyl form can be stabilized by chelation e.g. 506). The derived ambident anions react with electrophiles at O or C. Replacement of the hydroxyl group is sometimes possible provided electron-withdrawing groups are present as, for example, in 5-substituted 4-hydroxypyrazoles. 

The pattern of reactivity is similar to that discussed for the azolinones in Sections 4.02.1.1.4 and 4.02.3.7.1. A difference is the greater nucleophilicity of sulfur, and thus more reaction of the ambident anion with electrophiles occurs at sulfur. 

A mechanism of this type permits substitution of certain aromatic and ahphatic nitro compounds by a variety of nucleophiles. These reactions were discovered as the result of efforts to explain the mechanistic basis for high-yield carbon alkylation of the 2-nitropropane anion by p-nitrobenzyl chloride. p-Nitrobenzyl bromide and iodide and benzyl halides that do not contain a nitro substituent give mainly the unstable oxygen alkylation product with this ambident anion ... 

The reaction of dichlorocarbene with 2 f-thiachromen (42) was exceptional since it gave none of the expected adduct but rather the products of substitution at the 2- (43) and 4-position (44) together with a bis-adduct of unknown structure. The substitution products could arise by reaction of the ambident anion 45 with dichlorocarbene, but the absence of these products in the same reaction of 4jy-thiachromen argues against this mechanism. The... 

For a successful application in synthesis, several problems have to be solved regioselectivity, whether the C-C bond is formed with the 1- or 3-position in an unsymmetrical ambident anion, EjZ selectivity in the formation of the double bond, and simple diastereoselectivity, since two new stereogenic centers are created from prostereogenic compounds. Further, different types of induced stereoselectivity or enantioselectivity may be required. Allylmetals with a wide choice of substituents are accessible by various methods (Sections D. 1.3.3.3.1.-10.). 

For a monograph, see Reutov, O.A. Beletskaya, I.P. Kurts, A.L. Ambident Anions Plenum NY, 1983. For a review, see Black, T.H. Org. Prep. Proced. Int., 1989, 21, 179. Both cyanates and isocyanates have been isolated in treatment of secondary alkyl iodides with NCO Holm, A. Wentrup, C. Acta Chem. Scand., 1966, 20, 2123. 

At room temperature under photostimulation a-nitrosulfones react with a variety of nucleophiles via radical anion chain reactions interestingly, in none of the cases where the PhSOj group is involved in SrnI type of substitution does the O end of the ambident anion " play a role. This strong regioselectivity is reminiscent of the one reported for other ambident anions involved in these radical chain substitutions. ... 

Reactions of trident and ambident anions of hydroxy compounds with alkylating reagents were also studied.121 The ion-pair extraction method was found to be superior alkylating agents were methyl iodide (soft) and dimethyl sulfate (hard). Upon alkylation by ion-pair extraction the 5-methyl-substituted selenolene-2-one system gives mainly C-alkylation with the soft acid, methyl iodide, and mainly O-alkylation with the hard acid, dimethyl sulfate. 

However, in our opinion, the rigorous assignment of products to covalent nitronic esters rather than to their structural isomers, which are true nitro compounds or ionic salts, is a more important and complex problem This problem involves difficulties, because ambident anions of nitro compounds (which are evident precursors of nitronates) have comparable O- and C-nucleophilicities and, therefore, the resulting substrates can belong to any of the above mentioned series. Incorrect structure assignments of derivatives of polynitro compounds prepared from tetranitromethane were made in former studies. In addition, the structures of nitronates assigned to some products in early studies, should not have been accepted without the use of modem spectral methods. 

Smith and Hanson, 1971). Upon addition of NaBPh4, the free anion was converted into the ion pair, and upon addition of dibenzo-18-crown-6 [11] the ion pair was converted into the free anion. The results (Table 26) show the free anion to be much more reactive than the ion pair towards both methyl iodide and methyl tosylate. The increase in rate is again mainly due to the enhanced reactivity of the hard oxygen centre. The ratio of the rates of alkylation at the two sites of the ambident anion (kN/k0) decreased from about 1.2 for the ion pair to 0.55 and almost zero for the free anion. Increased alkylation of the hard... 

Kornblum et al. (1963) demonstrated that O- vs. C-alkylation (24) of yS-naphthoxide ion (an ambident ion) is markedly solvent dependent. For example, the reaction with benzyl bromide conducted in dimethylformamide gave 97% O-alkylated product, whereas in water 81% C-alkylated product resulted. The difference is attributed to changes in the solvation of ambident anions. The course of the reaction is also influenced by water concentration in... 

As is also true for ambident anions, substances exhibiting alpha effects in their reactions consistently deviate from the anticipated structure-reactivity correlations known for simple nucleophiles. 

The chemistry used to prepare the antischistosomal hydroxyquinolines provided the initial entry to this series. Thus, addition-elimination of aminopicoline (38-1) to EMME (38-2) gives the corresponding enamino ester (38-3). Thermal cyclization of that intermediate leads to the hydroxyquinoline (38-4). Reaction of the ambident anion from that compound leads to alkylation via the keto tautomer and thus the formation of the Al-alkylated derivative (38-5). Saponification of the ester then gives nalidixic acid (38-6) [44]. It has incidentally been shown that the presence of the strong Michael acceptor function in this series plays a little role in the mechanism of action in these compounds. 

PhO " is an ambident anion with negative charge on both O and the ortho C atoms of the ring. Attack by O gives the ether attack by the ortho carbanion gives o-allylphenol. 

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