Ambident reactivity

Ambident reactivity occurs for any substance displaying protomeric behavior. In basic medium anions in which negative charge is delocalized are formed this may be represented by the resonance formulas in Scheme 2. Each charged atom may react with an electrophilic center. The... 

The equation does not take into account such pertubation factors as steric effects, solvent effects, and ion-pair formation. These factors, however, may be neglected when experiments are carried out in the same solvent at the same temperature and concentration for an homogeneous set of substrates. So, for a given ambident nucleophile the rate ratio kj/kj will depend on A and B, which vary with (a) the attacked electrophilic center, (b) the solvent, and (c) the counterpart cationic species of the anion. The important point in this kind of study is to change only one parameter at a time. This simple rule has not always been followed, and little systematic work has been done in this field (12) stiH widely open after the discovery of the role played by single electron transfer mechanism in ambident reactivity (1689). 

These genera] trends direct the organization of Chapters VI and VII syntheses from the already formed thiazole ring, physicochemical studies, ambident reactivity ring carbon reactivity, main derivatives, and aminothiazole applications. 

The ambident reactivity of 2-amino-4,5-disubstituted thiazoles toward benzoylthiocyanate 153 has been studied (311) and parallels that of ethoxycarbonyl isothiocyanate (Scheme 98) the percentages of 154. 155. 

Ambident reactivity of the same nucleophilic species toward different nitrosation electrophilic centers. 

Ambident reactivity of A-4-thiazoline-2-thione has been discussed (101) in terms of the Hard and Soft Acids and Bases classification (199) and the Klopman-Hudson approach (200). 

Substituted 1,2,3-triazolium-l-aminide 1,3-dipoles (382) react with aryl isothiocyanates at both the N=C (path a) and C=S (path b) sites to give mixtures of substituted imidazolo[4,5-fi(][l,2,3]triazoles (383) and new thiazolo[4,5-fi(][l,2,3]-triazoles (384) including tricyclic derivatives with the C(3a) and C(6a) bridgeheads linked via (CH2)4 and phenanthro groups (Scheme 50). The product distribution is controlled by the para-substituent of the aryl isothiocyanate. Theoretical calculations at the 3-210 and 6-3IG levels suggest that linear triple-bonded canonical forms of the aryl isothiocyanate system play a key role in the ambident reactivity of these systems. 

In the new structures of type (59) the reactive centre is the methanide site which behaves as a nucleophile. <86JCS(Pi)ii57, 92JCS(P1)1483> (Section 4.17.8). Tautomeric tetrazole-tetrazoline structures of general type (4 R = H) may show ambident reactivity with reactions occurring on the ring or the exocyclic X atom (Sections 4.17.6 and 4.17.7). 

El Shafei et al.162 have studied the ambident reactivity of quinoxalino-[2,3b]-l,4-benzothiazine(103) and observed that under phase transfer conditions the ratio of benzothiazine N-alkylation versus quinoxaline N-alkylation was nearly 2 1. 

Gonzalez and Galvez269 have described an improved method for the preparation of 3-diazoindoles (174), using PTC. Indole derivatives 173 react in position 3 because of the ambident reactivity of the molecule. Yields are 75-90% when R is acyl or heteroaryl. 

The reaction of alkyl isothiocyanates, RNCS, with diphenylphosphinic hydrazide (338) in benzene has been reported.308 The bis(diethylamino)[(methylthio)thiocarbon-yl]carbenium salts (339 X = I or BF4) display ambident reactivity and can react either at carbenium carbon (hard nucleophiles) or at the thiocarbonyl sulfur atom (soft nucleophiles).309 Electrochemically generated superoxide reacts with dithioic S,S -diesters (dicarbothiolates) (340 Ar = C5H3N or C6H4) to give the monocarboxylate anions in 100% yield before giving the dicarboxylate anions.310... 

The connectivity of the silaformamide ion [HSi(0)NH] 762 was established by deu-teriation studies using both ND2 and D20. The reaction chemistry with neutral reagents such as C02, CS2, COS, fluoro and aliphatic alcohols has been studied. An example is shown in equation 255, which displays the ambident reactivity versus COS. 

The applications of nitronium salts as a synthetic reagent530 are discussed in Chapter 5. Until recently, the nitronium ion was recognized only as a nitrating agent. However, it has been found that it possesses significant ambident reactivity. This has been recently shown in the oxidation of sulfides, selenides, and phosphines. In fact, the sulfide reaction has been monitored by 15N NMR spectroscopy wherein both nitrosulfonium and nitritosulfonium ions 88 and 89 were detected as distinct intermediates [Eq. (4.147)]. 

Reactions of carbocations with free CN- occur preferentially at carbon, and not nitrogen as predicted by the principle of hard and soft acids and bases.69 Isocyano compounds (N-attack) are only formed with highly reactive carbocations where the reaction with cyanide occurs without an activation barrier because the diffusion limit has been reached. A study with the nitrite nucleophile led to a similar observation.70 This led to a conclusion that the ambident reactivity of nitrite in terms of charge control versus orbital control needs revision. In particular, it is proposed that SNl-type reactions of carbocations with nitrite only give kinetically controlled products when these reactions proceed without activation energy (i.e. are diffusion controlled). Activation controlled combinations are reversible and result in the thermodynamically more stable product. The kinetics of the reactions of benzhydrylium ions with alkoxides dissolved in the corresponding alcohols were determined.71 The order of nucleophilicities (OH- MeO- < EtO- < n-PrCT < / -PrO ) shows that alkoxides differ in reactivity only moderately, but are considerably more nucleophilic than hydroxide. 

Phenylation and arylation have also been performed in bifunctional compounds such as malonates, /1-diketones and /1-ketoesters (Table 8.4). Diethyl malonate was arylated at room temperature affording mixtures of mono- and bis-arylated products, whereas isopropylidene malonate (Meldrum s acid) underwent bis arylation directly. Dimedone, the all carbon analogue of Meldrum s acid, was also mono-and bis-phenylated, with some concomitant O-phenylation [33], Generally, / -diketones show often ambident reactivity but the O-arylated product is normally the minor one an exception was noted in the triketone (PhCO)2CHCOPh which underwent mainly O-phenylation (68%) [33], Several dianions from /1-diketones have been arylated in high yields at the a-position, in a procedure superior to other methods [35]. 

Ambident reactivity was shown by oximate anions normally, Oarylation predominated over N-arylation, with ratios of oxime ethers to nitrones ranging from 9 1 (for the benzophenone oxime anion) to 1.7 1 (for the fluorenone oxime anion) [77]. The arylation of two heterocyclic oximes was performed under mild conditions and led mainly to the corresponding oxime ethers which served as good precursors for the generation of unstable aryl fulminates, ArONC [79,80],... 

Aminopyridine, and ambident reactivity, 63 bromination of. 79 by Chichibabin reaction, 12 diazotization of. 67 and HSAB, 63 nJtration of. 72... 

DMF, in alkylation of aminothiazoles, 35 in ambident reactivity, 36 in cyclizations, 50 DMSO, reaction with CS2,61 Dopamine content in brain, 146 Dopamine hydroxylase inhibitor, 152 Double bond, addition to, 40 ozonolysis of, 71... 

Horticultural uses, 134 HSAB theory, and ambident reactivity. 5, 61,62... 

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