Mechanisms protic solvents

Solvent Effects on the Rate of Substitution by the S 2 Mechanism Polar solvents are required m typical bimolecular substitutions because ionic substances such as the sodium and potassium salts cited earlier m Table 8 1 are not sufficiently soluble m nonpolar solvents to give a high enough concentration of the nucleophile to allow the reaction to occur at a rapid rate Other than the requirement that the solvent be polar enough to dis solve ionic compounds however the effect of solvent polarity on the rate of 8 2 reactions IS small What is most important is whether or not the polar solvent is protic or aprotic Water (HOH) alcohols (ROH) and carboxylic acids (RCO2H) are classified as polar protic solvents they all have OH groups that allow them to form hydrogen bonds... 

There seem to have been only two investigations on dediazoniations in a protic solvent, where the observed products indicate that, in addition to DN + AN solvolysis, an aryne is likely to be present as a metastable intermediate. Broxton and Bunnett (1979) have found that 3-nitroanisole is formed in the dediazoniation of 2-nitroben-zenediazonium ions in methanol in the presence of methoxide ions. This has to be interpreted as a product arising from 3-nitro-l,2-benzyne as an intermediate. The occurrence of the aryne mechanism in poly (hydrogen fluoride)-pyridine mixtures, as discovered by Olah and Welch (1975), is mentioned in Section 8.2. 

Majeti11 has studied the photochemistry of simple /I-ketosulfoxides, PhCOCH2SOCH3, and found cleavage of the sulfur-carbon bond, especially in polar solvents, and the Norrish Type II process to be the predominant pathways, leading to both 1,2-dibenzoylethane and methyl methanethiolsulfonate by radical dimerization, as well as acetophenone (equation 3). Nozaki and coworkers12 independently revealed similar results and reported in addition a pH-dependent distribution of products. Miyamoto and Nozaki13 have shown the incorporation of protic solvents into methyl styryl sulfoxide, by a polar addition mechanism. 

The following overall nucleophilicity order for Sn2 mechanisms (in protic solvents) was given by Edwards and Pearson RS > ArS >1 >CN > OH > Nj > Br > ArO > Cl > pyridine > AcO > H2O. A quantitative relationship (the Swain-Scott equation) has been worked out similar to the linear free energy equations considered in Chapter 9 ... 

Theoretical studies aimed at rationalizing the interaction between the chiral modifier and the pyruvate have been undertaken using quantum chemistry techniques, at both ab initio and semi-empirical levels, and molecular mechanics. The studies were based on the experimental observation that the quinuclidine nitrogen is the main interaction center between cinchonidine and the reactant pyruvate. This center can either act as a nucleophile or after protonation (protic solvent) as an electrophile. In a first step, NH3 and NH4 have been used as models of this reaction center, and the optimal structures and complexation energies of the pyruvate with NH3 and NHa, respectively, were calculated [40]. The pyruvate—NHa complex was found to be much more stable (by 25 kcal/mol) due to favorable electrostatic interaction, indicating that in acidic solvents the protonated cinchonidine will interact with the pyruvate. 

The mechanism for reduction by LiAlH4 is very similar. However, since LiAlH4 reacts very rapidly with protic solvents to form molecular hydrogen, reductions with this reagent must be carried out in aprotic solvents, usually ether or tetrahydrofuran. 

Fig. 20 The proposed mechanism of ESPT incorporating a solvent-polarity-induced barrier in protic solvents following optical charge transfer and solvent relaxation. See full name of each compound in text (reprint from ref. [141], Copyright 2008 Wiley-VCH)...

Fig. 21 The proposed ESPT/ESCT coupled mechanism of 5CNAI in protic solvents...

These findings can be interpreted in terms of a normal ring-opening mechanism of intermediate 325 with proton transfer favored by protic solvent, whilst in aprotic solvent cycloreversion of the unstable aziridinium grouping in 325 followed by ring expansion prevails. Likewise, 2,3-disubstituted aziridines follow this reaction pattern, while N-substituted aziridines do not225. ... 

In fact, the analogy between the mechanisms of heterolytic nucleophilic substitutions and electrophilic bromine additions, shown by the similarity of kinetic substituent and solvent effects (Ruasse and Motallebi, 1991), tends to support Brown s conclusion. If cationic intermediates are formed reversibly in solvolysis, analogous bromocations obtained from bromine and an ethylenic compound could also be formed reversibly. Nevertheless, return is a priori less favourable in bromination than in solvolysis because of the charge distribution in the bromocations. Return in bromination implies that the counter-ion, a bromide ion in protic solvents, attacks the bromine atom of the bromonium ion rather than a carbon atom (see [27]). Now, it is known (Galland et al, 1990) that the charge on this bromine atom is very small in bridged intermediates and obviously nil in /f-bromocarbocations [28]. 

In 1950, Pruett et al. synthesized tetrakis(dimethylamino)ethylene, a clear, slightly yellow and mobile liquid. The authors observed a prolonged bright blue-green luminescence when the compound was exposed to oxygen or air in protic solvents [81]. The mechanism for this CL reaction, as proposed by Fletcher and Heller in 1967 [82], is shown in Figure 7. 

Three of the four photophores, listed in Scheme 3, eliminate nitrogen upon excitation while the biradicaloid triplet state of benzophenone can be reversibly activated, and creates covalent linkage upon excitation-relaxation cycling. This fact and their extremely low reactivity towards protic solvents make them very efficient in the majority of the cases. [7, 19, 20]. Unsaturated ketones can be activated by a similar mechanism, although the secondary processes are much more complex [21]. That mechanism is mainly utilized in steroid hormones possessing unsaturated ketones as intrinsic photophores. 

An alternative procedure to effect elimination resolves this problem. Opening the oxaspiropentane 26 with selenide anion in a non-protic solvent effects a direct elimination via a merged substitution — elimination mechanism to give the vinyl-... 

Scheme 2. Mechanisms for alkene bromination in aprotic and protic solvents. 

Furthermore, although the intercepts k kiK/k- ) and the slope (kikjK/k-i) are equally influenced by the dimerization constant K in equation 28, this does not imply that they should show the same effect on changing the solvent. According to the dimer mechanism , it could be expected that the base catalysed decomposition of the transition state SB2, measured by Ag, should be more depressed by small additions of protic solvents than the spontaneous decomposition measured by Ag. Indeed, the overwhelming evidence on the classical base catalysis by amines shows that usually Ag is more important in aprotic than in protic solvents1. 

S[ 2 reactions lead to an inversion of stereochemistry. Nucleophilicity is decreased by protic solvents in Sp 2 reactions. The presence of a polcir aprotic solvent is a clue that the mechanism is Sf 2. 

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