Pro tic solvent

Secondary alkyl halides Sjvj2 substitution occurs if a weakly basic nucleophile is used in a polar aprotic solvent, E2 elimination predominates if a strong base is used, and ElcB elimination takes place if the leaving group is two carbons away from a carbonyl group. Secondary allylic and benzyiic alkyl halides can also undergo S l and El reactions if a weakly basic nucleophile is used in a pro tic solvent. 

The diynyl ligand behaves chemically as a rather electron-rich organic alkyne. The complexes MLn C=CCsCSiMea (and those with longer chains) are readily protodesilylated under standard conditions, such as treatment with fluoride in pro-tic solvents or carbonate in methanol, to give the corresponding terminal diynyl complexes in high... 

A benzo[18]crown-6 adduct (72) of Cgg (not shown) has been synthesized by the addition of the corresponding o-quinodimethane 71 in toluene [58]. The solubility of 72 in pro tic solvents such as MeOH strongly increases after the complexation of ions, as shown by extraction experiments. The combination of the crown ether and the fullerene moiety in 72 provides a highly amphiphilic character. This behavior allowed the preparation of Langmuir-Blodgett films of monolayers on mica of 72 and its complex. 

For pro tic solvents with larger dielectric constants and stronger basicity, the La and 1Lb states are inverted and relaxation from xLb to xLa takes places but there is no proton transfer to the solvent. The fluorescence is then due to the 1LB state with a small Stokes shift. The intermediate sized water clusters (n = 10-20) belong in this category. The clusters with methanol for any size n < 10 (due to a weak basicity or a small dielectric constant) follow this mechanism. From the evaluated proton affinities (see Figure 4-16), it can be seen that for n k 10 molecules of methanol (PA 243 kcal mol-1 which corresponds to the limit for proton transfer evidence in 1-naphthol complexes with piperidine or ammonia), a proton transfer should be observed. The absence of such a transfer can be related to a cluster structure effect. 

Primary, secondary, and tertiary alkyl halides also can be reduced with dissolving metals. The primary reduction product is an organometallic compound. Whether the latter is formed quantitatively or whether prior to that, it is converted into the corresponding hydrocarbon by protonation depends on the solvent. The organometallic compound is stable in aprotic solvents (hexane, ether, THF), while it is protonated in pro-tic solvents (HOAc, alcohols). 

Fig. 14. Plot of solvent vs. s/n ratio losses in 3 and 5mm NMR tubes in a cryogenic NMR probe. Better probe performance is obtained in all cases with a 3 mm tube rather than a 5 mm tube, even for polar pro tic solvents such as methanol and 100 mM Tris buffer. (Data generously provided by D. Avizonas and T. de Swiet, Varian NMR Instruments, Palo Alto, CA. Reproduced with permission.)...

A second limitation of the Hughes-Ingold theory concerns the fact that the solvent is treated as dielectric continuum, characterized by one of the following its relative permittivity, e, the dipole moment, fi, or by its electrostatic factor, EF, defined as the product of and [27]. The term solvent polarity refers then to the ability of a solvent to interact electrostatically with solute molecules. It should be remembered, however, that solvents can also interact with solute molecules through specific inter-molecular forces like hydrogen bonding or EPD/EPA complexation cf. Section 2.2). For example, specific solvation of anionic solutes by pro tic solvents may reduce their nucleophilic reactivity, whereas in dipolar aprotic solvents solvation of anions is less,... 

Similar results are found for the above-mentioned Menschutkin reaction (c). The added pro tic solvent can also combine with the main solvent. Such solvent/solvent association leads to a diminution of the specific inhibitory and catalytic effect of protic solvents on the Sn2 reaction (c) [584], The basicity of the main solvent determines the extent of deactivation of the protic solvent through H-bond association this is analogous to Eq. (5-107). 

Reaction type 3 in Table 5-25 is best represented by the SnI solvolysis of 2-chloro-2-methylpropane cf. Eq. (5-13) in Section 5.3.1. Considering the heterolysis of the C—Cl bond, one would expect the activation volume to be positive because of the C—Cl stretching during the activation process. However, a negative activation volume of AF = —22.2 cm mol has been found for this solvolysis at 30 °C in ethanol/ water (80 20 cL/L), indicating a strong volume contraction due to solvation of the dipolar activated complex (electrostriction) [756]. Typical activation volumes for halo-alkane solvolyses in pro tic solvents are in the range of —15... —30 cm mol ... 

A variety of heteroatom nucleophiles have proven suitable for the desired ring-opening at the 3-position (eq 3), such as Nu =NH3, NMc3, OAc , SBn , Cl , Br , pyrazole, and thiourea (S-attack). Sulfur nucleophiles appear to require pro-tic solvent for good results in this process. 

Structure 5 is one example of a number of dipyridones that incorporate different spacer groups.Since 5 was designed to be self-complementary, it was anticipated that it would self-associate to produce a dimer of type 6. Indeed, this was shown to be so in chloroform (> 90% dimer) by means of vapour pressure osmometry. X-Ray crystallography also confirmed that the dimer persists in the solid state. The behaviour of 5 contrasts markedly with that of 7 which was designed to be complementary only in an offset manner, such that linear polymerisation might be promoted. Under the dilute conditions of measurement, vapour pressure osmometry indicated that this species remains predominantly monomeric in chloroform however. X-ray diffraction confirmed that 7 adopts the linear polymeric structure illustrated by 8 in the solid state. As anticipated, since self-association involves hydrogen bonding, both 5 and 7 were shown to exist only as monomers in the pro-tic solvent methanol. 

In the second study, the above one-step mechanism was discounted and a two-step mechanism (a Baeyer-Villiger type) was advanced. Although the rates are summarized as r" =/fobs [C= N] [perbenzoic acid], the reaction exhibits complex kinetics because of the two adverse effects, acceleration by carboxylic acids and pro tic solvents, and retardation by basic solvents including ethers and alcohols (Scheme II). 

The crucial step in this mechanism is the second one in which the a-haloether moiety 115 solvolyzes to give an oxocarbocation. In order to obtain the ionic bicyclobutane this step has to compete effectively with both protonation of the carbanion and the 1,3-elimination reaction. By using oxygen nucleophiles, e.g. MeO", EtO" and CF3CH2O", in pro tic solvents, the rate of these three reactions was found to decrease in the order solvolysis > elimination > protonation. Although an apolar medium is expected to enhance the elimination reaction and to slow down the solvolytic step, it was shown that for MeO" in THF, the ionic bicyclobutane route still prevails. ... 

Stabilized Ylides.The carbanion center of phosphorus ylides is further stabilized by conjugation, usually with a carbonyl group (-CHO, -COR, -CO2R). Hence, these ylides are less reactive and weaker bases, but are more stable toward oxygen and pro-tic solvents than nonstabilized ylides. This type of stabilized ylide is mainly used in olefmations with aldehydes. 

The first step is the formation of H-bonded intermediate 49, in which Ccarbene takes on substantial cationic character. Next, termolecular attack by the amine in the presence of Y provides tetrahedral intermediate 50, which then breaks down into products. The reaction is sensitive to steric hindrance, with ammonia and primary amines reacting rapidly (several orders of magnitude faster than aminolysis of carboxylic acid esters) and secondary amines reacting much more sluggishly. The actual kinetic order associated with the amine is also a function of the solvent. Aprotic solvents such as hexane require a rate law with a third-order contribution from the amine pro tic solvents such as methanol show a mixed first- and second-order contribution from the amine. 

Bromine Addition to Alkenes. Alumina can advantageously replace protic solvents thus avoiding secondary reactions due to their nucleophdicity. This situation is evidenced in the bromation of alkenes [14]. When performed in methanol, bromine addition leads to a mixture of a frans-dibromo adduct and a trans-bromo ether compound. The latter results from competitive attack by pro-tic solvent on the bromonium ion intermediate. This byproduct can be suppressed using Br2/alumina, as the support behaves as a non-nucleophilic polar medium (Scheme 3). 

Nucleophiles therefore attack exclusively at the gem-difluoromethylene carbon of diflu-oroalkenes to form (3-fluorocarbanions (1). The chemical fates of 1 are mostly dependent on the structures of the alkenes and the reaction conditions. The typical reaction pathways of 1 are classified into three as shown in Scheme 2.17. In aprotic solvents, the carbanions (1) undergo defluorination, affording a-substituted monofluoroalkenes (2). Meanwhile, in pro tic solvents or in the presence of electrophiles in aprotic solvents, the carbanions (1) can be trapped with a proton or an electrophile to give addition products (3). The third case is S -type addition where substrates must have a leaving group on the y -carbon of 1 such as an alkoxy or an acyloxy group. 

Although the presence of a protic solvent aids these proton-transfer steps, pro-tic solvents are not a necessity for successful Michael addition reactions. Proton abstraction and conjugate addition can be carried out in the presence of a Lewis acid or by using a base in an aprotic solvent. For example, deprotonation of the dicarbonyl compound 19 with sodium hydride in THF and addition of the Michael... 

Since the monomer is prone to form cations, in cases where such cations are not trapped, say by a pro-tic solvent, both radical and cationic polymerization may occur concomitantly. 

Normally, the nonnucleophilic solvent carbon tetrachloride (CCI4) is used for the bromination or chlorination of alkenes. But the reaction will also work in pro-tic solvents such as water and simple alcohols. In these reactions, new products appear that incorporate molecules of the solvent (Rg. 10.14). How do the OH or OR groups get into the product molecule To see the answer, write out the mechanism and look for an opportunity to make the new products. The first step... 

Saline hydrides react immediately with pro tic solvents such as H2O (eq. 10.35), NH3 or EtOH, showing that the H ion is an extremely strong base. Widespread use is made of NaH and KH as deprotonating agents (e.g. reaction 10.36). 

Solubility sol ethers, pentane, benzene reacts violently with pro-tic solvents. 

Computations have revealed that direct formation of iminium could involve a high barrier whereas a pro tic solvent assisted pathway offers lower barriers. However, in a related series, such as, say the formation of enamine from an aldehyde and iminium from MVK, the latter is reported to be energetically more costly [5b). 

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