Chapter 1. Organic chemistry basics

Reaction basics

Substitution (SN1/SN2)

Polar solvents like aceton, ether, dioxan or above all dimethylformamid and dimethylsulfoxid does not possess any polar hydrogen atoms for the formation of hydrogen-bridges. Anions will less dissolve anions, because dipolar aprotic solvents results in a weaker solvation and an increased basic character (nucleophilic character of the anions).

Substitutions in these solvents use mainly the SN2 mechanism, because the carbenium ion (leaving group) is less slovated. Is the nucleophil an anion the SN2 substitution faster than reactions in alcohol or water.

Strong lewis-acids like BF3, AlX3, ZnCl2, Ag+ forms with bases (nucleophilics) covalent bonds and catlyses SN1 reactions since they coordinates to the anion and faciliates the dissociation of the C-X bond. The elecctron density at the cabon atom C is reduced which allows an easier dissociation of the X group.

For example AgNO2 with halogen alkan leads to an alkylnitrit (R-O-N=O), while NaNO2 leads to a nitroalkan (R-NO2). By using AgNO2 arises almost a carbenium ion, because AgX is falling out .

Table 1-1. Substituion by using weak and strong acids

AcidMain mechanismDescription
AgNO2SN1rather strong acid, charge controlled
NaNO2SN2rather weak acid, orbital controlled

Analogue protons catalyses SN reactions for the lazy fluoralkanes (Hydrogen bridges with the created HF). So fluoralkanes hydrolysis easily to alcohols whereas by chloralkanes no catalysis is observed.

Leaving ability / leaving ability

The energy for the heterolytic cleavage of the R-X bond consits of the homolltic bond dissociation energy, the ionisation energy of R. and the electron affinity of X..

The reactivity of R-X (in DMF) is (leaving ability is analogue to 1/basicity): R-NH2 << R-OH << R-F; << R-Cl < R-Br < R-I

The low leaving ability of the hydroxy group (-OH) can be improved, if it will be converted to a much weaker base, the p-Toluensulfon group (-OTs). An even higher reactivity have trifluormethylsulfonats (-OSO2CF3), which can be up to 10^4 times greater then tosyl groups.

For SN2 reactions we can observe that substrats in which the leaving X group is easily polarisable (soft, e.g. huge I- ions) reacts faster with soft reagents. In opposite leaving groups with weak polarisable (hard) hetero groups (e.g. OTs-) will be faster replaced by hard nucleophils.

Nucleophilicity

The factors of setting free energy by creating the R-Y bond and changing the energy by changing the solvation state determines the reactivity of a nucleophil reagens, its nucleophilicity.

polar aprotic solvents

Solvents like DMF, DMSO, HMPT are polar aprotic solvents. The nucleophils are not as strongly solvated as in protic solvents and the energy gain by forming the Y-R bond is decisive for the reactivity. This is analoguoe to the affinity of the nucleophil reagens to the electrophil partner R.

It can be seen that the nucleophilicity of a reagens is approximatively growing if the (Bronsted-) basicity is growing.

anionic nucleophils

Anionic nucleophils must be partially desolvated if it turns over to an activated complex of the SN2 reaction. So the reactivity is greater if the anion is less solvated. Additinally solvents wth a higher lewis-acidity (ability to solvate anions, electron drawing ability) have a lower nucleophilicity of the anionic reagens in a aprotic solvens.

Table 1-2. Nucleophilicity of an anionic reagent in aprotic solvents (decreasing lewis acidity)

NucleophilMechanismAprotic solvent
anionSN2nitromethan < DMSO = acetonitril = propylencarbonat < DMF < aceton < HMPT

neutral nucleophils

When using neutral nucleophils, like alcohols or amins, the transition state is stronger solvated than the reagents. The reaction time increases with a larger lewis acidity.

Table 1-3. Nucleophilicity of a neutral reagent in aprotic solvents (increasing lewis acidity)

NucleophilMechanismAprotic solvent
neutralSN2HMPT < aceton < DMF < DMSO < nitromethan

protic solvents

In protic solvents the nucleophiicity depends mainly on the polarisability, not the basicity. Hard anions are weakly solvated soft anions are strongly solvated.

The reaction time constant depends additionally on the dissociation consant of the used salt complex of the anion. It is clear that the anionic nucleophi can only react if it is available as free ion. The dissociatioa ability and reactivity increases approximately with the polarity (dielectricc constant) of the solvent and with the size of the ction and anion.

Comparison of the nucleophilicity for different solvent types

Comparison of the nucleophilicity for different solvent types.

Table 1-4. Comparison of the nucleophilicity of anions for different solvent types

SolventMechanismCharacterAnion
polar aproticSN2analogous to the basicitySCN- < I- < Br- < Cl- < F- < N3- < CH3COO- < CN-
protic solventSN2analogous to the polarisabiity and sizeCH3COO- = F- < Cl- < OH- = Br- = I- < CN- < SCN- < S2O3
protic solventSN2analogous to the polarisabiity, size, and dissocciation abilityLiCl < NaCl < KCl = LiF <LiCl <LiBr < LiI

The paradox result that highly concentrated reagents leads to steric uniform results, is a direct relatinship between inversion and racemisation. By the inversion is the reaction speed of the SN2 reaction proportional to the concentration of the nucleophil Y. By the racemisation is the reaction speed of the SN1 is independent of Y. If the concentration of the nucleophil Y is increased the portion of the SN2 reaction will be preferred against the SN1 reaction.

Neighbour group effect

Retention is the result of two sucessive (gradul occuring) inversions. A neighbour atom with a free electron pair or electrons encourage SN reatioons.

Table 1-5. Neighbour group effect with two SN2 over a tight alpha-lacton

SolventAnion

  1. Intramolecular SN2 reaction