Unimolecular 1,2-Elimination

In summary, the regiochemistry of E2 reactions can be predicted by using the following rules  

Most E2 reactions follow Zaitsev s rule the more highly substituted alkene is the major product. 

Hofmann eliminations follow Hofmann s rule the less highly substituted product is the major product. 

A conjugated alkene is always preferred to an unconjugated alkene. 

Show the major products of these elimination reactions  

Chapter 2. Acids, Bases, Functional Group Exchanges 

REAL LIFE MEDICINE 7-1 Unusually Stereoselective 5, 1 Displacement in Anticancer 

SnI displacements normally give mixtures of stereoisomeric products. The high-energy carbocation intermediate reacts with the first nucleophilic species it encounters, regardless of which lobe of the carbocation p orbital the nucleophile approaches. The example shown below is a very unusual 

The structure of the relevant carbocation is shown at the right. Approach of a nucleophile toward the top lobe of its p orbital is partly blocked by the ethyl group two carbon atoms over and to a lesser extent by the ester function one carbon farther away (green). In addition, the hydroxy group on the bottom face of the ring directs nucleophilic addition of a water molecule from below by hydrogen bonding, as shown. 

This stereochemical result is of critical importance because the product, named aklavinone, is a component in a powerful anticancer drug called aclacinomycin A. This compound belongs to a class of chemotherapeutic agents called anthracydines, whose clinical utility is compromised by 

We know that carbocations are readily attacked by nucleophiles at the positively charged carbon. However, this is not their only mode of reaction. A competing alternative is depro-tonation by the nucleophile acting as a base, furnishing a new class of compounds, the alkenes. This process is possible because the proton neighboring the positive charge is unusually acidic. 

---

Like the reaction of terr-butyl alcohol with hydrogen chloride step 2, in which tert-butyloxonium ion dissociates to (CH3)3C and water, is rate-deter-mining. Because the rate-determining step is unimolecular-, the overall dehydration process is refened to as a unimolecular elimination and given the symbol El. 

These reactions are often promoted by a strong base, which assists the departure of the proton. X is the leaving group. Both El and E2 mechanisms are known, as is a variant designated Elcb, for unimolecular elimination from the conjugate base of the substrate. ... 

El reaction (Section 11.10) A unimolecular elimination reaction in which the substrate spontaneously dissociates to give a carbocation intermediate, tvhich loses a proton in a separate step. 

It is possible to take advantage of the differing characteristics of the periphery and the interior to promote chemical reactions. For example, a dendrimer having a non-polar aliphatic periphery with highly polar inner branches can be used to catalyse unimolecular elimination reactions in tertiary alkyl halides in a non-polar aliphatic solvent. This works because the alkyl halide has some polarity, so become relatively concentrated within the polar branches of the dendrimer. This polar medium favours the formation of polar transition states and intermediates, and allows some free alkene to be formed. This, being nonpolar, is expelled from the polar region, and moves out of the dendrimer and into the non-polar solvent. This is a highly efficient process, and the elimination reaction can be driven to completion with only 0.01 % by mass of a dendrimer in the reaction mixture in the presence of an auxiliary base such as potassium carbonate. 

The first step (loss of the leaving group) is the rate-determining step, much Uke we saw for SnI processes. The base does not participate in this step, and therefore, the concentration of the base does not affect the rate. Because this step involves only one chemical entity, it is said to be uiumolecular. Unimolecular elimination reactions are called El reactions, where the 1 stands for unimolecular. ... 

Olefins [46] have been shown to derive from unimolecular -elimination of HBr from the CH2CH2Br end of [1] promoted by the distal phenoxide end (Dalla Cort et al., 1983), as depicted in [47]. Rate constants and EM s have been measured in 99% Me2SO at 25°C for reactions occurring via 7-, 8-, 9-,... 

Wu, F., and R. W. Carr, Time-Resolved Observation of the Formation of CF20 and CFCIO in the CF2C1 + 02 and CFCI2 + 02 Reactions. The Unimolecular Elimination of Cl Atoms from CF2CIO and CFCI20 Radicals, J. Phys. Chem., 96, 1743-1748 (1992). 

Depending on the relative timing of the bond breaking and bond formation, different pathways are possible El reaction or unimolecular elimination and E2 reaction or bimolecular elimination. 

Additional compelling evidence for the unimolecular elimination mechanism (4)... 

A or B acid or base catalysis AC or AL acyl-oxygen or alkyl-oxygen fission 1 or 2 unimolecular or bimolecular. E10B designates unimolecular elimination through the conjugate base. 

In competition with these oxidation reactions are two unimolecular elimination-reactions which eventually lead to 64 and 65 (Table V, reactions 128 to 133). Product 65 may also have the radical at C-3, namely, 66, as a precursor (reaction 134). As expected, the precursor radicals 62 and 66 are rapidly oxidized in the presence of Fe3+ ions, and the formation of 65 and 65 is suppressed (see Table V). 

The great stability of tertiary carboeations is the reason why alcohols like 8 undergo unimolecular elimination especially readily. 

A unimolecular elimination involving a semi-polar five-membered cyclic transition state (81) (Scheme 9, R1 = Ph, R2 = R3 = H) appears to account for the formation of benzaldehyde, CO, and H2O on eliminative fragmentation of mandelic acid in the gas phase.44 The same type of transition state has been proposed for gas-phase pyrolysis of ROCH2COOH (R = MeO, EtO, and Ph O) with corresponding formation of ROH, CO, and formaldehyde the rate of reaction is little dependent on R.45... 

Preliminary results on the enantioselective formation of sulfur and nitrogen mediumsized heterocycles by base-induced ring opening of hetero-oxabicyclic [3.2.1] and [3.3.1] systems have been reported.91 The reaction involves a deprotonation-C—O bond elimination sequence. The kinetics and mechanism of gas-phase unimolecular elimination reactions of some substituted aminoazoles have been studied as an aid to heterocycle synthesis.92... 

An ab initio study on the unimolecular elimination reactions of methacrylonitrile has revealed a direct four-centre elimination of HCN and three-centre elimination of H2 channels.17 A methylcyanoethylidene intermediate has also been identified. 

The gas-phase unimolecular elimination reactions of 2-substituted ethyl N,N-dimethylcarbamates23,24 and several heterocyclic carbamates25 have been studied using the Moller-Plesset MP2/6-31G method. On the basis of these calculations, the mechanism appears to be concerted, asynchronous, through a six-membered cyclic transition-state structure. 

Since the estimated half-time for unimolecular elimination of hydrogen chloride from the allylic chloride is considerably greater than the half-times for reaction with stabilizers, the stabilizers do not function only by reacting with liberated hydrogen chloride. Stabilizers function by substituting the labile chlorine atoms with more thermally stable groups, thereby mending the polymer. 

A generalized rate expression for the reaction of allylic chloride (RC1) with metal stabilizers (MX2) includes terms for the unimolecular elimination of HC1 from RC1 and for the bimolecular reaction of RC1 with all metal containing species. 

TABLE 5. Kinetic parameters for unimolecular elimination of HC1 in pyrolysis of ZCH2CH2C1 at 440 °C... 

TABLE 6. Kinetic parameters for the unimolecular elimination of HC1 from pyrolysis of ZCH(C1)CH3 at 360 °C... 

An IR laser pyrolysis method was developed for the determination of Arrhenius parameters for unimolecular elimination of chloroalkanes97. This technique was reported to be a clean, efficient method for the measurement of high-temperature homogeneous gas-phase reaction rates. A pulse of C02 laser radiation was used to excite multiphoton SiF4... 

The presence of the chain inhibitors cyclohexene and propene, and HBr catalyst showed that the dibromopropane decomposed by concurrent mechanisms of unimolecular elimination and a free-radical chain process. The rate coefficient at maximal inhibition was... 

---