Generally, elimination is favored over substitution when steric hindrance around the α-carbon increases. a stronger base is used. temperature increases An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one- or two-step reaction mechanism. The most common types of reaction mechanisms are a one-step mechanism known as the E2 reaction and a two-step mechanism is known as the E1 reaction. The numbers in the Hughes–Ingold symbols refer not to the number of steps in the mechanism, b ste… It is typically undergone by primary substituted alkyl halides, but is possible with some secondary alkyl halides and other compounds. The reaction rate is second order, because it is influenced by both the alkyl halide and the base (bimolecular). Because the E2 mechanism results in the formation of a pi bond, the two leaving groups (often a hydrogen and a halogen) need to be antiperiplanar. An antiperiplanar transition state has staggered conformation with lower energy than a synperiplanar transition state which is in eclipsed conformation with higher energy. The reaction mechanism involving staggered conformation is more favorable for E2 reactions (unlike E1 reactions). E2 typically uses a strong base. It must be strong enough to remove a weakly acidic hydrogen. In order for the pi bond to be formed, the hybridization of carbons needs to be lowered from sp3 to sp2. The C-H bond is weakened in the rate determining step and therefore a primary deuterium isotope effect much larger than 1 (commonly 2-6) is observed. E2 competes with the SN2 reaction mechanism if the base can also act as a nucleophile (true for many common bases). An example in scheme 2 is the reaction of tert-butylbromide with potassium ethoxide in ethanol. E1 eliminations happen with highly substituted alkyl halides for two main reasons. steric hindrance around the α-carbon increases. a stronger base is used. temperature increases (increase entropy) the base is a poor nucleophile. Bases with steric bulk, (such as in potassium tert-butoxide), are often poor nucleophiles. For example, when a 3° haloalkane is reacts with an alkoxide, due to strong basic character of the alkoxide and unreactivity of 3° group towards SN2, only alkene formation by E2 elimination is observed. Thus, elimination by E2 limits the scope of the Williamson ether synthesis (an SN2 reaction) to essentially only 1° haloalkanes; 2° haloalkanes generally do not give synthetically useful yields, while 3° haloalkanes fail completely. With strong base, 3° haloalkanes give elimination by E2. With weak bases, mixtures of elimination and substitution products form by competing SN1 and E1 pathways. The case of 2° haloalkanes is relatively complex. For strongly basic nucleophiles (pKaH > 11, e.g., hydroxide, alkoxide, acetylide), the result is generally elimination by E2, while weaker bases that are still good nucleophiles (e.g., acetate, azide, cyanide, iodide) will give primarily SN2. Finally, weakly nucleophilic species (e.g., water, alcohols, carboxylic acids) will give a mixture of SN1 and E1. For 1° haloalkanes with β-branching, E2 elimination is still generally preferred over SN2 for strongly basic nucleophiles. Unhindered 1° haloalkanes favor SN2 when the nucleophile is also unhindered. However, strongly basic and hindered nucleophiles favor E2. In general, with the exception of reactions in which E2 is impossible because β hydrogens are unavailable (e.g. methyl, allyl, and benzyl halides), clean SN2 substitution is hard to achieve when strong bases are used, as alkene products arising from elimination are almost always observed to some degree. On the other hand, clean E2 can be achieved by simply selecting a sterically hindered base (e.g., potassium tert-butoxide). Similarly, attempts to effect substitution by SN1 almost always result in a product mixture contaminated by some E1 product (again, with the exception of cases where the lack of β hydrogens makes elimination impossible). In one study the kinetic isotope effect (KIE) was determined for the gas phase reaction of several alkyl halides with the chlorate ion. In accordance with an E2 elimination the reaction with t-butyl chloride results in a KIE of 2.3. The methyl chloride reaction (only SN2 possible) on the other hand has a KIE of 0.85 consistent with a SN2 reaction because in this reaction type the C-H bonds tighten in the transition state. The KIE's for the ethyl (0.99) and isopropyl (1.72) analogues suggest competition between the two reaction modes. The next most common type of elimination reaction is α-elimination. For a carbon center, the result of α-elimination is the formation of a carbene, which includes "stable carbenes" such as carbon monoxide or isocyanides. For instance, α-elimination the elements of HCl from chloroform (CHCl3) in the presence of strong base is a classic approach for the generation of dichlorocarbene, :CCl2, as a reactive intermediate. On the other hand, formic acid undergoes α-elimination to afford the stable products water and carbon monoxide under acidic conditions. α-Elimination may also occur on a metal center, one particularly common result of which is lowering of both the metal oxidation state and coordination number by 2 units in a process known as reductive elimination. (Confusingly, in organometallic terminology, the terms α-elimination and α-abstraction refer to processes that result in formation of a metal-carbene complex. In these reactions, it is the carbon adjacent to the metal that undergoes α-elimination.) In certain special cases, γ- and higher eliminations to form three-membered or larger rings is also possible in both organic and organometallic processes. For instance, certain Pt(II) complexes undergo γ- and δ-elimination to give metallocycles. More recently, γ-silyl elimination of a silylcyclobutyl tosylate has been used to prepare strained bicyclic systems.