The word "conjugation" is derived from a Latin word that means "to link together". In organic chemistry, it is used to describe the situation that occurs when p systems are "linked together".
• An "isolated" p system exists only between a single pair of adjacent atoms (e.g. C=C) • An "extended" p system exists over a longer series of atoms (e.g. C=C- C=C or C=C-C=O etc.). • An extended p system results in a extension of the chemical reactitvity.
The fundamental requirement for the existence of a conjugated system is revealed if one considers the orbital involved in the bonding within the system.
• A conjugated system requires that there is a continuous array of "p" orbitals that can align to produce a bonding overlap along the whole system. • If a position in the chain does not provide a "p" orbital or if geometry prevents the correct alignment, then the conjugation is broken at that point.
You can investigate these differences by studying the following examples, pay particular attention to the "p" orbitals:
System p system Type
ethene isolated
propene isolated
1,2-propadiene cumulated (allene)
1,3-butadiene conjugated
1,3-pentadiene conjugated
1,4-pentadiene isolated
1,3- conjugated cyclopentadiene
1,3- conjugated cyclohexadiene
1,4- isolated cyclohexadiene
benzene conjugated
The result of conjugation is that there are extra p bonding interactions between the adjacent p systems that results in an overall stabilisation of the system.
Resonance is probably one of the most important concepts that one needs to master in order to understand organic chemistry, yet it is often under appreciated or misunderstood.
We first met resonance in Ch 1
Things to remember about resonance :
• It's a property of π systems, therefore double or triple bonds must be present. • Only the position of π electrons changes in resonance contributors. • Resonance structures can (best) be derived by pushing curved arrows. • The actual molecluar structure is a composite of all the resonance contributors with the more favorable ones contributing the most character. • Delocalisation increases the stablility of systems (esp. for charged systems)
Resonance stabilization of a cation
Resonance stabilization of an anion
• Functional groups next to π systems (i.e. conjugated functional groups) have some reactivity trends that are modified compared to those of the non-conjugated system. Here are a few simple examples:
1. allyl chloride : very reactive in nucleophilic substitution reactions 2. 1,3-butadiene : can undergo addition via two different modes 3. propenal : nucleophiles can add to the C=C due to the presence of the conjugated C=O
Allylic systems
The positions adjacent to C=C often show enhanced reactivity compared to simple alkanes due to the proximity of the adjacent p system. Such positions are referred as "allylic". Recall that the term "vinylic" is used to described the atoms directly associated with the C=C unit. Allylic carbocations
The p system of a double bond can stabilize an adjacent carbocation by donating electron density through resonance. Remember that delocalising charge is a stabilizing effect. This stabilisation is equivalent to that of two alkyl groups, so the allyl cation has similar stability to the 2-propyl cation.
Note that in the two resonance forms of the allylic cation, the positive charge is located on the terminal carbon atoms and never on the middle carbon. This is reflected in the resonance hybrid and the positive areas of the electrostatic potential shown to the right (blue). Note that either of the carbons with +ve charge could be attacked by a nucleophile.
Due to the stability of these allylic cations, they are readily formed as intermediates during chemical reactions, for example SN1 reactions of allylic halides.
Allylic radicals
The p system of a double bond can also stabilize an adjacent radical through resonance. Remember that delocalising the radical is a stabilizing effect.
Due to the stability of these allylic radicals, they are readily formed as intermediates during chemical reactions, for example allylic halogenation. . Reactivity
• Allylic bonds are often weaker and are easily broken, for example compare the bond dissociation energies:
• The stability of the allylic radical can be utilised in the preparation of allylic halides (esp. -Cl and -Br) • Allylic halides readily undergo substitution reactions via either SN1 or SN2 pathways.
Radical Halogenation of Allylic systems
Reaction type: Radical Substitution
Summary:
• When treated with Br2 or Cl2, radical substitution of allylic C-H generates the allyl halide and HX. • The process is very similar to that of alkanes • Reaction proceeds via an radical chain mechanism which involves radical intermediates. • The stability of the allylic radical (due to resonance) favours substitution at the allylic position. • N-bromosuccinimide (NBS) can be used as an alternative source of Br2.
Related reactions
• Halogenation of alkanes • Halogenation of benzylic systems
RADICAL
CHAIN MECHANISM FOR ALLYLIC BROMINATI ON Step 1 (Initiation) Heat or uv light causes the weak halogen bond to undergo homolytic cleavage to generate two bromine radicals and starting the chain process. Step 2 (Propagation ) (a) A bromine radical abstracts a hydrogen to form HBr and an allyl radical, then (b) The allyl radical abstracts a bromine atom from another molecule of
Br2 to form the allyl bromide product and another bromine radical, whic h can then itself undergo reaction 2(a) creating a cycle that can repeat. Step 3 (Termination ) Various reactions between the possible pairs of radicals allow for the formation of Br2 or the product, allyl bromide.
These reactions remove radicals and do not perpetuate the cycle.
Substitution Reactions of Allyl Halides
• Allyl chlorides, bromides and iodides are good substrates for substitution reactions. • A variety of nucleophiles can be used to generate a range of new functional groups. • The process can be complicated by the allylic rearrangement where the nucleophile can attack either of the deficient sites.
Related reactions
• Substitution reactions of alkyl halides • Substitution reactions of benzylic halides
Dienes
• The simplest types of polyenes are those in which there are two double bonds, "dienes". • The relative arrangement of the double bonds dictates the characteristic reactions of the systems. • There are three possible scenarios, which are described below (from most to least stable)
The double bond units occur consecutively giving a continuous π system since the adjacent "p" orbitals can all overlap with each other. The result is that conjugated dienes Conjugated reactivity differs to that of simple alkenes. The extra bonding interaction between
the adjacent p systems makes the conjugated dienes the most stable type of diene. The double bond units occur separately. The π systems are isolated from each other by sp3 Isolated hybridized centers. The result is that isolated dienes have reactivity that is characteristic of
simple alkenes. The double bond units share a common sp hybridized C atom. The Cumulated result is that cumulated dienes have reactivity more like simple alkynes.
Preparation of Conjugated Dienes
• Dienes can be prepared by elimination reactions (review) of unsaturated alcohols and alkyl halides. • The outcome of eliminations typically favors the more stable product, • Since conjugated dienes are more stable than isolated dienes, the formation of the conjugated diene is usually favored over the isolated diene unless the structure prevents the formation of the conjugated system.
Kinetic and Thermodynamic Control
The potential outcome of a reaction is usually influenced by two factors:
1. the realtive stability of the products (i.e. thermodynamic factors) 2. the rate of product formation (i.e. kinetic factors)
The following simple reaction coordinate diagram provides a basis for the key issues about kinetic and thermodynamic control:
Consider the case where a starting material, SM, can react to give two different products, P1 and P2 via different pathways (represented by green and blue lines).
Reaction 1 (green) generates P1. This will be the faster reaction since it has a more stable transition state, TS1, and therefore a lower activation barrier. So P1 is the kinetic product.
Reaction 2 (blue) generates P2. P2 is the more stable product since it is at
lower energy than P1. So P2 is the thermodynamic product.
Now consider what happens as we alter the reaction temperature and so the average energy of the molecules changes.
1. At low tempearture, the reaction preferentially proceeds along the green path to P1 and stops since they lack sufficient energy to reverse to SM, i.e. it is irreversible, so the product ratio of the reaction is dictated by the rates of formation of P1 and P2, k1: k2.
2. At some slightly higher temperature, reaction 1 will become reversible while reaction 2 remains irreversible. So although P1 may form initially, over time it will revert to SM and react to give the more stable P2.
3. At high temperature, both reaction 1 and 2 are reversible and the product ratio of the reaction is dictated by the equilibrium constants for P1 and P2, K1 : K2. Summary :
At low temperature, the reaction is under kinetic control (rate, irreversible conditions) and the major product is that from fastest reaction.
At high temperature, the reaction is under thermodynamic control (equilibrium, reversible conditions) and the major product is the more stable system
Reactions of Dienes
In general terms, dienes undergo electrophilic addition reactions in a similar fashion to alkenes
However, in a little more detail:
• Conjugated dienes undergo addition but the proximity of the conjugated C=C influences the reactions • Isolated dienes react just like alkenes • Cumulated dienes react more like alkynes (after all, both have sp hybridised C atoms)
Our attention here will focus on conjugated dienes.
• The π bonds are a region of high electron density (red) so dienes are typically nucleophiles. • Dienes react with electrophiles + + (e.g. H , X ) • Dienes can undergo addition reactions in which one or both of the π bonds are converted to new stronger s bonds. • Overall reaction : Electrophilic addition
The reactions that will be considered here are:
• addition of hydrogen halides • addition of halogens • Diels-Alder reaction
Addition of Hydrogen Halides to Dienes
Conjugated dienes undergo addition reactions in a similar manner to simple alkenes, but two modes of addition are possible. These differ based on the relative positions of H and X in the products:
Direct H-X adds "directly" across the ends of a C=C Conjugate H-X adds across the ends of the conjugated system The numbers 1,2- and 1,4- denote the relative positions of H and X in the products The distribution of the products depends on the reaction conditions as shown by the example below:
At low temperature, the reaction is under kinetic control (rate, irreversible conditions) and the major product is the from fastest reaction, that of the bromide with the secondary cation.
At room temperature, the reaction is under thermodynamic control (equilibrium, reversible conditions) and the major product is the more stable system (note the more highly substituted alkene). This is supported by the fact that heating pure samples of either 3-bromo-1-butene (direct addition product) or 1-bromo-2- butene (conjugate addition product) gives the same 15 : 85 ratio of 3-bromo-1- butene to 1-bromo-2-butene.
Addition of Halogens to Dienes
Like the addition of hydrogen halides to conjugated dienes, halogens add to dienes via direct and conjugate addition pathways:
The major products are usually the more stable, conjugate addition products with the more stable E configuration of C=C.
Diels-Alder Reaction (Nobel Prize in 1950) • The Diels-Alder reaction is a conjugate addition reaction of a conjugated diene to an alkene (the dienophile) to produce a cyclohexene. • The simplest example is the reaction of 1,3-butadiene with ethene to form cyclohexene:
• The analogous reaction of 1,3-butadiene with ethyne to form 1,4- cyclohexadiene is also known:
• Since the reaction forms a cyclic product, via a cyclic transition state, it can also be described as a "cycloaddition". • The reaction is a concerted process:
• Due to the high degree of regio- and stereoselectivity (due to the concerted mechanism), the Diels-Alder reaction is a very powerful reaction and is widely used in synthetic organic chemistry. • The reaction usually thermodynamically favorable due to the conversion of 2 π-bonds into 2 new stronger σ-bonds. • The two reactions shown above require harsh reaction conditions, but the normal Diels-Alder reaction is favored by electron withdrawing groups on the electrophilic dienophile and by electron donating groups on the nucleophilic diene. • Some common examples of the components are shown below:
Dienes
Dienophiles
Stereoselectivity:
• The Diels-Alder reaction is stereospecific with respect to both the diene and the dienophile. • Addition is syn on both components (bonds form from same species at the same time) • This is shown by the examples below: cis- dienophile gives cis- substituents in the product. trans- dienophile gives trans- substituents in the product. If both substituents on the diene are Z, then both end up on the same face of the product
If substituents on the diene are E and Z, then they end up on opposite fa ces of the product
Cyclic dienes can give stereoisomeric products depending on whether the dienophile lies under or away from the diene in the transition state. The endo product is usually the major product (due to kinetic control)
Diene and dienophile staggered with Diene and dienophile aligned directly respect to each other gives the exo over each other gives the endo product product (dienophile under or in = endo) (dienophile exposed or out = exo)
Compare the relative position of the dienophile fragment in the following CHIME images
Diels-Alder Reaction (Nobel Prize in 1950)