The allylic bromides that can be made by these radical reactions display interesting regio selectivity. We shall start with some substitution reactions with which you are familiar. There we said that allyl bromide is about 100 times more reactive towards simple SN2 reactions than is propyl bromide or other saturated alkyl halides. The double bond stabilizes the SN2 transition state by conjugation with the p orbital at the carbon atom under attack. This full p orbital (shown in orange in the diagram below) forms a partial bond with the nucleophile and with the leaving group in the transition state. Any stabilization of the transition state will, of course, accelerate the reaction by lowering the energy barrier.

There is an alternative mechanism for this reaction that involves nucleophilic attack on the alkene instead of on the saturated carbon atom. This mechanism leads to the same product and is often called the SN2' (pronounced ‘S-N-two-prime’) mechanism.

We can explain both mechanisms in a unified way if we look at the frontier orbitals involved. The nucleophile must attack an empty orbital (the LUMO), which we might expect to be sim ply σ* (C–Br) for the SN2 reaction. But this ignores the alkene. The interaction between π* (C=C) and the adjacent σ* (C–Br) will asusual produce two new orbitals, one higher and one lower in energy. The lower-energy orbital, π* + σ*, will now be the LUMO. To construct this orbital, we must put all the atomic orbitals parallel and make the contact between π* + σ* a bonding interaction.

If the allylic halide is unsymmetrically substituted, a question of regioselectivity arises. The products from SN2 and SN2' are different and the normal result is that nucleophilic attack occurs at the less hindered end of the allylic system, whether that means SN2 or SN2'. This important allylic bromide, known as prenyl bromide, normally reacts entirely via the SN2 reaction.

The two ends of the allylic system are contrasted sterically: direct (SN2) attack is at a primary carbon while allylic (SN2') attack is at a tertiary carbon atom so that steric hindrance favours the SN2 reaction. In addition, the number of substituents on the alkene product means that the SN2 product is nearly always preferred—SN2 gives a trisubstituted alkene while the SN2' product has a less stable monosubstituted alkene. An important example is the reaction of prenyl bromide with phenols. This is simply carried out with K₂CO₃ in acetone as phenols are acidic enough (pKa ~ 10) to be substantially deprotonated by carbonate. The product is almost entirely from the SN2 route, and is used in the Claisen rearrangement.

If we make the two ends of the allyl system more similar, say one end primary and one end secondary, things are more equal. We could consider the two isomeric butenyl chlorides.

All routes look reasonable, although we might again expect faster attack at the primary carbon. The reactions in the left-hand box are preferred to those in the right-hand box. But there is no special preference for the SN2 over the SN2' mechanism or vice versa—the individual case decides. If we react the secondary butenyl chloride with an amine we get the SN2' mechanism entirely.

If the primary chloride is used, once again we get nucleophilic attack at the primary centre. The more stable product with the more highly substituted alkene is formed this time by the SN2 reaction. Here is a slightly more advanced example:

Notice that these reactions take place with allylic chlorides. We should not expect an alkyl chloride to be particularly good at SN2 reactions as chloride ion is only a moderate leaving group and we should normally prefer to use alkyl bromides or iodides. Allylic chlorides are more reactive because of the alkene. Even if the reaction occurs by a simple SN2 mechanism without rearrangement, the alkene is still making the molecule more electrophilic. You might ask a very good question at this point. How do we know that these reactions really take place by SN2 and SN2' mechanisms and not by an SN1 mechanism via the stable allyl cation? Well in the case of prenyl bromide, we don’t! In fact, we suspect that the cation prob ably is an intermediate because prenyl bromide and its allylic isomer are in rapid equilibrium in solution at room temperature.

The equilibrium is entirely in favour of prenyl bromide because of its more highly substi tuted double bond. Reactions on the tertiary allylic isomer are very likely to take place by the SN1 mechanism: the cation is stable because it is tertiary and allylic and the equilibration tells us it is already there. Even if the reactions were bimolecular, no SN2' mechanism would be necessary for the tertiary bromide because it can equilibrate to the primary isomer more rap idly than the SN2 or SN2' reaction takes place. Even the secondary system we also considered is in rapid equilibrium when the leaving group is bromide. This time both allylic isomers are present, and the primary allylic isomer (known as crotyl bromide) is an E/Z mixture. The bromides can be made from either alcohol with HBr and the same ratio of products results, indicating a common intermediate in the two mechanisms. You saw at the beginning of Chapter 15 that this reaction is restricted to alco hols that can react by SN1.

Displacement of the bromide by cyanide ion, using the copper(I) salt as the reagent, gives a mixture of nitriles in which the more stable primary nitrile predominates even more. These can be separated by a clever device. Hydrolysis in concentrated HCl is successful with the predominant primary nitrile but the more hindered secondary nitrile does not hydrolyse. Separation of compounds having two different functional groups is easy: in this case the acid can be extracted into aqueous base, leaving the neutral nitrile in the organic layer.

Once again, we do not know for sure whether this displacement by cyanide goes by the SN1 or SN2' mechanism, as the reagents equilibrate under the reaction conditions. However, the chlorides do not equilibrate and so, if we want a clear-cut result on a single well-defined start ing material, the chlorides are the compounds to use. But you already see that regioslectivity with allylic compounds may depend on steric hindrance, rates of reaction, and stability of the product.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الشؤون الدينية يُطلق دورة فقهية دينية لملاكات مستشفى الكفيل

شعبة فاطمة بنت أسد للدراسات القرآنية تعلن نتائج مسابقة (ميثاق الرسول)

شعبة الخطابة الحسينية النسوية تنظّم مسابقة فرقية لطالبات برنامج ثمار العطاء

قسم العلاقات ينظم ورشة عن فن الإقناع والتواصل الفعّال للطلبة المنسقين

المزيد

الآخبار الصحية

تغيير بسيط في نمط التفكير قد يحدث فرقا كبيرا لصحة الدماغ ؟

لماذا ينعشنا المشروب الساخن في الطقس الحار؟

علماء يكتشفون فئة دم فريدة من نوعها في العالم !

لماذا ينصح الأطباء بزيت الزيتون يوميا؟

المزيد

الآخبار التكنلوجية

حساس الإطارات.. ما هو وعلامات تلفه وكيفية صيانته؟

ما معنى أودي Quattro؟ سر الأداء والتميز الهندسي ؟!

فصل الشاحن أم الهاتف أولا؟.. عادات بسيطة تطيل عمر البطارية

تعود للقرن الرابع قبل الميلاد.. اكتشاف بقايا "إيمت" المصرية

المزيد

مواضيع ذات صلة

Alkylation of nitroalkanes

Alkylation of nitriles

Some important considerations that affect all alkylations

Conjugate addition

Electrophilic attack on conjugated dienes

Regiospecific preparation of allylic chlorides

Radical abstraction

Radical addition

Electrophilic attack on alkenes

Regioselectivity of intramolecular reactions

Regiocontrol by choice of route

Regioselective reactions of naphthalene