Pyridine N-oxides are reactive towards both electrophilic and nucleophilic substitution

 This is all very well if the molecule has such activating groups, but supposing it doesn’t? How are we to nitrate pyridine itself? The answer involves an ingenious trick. We need to activate the ring with an electron-rich substituent that can later be removed and we also need to stop the nitrogen atom reacting with the electrophile. All of this can be done with a single atom! Because the nitrogen atom is nucleophilic, pyridine can be oxidized to pyridine N-oxide with reagents such as m-CPBA or just H₂O₂ in acetic acid. These N-oxides are stable dipolar species with the electrons on oxygen delocalized round the pyridine ring, raising the HOMO of the molecule. Reaction with electrophiles occurs at the 2- (ortho) and 4- (para) positions, chiefly at the 4-position to keep away from positively charged nitrogen.

Now the oxide must be removed and this is best done with trivalent phosphorus com pounds such as (MeO)₃P or PCl₃. The phosphorus atom detaches the oxygen atom in a single step to form the very stable P=O double bond. In this reaction the phosphorus atom is acting as both a nucleophile and an electrophile, but mainly as an electrophile since PCl₃ is more reactive here than (MeO)₃P. The same activation that allowed simple electrophilic substitution—oxidation to the N-oxide—can also allow a useful nucleophilic substitution. The positive nitrogen atom encourages nucleophilic attack and the oxygen atom can be turned into a leaving group with PCl3. Our example is nicotinic acid.

The N-oxide reacts with PCl₃ through oxygen and the chloride ion released in this reaction adds to the most electrophilic position between the two electron-withdrawing groups. Now a simple elimination restores aromaticity and gives a product looking as though it results from chlorination rather than nucleophilic attack.

The reagent PCl₃ also converts the carboxylic acid to the acyl chloride, which is hydrolysed back again in the last step. This is a useful sequence because the chlorine atom has been intro duced into the 2-position, from which it may in turn be displaced by, for example, amines.

●Pyridine N-oxides Pyridine N-oxides are useful for both electrophilic and nucleophilic substitutions on the same carbon atoms (2-, 4-, and 6-) in the ring.

 Nucleophilic addition at an even more distant site is possible on reaction with acid anhydrides if there is an alkyl group in the 2-position. Acylation occurs on oxygen as in the last reaction but then a proton is lost from the side chain to give an uncharged intermediate.

This compound rearranges with migration of the acetate group to the side chain and the restoration of aromaticity. This may be an ionic reaction or a type of rearrangement that you will learn to call a [3,3]-sigmatropic rearrangement.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الشؤون الفكرية يختتم المرحلة الثالثة من مشروع استعادة مكتبة جامعة الموصل

جامعة الكفيل تنظّم دورة حول نظام (كوها) العالمي لإدارة المكتبات الجامعية في النجف

مجموعة مشاتل الكفيل: إضافة نحو 70 نوعًا جديدًا من المغروسات تتناسب مع الظروف المناخية المحلية

المجمَع العلمي يطلق الدورة التطويرية الخامسة لمعلمي التربية الإسلامية ومدرسيها في النجف الأشرف

المزيد

الآخبار الصحية

اختراق علمي.. دواء يؤخر ظهور السكري من النوع الأول لسنوات

هذا ما يحدث لجسمك إن أهملت نظافة فراشك

لماذا تعتبر النساء أكثر عرضة للإصابة بألزهايمر من الرجال؟

لماذا يحذر الخبراء من الإفراط في تناول الفراولة؟

المزيد

الآخبار التكنلوجية

السيارات الكهربائية أنظف بنسبة 73% من سيارات الوقود

سيارة لوسِد الكهربائية تدخل "غينيس" بأطول مدى في العالم

نظرية جديدة تنسف كل ما نعرفه عن تشكل أول قارة في الأرض

منذ 37 ألف عام.. دراسة تكشف "أقدم أمراض" أصابت البشر

المزيد

مواضيع ذات صلة

Furan and thiophene are oxygen and sulfur analogues of pyrrole

Five-membered aromatic heterocycles are good at electrophilic substitution

Pyridine as a catalyst and reagent

Pyridones are good substrates for nucleophilic substitution

Nucleophilic substitution is easy with pyridines

Pyridine is bad at electrophilic aromatic substitution

Pyridine is a very unreactive aromatic imine

Aromaticity survives when parts of benzene’s ring are replaced by nitrogen atoms

The Claisen ester disconnection: a 1,3-diO relationship needing two carbonyl groups

Aldol-style disconnections with N and O in a 1,3-relationship: I

Look out for concealed functional group relationships

Donor and acceptor synthons