Six membered heterocyclic compounds with one X Structure and Properties The aromatic sextet is complete without participating of the lone pair of nitrogen Molecular orbital The unshared electrons is in sp2 orbital and in the same plane of the ring but other P orbital (including N) is ┴ and has one electron, where it overlapped making the aromatic system

Six membered heterocyclic compounds with one X The difference between benzene and pyridine 1- Benzene symmetrical non-polar but pyridine polar It resist electrophilic substitution only in N-atom or at meta-position It is highly susceptible to neucleophilic substitution

Six membered heterocyclic compounds with one X The difference between benzene and pyridine 2- It is basic compound [its basicity less than aliphatic amine]

Six membered heterocyclic compounds with one X Similarity Like that of benzene ,pyridine is resistant to oxidation, side chain can be oxidized

Six membered heterocyclic compounds with one X Sources of Pyridine Found in coal tar Oxidation of picolines yields the pyridine carboxylic acids α β γ

Six membered heterocyclic compounds with one X

Six membered heterocyclic compounds with one X The 3- isomer is Vitamin The 4- isomer has been used in the form of its hydrazide in treatment of T.B

Six membered heterocyclic compounds with one X Synthesis of Pyridine Hantzsch pyridine synthesis

Six membered heterocyclic compounds with one X Reaction of Pyridine Pyridine behave as both Tertiary amine with protonation, alkylation's, acylation, and N-oxidation Aromatic compounds with Neocleophilic substitution and Electrophilic substitution

Six membered heterocyclic compounds with one X Reaction of Pyridine A: Electrophilic Substitution SE Pyridine resemble highly deactivated benzene derivatives It undergo nitration , sulfonation, and halogenation only under very vigrous condition chiefly at the 3-position

Six membered heterocyclic compounds with one X Why mainly at c-3 ?

Six membered heterocyclic compounds with one X In contrast to benzene, Pyridine is very unreactive to SE reaction ? 1- due to electron withdrawing effect of N in the ring 2- the intermediate is destabilized by electro negativity effect of N 3- rapid formation of pyridinium cation …. So resist further SE reaction

Six membered heterocyclic compounds with one X B: Neucleophilic Substitution SN

Six membered heterocyclic compounds with one X Example 1- Chichibabin Reaction

Six membered heterocyclic compounds with one X Example 2- Alkylation or Arylation Reaction by Organolithium compounds

Six membered heterocyclic compounds with one X C: Reaction at N-1 Alkylation

Six membered heterocyclic compounds with one X C: Reaction at N-1 Acylation

Six membered heterocyclic compounds with one X C: Reaction at N-1 Rx with lewis acid Rx with peracids

Pyridine N-oxide

Six membered heterocyclic compounds with one X Electrophilic ( Nitration)

Six membered heterocyclic compounds with one X Neucleophilic

As before oxidation of Picolines Reduction Oxidation D: Oxidation and Reduction As before oxidation of Picolines

Fused Six membered heterocyclic compounds with one X Quinoline Benzo[b]pyridine 1-azanaphthaline Isoquinoline Benzo[c]pyridine 2-azanaphthaline Both are weak bases Both undergo SE more easly than pyridine in position 5 and 8 on benzoid ring, no on the deactivated N-ring Why? Like pyridine , N-ring of quinoline and isoquinoline undergo SN at α position

Fused Six membered heterocyclic compounds with one X

Fused Six membered heterocyclic compounds with one X

Fused Six membered heterocyclic compounds with one X Synthesis of Quinoline Skraup Synthesis Describe the mechanism

Fused Six membered heterocyclic compounds with one X Bischler Nepieralski Synthesis

Fused Six membered heterocyclic compounds with one X Electrophilic Substitution Nitration Sulfonation Halogenation

Fused Six membered heterocyclic compounds with one X Nucleophilic Substitution Hydroxylation Alkylation Or Arylation with organo- Amination

Fused Six membered heterocyclic compounds with one X Oxidation & Reduction Reduction Oxidation

Fused Six membered heterocyclic compounds with one X Other fused ring

Fused Six membered heterocyclic compounds with one X Diazines Used only in research as building block for more complex comp. Three neucleobases found in nucleic acid cytosine thyamine uracil -Found in folic acid & cigarette der. - Less basic than the other two

Six membered heterocyclic compounds with two N Diazines In DNA & RNA, these bases form H-bonds with their complementary Purines DNA A________ T G________ C RNA A________ U Chemical properties of Pyrimidines in common with pyridine, as number of N-atoms in the ring increase the ring π- electrons become less energetic So SE gets more difficult while SN gets easier

Fused Six membered heterocyclic compounds with two X Purines Contain pyrimidine fused to imidazole ring

Fused Six membered heterocyclic compounds with one X

Miscellaneous Dibenzothiazine or Thiodiphenylamine Drugs containing this nucleus used as antipsychotic and adrenergic blocker H.W find 2 drugs and draw their structures

Miscellaneous Hypnotic, Sedative, Anxiolytic Anticonvulsant, Muscle relaxant Properties Valium

Miscellaneous Preparation of Valium