lecture72012nonotes

lecture72012nonotes - 1 2 3 Basicity of heterocyclic amines...

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: 1 2 3 Basicity of heterocyclic amines H N N pKb 3.0 pKaH 11 N H H 2.8 H N H N O 4.2 8.4 9.8 11.2 5.6 H N N H H N N H H H O N H H H 4 DNA and RNA delivery 5 Basicity of heterocyclic amines H N N pKb 3.0 pKaH 11 N H H 2.8 H N H N O 4.2 8.4 9.8 11.2 5.6 H N N H H N N H H H O N H H H 6 7 BaylisBaylis-Hillman Reaction 1. Aldol Condensation 8 BaylisBaylis-Hillman Reaction 2. Elimination and formation of -carbonyl product 9 BaylisBaylis-Hillman Reaction 3. Conjugate Addition 10 BaylisBaylis-Hillman Reaction 11 BaylisBaylis-Hillman Reaction 12 BaylisBaylis-Hillman Reaction 13 14 Aziridines and Azetidines – Ring Strain 1. s- Character and Basicity 15 16 Aziridines and Azetidines – Ring Strain 1. s- Character and Basicity 17 Aziridines and Azetidines – Ring Strain 2. Resonance Structures 18 Aziridines and Azetidines – Ring Strain 3. Pyramidal Inversion and Chirality 19 Aziridines and Azetidines – Ring Strain 4. Reactivity 20 21 Rates of Ring-Closing Reactions H2N n Product: Br NH Relative Rate: 0.07 N H 0.001 HN 100 N H 1 N H 0.002 N H 22 Rates of Ring-Closing Reactions H2N n Product: 5-membered>6>3>7>4>8-10 Br NH Relative Rate: 0.07 N H 0.001 HN 100 N H 1 N H 0.002 N H 23 Rates of Ring-Closing Reactions H2N 5-membered>6>3>7>4>8-10 n Product: G = H - T S Br NH Relative Rate: 0.07 H Enthalpy of activation: RING STRAIN N H 0.001 HN 100 N H 1 N H 0.002 N H 24 Rates of Ring-Closing Reactions H2N n 5-membered>6>3>7>4>8-10 Product: G = H - T S Br NH Relative Rate: 0.07 N H H RING STRAIN 0.001 6-membered, most stable > 5 >>4>3 HN 100 N H 1 N H 0.002 N H 25 Rates of Ring-Closing Reactions H2N n 5-membered>6>3>7>4>8-10 Product: G = H - T S Br NH Relative Rate: 0.07 N H H RING STRAIN 0.001 6-membered, most stable > 5 >>4>3 HN 100 Medium rings (8-10) – transannular interactions N H 1 N H 0.002 N H 26 Rates of Ring-Closing Reactions H2N n 5-membered>6>3>7>4>8-10 Product: G = H - T S Br NH Relative Rate: 0.07 N H H RING STRAIN 0.001 6-membered, most stable > 5 >>4>3 HN 100 Medium rings (8-10) – transannular interactions N H 1 DOES NOT EXPLAIN WHY 5>6 and 3>4 NOT EXPLAIN WHY 5>6 and 3>4 N H 0.002 N H 27 Rates of Ring-Closing Reactions 5-membered>6>3>7>4>8-10 G = H - T S H RING STRAIN STRAIN 6-membered, most stable > 5 >>4>3 Medium rings (8-10) – transannular interactions S ENTROPY of ACTIVATION 5>6 3>4 4, both ring strain and more negative entropy 8-10, significantly negative entropy and transannular interactions 28 29 30 Aromatic Heterocycles N N S O H Pyridine Furan Pyrrole N N N N Pyridazine Pyrimidine Thiophene N N Pyrazine (DNA/RNA) N N N N H H N Pyrazole Imidazole (DNA/RNA) Quinoline 31 Antipyrine One of the oldest synthetic drugs (1887) Quinine 16th century (antimalarial) Sulfapyridine First effective Antibiotic (1938) Chloroquine (antimalarial) Tagamet Ulcer treatment (1970) Viagra (1997) 32 33 Huckel’s Aromaticity Rules: If a molecule is: Aromatic molecules have full outer shell: stable, inert inert 1. Cyclic 2. Planar, fully conjugated Each member of the cycle has a p orbital parallel to all the others 3. Total number of electrons in p orbitals: orbitals: 4n+2, n= integer= 0, 1, 2, 3, n= 0, 4n+2= 2 n= 3, 4n+2=14 4n+2 n= 1, 4n+2= 6 n= 2, 4n+2= 10 34 Benzene 1. Cyclic 2. Planar, conjugated Each atom sp2 There is a p orbital on each C parallel to all others 3. 6 electrons (4x1 + 2) Aromatic extra stable 35 Heterocyclic Molecules Pyrrole N H 36 Heterocyclic Molecules Pyrrole 1. Cyclic N H 2. Fully conjugated 3. 6 electrons AROMATIC 37 Heterocyclic Molecules 1. Cyclic Furan O O 2. Fully conjugated 3. How many electrons? Second lone pair in perpendicular sp2 orbital, does not participate 6 electrons, aromatic Count ONLY 1 pair of e- on each atom 38 Pyridine 1. Cyclic N 2. Fully conjugated 3. 6 electrons Not counted (we already counted N bond) N 39 Aromatic Heterocycles N N S O H Pyridine Furan Pyrrole N N N N Pyridazine Pyrimidine Thiophene N N Pyrazine (DNA/RNA) N N N N H H N Pyrazole Imidazole (DNA/RNA) Quinoline 40 Antipyrine One of the oldest synthetic drugs (1887) Quinine 16th century (antimalarial) Sulfapyridine First effective Antibiotic (1938) Chloroquine (antimalarial) Tagamet Ulcer treatment (1970) Viagra (1997) 41 Huckel’s Aromaticity Rules: If a molecule is: Aromatic molecules have full outer shell: stable, inert inert 1. Cyclic 2. Planar, fully conjugated Each member of the cycle has a p orbital parallel to all the others 3. Total number of electrons in p orbitals: 4n+2, n= integer= 0, 1, 2, 3, n= 0, 4n+2= 2 n= 3, 4n+2=14 4n+2 n= 1, 4n+2= 6 n= 2, 4n+2= 10 42 Nucleophilicity of acyclic vs. cyclic amines 43 44 BaylisBaylis-Hillman Reaction 45 46 47 48 ...
View Full Document

This note was uploaded on 03/06/2012 for the course CHEM 302 taught by Professor Sleiman during the Winter '12 term at McGill.

Ask a homework question - tutors are online