Methodical Instruction for Students of the 2 Course pharmaceutical Faculty
LESSON № 19 (PRACTICAL – 6 HOURS)
Themes: 1. Pyrane, pyridine. Small practicum.
2. Condensed azines. Quinoline. Isoquinoline. Acridine. Small.
Aim: To learn: a structure, classification, nomenclature, isomerism, methods of getting and chemical properties of the sixmember heterocycliccompounds with one heteroatom.
Professional orientation of students:
Heterocycles containing as a heteroatom atom of nitrogen, behave to the most widespread representatives of this group of connections (azynes).
Pyridine, obtained commercially by distillation of coal tar, is the nitrogen – containing heterocyclic analog of benzene. Like benzene, pyridine is a flat, aromatic molecule with bond angles of 120° and C-C bond lengths of 139 pm, intermediate between typical single and double bonds. The five carbon atoms and sp²- hybridized nitrogen atom each contribute one π electron to the aromatic sextet. Unlike the situation in pyrrole, the lone pair of electrons on the pyridine nitrogen atom occupies ansp² orbital in the plane of the ring and is not involved in bonding.
Pyrones or pyranones are the class of cyclic chemical compounds. They contain an unsaturated six member ring containing one oxygen atom and a ketone functional group. There are two isomers denoted as 2-pyrone and 4-pyrone. The 2-pyrone structure is found iature as part of the coumarin ring system. 4-Pyrone is found in some natural chemical compounds such as meconic and helidonic acid.
Methodology of Practical Class (900-1200).
Experiment 1. Pyridine and its properties
Reagents: pyridine, iron (III) chloride (5% solution), hydrochloric acid (concentrated), picric acid (saturated aqueous solution), potassium permanganate (1% and solution), sodium carbonate (5% and solution) , methyl iodide. Experiments with pyridine should be conducted under the drawing cupboard.
A. Pyridine solubility in water
Technique of the experiment. In the test tube pour 1 ml of pyridine and 3,5 ml of distilled water. The transparent solution forms. Thus, pyridine is well soluble in water. Obtained aqueous solution of pyridine is kept for the next experiments.
B. Basic properties of pyridine
Technique of the experiment. Drop of the obtained aqueous solution of pyridine is applied on the strip of red litmus paper. Red litmus becomes blue. Thus, pyridine has basic properties and interacts with water with the formation of pyridine hydroxide.
C. Interaction of iron (III) chloride with aqueous solution of pyridine
Technique of the experiment. In test-tube pour 1 ml of aqueous pyridine solution with a few drops of 5% solution of iron chloride (III). Precipitate of iron (III) hydroxide forms, which confirm the presence of hydroxide anion in the aqueous solutions of pyridine.
D. Interaction pyridine with acids and formation of pyridine salts
Technique of the experiment. To the dry test tube carefully add one drop of pyridine and a few drops of concentrated hydrochloric acid. Strong warming is observed in the reaction mixture and formation of white precipitate of pyridine chloride. Add water to the obtained precipitate of pyridine chloride, the sediment dissolved. Pyridine chloride is well soluble in water.
E. Formation of pyridine picrate
Technique of the experiment. To 2-3 ml of the saturated aqueous solution of picric acid add 0,5 ml of the aqueous solution of pyridine, (prepared in experiments A). While standing for 5-10 minutes beautiful needle crystals of pyridine picrate are gradually allocated in the reaction mixture.
Experiment 2. Quinoline and its properties
Reagents: quinoline; red litmus paper, hydrochloric acid (concentrated),picric acid (saturated aqueous solution), potassium permanganate (1% and solution), sodium carbonate (5% solution), methyl iodide. Experiments with quinoline should be conducted under the drawing cupboard.
A. Solubility of quinoline in water
Technique of the experiment. To the test tube bring 1 ml of quinoline and 5 ml of distilled water. Observe that unlike the pyridine quinoline is less soluble in water.Obtained water solution of quinoline is separated by decantation from quinoline which did not dissolve in water, and is used for the next experiments.
B. Basic properties of quinoline
Technique of the experiment. Drop of the obtained aqueous solution of quinoline is applied on the strip of red litmus paper. Red litmus paper becomes blue. So, like pyridine quinoline has basic properties.
C. Interaction of quinoline with acids and formation of quinoline salts
Technique of the experiment. To the dry test tube bring one drop of quinoline carefully add by drops concentrated hydrochloric acid solution. Strong warming is observed in the reaction mixture and formation of white precipitate of quinoline chloride. If you add water to the obtained reaction mixture, sediment dissolved because quinoline chloride is well dissolved in water.
D. Formation of quinoline picrate
Technique of the experiment. Up to 2 ml of saturated aqueous solution of picric acid 0,5 ml of quinoline aqueous solution is added. Observe formation of the quinoline picrate sediment.
E. Oxidation of quinoline
Technique of the experiment. To 1 ml of water solution of quinoline 2 ml of 1% solution of potassium permanganate and 0,5 ml 5% solution of sodium carbonate are added. The obtained reaction mixture is heated in a flame of a gas burner or spirit lamp. Observe the rapid bleaching of permanganate. So, unlike the pyridine quinoline can be easily oxidized by permanganate. It undergoes oxidation of benzene nucleus of quinoline molecules and dibasic α,β-pyridinedicarboxylic acid (quinoline acid) forms.
F. Formation of the quinoline tetraammonium salts.
Technique of the experiment. In a dry test tube mix 0,5 ml of quinoline and 0,5 ml of methyl iodide. Reactionary mixture quickly becomes cloudy, oil product – iodide of N-methylquinoline evaporates, which quickly becomes solid.
Individual Students Program.
1. Nomenclature of pyridine and its derivatives.
2. Methods of obtaining of pyridine and its homologues.
3. Physical and chemical properties of pyridine:
a. reactions, which lead by heteroatom;
b. reactions of hydrogen atoms substitution in the pyridine cycle (electrophilic (SЕ) and nucleophilic (SN) substitution);
c. reduction;
d. oxidation.
4. Pyridine-N-oxide: structure, ration to electrophilic and nucleophilic reagents.
5. Pycolines: obtaining, properties.
6. Hydroxypyridines and aminopyridines: methods of obtaining, tautomery, chemical properties.
7. Pyridinecarboxylic acids: nomenclature, methods of obtaining, chemical properties, the most important functional derivatives.
8. Identification of pyridine and its derivatives.
9. Some representatives, usage.
10. Physical and chemical properties of quinoline, isoquinoline and acridine:
a. reactions, which lead by heteroatom;
b. reactions of electrophilic substitution, their specialties and rules of orientationsin the quinoline and isoqunoline nuclei;
c. reactions of nucleophilic substitution;
d. reduction;
e. oxidation.
Seminar discussion of theoretical issues (1230 – 1400 hour).
Test evaluation and situational tasks.
Home task. 1, 2, 3.
1. Write structural formulas of these compounds:
1)β-pycoline; 2) pyridine-N-oxide; 3) pyridine sulfate; 4) γ-ethylpyridine; 5) N-methylpyridine iodide; 6) N-acetylpyridine chloride; 7) isonicotinic acid; 8) 2-pyridinole; 9) 4-pyridone; 10) 3-pyridineamine; 11) piperidine chloride.
2. Give the correct names of the next structural formulas:
3. Write the scheme of the receiving of pyridine:
from acetylene and hydrocyanic acid; 2) from corresponding aldehydes and ammonia.
4. Characterize electronic structure of pyridine. Explain why pyridine is π-deficit aromatic system.
5. Write the scheme of possible reactions of pyridine with the following reagents:
1)НВг; 2) conc. Н2SО4, 0°C; 3) conc. Н2SО4, SО3, НgSО4, t; 4) KNO3, conc. Н2SО4, t; 5) Вг2 (СС14); 6) Вг2, SО3, t; 7) КМnО4 (Н20); 8) СН3СОООН;9) С2Н5Вг; 10) (СН3СО)2О; 11) СН3СОС1 (А1С13); 12) КОН (Н2О); 13) КОН (s), t; 14) NaNH2, NН3 (l). Name the products.
6. Give the right names of the next structural formulas:
7. Note similarities and differences in the chemical properties of benzene and pyridine. Explain why pyridine dose not react with alkylation and acylation agents by Friedel-Crafts.
8. Point the scheme of obtaining of pyridine-N-oxide. Write to the scheme of nitration, sulfonation, amination, hydroxylation and acylation of pyridine-N-oxide. Name the products.
9. Write to the scheme of partial and total reduction of pyridine. Note specify conditions. Name the products. Compare basic properties of pyridine and piperidine. Explain your answer.
10. Write structural formulas of the next compounds: 1) benzo[6] pyridine; 2) benzo[c]pyridine; 3) 8-hydroxyquinoline; 4) 8-hydroxy-7-iodine-5-chloroquinoline; 5) dibenzo [6, e] pyridine; 6) 6,9-diamino-2-etoxyacridine; 7) 9-(4′-dietylamino-N-metylbutylamino)-2-methoxy-6-chloracridine dihydrochloride; 8) 3,6-diamino-9-metylacridine chloride; 9) 2,3-quinolinedycarbonic acid. Provide other possible names of these compounds.
11. Give the right names of the next structural formulas:
12. Using of the Skraup synthesis, write the schemes of receiving:
8-hydroxyhinoline; 2) 6-methoxi-8-nitroquinoline; 3) 8-hydroxi-5-nitroquinoline.
13. Write structural formulas of the next compounds: 1) α-pyrane; 2) β-pyrone; 3) 4-methoxypyrile iodide; 4) 4-hydroxycoumarone; 5) benzo[b]-4-pyrone; 6) 2-phenylchromone.
14. Compare the reaction ability of pyrrole and pyridine. Explain ratio of heterocycles to mineral acids. Point the schemes of nitration, sulfonation, halogenation ofpyrrole and pyridine. Name the products.
15. Nitrogen atom in the pyridine molecule can react with:
A. Chloride acid.
B. Potassium hydroxide.
C. Calcium oxide.
D. Potassium carbonate.
E. Potassium amide.
16. Which of the following acids is pro-vitamin РР?
A. Pycolinic.
B. Isonicotinic.
C. Nicotinic.
D. Salicylic.
E. Anthranilic.
17. Choose correct name of the following compound:
A. 5-isoquinoline sulfoacid
B. 9-chloroacridine
C. α-pyrone
D. Pyridone-4
E. Pyridine sulfotrioxide
18. Choose correct name of the following compound:
A. 3-aminopyridine
B. 4-hydroxypyrane chloride
C. Benzo[c]pyridine
D. Pyridine chloride
E. 2-aminoquinoline
Correct answers of test evaluations and situational tasks:
15. A; 16. C; 17.E; 18 D.
Individual student work (1415-1500 hour) are checked by solving situational tasks for each topic, answers in test evaluations and constructive questions (the instructor has tests & situational tasks).
Student should know:
– structure, classification, nomenclature, isomers, methods of getting and chemical properties of sixmember heterocycliccompounds with one heteroatom.
Student should be able to:
-on the basis of functional groups to attribute matters to the certain class of organic compounds;
– to give the names of organic connections with the help of rational and international (IUPAC) top- level systems;
– to conduct reactions which characterize of chemical properties of sixmember heterocyclic compounds with one heteroatom.
References:
Main:
1. Clayden Jonathan. Organic Chemistry. Jonathan Clayden, Nick Geeves, Stuart Warren // Paperback, 2nd Edition. – 2012. – 1234 p.
2. Bruice Paula Y.Organic Chemistry / Paula Y. Bruice // Hardcover, 6th Edition. – 2010. – 1440 p.
3. Brückner Reinhard. Organic Mechanisms – Reactions, Stereochemistry and Synthesis / Reinhard Brückner // Hardcover, First Edition. – 2010. – 856 p.
4. Moloney Mark G. Structure and Reactivity in Organic Chemistry / Mark G. Moloney // Softcover, First Edition. – 2008. – 306 p.
5. Carrea Giacomo. Organic Synthesis with Enzymes in Non-Aqueous Media / Giacomo Carrea, Sergio Riva // Hardcover, First Edition. – 2008. – 328 p.
6. Smith Michael B. March’s Advanced Organic Chemistry. Reactions, mechanisms, and structure / Michael B. Smith, Jerry March // Hardcover, 6th Edition. – 2007. – 2384 p.
7. Carey Francis A. Advanced Organic Chemistry / Francis A. Carey, Richard A. Sundberg // Paperback, 5th Edition. – 2007. – 1199 p.
8. http://intranet.tdmu.edu.ua/data/kafedra/internal/zag_him/classes_stud/pharmaceutical/pharmacy/full_time_study/organic_chemistry/2_course/lesson_19.Pyrane, pyridine. Condensed azines. Quinoline. Isoquinoline. Acridine.
9. http://intranet.tdmu.edu.ua/data/kafedra/internal/zag_him/presentations/pharmaceutical/pharmacy/full_time_study/organic_chemistry/2_course/lecture_12.Sixmember heterocyclic compounds with one heteroatom. Pyrane. Pyridine.
Additional:
1. Francotte Eric. Chirality in Drug Research / Eric Francotte, Wolfgang Lindner //
Hardcover, First Edition. – 2006. – 351 p.
2. Quin Louis D. Fundamentals of Heterocyclic Chemistry: Importance in Nature and in the Synthesis of Pharmaceuticals / Louis D. Quin, John Tyrell // Hardcover, 1st Edition. – 2010. – 327 p.
3. Zweifel George S. Modern Organic Synthesis – An Introduction / George S. Zweifel, Michael H. Nantz // Softcover, 1st Edition. – 2007. – 504 p.
4. K. C. Nicolaou. Molecules that changed the World / Nicolaou K. C., Tamsyn Montagnon // Hardcover, First Edition. – 2008. – 385 p.
5. Mundy Bradford P. Name Reactions and Reagents in Organic Synthesis / Bradford P. Mundy, Michael G. Ellerd, Frank G. Favaloro // Hardcover, 2nd Edition. – 2005. – 886 p.
6. Li Jie Jack. Name Reactions. A Collection of Detailed Reaction Mechanisms / Jie Jack Li // Hardcover, 4th Edition. – 2009. – 621 p.
7. Gallego M. Gomez. Organic Reaction Mechanisms / M. Gomez Gallego, M. A. Sierra // Hardcover, First Edition. – 2004. – 290 p.
8. Sankararaman Sethuraman. Pericyclic Reactions – A Textbook / Sethuraman Sankararaman // Softcover, First Edition. – 2005. – 418 p.
9. Tietze Lutz F. Reactions and Syntheses / Lutz F. Tietze, Theophil Eicher, Ulf Diederichsen // Paperback, First Edition. – 2007. – 598 p.
10. Olah George A. Superelectrophiles and Their Chemistry / George A. Olah, Douglas A. Klumpp // Hardcover, First Edition. – 2007. – 301 p.
11. Grossmann Robert B. The Art of Writing Reasonable Organic Reaction Mechanisms / Robert B. Grossmann // Hardcover, 2nd Edition. – 2003. – 355 p.
12. Cole Theodor C.H. Wörterbuch Labor – Laboratory Dictionary / Theodor C.H. Cole // Hardcover, 2nd Edition. – 2009. – 453 p.
The methodical instruction has been worked out by: associate prof. Dmukhulska Ye.B., assistant Medvid I.I., assistant Burmas N.I.
Methodical instruction was discussed and adopted at the Department sitting
25.06.2013. Minutes N 11
Methodical instruction was adopted and reviewed at the Department sitting
27.08.2013. Minutes N 1
