Amides and amines presentation.

Amides and amines.. introduction, structure, nomenclature, physiochemical properties and pharmaceutical application of amides and amines

1. AMIDES AND AMINES Their chemistry Therapeutic importance

2. FUNCTIONAL GROUP Definition: the functional group is define as, ‘An atom or group of atoms joined in specificmanner which gives the chemical properties of the organic compounds and are the center for chemical reactivity.’

3. Compounds having a similar functional group have under gone similar reactions The presence of functional groups enables the systematization of organic compound into different classes Examples alkene, alcohols, carboxylic group, amines and amides etc

4. Amides Definition ‘ An amide is a functional group in which a carbonyl group is linked to a nitrogen atom .’ Amide linkage is in a biochemical context is called peptide bond

5. GENERAL FORMULAS

6. CHARACTERISTICS amides are derived from carboxylic acid amides are amphoteric in nature REASONS: Lone pair present in nitrogen of amides is involving in resonance and less available for donating. Hence ,behave as weak base. During resonance it forms positive charge on nitrogen which has tendency to lose proton and behave as acid.

7. POINT TO PONDER cyclic amide are called “lactams” ; they are necessarily secondary or Tertiary amides . Functional groups consisting PHOSPHOAMIDES [P(O)NR2] and sulfonamides [SO2NR2]

8. Nomenclature ; In the usual nomenclature we add the term “amide” to the stem of the parent acid’s name . EXAMPLE ; the amide derived from acetic acid is named as acetamide CH з CONH2 IUPAC ; IuPAC recomand it as ethanamide .Amide take the suffix “amide” to the alkane chain of the carbons . If amides have additional substituents on the nitrogen then name them “ Alphabetically “

9. PHYSICAL PROPERTIES THE amides generally have high melting and boiling points . Their polar nature in water result from the polar nature of the amide group and hydrogen bonding.This hydrogen bonding affect their chemical and physical properties to great extent. They are present in solids, liquids,and even crystalline form. Solid ( stearamide ), liquid ( formamide ),and crystal ( choroacetamide ).

10. CONTINUED Methanamide is a liquid at room temperature,but other simple amines are solids. Ethanamide is said to have smell like of mice.Infact,the smell is due to impurity called N- methylethanamide .(CH з COHCH з )

11. HYDROGEN BONDING IN AMIDES

12. NAME MELTING POINT ċ BOILING POINT ċ SOLUBILITY IN WATER FORAMIDE 2 193 SOLUBLE ACETAMIDE 82 222 SOLUBLE PROPIONAMIDE 81 213 SOLUBLE BUTYRAMIDE 115 216 SOLUBLE BENZAMIDE 132 290 SLIGHTLY SOLUBLE

13. CHEMICAL PROPERTIES

14. PREPARATIONS AMIDES undergo many chemical reactions,although they are less reactive than esters.Amides are also versalite precursors to many other functional group…… NUCLEOPHILIC ACYL SUBSTITUTION: GENERIC MECHANISM:BASIC HYDROLYSIS It represent a type of reactions in which nucleophile and acyl compounds react to form amide. R–CO–CL + R––NH2 → R–CO–NH–R + HCL

15. PARTIAL HYDROLYSIS OF NITRILES NITRILES can be converted to primary amines under acidic or basic conditions. General reaction: R—C≡N + H2O +ACID → R—CO—NH2 EXAMPLE: CH з— C≡N + H2O + HCL → CH з— CO—NH2

16. CARBOXLYIC ACID WITH AMMONIA IN this reaction , carboxylic acid containing different alkyl groups react with ammonia to form different alkyl amides. General Reactions: R—CO—OH + NH3 → R—CO–NH2 Example CH3–CH2–CO–OH + NH3 →CH3–CH2–CO–NH2 + H2O

17. AMINES WITH CARBOXLYIC ACID The reaction of carboxylic acid with amines to form different alkyl amide. General Reaction : R–CO—OH +H2N—R → R—CO—NH—R Example : CH з— CO–OH + H2N—CH з → CH з –CO–NH–CH з

18. AMINE WITH ANHYDRIDE Amides with aldehydes It is much more common however to prepare amides by treating an amine with aldehyde. General reaction : R—CO—O—CO—R + R—NH—R ↔ R—CO—NR2 + HO—CO—R Example: CH з– CO–O––CO–CH з + CH з– NH—CH з ↔CH з– CO–NH2 +HO–CO––CH з

19. CARBOXYLIC ACID WITH THIONYL CHLORIDE During the reaction the carboxylic acid is converted to a chlorosulfite intermediate making it a better leaving group.The chloride anion produced during the reaction acts a nucleophile to produce acid chloride and then react with amine(RNHR) to form AMIDE. Chemical Reaction: R–CO–OH + SOCL2 →R–CO–CL +RNHR→R–CO–NR–R (TERTIARY AMINE)

20. CHEMICAL PROPERTIES CHEMICAL REACTIONS HYDROLYSIS OF AMIDE Amides hydrolyze to form parent carboxylic acids. Chemical Reaction: R-CO-NH2+H2O→RCOOH+RNH2

21. NITRILE FROM AMIDES Amide are dehydrated by heating a solid mixture of the amide and phosphorus oxide P 4 O 10 . Water is removed from the amide group to leave a nitrile group CN - CN . The liquid nitrile is collected by simple distillation . FOR EXAMPLE: Ethane nitrile is formed by dehydrating ethane amide. CH 3 CONH 2 +P 4 O 10 →CH 3 CN+H 2 O

22. HOFFMANN’S REARANGEMENT: The Hoffmann Re-arrangement is the organic reaction of a primary amide to a primary amine with one fewer carbon atom. CHEMICAL REACTION : RCONH2+Br2+NaOH → R-N=C=O R-N=C=O+H2O → R-NH2+CO2

23. AMIDE REDUCTION RCONR2 AMIDES are converted to amines (RCH2NR’2 )by conversion of the C═O to –CH2–. Chemical Reaction : LiALH4 + R–CO–NH2 → H–CHR–NH2

24. VILSMEIER –HAACK REACTION SUBSTITUTION REACTION It is a chemical reaction of a substituted amide with phosphorous oxychloride and an electron –rich arene to produce an aryl aldehyde or ketone. The reaction is named after ANTON VILSMEIER and ALBRECT HAACK.

25. CHEMICAL REACTION

26. BISCHLER –NAPIERALSKI REACTION The BISCHLER-NAPIERALSKI REACTION is an electrophilic aromatic substitution reaction that allows for the cyclizatin of β - arylethylamides .

27. COMPLEX MECHANISM OF BISCHLER –NAPIERALSKI REACTION

28. THERAPEUTIC USES OF AMIDES AMIDES ARE IMPORTANT CLASS OF ORGANIC COMPOUNDS WHICH HAVE MANY APPLICATIONS IN MEDICAL FIELD…… ACETAMIDE It act as antidote when fluoroacetamide attacks on cardiac muscles because this poison cause degeneration,necrosis of cardiac muscles.Actamide is the only compound which reverse its effects. Actamalide tablet ( 250mg )is used to various serious disease; EDEMEA EPILEPSY GLAUCOMA

29. BENZAMIDE Its drugs are used to block DOPAMINE and SEROTONIN receptors and stimulate acetylcholine receptors in smooth muscles. It is mainly used for vomiting and nausea. Its derivative (procainamide ) is used against life threatening ventricular arrhythmias. PROCAINAMIDE is used as anticancer drugs for the treatmentof stage 3 and stage 4 hodgkin’s disease . MOCLOBEMIDE is used for depression disorder and pipolar disorder SULPIRIDE is used to treat SCHIZOPHRENIA.

30. SULFONAMIDE (SULFA DRUGS) They are used to treat bacterial infections . They are prescribed for following disease; Urinary tract infection Bronchitis Eye infections Pneumonia Ear infections Severe burns Traveller’s diarrhea

31. AMINES Their chemistry Therapeutics importance

32. DEFINATION “ AMINES are derivative of ammomia (NH з ) in which one or more hydrogen atomhave been replaced by alkyl group.”

33. CLASSIFICATION ALKYL AMINES Primary Secondary Tertiary According to the number of alkyl groups attach to the nitrogen atom. AROMATIC AMINES

34. GENERAL CLASSIFICATION OF AMINES

35. NOMENCLATURE Amines are named in several ways ; Typically , the compound is given the prefix ‘AMINO—’ or the suffix ‘AMINE’ LOWER AMINES ARE NAMED WITH SUFFIX ‘ AMINE ’.like methylamine HIGHER AMINES HAVE PREFIX AMINO AS A FUNCTIONAL GROUP IUPAC NAMING Amines are written as “ALKANAMINE”

36. PHYSICAL PROPERTIES Amines have characteristic ammonia smell ,liquid amines have a distinctive fishy smell. Aromatic amines such as aniline, have their lone pair electrons conjugated into the benzene ring. Thus , their tendency to engage in hydrogen bonding is diminished. Aromatic boiling point are high but solubility in water is low . The water solubility of simple amines is enhanced by hydrogen bonding involving these lone electron pairs.

37. The order of boiling point of amines is as follows :Primary > Secondary > Tertiary. The low aliphatic amines are gaseous in nature . Primary amines with three or four carbon atoms are liquids at room temperature whereas higher ones are solid. Aniline and other arylamines are generally colorless . However , they get colored when we stored them in open due to atmospheric oxidation. Low aliphatic amines can form hydrogen bonds with water molecules. Therefore , such amines are soluble in water. Increase in the size of hydrophobic alkyl part increases the molar mass of amines. This usually results in a decrease in its solubility in water .

38. Higher amines are insoluble in water . Organic solvents like alcohol , benzene and ether readily dissolves amines . Alcohols have high polarity as compared to amines and hence , they form stronger intermolecular bonds . Primary and secondary amines are often engaged in the intermolecular association as a result of hydrogen bonding between the nitrogen of one and hydrogen of the other molecule . The intermolecular associations is more prominent in case of primary amines as compared to the secondary due to the availability of two hydrogen atoms . In tertiary amines , there is no intermolecular association due to the absence of free hydrogen atom for bonding .

39. PREPERATION OF AMINES PRIMARY AMINES Hofmann's Degradation of Amides: IN this reaction, primary amines are formed by this method.so this reaction is used widely to that purpose. Chemical Reaction: R—CO–NH 2 + BR 2 + 4NAOH → R–NH 2 +2NABR +NA 2 CO з +2 H 2 O

40. GABRIEL PHTHALIMIDE METHOD This r eaction is used to convert alkyl halides into primary amines. This reaction is named after German chemist who first introduced it

41. SECONDARY AMINES PREPARATION REDUCTION OF N –SUBSTITUTED AMIDES Amides on reduction by lithium aluminium hydride produce secondary amines

42. REDUCTION OF ISONITRILES THIS REACTION IS VERY UNIQUE ONE. Because in this reaction the secondary amine produced by it will always have __CH з CHEMICAL REACTION: R___N+≡C- + PT. → R___NH__CH з

43. TERTIARY AMINES When an alcoholic ammonia solution is heated with an excess of alkyl halide,a tri –alkyl ammonium halide is formed.This when heated With sodium hydroxide solution gives free tertiary amine.

44. REDUCTION OF N,N- DISUBSTITUTEDAMIDES The below reactions show that how tertiary amines are produced

45. CHEMICAL PROPERTIES CHEMICAL REACTIONS Due to unshared paired electrons pair , amines can act both as bases and as nucleophile REACTION WITH ACIDS: When react with acids,amine donate electrons to form ammonium salts. Chemical Reaction:

46. REACTION WITH ACID HALIDES Acid halides reacts with amines to form substituted amides. Chemical Reaction:

47. REACTION WITH SULPHONYL CHLORIDE Amines react with sulphonyl chloride to produce sulphonamide .

48. OXIDATION OF AMINE Although we can oxidize all amines but tertiary amines give isolated product…

49. REACTION WITH NITROUS ACID Nitrous acid is unstable and must be prepared in the reaction solution

50. REACTION WITH WATER AMINES ALSO REACT WITH WATER…..

51. THERAPEUTIC IMPORTANCE

52. DRUGS Many drugs are designed to mimic or interfere with natural amine neurotransmitter,exemplified by the amine drugs; Chlorpheniramine is an antihistamine that help to cure allergic reactions due to cold ,hay fever,itchy skin,insect bites, and stings. Chlorpromazine is a tranquilizer that sedates without inducing sleep. It is used to relieve anxiety,excitement , restlessness,and even mental disorders. Ephedrine and phenylephrine , as amide hydrochloride are used as decongestants.

53. Ephedrine Chlorpheniramine

54. Amphetamine,methamphetamine ,and methcathinone , are used As physhostimulant amines. Amitriptyline,imipramine,lofepramine ,and clomipramine are used as anti depressants and are tricyclic amines. Opiate analgesics such as heroin, morphine,and codeine are also tertiary amines.

55. Methamphetamine and Methcathinone