Pharmaceutical Organic Chemistry-3 Lecture Notes PDF

Pharmaceutical organic chemistry-3 Pc305- level two Part i: heterocyclic chemistry. Lec. 1 Ass. Prof. samar samir tawfik  Heterocyclic compounds are cyclic molecules with at least one atom other than carbon in the ring structure.  The most common heteroatoms are N, O and S. ...

Pharmaceutical organic chemistry-3 Pc305- level two Part i: heterocyclic chemistry. Lec. 1 Ass. Prof. samar samir tawfik  Heterocyclic compounds are cyclic molecules with at least one atom other than carbon in the ring structure.  The most common heteroatoms are N, O and S.  Others as Se, P, Si, B can be incorporated into ring structures.  They might contain one or more heteroatoms, which may be similar or different.  They may be isolated or fused.  Heterocycles make up an exceedingly important class of compounds, more than half of all known organic compounds are heterocyclic.  Almost all the compounds we know as drugs, most vitamins and many other natural products are Heterocycles.  Nomenclature of Heterocyclic Compounds: It is based on: 1. Trivial name (common name) This usually originates from the compounds occurrence, its first preparation or its special properties. 2. Systematic name (IUPAC/ Hantzsch-Widman) a. Type of the heteroatom b. Ring size c. Nature of the ring (saturated/ unsaturated) I. Trivial names: A- Heterocyclic compounds containing one heteroatom: 1) Unsaturated heterocyclic compounds: Numbering starts at the heteroatom. aromatic compounds not aromatic compounds  B- Heterocyclic compounds containing two or more heteroatoms: Numbering begins with the heteroatom (priority is O, S, then N) and goes in a direction so as to give substituents (or other heteroatoms) the lowest possible number. If more than one heteroatom of the same type numbering starts at the saturated one, e.g. imidazole.  If substituents are present, their position should be identified by the number of the atoms bearing them and then they should be listed in alphabetical order. The words dihydro, trihydro or tetrahydro are used if two or three or four atoms are saturated. These words are preceded by numbers indicate the position of saturated atoms and followed by the fully unsaturated trivial name.  C- Fused Heterocyclic compounds: Numbering starts with the nearest atom to the junction and giving the heteroatom the lowest numbering. There is no numbering of the contact position of fused rings if it is carbon. N.B. Fused Heterocyclic compounds: with exception in numbering  II. Systematic names: IUPAC name = locants +Prefix + suffix A- Monocyclic systems: Three to ten-membered monocyclic systems are based on the Hantzsch-Widnman-system. Rule 1: a. The heteroatom is always assigned position 1 and if substituents are present then counted around the ring in a manner so as to take the lowest possible numbers. b. The kind of heteroatom is indicated by the prefix oxa-, thia-, selena-, aza-, phospha-, sila-, bora- for oxygen , sulphur, selenium, nitrogen, phosphorus, silicon, and boron, respectively. c. Multiplication of prefixes as dioxa-, dithia- and diaza- are used when the ring contains two oxygen, two sulphur or two nitrogen atoms. d. If two or more different heteroatoms are present, priority: O > S > N e.g. the prefix oxaza is used for one oxygen and one nitrogen and thiaza for one sulphur and one nitrogen (vowel at the end of the first part is omitted).  Ring N present N absent Unsaturate Saturate Size Unsaturated Saturated d d Rule 2 3 - irine - iridine - irene -irane a) The prefix is followed by a suffix 4 -ete - etidine - ete - etane indicating the ring size and the degree of unsaturation as follows: 5 -ole - olidine - ole - olane 6 -ine - ine - ane Perhydro is followed by the fully unsaturated name 7 -epine perhydro - epine - epane 8 -ocine ,, - ocine - ocane 9 -onine ,, - onine - onane 10 -ecine ,, - ecine - ecane ,,  H N Example: This ring contains (N) Prefix is aza The ring is 3-membered and fully saturated suffix is iridine By combining the prefix and suffix, two vowels ended up together (azairidine), therefore the vowel on the end of the first part should be dropped. This gives the correct name: Aziridine  This ring contains (O) prefix 1 oxa two (N) prefix 2 diaza Locants, since (O) is higher priority than (N) so it is in position 1 by default and the two (N) are at positions 2 and 5, this gives the combined prefixes as 1,2,5- oxadiaza (note that the a in oxa is not dropped) It is 5-membered,fully unsaturated ring with (N) the suffix is ole  By combining the prefixes and the suffix and dropping the appropriate vowels we get the correct name as 1,2,5-Oxadiazole 1,3-oxathiolane 1,3,5-triazine oxirene 4-bromo-1,3-thiazole  Rule 3: The state of hydrogenation is indicated:  in the suffix according to the above tables, or  by the prefixes dihydro, tetrahydro,. etc., or  by prefixing the name of the parent unsaturated compound with the symbol H preceded by a number indicating the position of saturation.  Rule 4: a) Numbering of the rings starts with the heteroatom and proceeds around the ring so as to give substituents (or other heteroatoms) the lowest numbers possible. b) When two or more different heteroatoms are present, oxygen takes precedence over sulphur and sulphur over nitrogen for the number one position. c) If different heteroatoms are present, numbering starts with the heteroatom which gives the lowest set of numbers for all the heteroatoms. d) The lowest set of locants is then arranged according to the priority rule which is also considered by naming the heteroatoms. Wrong name  Ring N present N absent Size Unsaturated Saturated Unsaturated Saturated NH (mnc) N N 3 - irine - iridine - irene -irane H H O O 4 -ete - etidine - ete - etane 5 -ole - olidine - ole - olane 1H-azirine azirdine oxirane oxaziridine 6 -ine perhydro* - ine - ane 7 -epine ,, - epine - epane 8 -ocine ,, - ocine - ocane 9 -onine ,, - onine - onane N N H S N H 10 -ecine ,, - ecine - ecane H azetidine thietane Pyrrole pyrrolidine (azole) (azolidine)  S N N N O N N H H 6H-1,2,5-oxadiazine 4H-1,3,4-thiadiaziine azepine  B- Polycyclic rings or fused heterocyclic systems: Rule 1: Benzene ring + heterocyclic ring When one heterocyclic ring is present, it is chosen as the parent component and the name of the fused carbocyclic ring is attached as a prefix (Benzo). Benzo[d]thiazole Benzo[b]pyridine