CYCLOALKANES.pptx

Pharmaceutical organic chemistry

1. CYCLO ALKA N ES

2. Introduction The carbocyclic or homocyclic compounds containing closed chains or ring of carbon atom and bearing certain resemblance to aliphatic compounds in their properties are known as cycloalkanes . They vary from aliphatic compounds in that they possess a cyclic structure.

3. 3 Simple saturated cycloalkanes, also known as alicyclic hydrocarbons , have the general formula C n H 2n . The general formula is isomeric with those of alkenes but cycloalkanes do not have any double bond but they contain the ring of carbon atoms linked together by single bonds.

4. Nomenclature of Cycloalkanes There are two systems for naming cycloalkanes: 1. Common system: Since cycloalkanes are made up of methylene groups joined together to form a ring, they are known as polymethylenes in a trivial system. The number of carbon atoms forming the ring is indicated by a Greek or Latin prefix such as tri, tetra, penta , etc., before the word methylene. Thus, C 3 H 6 is known as trimethylene , C 4 H 8 as tetramethylene and C 5 H 10 as pentamethylene and so on.

5. Cycloalkanes are classified roughly into four groups: Small rings (cyclopropane, cyclobutane ) Common rings (cyclopentane, cyclohexane, cycloheptane) Medium rings (from 8- to 12-membered) Large rings (13-membered and higher) The cycloalkanes having more than 20 carbon atoms are generally called cycloparaffins.

6. 7

7. Preparation of Cycloalkanes Following methods are commonly used for the preparation of cycloalkanes. 1. Freund’s Method from α, ω-dihalides: Dichloro or dibromoalkanes having terminal halogen atoms, when treated with sodium or zinc, yield the corresponding cycloalkanes. For example,

8. IUPAC rules for nomenclature: The general molecular formula of cycloalkanes is C n H 2 n . These are simplest cyclic molecules. These are named after their corresponding linear alkanes with the prefix cyclo . a. Determine the cycloalkane to use as parent chain: The parent chain is one with the maximum amount of carbon atoms. if there are two cycloalkanes, then the cycloalkanes with more carbons will be considered as the parent chain.

9. Big concept 10

10. 11 2. From barium or calcium salts of dibasic acids ( Wislicenus method): On dry distillation of barium or calcium salts of dicarboxylic acids, a cycloketone is obtained which can be reduced to cycloalkane by Clemmenson’s reduction (Zn–Hg/HCl). This method is useful for the preparation of only, six- and seven-membered ring ketones which can be further reduced to cycloalkanes. This method is not suitable for preparation of cyclopropane or its derivatives.

11. 12

12. 13 3. From alkenes: Derivatives of cycloalkanes are prepared by treating alkenes with CH 2 I 2 in presence of Zn–Cu couple or by diazomethane (CH 2 N 2 ) in presence of UV light.

13. 14 4Dieckmann cyclization: By Cyclic β-keto esters are prepared by heating esters of dicarboxylic acids in the presence of sodium ethoxide. it undergoes intramolecular Claisen condensation. These β-keto esters on hydrolysis and subsequent heating gives cyclic ketones, which are reduced by Zn–Hg/HCl to give cycloalkanes:

14. 15

15. 5. From aromatic compounds: By the catalytic reduction of benzene and its derivatives, we can easily obtain six-membered cyclo compounds:

16. 6. a. Condensation of α,ω-dihalide with malonic ester (Perkin’s method): α,ω-Dihalide is condensed with malonic ester in the presence of NaOC 2 H 5 . Alicyclic carboxylic ester thus obtained is hydrolysed and decarboxylated to yield cycloalkane.

17. 19

18. c. Condensation of 1,2-dibromoethane with monosodiomalonic ester yields cyclobutane according to the following sequence of steps:

19. 21 7. From disodio acetoacetic ester and dihalogenated paraffins: Disodio derivative of acetoacetic ester condenses with dihalogenated paraffin to form an ester which on hydrolysis and decarboxylation gives cycloparaffins. Cyclobutane cannot be obtained by this method.

20. 22

21. 23 8. Addition of carbene to olefins—Synthesis of cyclopropane derivatives: Highly reactive bivalent carbon species, carbenes, add on to alkane molecules forming cyclopropane derivatives. For example, dichloro or dibromocarbenes, obtained by the reaction of potassium tertiary butoxide on chloroform or bromoform, when treated with alkenes undergo cis -addition to form cyclopropane derivatives.

22. 24 9. Thorpe–Ziegler reaction: When aliphatic α,ω-dinitriles are treated with bases such as metal salts of secondary amines (e.g. LiN (Et) 2 ), an intramolecular cyclization occurs resulting in the formation of cyclic imino compounds, which on hydrolysis furnish the corresponding cyclic ketone in good yield.

23. 25 10. Photochemical [2+2] cycloaddition reactions: [2+2] Cycloaddition reaction refers to an addition of two alkene molecules using two π electrons each to form a cyclobutane ring. A convenient method for the synthesis of cyclobutane derivatives is photodimerization reaction between two alkenes. These reactions take place in a concerted manner involving a cyclic transition state. Some suitable substituted alkenes such as R 2 C = CF 2 or CH 2 = CH — X (X = —COR, —CN, —COOR, etc.) yield cyclobutane derivatives under thermal conditions.

24. 26

25. 27 11. Diels–Alder reaction [4+2] Cycloaddition: The [4+2] cycloaddition reaction between a conjugated diene (4π-electron system) to form an adduct is known as Diels–Alder reaction named after the two German chemists, who received the noble Prize for chemistry in 1950. a typical example is the addition of 1,3-butadiene with acrolein at 100°C to form tetrahydrobenz -aldehyde.

26. 28

27. 29

28. 30 12. Demjanov rearrangement: The rearrangement has been used for ring expansion or contraction of alicyclic ring. The reaction of nitrous acid on cycloalkymethylamines is a general method for ring expansion. Cyclobutylmethylamine will illustrate the behaviour of this class of amines. In general four products are formed; in this instance they are cyclopentanol , cyclopentene, cyclobutylcarbinol and methylene cyclobutane .

29. 31