organic chemistry lecture module - Ether.pdf
- 1. MEDICAL BIOCHEMISTRY DEPARTMENT Organic Chemistry (MBC 233.1) OPURUM H. C ALCOHOLS, Phenols, ETHERS & ALKYL HALIDES 1
- 2. Learning Objectives ØUNDERSTANDING ØETHERS ØMEDICAL USES OF ETHERS ØSYNTHESIS OF ETHERS ØREACTIONS OF ETHERS 2
- 3. ETHERS 3
- 4. qEthers are alkoxy (RO&bond;)‐ substituted alkanes, alkenes, alkynes. qAs with alcohols, only saturated carbon atoms may be substituted in alkenes and alkynes. 4
- 5. Nomenclature Ø Ethers are commonly named by listing the names of the groups attached to the oxygen atom and adding the word ether. Ø Examples include: 5
- 6. Ø IUPAC nomenclature names ethers as alkoxy alkanes, alkoxy alkenes, or alkoxy alkynes. Ø The group in the chain that has the greatest number of carbon atoms is designated the parent compound. Ø In the case of aromatic ethers, the benzene ring is the parent compound. 6
- 7. ØCyclic ethers, oxygen‐ containing ring systems, are normally called by their common names. 7
- 8. Physical properties ØThe bonds between the oxygen atom and the carbon atoms of the alkyl groups in an ether molecule are polarized due to a difference in electro-negativities between carbon and oxygen. ØIn addition, the bond angle between the alkyl groups on the oxygen is 110°. 8
- 9. ØThese facts show that ether molecules must be dipoles (molecules having both a center of positive and negative charge) with weak polarities. ØThus, the structure of ether is similar to that of water. 9
- 10. ØHowever, in water the hydrogen atoms have a greater partial positive charge than the hydrogen atoms on ether. ØIn water, the charge is localized (only on) the hydrogens and not delocalized (spread throughout) as with the alkyl groups, so the charge is stronger in water than in ethers. 10
- 11. Ø Like water, ether is capable of forming hydrogen bonds. Ø However, because of the delocalized nature of the positive charge on the ether molecule's hydrogen atoms, the hydrogens cannot partake in hydrogen bonding. Ø Thus, ethers only form hydrogen bonds to other molecules that have hydrogen atoms with strong partial positive charges. 11
- 12. ØTherefore, ether molecules cannot form hydrogen bonds with other ether molecules. ØThis leads to the high volatility of ethers. ØEthers are capable, of forming hydrogen bonds to water, which accounts for the good solubility of low molecular weight ethers in water. 12
- 13. Ø Table shows boiling points for some simple ethers and the boiling points of alcohols of the same number of carbon atoms. Ø Notice that due to the hydrogen bonding between alcohol molecules, all alcohols have appreciably higher boiling points than their isomeric ethers. 13
- 14. Uses of Ether qThere are many uses of ethers in various fields: qmedicine, qlaboratory purposes, qperfume, qflavouring agents etc. 14
- 15. Uses of Ether in Medicine 1. Anaesthesia: § Ethers are volatile liquids, that release vapours which are inhaled by the patients or administered intravenously. § They cause loss of consciousness to the patients before surgery. For example, diethyl ether is used as potent anaesthesia, and its actions are accompanied by analgesic drugs and also in the relaxation of muscles. 2. Halogenated ethers such as Isoflurane, Desflurane and many others are used as effective anaesthesia because of their low toxicity and flammability. § 15
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- 17. 3. Ethers were used in the treatment of diseases like scurvy and pulmonary inflammation. 4. Antiseptic: Ethers were also used as antiseptics. During World War II, Ether was used to disinfect the wounds of patients and save them from deadly infections. Still, they are used as antiseptics. 17
- 18. 5. Recreational Drugs: Due to their intoxicating and anaesthetic effects, ethers such as diethyl ethers are used as recreational drugs. This means they cause unconsciousness and desired effects in drug addicts and can be used in recreational activities as they are harmless when taken in therapeutic doses. 6. Spirit of Ether: This is a solution of one part diethyl ether and three parts of alcohol (ethanol) and is used as an anodyne (pain killer or hypnotic effect). 18
- 19. Uses of Ether as Solvents v Ethers are quite unreactive. v As a result, they are commonly used as solvents for oil, fats, resins, wax, perfumes, etc. v Their ability to form Hydrogen-bonds and combine with the weak London forces of the alkyl groups that are bonded to the oxygen makes ethers a good solvent for a wide range of organic compounds. 19
- 20. Some examples of the use of Ether as solvents are: 1. Diethyl ether - commonly used in laboratories as an aprotic solvent. It is mostly used as a solvent in Grignard’s reactions. 2. Tetrahydrofuran (THF) – cyclic Ether commonly used as a solvent in organic compounds. They have a low boiling point that makes their use more favourable as a solvent because they can be removed easily after a chemical reaction from the compound by evaporation. 20
- 21. 3. Dimethyl ether (DME) – solvent that is quite miscible in water and is used as a solvent in lithium batteries. 4. 1,4-Dioxane - cyclic Ether that is soluble in water and is widely used as a solvent in laboratories for the synthesis of chemicals. 21
- 22. Uses of Ether as Perfuming and Flavouring Agents § Ethers are widely used in the perfumery and aroma industry due to their olfactory and organoleptic properties. § They provide flavours to a variety of food and drugs, including fruit-based foods and beverages, desserts, fruit jams, yoghurts, ice cream, chewing gum, or some pharmaceutical preparations. 22
- 23. Common examples: 1. diethyl ether, are particularly useful in the preparation of perfumes or perfumed articles, including soaps, detergents, and household materials in general use such as essential oils, medicines, etc. 2. 1-methoxy-3-hexanethiol, imparts the flavour of grapefruit, giving beverages a fruity-green, exotic type flavour. 23
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- 25. Common examples: 3. Some ethers are also used in giving salty aromas, particularly meat-like aromas, to impart the typical meaty taste to food such as soups and broths, seasonings, snacks, sauces, or ready-to-eat non-veg meals. 4. 5. Methoxy benzene (anisole) is commonly used as a constituent to impart fragrance in the essential oil of anise seeds. 25
- 26. Uses of Ether in Paints v Ethers are used in dyes and paint industries. e.g. v Cellulose Ethers- polymers used extensively in paint industries as thickening agents. v cellulose ethers are used as adhesives, ceramics, food, and pharmaceutical industry to provide colours to food and drugs because they are biodegradable. v Glycol ether is used as a solvent in spray paints as they do not dry in mid-air. Due to their slow drying character, they give smooth and flawless paint to cars. 26
- 27. Other Uses of Ether in Our Daily Life v Ethers are used as cleansing agents e.g. Glycol ether is used as cleaners for window glasses, carpets, floors, etc. v Ethers are highly volatile compounds, therefore, their vapours are used as insecticides, miticides, and fumigants for soil microorganisms. v Dimethyl ethers are used to manufacture cosmetic products. 27
- 28. Other Uses of Ether in Our Daily Life vDimethyl ethers (DME) are used as refrigerants with carbon dioxide in the air conditioning system for space ground-based infrastructure. v Aerosol spray propellant. vDimethyl ethers are used as an alternative fuel for diesel engines as they are renewable in nature. 28
- 29. Complex Compound of Ether There are some very useful ether compounds besides simple compounds like dimethyl ether, diethyl ether, and methoxy benzene. Examples of such compounds are: • Crown Ether: Crown ethers are cyclic chemical compounds that consist of several ether groups in a cyclic manner. • There are several uses of Crown Ethers. • Crown ethers are useful for dissolving ionic substances such as potassium permanganate in organic solvents such as isopropanol as they have cavities of different sizes, hence allows binding of specific cations and to be solvated with a high degree of selectivity. 29
- 30. Crown Ether: 30
- 31. Ether Lipid: v Ether Lipid is a glycerophospholipid in which the SN–1SN–1 position of the glycerol backbone has a lipid attached by an alkyl group and a lipid attached to the SN–1SN– 1 position by an acyl group. v They form a major part of cell membranes in mammals and even in some anaerobic bacteria’s. v Ether lipids are also known for their antioxidant properties. 31
- 32. Disadvantages of Using Ether vEthers are highly flammable compounds that catch fire very easily. Hence they should be handled with utmost care in laboratories and industries. vUnder certain conditions, Ether gets oxidised and turns into an explosive. vEther is an anaesthetic, but may lead to nausea and unconsciousness while working with it chemistry laboratories. 32
- 33. Disadvantages of Using Ether vUncontrolled exposure to Ether may be toxic to our health and cause many harmful side effects to the major organs of our body. vAs Ether is a very volatile liquid, its vapour is dense and will spread around the floor of the place where it is used and on meeting a flame or even a small spark cause an explosion. 33
- 34. Summary vEthers are a class of organic compounds having the general formula R–O–R′,R–O–R′, and they are very useful in different fields. vEthers were the first used anesthesia in the history of the medical field. They are also widely used in medicines as antiseptics. 34
- 35. Summary v Some common ether compounds, such as dimethyl ether, diethyl ether, etc., are used as solvents as well as in other fields like perfumery due to their pleasant smell, food flavouring techniques, adding colour and flavours to medicines, paints, and many more. v Like alcohols, ethers are very useful chemical compounds. v Toxic exposure to ethers may cause severe side effects to our health. 35
- 37. Ø The sulfuric acid process and the Williamson method are both used to form ethers. Ø Sulfuric acid process Ø This method is used to make sterically hindered symmetrical ethers. 37
- 38. The mechanism of the sulfuric acid process involves the following five steps. 1. Sulfuric acid dissociates, giving a proton plus the bisulfate ion. 2. 3. 4. The alcohol's oxygen atom is protonated via an acid base reaction, leading to the ‐ formation of an oxonium ion. 38
- 39. 3. The oxonium ion decomposes, generating a 3° carbocation and water. Because carbocations are planar, this decomposition destroys the steric hindrance effect that the t‐ butyl group created. 39
- 40. 4. In this step, the acid base ‐ reaction between the carbocation and a second molecule of alcohol takes place, which forms an oxonium ion. 40
- 41. 5. The oxonium ion liberates a proton to yield the ether. 41
- 42. Williamson method Ø The Williamson ether synthesis proceeds via an S N2 mechanism, in which an alkoxide ion displaces a halogen ion. Ø Ø Ø This method cannot be used with tertiary alkyl halides, because the competing elimination reaction predominates. Ø The elimination reaction occurs because the rearward approach that is needed for an S N2 mechanism is impossible due to steric hindrance. 42
- 43. Ø An S N1 mechanism is likewise unfavored, because as the 3° carbon attempts to become a carbocation, the hydrogens on the adjacent carbons become acidic. Ø Under these conditions, the alkoxide ion begins to show less nucleophilic character and, correspondingly, more basic character. Ø This basic character leads to an acid base reaction, ‐ which results in the generation of an elimination product (an alkene). 43
- 45. ØAlthough ethers are relatively inert toward reaction, they usually show good solvent properties for many nonpolar organic compounds. ØThis strong dissolving power coupled with low reactivity makes ethers good solvents in which to run reactions. 45
- 46. ØAn acid catalyzed cleavage that ‐ occurs when hydriodic acid (HI) mixes with ethers is the most significant reaction that ethers experience. ØThis reaction proceeds via a nucleophilic substitution mechanism. 46
- 47. ØPrimary and secondary alkyl ethers react by an S N2 mechanism, while tertiary, benzylic, and alcylic ethers cleave by an S N1 mechanism. ØA typical S N2 reaction would be the reaction of ethylisopropyl ether with HI. 47
- 48. Ø The mechanism for this reaction is: Ø Ø Ø Ø Notice that for S N2 substitution, the alkyl halide came from the less sterically hindered group. Ø For S N1 type reactions, the alkyl halide forms from the fragment of the original molecule that forms the more stable cation. Ø Thus, the reaction of t butyl ethyl ether with HI ‐ gives t butyl iodide and ethyl alcohol. ‐ 48
- 49. Ø The following mechanism occurs: Ø Ø Ø Ø Ø Ø Ø Notice that if the original ionization of the t‐ butyl ethyl ether formed a t butoxide ion ‐ and an ethyl carbocation, this would be a less stable arrangement. Ø (Remember, the order of stability of carbocations is 3° > 2° > 1°.) 49