Ethers, Epoxides, Sulfides - Organic Chemistry - Lecture Notes, Study notes of Organic Chemistry

Download Ethers, Epoxides, Sulfides - Organic Chemistry - Lecture Notes and more Study notes Organic Chemistry in PDF only on Docsity! 1 Ethers, Epoxides, Sulfides Ethers are much less reactive than alcohols but epoxides – three-membered ring ethers – are very reactive as we saw in the last chapter. Nomenclature In substitutive IUPAC nomenclature ethers are named as alkoxy derivative derivatives of alkanes. CH3CH2 O CH2CH3 ethoxy ethane CH3 O CH2CH3 methoxyethane CH3CH2 O CH2CH2CH2 Cl -3-chloro-1-ethoxypropane Functional class names: list the two alkyl groups in ROR’ in alphabetical order as separate words followed by the word “ether”. If the two alkyl groups are the same, use “di-“. CH3 O CH2CH3 ethyl methyl ether CH3CH2 O CH2CH2CH2 Cl 3-chloropropyl ethyl ether CH3CH2 O CH2CH3 diethyl ether Ethers can be symmetrical or unsymmetrical. In unsymmetrical ethers, the two alkyl groups are different. We can have cyclic ethers: O O O Ooxirane (ethylene oxide) oxetane oxolane oxane tetrahydropyrantetrahydrofuran Number the ring starting at the oxygen. Many compounds have more than one ether linkage. For example, some diethers are useful solvents and there are useful solvents that contain multiple ethers. These have higher boiling points and more ether linkages can be added to increase the boiling point even further. CH3 O CH2CH2 O CH3 1,2-dimethoxyethane O O 1,4,-dioxane CH3 O CH2CH2 O CH2CH2 O diethylene glycol dimethyl ether (diglyme) CH3 b. p. 85°C b. p. 162°C b. p. 100 - 102 °C Sulfur analogs of alkoxy groups are called alkylthio groups. Name as sulfides or alkyl thio alkanes. docsity.com 2 CH3CH2 S CH2CH3 diethyl aulfide or, ethyl thioethane S CH3 (methylthio)cyclopentane cyclopentyl methyl sulfide Structure and Bonding Ethers have large bond angles than water and alcohols due to van der Waals strain. O H H 105° O H CH3 108.5° O CH3 CH3 112° O (CH3)3C C(CH3)3 132 Typical C-O bond lengths are similar to C-O bonds in alcohols (~1.42 A°). These are shorter than typical C-C bonds (~1.52A°) The most stable conformation of diethyl ether is the all-staggered anti-conformation. Tetrahydropyran is most stable in the chair conformation. In a three-membered ring the bond angles are much small than normal tetrahedral angles and the C-C bond and C-O are slightly longer than normal due to the severe angle strain. CH2 O CH2 CH3CH3 diethyl ether O O H H H H 1.44 A° 1.47 A° C O C tetrahydropyran angle = 61.5 C C O angle = 59.2 Physical Properties Look at diethyl ether as compared to pentane and 1-butanol. Compound b. p. H2O solubility (g/100 mL H2O) diethyl ether 35 °C 7.5 g/100 mL pentane 35 °C dipole 1.2 0~0 g/100 mL butanol 117 °C 9 g/ 100 mL 1.7 So, we see that diethyl ether is more like pentane than an alcohol in terms of its boiling point. This means that there are little intermolecular interactions. Ethers are not capable docsity.com 5 CH3CH2CH2 OH2 H2SO4 120 °C CH3CH2CH2 O CH2CH2CH3 + H2O Mechanism CH3CH2CH2 OH H2SO4 CH3CH2CH2 O H H CH3CH2CH2 OH CH3CH2CH2 O CH2CH2CH3 H CH3CH2CH2 OH CH3CH2CH2 O CH2CH2CH3CH3CH2CH2 O H H + + H2O As we shall see, the reaction is reversible. To drive the equilibrium in favor of ether formation, use an excess of alcohol in initially anhydrous conditions and remove the water as it is formed if possible. Williamson Ether Synthesis For unsymmetrical ethers, we need to use basic conditions. This is a simple SN2 reaction and is a very useful reaction. We activate the alcohol by first removing the proton with a base to make the alkoxide. A relatively mild base such as sodium hydroxide will work because even though the alkoxide exists in roughly equal amount with the starting alcohol (Keq ~1), the second step of the reaction will drive the equilibrium to the right. We can use a strong base such as sodium hydride, NaH. The starting alcohol can be primary or secondary but when it is tertiary we start to see elimination reactions. The alkyl halide or alkyl sulfonates portion should be primary; otherwise we start to see elimination reactions. General Reaction: R O H + base R O R X R O R' X= good leaving group such as halogen or sulfonate ester R' should be non-hindered such as a primary alkyl halide; otherwise we start to see elimination. R can be primary or secondary but with tertiary we start to see elimination. For example: docsity.com 6 CH3CH2CH2 O H + Na+ -H pKa ~16 pKa H2 36 CH3CH2CH2 O CH3CH2 Br CH3CH2CH2 O CH2CH3 CH3CH2 H C CH3CH2 O H NaOH H2O CH3CH2 CH CH3CH2 O pKa ~16 pKa H20 15.7 CH3CH2CH2 O S O O CH3 CH3CH2 CH CH3CH2 O CH2CH2CH3 O S O O CH3 + But if the alkyl halide component is secondary or tertiary or if the alcohol component is tertiary we start to see elimination. CH3CH2 CH CH3CH2 O H NaOH H2O CH3CH2 CH CH3CH2 O Cl H major product CH3 C CH3 CH3 O H Na+ -H CH3 C CH3 CH3 O CH2 BrCHCH3CH2 H CH3CH2 CH CH2 major product Tertiary alkoxides are very hindered and are realtively strong bases (pKa ~18) but poor nucleophiles. So we see elimination even with primary alkyl halide substrates. So how do we make tertiary ethers (i.e. ethers with t-butyl groups)? We cannot use a tertiary alcohol or a tertiary alkyl halide. We need to use acid catalyzed addition of an alcohol to an alkene such a 2-methylpropene, a reaction we studied last semester. C CHR'' RCH2 R'CH2 H2SO4 HOR''' R''CH2 C CH2R CH2R' OR''' Ex C CH2 CH3 CH3 H2SO4 HOCH2CH2CH3 CH3 C CH3 CH3 HOCH2CH2CH3 CH3 C CH3 CH3 O H CH2CH2CH3 CH3CH2CH2OH CH3 C CH3 CH3 O CH2CH2CH3 docsity.com 7 Reactions of Ethers Ethers are relatively unreactive. They are stable to (1) nucleophiles (2) strong bases (3) oxidizing agents (4) reducing agents. CH3CH2 O CH CH3 H Not an acidic proton Not a good leaving group because -OCH2CH3 is too strong a base. oxidizing reagents will not cleave a C-O bond. Ethers such as diethyl ether and THF are moderately polar solvents and good at dissolving non-polar and moderately polar compounds. They are excellent solvents for Grignard and organolithium reactions as we saw. Ethers, however, are cleaved by acids. Acid-Catalyzed Ether Cleavage The reaction is analogous to the reaction of alcohols with halogen acids, HX. R O R' + H X RX + R'OH and R'X + ROHGeneral Reaction: ether cleavage Reaction of HX with alcohols: R O H H X RX+ + H2O Usually the reaction is carried out with an excess of the HX and usually the alcohol that is formed initially is also converted to the alkyl halide. Using milder conditions, it is possible to isolate the alcohol intermediate. CH3CH2 O CH2CH3 H Br+ CH3CH2 O CH2CH3 H Protonation of the ether oxygen transforms it into a good leaving group. The leaving group now is a neutral alcohol. Br- CH3CH2 OH + CH3CH2Br H Br CH3CH2 O H H Br- CH3CH2Br Note that unsymmetrical ethers can give two sets of products, since the bromine nucleophile can attack the carbon on either side of the protonate oxygen. docsity.com 10 C C Br H H OH H CH3 NaOH H2O HO- C C Br H H O H CH3 C C H H H CH3 O + enantiomer H O Br H H -OH NaOH H2O HO Br H H H O The reaction is stereospecific. If you start with a cis-alkene, you will get a cis-epoxide and a trans-alkene give a trans-epoxide. C C HH CH3CH3 Br CH3H CH3 HBr2, H2O H O H Br H CH3 O CH3H HHH2O Br H CH3 O CH3H H NaOH -OH Br H CH3 O CH3H O CH3 H H CH3 C C HCH3 CH3H Br HH3C CH3 HBr2, H2O H O H Br H CH3 O HCH3 HHH2O Br H CH3 O HCH3 H NaOH -OH Br H CH3 O HCH3 O H CH3 H CH3 cis epoxide trans epoxide Reactions of Epoxides Ring-Opening Epoxides react with nucleophiles in ring-opening reactions in both (1) basic and (2) acid conditions. docsity.com 11 (1) In basic conditions the nucleophile attacks the epoxide directly at the less-substituted product. This is an SN2 like process in which the new C-Nucleophile bond and the OH group are trans. CH2MgCl O CH2 CH2 + THF CH2 CH2 CH2 O- MgCl+ H3O+ CH2 CH2 CH2 OH Again, attack is at the LESS substituted carbon because is less hindered. CH3CH2MgBr + O CH2 C CH3 CH3 THF CH2 C CH3 CH3 O- MgBr+ CH3CH2 H3O+ CH2 C CH3 CH3 OH CH3CH2 Other nucleophiles besides Grignards will attack epoxides and all attack at the less substituted carbon to give the trans product. R C C:- N C:-RO - RS- NH3 Na+ N3-R3N Rli alkoxides alkyl and aryl thiolates ammonia amines azides alkyl and aryl lithium reagents acetylides nitriles For Example: N C:- Na+ + O CH2 C CH3 CH3 C CH3 CH3 O- Na+ CH2 C N H3O+ C CH3 CH3 OH CH2 C N O CH3 H CH3CH2O- Na+ + O CH3 OCH2CH3 H δ− δ− CH3 OCH2CH3 O- H CH3 OCH2CH3 OH H Note here how the substituent that is at the carbon that is attacked moves during the reaction, just like in an SN2 reaction and we get inversion of configuration at that carbon. We can make the trans 1,2-diol by nucleophile attack on the epoxide using sodium hydroxide. docsity.com 12 O H H HO- Na+ + H OH O- H H3O+ H OH OH H Lithium aluminum hydride, LiAlH4, will reduce the epoxide to the alcohol by attack of hydride (H:-) at the less substituted carbon. + O CH2 C CH3 CH3 LiAlH4 CH2 C CH3 CH3 O AlH3 - H3O+ H2O CH2 C CH3 CH3 OH H H Acid Catalyzed Ring Opening of Epoxides Epoxides will also react with nucleophiles under acidic conditions to give the ring opening reaction. In acidic conditions we cannot have strongly basic nucleophiles present. Those most commonly used at the halides (I-, Br-, Cl-), water, H2O, and alcohols, ROH. In acidic conditions the nucleophile attacks at the more substituted carbon. Because there is lots of carbocation character and, as we know, the more substituted carbon is the one that is best able to stabilize the positive charge. General Reaction: H Y + R C R O CH2 R C R O CH2 H R C R CH2 OH Y:- More of the (+) charge is on the more substituted carbon since it has electron donating alkyl groups that help to stabilize the charge. R C Y CH2 OHR 1 122 2 1 We still see backside attack because there is still a partial bond to C2. A good way to represent the two resonance structures, which contribute to the overall structure, is to show one of the bonds as longer than the other. R C R O CH2 H R C R CH2 OH 122 1 C C O δ+ δ+ H Composite structure. R H HR docsity.com