Organic Chemistry - Alcohols, Ethers, and Epoxides PDF

Organic Chemistry Sixth Edition Chapter 9 1  Alcohols, Ethers and Epoxides Alcohol, ether and epoxide carbon-oxygen σ bonds describe the functionality but molecules can contain these functionalities and also a C-O multiple bond First part of chap...

Organic Chemistry Sixth Edition Chapter 9 1  Alcohols, Ethers and Epoxides Alcohol, ether and epoxide carbon-oxygen σ bonds describe the functionality but molecules can contain these functionalities and also a C-O multiple bond First part of chapter deals with classifying and distinguishing these functionalities as they exist in various compounds 2 Chapter sequence: Classifying these oxygen compounds Synthesis of these compounds Reactions (a number of different types); We have seen the general concepts…..we now deal with mechanisms and conversions……examples are minimized…..general concept look for the change (same as done before) 3  Alcohols—Structure and Bonding Alcohols contain a hydroxy group (OH) bonded to an sp3 hybridized carbon….R-OH classified according to the number of alkyl groups attached to carbon bearing the OH…same as the halides 4  Ethers Ethers have two alkyl groups bonded to an oxygen atom. 5  Epoxides Epoxides (oxiranes) are ethers…oxygen atom is in a 3-membered ring C—O—C bond angle for an epoxide is 60o, not ~109.5o as in ROH. epoxides have angle strain, more reactive than other ethers. 6  Naming Alcohols Change the –e ending of the parent alkane to the suffix –ol Number the carbon chain to give the OH group the lower number, and apply all other rules of nomenclature (for both straight chains and cyclic) Hexane........ Hexanol Cyclohexane ….. Cyclohexanol 7  Diols and Triols two hydroxy groups …….diols or glycols. three hydroxy groups…….. triols. 8  Naming Ethers Simple ethers are usually assigned common names. To do so: Name both alkyl groups bonded to the oxygen, arrange these names alphabetically, and add the word ether. For symmetrical ethers, name the alkyl group and add the prefix “di-”. 9  Common Cyclic Ethers Cyclic ethers have an O atom in the ring. 1,4-Epoxybutane Oxacyclopentane Furan 1-Oxacyclopenta-2,4-diene 10  Naming Epoxides Epoxides can be named in three different ways—epoxyalkanes, oxiranes, or alkene oxides. epoxyalkane, first name the alkane chain or ring to which the O atom is attached, and use the prefix “epoxy” to name the epoxide as a substituent. Use two numbers to designate the location of the atoms to which the O is bonded. 11  Naming Epoxides as Alkene Oxides Epoxides are also named as alkene oxides, since they are often prepared by adding an O atom to an alkene. Mentally replace the epoxide oxygen with a double bond. Name the alkene. Add the word oxide. 12  Hydrogen Bonding in Alcohols Alcohols are capable of intermolecular hydrogen bonding. alcohols are more polar than ethers and epoxides. 13  Sterics and Hydrogen Bonding Solubility…..important 14  Preparation of Alchols and Ethers Alcohols and ethers are both common products of nucleophilic substitution. These covered in previous chapters 15  Williamson Ether Synthesis unsymmetrical ethers can be synthesized in two different ways. alkoxide attack on a less hindered alkyl halide is preferred. Same product but reversing the nucleophile and the alkyl halide role 16 Reminder: Alcohols react with bases to produce alkoxides (acid base reaction) Alkoxide is the salt from the reaction 17  Forming Epoxides from Halohydrins Halohydrins contain both a hydroxy group and a halogen atom on adjacent carbons an intramolecular version of the Williamson ether synthesis can occur to form epoxides. NaOH 18  Reactions of ROH (and ROR) OH group in alcohols is a very poor leaving group. (last semester) For an alcohol to undergo nucleophilic substitution, OH− must be converted into a better leaving group. 19 Alcohols can be protonated to allow water to be a leaving group very strong acids are needed Leads to substitution and elimination reactions on alcohols. 20 examples Ref: cdn.masterorganicchemistry.com/wp-content/uploads/2019/12/2-formation-of-alkyl-halides-from-alcohols-with-hb4-primary-alcohols-go-through-sn2-mechanism.gif 21 examples Ref: cdn.masterorganicchemistry.com/wp-content/uploads/2019/12/3-forming-tertiary-halides- from-tertiary-alcohols-with-hx-addition-occurs-through-sn1-pathway-more-stable-carbocation.gif 22 ethers do not contain a good leaving group undergo fewer useful reactions than alcohols. Epoxides are different; leaving group is contained in a strained 3-membered ring. Nucleophilic attack opens the 3-membered ring and relieves angle strain. 23  Reactions of Alcohols—Dehydration Dehydration elimination reaction OH and H are removed from the α and  carbon atoms respectively. 24 Dehydration requires A strong acid (H2SO4 and other strong acids), or phosphorus oxychloride (POCl3) in the presence of an amine base. Typical acids: H2SO4 or p-toluenesulfonic acid (TsOH). 25 More substituted alcohols dehydrate more easily, giving rise to the following order of reactivity. 2o & 3o alcohols react by an E1 mechanism 1o alcohols react by an E2 mechanism. 26  Zaitsev’s Rule holds for alcohols alcohol with two or three carbons, dehydration is regioselective and follows the Zaitsev rule. more substituted alkene is the major product when a mixture of constitutional isomers is possible. 27 Entropy favors product formation in dehydration since one molecule of reactant forms two molecules of the product. Enthalpy favors reactants, since the two σ bonds broken in the reactant are stronger than the σ and π bonds formed in the products. 28  Carbocation Rearrangements (generally) less stable carbocation will be converted into a more stable carbocation by a shift of a hydrogen or an alkyl group, called a rearrangement. How do we know that a rearrangement occurred? the double bond may be in an unexpected location. The carbon skeletons of the reactant and product are different. 29  Carbocation Rearrangements 1,2-shift moves with two bonding electrons, also moves the net positive (+) charge. Movement of a H atom is called a 1,2-hydride shift. Movement of an alkyl group is called a 1,2-alkyl shift. 30 Mechanism of the reaction using example from 2 slides back; 1,2 alkyl shift 31  1,2-Hydride Shifts 1,2-shift can make a more stable carbocation….Rearrangements If carbocation is formed as a reactive intermediate, then a rearrangement may occur. 2o carbocation may rearrange to the more stable 3o carbocation by a 1,2-hydride shift, stable 32  Dehydration of Alcohols Using phosphorus oxychloride (POCl3) and pyridine (an amine base) in place of H2SO4 or TsOH (in case the acid causes a decomposition of the alcohol POCl3 converts a poor leaving group (−OH) into a good leaving group (P-complex). Dehydration then proceeds by an E2 mechanism. Next slide 33 The reactivity of hydrogen halides increases with increasing acidity. 34  Use of 2 and Primary and secondary alcohols can be converted to alkyl halides SOCl2 (thionyl chloride) converts alcohols into alkyl chlorides. PBr3 (phosphorus tribromide) converts alcohols into alkyl bromides. Both reagents convert −OH into a good leaving group in situ allow nucleophile, either Cl− or Br−, to displace the leaving group. The mechanism of this reaction consists of two parts: 1. Conversion of OH group into a better leaving group. 2. Nucleophilic substitution via an SN2 reaction. 35 Conversion 36 𝟑 Conversion 37 38  Tosylates (p-toluenesulfonate) tosyl group, CH3C6H4SO2−, is abbreviated Ts or TOS Alcohols can be converted into alkyl tosylates. the tosylate be comes a good leaving group. ©2020 McGraw-Hill Education. 39  Tosylates p-toluenesulfonyl chloride (TsCl) / pyridine used for conversion 40  Stereochemistry of Tosylate Formation Ts group exchanges with the proton on the OH….to make a leaving group. No reaction at the carbon Configuration at the carbon is retained 41 tosylates are good leaving groups; behave like alkyl halides nucleophilic substitution and elimination SN2 and E2 mechanism (use of strong nucleophile or base, respectively) (inversion if sterogenic center) 42  Summary of converting OH to good leaving group Figure 9.8: Only substitution and elimination reactions…..recognize how reagents are used 43  Reaction of Ethers (HX) poor leaving group must first be converted into a good leaving group by reaction with strong acids such as HBr and HI. HBr and HI are strong acids that are also sources of good nucleophiles (Br− and I−, respectively). both C—O bonds are cleaved and two alkyl halides are formed if 2 equivalents of halide are used; if less then halide and alcohol form 44  Mechanism of Ether Cleavage cleavage is either SN1 or SN2, depending on R. 2o or 3o alkyl groups…. C—O bond is cleaved by an SN1 mechanism……carbocation. methyl or 1o alkyl groups… C—O bond is cleaved by an SN2 mechanism. Next slide: figure 9.9..mechanism may be complicated 45 2 parts 46  Reaction with sulfuric acid Under certain conditions (dilute H2SO4 and heat) R-O-R1 R-OH + HO-R1 C2H5-O-C2H5 2C2H5-OH (under pressure) Ref: https://www.masterorganicchemistry.com/reaction-guide/acidic-cleavage-of-ethers-sn2-reaction/ 47  Reaction with sulfuric acid Tertiary butyl ethers can result in eliminations products(dehydration of the alcohol).google.com/url?sa=i&url=http%3A%2F%2Fentrancechemistry.blogspot.com%2F2012%2F07%2Freaction-of-ether-with-sulphuric-acid.html&psig=AOvVaw1jVVqsGIpg0- wU9oJH7xTY&ust=1604939710369000&source=images&cd=vfe&ved=0CAMQjB1qFwoTCMitgsSw8-wCFQAAAAAdAAAAABAJ 48  Reactions of Epoxides Nucleophilic attack opens the strained three-membered ring, making it a favorable process even with a poor leaving group. 49  Addition of Nucleophiles to Epoxides Nucleophilic addition to epoxides occurs readily with strong nucleophiles and with acids like HZ, where Z is a nucleophilic atom. 50  Mechanism of Epoxide Reactions Virtually all strong nucleophiles open an epoxide ring by a two-step reaction sequence. In step , the nucleophile attacks an electron-deficient carbon, by an SN2 mechanism, thus cleaving the C—O bond and relieving the strain of the three-membered ring. In step , the alkoxide is protonated with water to generate a neutral product with two functional groups on adjacent atoms. Common nucleophiles that open the epoxide ring include −OH, −OR, −CN, −SR, and NH3. In an unsymmetrical epoxide, the nucleophile attacks at the less substituted C atom 51  Acidic Epoxide Ring Opening Acids HZ that contain a nucleophile Z also open epoxide rings by a two-step sequence. Step : Protonation of the epoxide oxygen making the good leaving group (OH). Step : Nucleophile opens the epoxide ring via backside attack. 52  Acidic Epoxide Ring Opening HCl, HBr, and HI, as well as and ROH in the presence of acid, all open an epoxide ring in this manner. trans-1,2-disubstituted cycloalkanes are formed from epoxides fused to rings. 53  Opening an Epoxide Ring with HCl Note: the more stable transition state so only one product is formed 54 Summary: (in general) 1. Alcohols and ethers involved the basic reactions of substitution and elimination as previously discussed in other chapters; 2. Involve the conversion of the oxygen into a better leaving group 3. Several different reactants are used to do the conversion in #2 4. stereochemistry , etc rules and concepts apply 5. Major/minor product rules apply 6. Alkyl, hydride shifts 55 Chapter 9 HW Problems # 43, 45 a-d, 50, 54a, 56c, 57, 60b, 61a 56