Learning Guide for Chapter 14 - Alcohols (I) I. Introduction to Alcohols and Thiols II. Acid/base Behavior of Alcohols, Phenols, and Thiols III. Nomenclature of Alcohols IV. Synthesis of Alcohols Previous reactions Reduction of C= functional groups rganometallic reagents I. Introduction to Alcohols and Thiols What does an alcohol functional group look like? ow are alcohols different from carboxylic acids? carboxylic acids ahve C= on same carbon as, alcohols do not What are some common alcohols? methanol C 3 wood alcohol; race car fuel; poisonous - causes blindness, then death; treatment - IV of ethanol ethanol grain alcohol; found in alcoholic beverages; comes from fermenting sugars and starches; denatured for use in labs; poisonous over time or in high doses isopropanol found in rubbing alcohol; used in first aid for disinfecting What does a thiol functional group look like? S What other name are they known by? mercaptan - captures mercury Why is their reactivity similar to alcohols? S and are in the same family What is the main difference in their reactivity? size - S is larger than thiols are more acidic, stronger Nu
What is the most noticeable characteristic of thiols? strong, disagreeable odor LG Ch 14 p 2 What are some examples of this? S S S natural gas additive Is this always the case? no skunk odor S grapefruit mercaptan - citrusy smell Classification of Alcohols ow are alcohols in which the carbon is sp 3 hybridized classified? 1 o, 2 o, 3 o 2 o 3 o 1 o ow are alcohols in which the carbon is sp 2 hybridized classified? enols or aryl alcohols enol attached to C=C tautomerize to form C= directly attached to benzene ring aryl alcohol ow would the following compounds be classified? phenol other aryl alcohols are sometimes called phenols allyl alcohol unsaturated alcohol not an enol aromatic alcohol not an aryl alcohol
Physical Properties of Alcohols LG Ch 14 p 3 Match up the following compounds with their boiling points and justify your answers. similar masses bp -42 o C bp -38 o C bp 78 o C dipole forces ethyl fluoride F bp -38 o C hydrogen bonding ethanol bp 78 o C much higher! Van der Waals propane bp -42 o C Which of the following would you expect to be soluble in water? C 3 soluble: 1-4 carbons with one ; up to at least 6 C's with more than one IR Spectra of Alcohols Is IR a good way to identify alcohols? yes Label the important bands in the following spectrum. - C- C 2 bending C- 3400-3200 cm -1 1300-1000 cm -1
NMR Spectra of Alcohols Consider the following compound. LG Ch 14 p 4 Where should you look for the 's next to the? 3-4 ppm, triplet Where should you look for the peak? 1-5 ppm, broad singlet What will happen if D 2 is added to this sample? disappears D peak appears Label the peaks in the following spectrum. II. Acid-base Behavior of Alcohols, Phenols, and Thiols What happens when an alcohol reacts with an acid? base acid pka -2.4 -base base 2 pka < -2.4 protonated alcohol a - 5, m, 7ppm b - 2, t, 2-3 ppm c - 2, t, 3-4 ppm d - 1, s, 1-5 ppm a > c > b > d What kind of acid would be required for this reaction to have a favorable equilibrium? pka less than 2.4 2 S 4-10 I -9 Br -8 Cl -7 What would happen if the protonated alcohol came in contact with a base? 2 Na 2 it would be protonated
LG Ch 14 p 5 What happens when an alcohol reacts with an base? pka 16-18 pka > 18 base -base acid alkoxide What kind of base would be required for this reaction to have a favorable equilibrium? pka of the conjugate acid must be greater than 18 most commonly used base - Na - pka 36 ow can alkali metals be used to form alkoxides? by a redox reaction 1 o Na Na 1/2 2 Na - methyl, 1 o K 3 o K 1/2 K - 2 o, 3 o 2 remember our friend from E2? What would happen if an alkoxide came in contact with an acid? (Na too slow) Cl Cl it would be protonated What would happen if a protonated alcohol and an alkoxide were reacted with each other? 2 2 they would neutralize each other ow does the acidity of alcohols vary? methyl > 1 o > 2 o > 3 o pk a 15.9 pk a 16.5 pk a 18.0
Why are aryl alcohols more acidic than aliphatic alcohols? LG Ch 14 p 6 conjugate base is stabilized by resonance base pk a 10.0 greatest resonance contributor Could Na be used as the base? yes -base Na 2 products favored pk a 10.0 pk a 15.7 stronger acid Why won't this work with regular alcohols? alcohols not acidic enough Na 2 reagents favored pk a 17 pk a 15.7 stronger acid Why are thiols more acidic than alcohols? sulfur is larger than oxygen, is further away, easier to remove base S S -base pka 10.5 thiolate ion Could Na be used as the base? yes S Na S 2 pk a 10.5 pk a 15.7 stronger acid
Common names III. Nomenclature of Alcohols LG Ch 14 p 7 Based on the common name for the following alkyl halide, deduce the common name of the alcohol shown. Br propyl bromide propyl alcohol name of substituent "alcohol" Give the common names of the following alcohols. C 3 methyl alcohol ethyl alcohol isopropyl alcohol isobutyl alcohol sec-butyl alcohol tert-butyl alcohol cyclopentyl alcohol allyl alcohol vinyl alcohol unstable benzyl alcohol phenol IUPAC names What are the four steps in naming an organic compound? 1. 2. 3. 4. Determine stereochemistry, if any. Choose the principle chain, give it a name. Number the principle chain. Name the substituents, alphabetize them, add them to the name.
What are the priorities for choosing the principle chain? LG Ch 14 p 8 1. 2. 3. 4. must contain the alcohol (or as many as possible) double or triple bonds longest chain most substituents ow does the alkane name change for each of the following? pentane pentanol drop "e", add "ol" cyclohexane cyclohexene cyclohexenol hexane hexadiene drop "ane" add "adiene" pentane pentanediol use entire alkane name, add "diol" What are the priorities for numbering the principle chain? 1. 2. 3. 4. lowest number to alcohol(s) lowest number to double or triple bonds lowest numbers to substituents (first point of difference) lowest number to first substituent alphabetically
LG Ch 14 p 9 Number the following compounds. 6 1 2 5 2 3 4 1 4 3 3 5 4 2 1 If you have to name an alcohol as a substituent, what is it called? hydroxy 2-(1-hydroxyethyl)-1-cyclopentanol Draw structures for the following names. 2-cyclohexyl-1-butanol 1,3-cyclopentanediol 5-bromo-4-methyl-2-hexanol Br 2-cyclopenten-1-ol 2-(1-hydroxyethyl)-1-cyclohexanol 5-methyl-3-hexanol Give the names of the following compounds. 2,3-pentanediol (3S,4S)-4-methyl-3-hexanol trans-3-penten-2-ol 4-(2-hydroxypropyl)-1-cyclohexanol
IV. Synthesis of Alcohols LG Ch 14 p 10 Reactions from Previous Chapters What reagents would be required to convert the following compounds to alcohols using the reaction given? S N 2 reactions 1 o Br Na 1 o RX to R Acid-catalyzed hydration 2 S 4 2 C=C to R xymercuration-reduction 1. g(ac) 2, 2 2. NaB 4 C=C to R ydroboration-oxidation 1. B 3 -TF 2. 2 2, - C=C to R ydroxylation KMn 4, K, 2 C=C to vicinal diol or s 4, 2 2 In this chapter, we will learn two more: reduction of a C= by adding hydrogen reduction of a C= by adding an alkyl group ketones aldehydes carboxylic acids esters to R R ketone aldehyde ester acid chloride to R
Reduction of C= groups to form alcohols LG Ch 14 p 11 ow is oxidation defined in organic chemistry? gaining bonds to and/or losing bonds to ow is reduction defined in organic chemistry? losing bonds to and/or gaining bonds to Which of these is occurring in the following reactions, and why? KMn 4 2, K 1. B 3 -TF 2. 2-2, - 2, Pd/C both C's gain bonds to oxidation one C gains bond to, one C gains bond to no net change in oxidation state both C's gain bonds to reduction What type of alcohol can be formed by the reduction of the following compounds? lose a bond to, gain a bond to aldehyde reduction 1 o alcohol ketone reduction 2 o alcohol carboxylic acid reduction 1 o alcohol ester reduction 2 alcohols
LG Ch 14 p 12 Which of the following reagents is effective in reducing the functional groups shown? C C C C to C C ketone, aldehyde C, ester to to C C C C 2, Pd/C yes no no NaB 4 no yes no most common reagent for ald/ket Al 4 Raney Ni no yes yes yes yes no most common reagent for ester, C Which is more reactive, NaB 4 or Al 4? Why? Na NaB 4 = B Al 4 = Al less reactive more reactive solvent - methanol solvent - ether Al- bond weaker than B- ow do they react? B Na!-! NaB 4 C 3 Na both steps taking place in the reaction Al Al 4 2. 3 first step has to finish, then add acid for second step What is Raney Ni? What is the advantage of using it? Ni catalyst with 2 molecules absorbed onto it it will also reduce C=C and C---C if they are present What safety hazards exist with these materials? Al 4 reacts vigorously with water, releases 2, can cause lab fires Raney Ni is pyrophoric - spontaneously ignites in air
What reagent(s) could be used to accomplish the following reactions? 4 functional groups * NaB 4, C 3 or Raney Ni or Al 4, 2) 3 Al 4, 2) 3 * NaB 4, C 3 or Raney Ni or Al 4, 2) 3 ketone --> 2 o alcohol LG Ch 14 p 13 C --> 1 o alcohol aldehyde --> 1 o alcohol Al 4, 2) 3 ester --> 2 alcohols * NaB 4, C 3 or Al 4, 2) 3 reduce aldehyde, leave C=C C= vs C=C Raney Ni reduce both aldehyde and C=C 2, Pd/C reduce C=C, leave aldehyde ketone vs ester Al 4, 2) 3 * NaB 4, C 3 or Raney Ni reduce both ketone and ester reduce ketone, leave ester can't be done! reduce ester, leave ketone
LG Ch 14 p 14 Addition of rganometallic Reagents to C= Groups to form Alcohols What is the advantage of using an organometallic reagent instead of a reducing agent to convert a C= group to an alcohol? reducing agent - same carbon structure organometallic reagent - new carbon group added What are the two most common kinds of organometallic reagents used in organic chemistry? Grignard reagents!-! MgBr organolithium reagents!-! What polarity do these reagents have? ow reactive are they, and why? C - partially negative highly reactive - C doesn't like to be -, usually formed and used, not stored ow are organometallic reagents formed? alkyl halide metal Br Mg MgBr ether Cl 2 ether Cl What other kinds of halides can be used? vinyl halides Cl Mg ether MgCl aryl halides Br 2 ether Br
What are the two ways in which a Grignard or organolithium reagent can react? LG Ch 14 p 15 base MgBr -base Mg Br base Nu MgBr E E Mg Br ow strong of bases are organometallic reagents? Why is this so? conjugate acid - alkane pka ~50 weakest acid - strongest base! C has low EN, unstable with partial neg charge What would happen if an organometallic reagent came in contact with water? it would be protonated What other kinds of compounds will react as acids with organometallic reagents? alcohols, amines, amides, carboxylic acids, terminal alkynes If this usually a reaction we desire? no - it ruins our reagent! Is there any way in which it could be useful? converts RX to alkane Br Mg MgBr C 3 C 3 adds a D ether Mg Br Cl 2 hexanes D 2 D D
In the absense of any compounds with acidic 's, organometallic reagents react as nucleophiles. LG Ch 14 p 16 What type of compound will be formed when a Grignard or organolithium reagent is reacted with an aldehyde or ketone, followed by mild, aqueous acid? attack-push up MgCl Mg Br react once aldehyde ketone 2. 3 2. 3 protonate 3 o alcohol 2 o alcohol Is there any way to get a primary alcohol? MgBr Mg Br 2. 3 formaldehyde 1 o alcohol What type of compound will be formed when a Grignard or organolithium reagent is reacted with an acid chloride, following by mild, aqueous acid? attack-push up push off can't stop here! reacts twice Cl acid chloride 2 eq 2. 3 MgCl Cl Cl attack-push up protonate 3 o alcohol w/2 identical groups Why doesn't this happen with aldehydes and ketones? no leaving group
What will happen to an ester? same thing LG Ch 14 p 17 reacts twice 2 2. 3 What type of compound is formed when a Grignard or organolithium reagent is reacted with ethylene oxide? reacts once attack-push off 2. 3 protonate What reagents would be needed to complete the following reactions? adds 2 C's 3 C MgBr 2. 3 2. 3 3 C MgBr 2. 3 2. 3 MgBr 2. 3 2. 3 ow could the following compound be synthesized? 3 C MgBr 2. 3 2 o alcohol - RM ald 2. 3
Summary of methods for synthesizing alcohols: LG Ch 14 p 18 S N 2: 1 o alkyl halide Na --> 1 o alcohol Acid-catalyzed hydration: alkene 2 S 4 2 --> 2 o or 3 o alcohol (more substituted side, rearrangments possible) xymercuration-reduction: alkene 1. g(ac) 2, 2 2. NaB 4 --> 2 o or 3 o alcohol (more substituted side, no rearrangements) ydroboration-oxidation: alkene 1. B 3 -TF, 2. 2 2, Na --> 1 o or 2 o alcohol (less substituted side, no rearrangements) Reduction of an aldehyde or ketone: aldehyde or ketone NaB 4, C 3 --> 1 o or 2 o alcohol Reduction of a carboxylic acid or ester: carboxylic acid or ester Al 4 --> 1 o alcohol (ester has a second alcohol) Addition of an organometallic reagent to an aldehyde or ketone aldehyde or ketone Grignard or organolithium reagent, 2. 3 --> 2 o or 3 o alcohol Addition of an organometallic reagent to and acid chloride or ester: acid chloride or ester Grignard or organolithium reagent, 2. 3 --> 3 o alcohol with two identical groups Addition of an organometallic reagent to an epoxide: ethylene oxide Grignard or organolithium reagent, 2. 3 --> 1 o alcohol