CHEM200-Unit8.pptx

8/18/2019 CHEM200-Unit8.pptx

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Unit VIII:Alcohols, Ethers and Thiols

UST – Faculty of pharmacy

Chem2 – !r"anic Chemistry


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Alcohols # Structure

• The functional "roup of an alcohol is an#!$ %hydro&yl' "roup (onded to an sp)

hy(ridi*ed car(on+

– ond an"les a(out the hydro&yl o&y"en

atom are appro&imately -.+/0+

• !&y"en is also sp) hy(ridi*ed+

– T1o sp) hy(rid or(itals form si"ma (onds

to car(on and hydro"en+

– The remainin" t1o sp) hy(rid or(itals each

contain an unshared pair of electrons+

Copyri"ht 2-3 4ohn 5iley 6 Sons, Inc+ All ri"hts reser7ed+


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Alcohols # 8omenclature

• IU9AC names – The parent chain is the lon"est chain that cont

#!$ "roup+

– 8um(er the parent chain in the direction that "#!$ "roup the lo1er num(er+

– Chan"e the su& -e to -ol+• Common names

– 8ame the al;yl "roup (onded to o&y"en follo11ord alcohol+



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• E&amples:



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• Problem: 5rite the IU9AC name of each a



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• Compounds containin" – t1o #!$ "roups are named as diols,

– three #!$ "roups are named as triols+

– #!$ "roups on ad


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• Unsaturated alcohols – The dou(le (ond is sho1n (y the in=& #en#+

– The hydro&yl "roup is sho1n (y the su& #ol+

– 8um(er the chain to "i7e !$ the lo1er num(e



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9hysical 9roperties

• Fi"ure >+2 9olarity of the C#!#$ (ond in me%a' 9artial positi7e char"es on car(on andhydro"en and a partial ne"ati7e char"e ono&y"en+ %(' An electron density map sho1ipartial ne"ati7e char"e in red and the part

positi7e char"e in (lue+



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$ydro"en ondin"

• Alcohols associate in the li?uid state (y hydro"en (on

• Hydrogen bonding: The attracti7e force (et1een a

positi7e char"e on hydro"en and a partial ne"ati7e ch

near(y o&y"en, nitro"en, or @uorine atom+

– The stren"th of hydro"en (ondin" in alcohols is appro&imat

;calmol+ – $ydro"en (onds are considera(ly 1ea;er than co7alent (o

e&ample, -- ;calmol for an !–$ (ond'+

– 8onetheless, hydro"en (ondin" can ha7e a si"ni=cant eBec

physical properties+



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$ydro"en ondin"

– Fi"ure >+) The association of ethanol molecule

li?uid state+



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$ydro"en ondin" Erythromy

– Problem: Follo1in" is a structural formula for

Erythromycin A, a 1idely used anti(iotic+ See nscreen for ?uestions+



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a' $o1 many hydro&yl "roups are present Class

as primary, secondary or tertiary+

(' $o1 many amine "roups are present Classifyprimary, secondary or tertiary+

c' Four of the hydro&yl "roups 1ithin Erythromycin7ol7ed in intramolecular %internal' hydro"en!ne of these is pointed out on the structural f8ote that this hydro"en (ond creates a =7e#mrin"+ Docate the other three intramolecular hy(onds and specify the si*e of the rin" created



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– Solution: Sho1n are the four intramolecular h

(onds+ They create one simem(ered rin" and=7e#mem(ered rin"s+



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oilin" 9oints



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Acidity of Alcohols

• ost alcohols are a(out the same or sli"ht1ea;er acids than 1ater+

– A?ueous solutions of alcohols ha7e the same pof pure 1ater+



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Acidity of Alcohols



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asicity of Alcohols

• In the presence of stron" acids, the o&y"en atom

alcohol (eha7es as a 1ea; (ase+ – 9roton transfer from the stron" acid forms an o&onium

– Thus, alcohols can function as (oth 1ea; acids and 1



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eaction 1ith Acti7e etals

• Alcohols react 1ith Di, 8a, G, and other acti7e meta

li(erate hydro"en "as and form metal al;o&ides+ – 8a is o&idi*ed to 8aH and $H is reduced to $2+

– Al;o&ides are some1hat stron"er (ases that !$–+

– Al;o&ides can (e used as nucleophiles in nucleophilic sureactions+

– They can also (e used as (ases in β#elimination reactio



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Con7ersion of !$ to

– 5ater#solu(le )0 alcohols react 7ery rapidly 1it

$r, and $I+

– Do1#molecular#1ei"ht -0 and 20 alcohols are uunder these conditions+



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Con7ersion of !$ to

– 5ater#insolu(le )0 alcohols react (y (u((lin" "

$Cl throu"h a solution of the alcohol dissol7ed diethyl ether or T$F+

– -0 and 20 alcohols re?uire concentrated $r anform al;yl (romides and iodides+



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eaction of a )0 !$ 1ith $

• )0 Alcohols react 1ith $ (y an S8- mechanism

– Step 1: Add a proton+ apid and re7ersi(le proton from the ac!$ "roup+

– This proton#transfer con7erts the lea7in" "roup from !$–, a poor"roup, to $2!, a (etter lea7in" "roup+



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eaction of a )0 !$ 1ith $

– Step 2: rea; a (ond to form a sta(le molecule

Doss of $2! "i7es a )0 car(ocation+

– Step ): eaction of an electrophile and a nucleform a ne1 co7alent (ond completes the react



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eaction of a -0 !$ 1ith $

• -0 alcohols react 1ith $ (y an S82 mechanism+

– Step 1: Add a proton. 9roton transfer to !$ con7ertpoor lea7in" "roup, to $2! a (etter lea7in" "roup+

– Step 2: Reaction of a nucleophile and an electroform a ne co!alent bond and (rea; a (ond+



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eaction of !$ 1ith $

• eactions are "o7erned (y a com(ination o

electronic and steric eBects



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eaction 1ith S!Cl2

• Thionyl chloride, S!Cl2, is the most 1idely

rea"ent for con7ersion of primary and secalcohols alcohols to al;yl chlorides+



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Kehydration of Alcohols

• An alcohol can (e con7erted to an al;ene (

elimination of $ and !$ from ad


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– e&amples:



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• 5hen isomeric al;enes are o(tained, the m

sta(le al;ene %the one 1ith the "reater numsu(stituents on the dou(le (ond' "enerallypredominates %"aitse!#s rule'+



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Kehydration of a 20 Alcoho

•

A three#step mechanism – Step 1: Add a proton+ 9roton transfer

$)!H to the –!$ "roup con7erts !$–, a po

lea7in" "roup, into $2!, a (etter lea7in"

"roup+



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Kehydration of a 20 Alcoho

– Step 2: $rea% a bond to form a stable mo

ion. Doss of $2! "i7es a car(ocation intermedi

– Step &: 'a%e a proton aay. 9roton transferad


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Kehydration of a -0 Alcoho

• A t1o#step mechanism

– Step 1: Add a proton. 9roton transfer from the acid o&onium ion+

– Step 2: 'a%e a proton aay and loss of H2( "i7es

and re"enerates the acid catalyst+



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$ydration#Kehydration

• Acid#cataly*ed hydration of an al;ene and

dehydration of an alcohol are competin"processes+

– Dar"e amounts of 1ater fa7or alcohol formatio

– Scarcity of 1ater or e&perimental conditions 1

1ater is remo7ed fa7or al;ene formation+Copyri"ht 2-3 4ohn 5iley 6 Sons, Inc+ All ri"hts reser7ed+


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!&idation of Alcohols

• !&idation of a -0 alcohol "i7es an aldehyde

car(o&ylic acid, dependin" on the o&idi*in"and e&perimental conditions+ !&idation of aalcohol "i7es a ;etone+

– The most common o&idi*in" a"ent is chromic ac

– Chromic acid o&idation of -#octanol "i7es octan



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!&idation of Alcohols

– To o&idi*e a -0 alcohol to an aldehyde, use 9CC

– 9CC o&idation of "eraniol "i7es "eranial+

• Tertiary alcohols are not o&idi*ed (y either

these rea"entsL they are resistant to o&idaCopyri"ht 2-3 4ohn 5iley 6 Sons, Inc+ All ri"hts reser7ed+


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Ethers # Structure

• The functional "roup of an ether is an o&y"

atom (onded to t1o car(on atoms+ – !&y"en is sp) hy(ridi*ed 1ith (ond an"les of

appro&imately -.+/0+

– In dimethyl ether, the C–!–C (ond an"le is --



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Ethers # 8omenclature

• IU9AC

– The lon"est car(on chain is the parent al;ane+ – 8ame the #! "roup as an al;o&y su(stituent+

• Common names: – 8ame the "roups (onded to o&y"en follo1ed (y the 1o



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Ethers # 8omenclature

• Althou"h cyclic ethers ha7e IU9AC names,

common names are more 1idely used+



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Ethers # 9hysical 9roperties

• Fi"ure >+/ Ethers are polar molecules+ – Each C#! (ond is polar co7alent+ – $o1e7er, only 1ea; attracti7e forces e&ist (et

ether molecules in the pure li?uid+



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h h i l i


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Fi"ure >+M Ethers are hydro"en (ond acceptors o

are not hydro"en (ond donors+


E h 9h i l 9 i


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eactions of Ethers

• Ethers resem(le hydrocar(ons in their resi

to chemical reaction+ – They do not react 1ith stron" o&idi*in" a"ents

chromic acid, $2Cr!3+

– They are not aBected (y most acids and (ases

moderate temperatures+• ecause of their "ood sol7ent properties a

"eneral inertness to chemical reaction, ethe&cellent sol7ents in 1hich to carry out or"reactions+


E id


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Epo&ides

• *po+ide: A cyclic ether in 1hich o&y"en is

atom of a three#mem(ered rin"+

– Ethylene o&ide is synthesi*ed from ethylene an


E id


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Epo&ides

–

!ther epo&ides can (e synthesi*ed from aal;ene (y o&idation 1ith a pero&ycar(o&yacid, C!)$+


ti f E id


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eactions of Epo&ides

Ethers are "enerally unreacti7e to a?ueous – Epo&ides, ho1e7er, react readily (ecause of th

strain in the three#mem(ered rin"+

– eaction of an epo&ide 1ith a?ueous acid "i7e"lycol+


!ther Epo ide in" !penin"


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!ther Epo&ide in" !penin"

– The mechanism of acid#cataly*ed hydrolysis of an epo

in7ol7es three steps+ – Step -: Add a proton

– Step 2+ Reaction of an electrophile and a nucleopform a ne co!alent bond.

– Step )+ 'a%e aay a proton.




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– The 7alue of epo&ides lies in the num(er of

nucleophiles that 1ill (rin" a(out rin" openin"com(inations of functional "roups that can (esynthesi*ed from them+


Epo&ides as uildin" loc;s


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Epo&ides as uildin" loc;s

– Follo1in" are structural formulas for t1o comm

dru"s, each synthesi*ed in part 1ith ethylene oa (uildin" (loc;+


Thiols Structure


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Thiols # Structure

• Fi"ure >+N The functional "roup of a thiol is

%sulfhydryl' "roup (onded to an sp) hy(ridicar(on+


Thiols 8omenclature


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Thiols # 8omenclature

• IU9AC names

•

The parent chain is the lon"est chain containin" "roup+ – Add #thiol to the name of the parent chain+

• Common names – 8ame the al;yl "roup (onded to sulfur follo1ed (y the

mercaptan+ – Alternati!ely, indicate the #S$ (y the pre=& mercap


Thiols 9hysical 9roperties


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Thiols # 9hysical 9roperties

• Do1#molecular#1ei"ht thiols ha7e a STE8C


Thiols 9hysical 9roperties


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Thiols # 9hysical 9roperties

•

The diBerence in electrone"ati7ity(et1een S and $ is 2+/ – 2+- O +3

• ecause of their lo1 polarity, thiols – sho1 little association (y hydro"en (ondi

–

ha7e lo1er (oilin" points and are less soluin 1ater than alcohols of compara(le 5+


Acidity of Thiols


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Acidity of Thiols

• Thiols are stron"er acids than alcohols+

• Thiols react 1ith stron" (ases to form salts


!&idation of Thiols


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!&idation of Thiols

• Thiols are o&idi*ed (y a 7ariety of o&idi*in"

a"ents, includin" !2, to disul=des+• Kisul=des, in turn, are easily reduced to th

se7eral rea"ents+

– This easy intercon7ersion (et1een thiols and dis 7ery important in protein chemistry+


!&idation of Thiols


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!&idation of Thiols

• 9ro(lem: Dipoic acid is a "ro1th factor for

(acteria and proto*oa and is an essentialcomponent of se7eral en*ymes in7ol7ed in

meta(olism+

a' 8ame the functional "roups in lipoic acid+

(' Kurin" human meta(olism, the disul=de (ond

reduced to t1o thiol rou s Kra1 the structuCopyri"ht 2-3 4ohn 5iley 6 Sons, Inc+ All ri"hts reser7ed+

Alcohols Ethers and Thiols


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Alcohols, Ethers, and Thiols


End Chapter >

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