Chapter 11 (reactions of alcohols) Flashcards
R - OH that undergoes dehydration forms
alkenes
R - OH that undergoes oxidation forms
ketones, aldehydes, and acids
R - OH that undergoes substitution forms
R - X (halides)
R - OH that undergoes reduction forms
R - H (alkanes)
R - OH that undergoes esterification forms
esters (R - O - C (=O) - R’)
R - OH that undergoes tosylation forms
tosylate esters (R - OTs), which are good leaving groups
Oxygen is more _____ whereas carbon is more ______
electronegative, electropositive
O - H is a ______ bond
polar covalent
in organic chemistry, oxidation signifies
gain of O, O2, or X2; loss of H2
in organic chemistry, reduction signifies
gain of H2 (or H-); loss of O or O2; and loss of X2
in organic chemistry, neither oxidation or reduction signifies
the gain or loss of H+, H2O, -OH, HX, etc.
_____ cannot be reduced any more (no reaction) due to the octet rule, and the lack of oxygen available to be removed
alkanes
when a secondary alcohol is oxidized, it produces a
ketone ( R - C ( =O) - R’ )
traditional oxidizing agents are _____ based such as _____ in ______
chromium, Na2CrO4, H2SO4
_____ is highly toxic and difficult to dispose of properly
chromium
CrO3 will produce ____ ___ in the presence of H2SO4 and H2O
chromic acid
a secondary alcohol + chromic acid will form ______ ____
chromate ester
aldehydes are _____ reactive than ketones because ___________
more, because there is less steric hindering ( aldehydes have a lone hydrogen that can be pushed around)
oxidation of primary alcohols with chromic acid produces ______ _____
carboxylic acids; the oxidizing agent (chromic acid) is too strong to only produce an aldehyde
_______ _________ is a weaker oxidizing agent than chromic acid. It is a complex of chromium trioxide, pyridine, and HCl
pyridinium chlorochromate (PCC) ; 6 edge aromatic ring with N+ substituted for one of the carbons, and an H attached to the N+, with a long CrO3Cl-
PCC oxidizes primary alcohols to ________, and secondary alcohols to _______
aldehydes, ketones
oxidation of primary alcohols ___________
is not possible, as the C does not have H, so oxidation is difficult and involves the breakage of a C - C bond.
the ____ ____ ___ is for primary and secondary alcohols because
tertiary alcohols do not react
as the bulkiness of a compound increases, the rate of a reaction ______
decreases, since there are less options for the reaction to proceed
______ ________ can oxidize alcohols without heavy metals or generating hazardous waste. It is a much better option for acid sensitive compounds.
sodium hypochlorite (NaOCl) aka household bleach
Swern oxidation is used to oxidize secondary alcohols to ______ and primary alcohols to ______
ketones, aldehydes
swern oxidation utilizes _______ with ________ and a ________ ____ solvent
dimethylsulfoxide (DMSO) first, oxalyl chloride second, and in an environment of a hindered base (ET3N)
_____ ______ ________ can oxidize primary alcohols to ______ and secondary alcohols to _______
dess-martin periodinane (DMP), aldehydes, ketones
________ is useful in mild conditions (room temperature and neutral pH), and gives excellent yield. Good to use if the compound will decompose in more extreme conditions
DMP reagent
reactions with DMP, swern oxidation, NaOCl, and PCC, will turn a primary alcohol into an ______ and a secondary alcohol into a _______
aldehyde, ketone
alcohols (ROH) are ____ nucleophiles
weak, because the reaction forces a positive charge onto an O
alkoxides (RO-) are _____ nucleophiles
strong
when an alcohol acts as a nucleophile,
new O - C bond forms, and O - H bond breaks
larger alcohols are _____ polar than smaller alcohols
less
if there is a weak nucleophile/electrophile in a reaction, a _____ of the other must be present for the reaction to occur
strong
-OH is a ___ leaving group
poor
alcohols are _____ electrophiles
weak, because -OH is not a good leaving group. protonation of the hydroxyl group converts it into a good leaving group/better electrophile (H2O)
_____ ____ reactions are favored compared to acid catalyzed because,
Tosylate ester; they are excellent leaving groups in nucleophilic substitution reactions, due to resonance delocalization of the developing negative charge on the leaving oxygen.
alcohols can be converted to _____ ____ through a condensation with TsOH (p-toluenosulfonic acid)
tosylate esters (ROTs)
when a compound has more resonance forms,
that compound/conformation is more favorable in a reaction
A backside nucleophilic attack results in ___________________
inversion of configuration for an SN2 reaction
the _______ ____ is a particularly stable anion, with its negative charge delocalized over 3 oxygen atoms
tosylate ion (-OTs)
R-OTs + -OH ->
R-OH + -OTs
R-OTs + -C≡N [cyanide] ->
R-C≡N (nitrile) + -OTs
R-OTs + halide ->
R-H + -OTs
R-OTs + R’-O- (alkoxide) ->
R-O-R’ (ether) + -OTs
an alkoxide is
the conjugate base of an alcohol and therefore consists of an organic group bonded to a negatively charged oxygen atom. They are written as RO−
R-OTs + NH3 (ammonia) ->
R-NH3+ (amine salt) + -OTs
R-OTs + LiAlH4 (aka LAH) ->
R-H (alkane) + -OTs
To reduce alcohols, you can dehydrate with ______, then add ____
H2SO4 (sulfuric acid), H2
To reduce an alcohol, you can make a _______, then reduce it with _____
tosylate, LiAlH4
pyridine is a ____ solvent
basic
it is easier to break a ____ bond than a ____ bond
Pi, sigma
SN1/2 and E1/2 are in competition with one another, the ______ determines which will occur
environment
when an alcohol is reacted with an acid,
the hydroxyl group is protonated by the acid, converting it to a good leaving group (H2O)
and once the alcohol is protonated, a substitution or elimination reaction can take place
H2O is a ___ leaving group
good
In order for a leaving group to leave,
it must be able to accept electrons. Strong bases cannot accept more electrons
A good leaving group is
- the conjugate base of a strong acid
- a weak base
- the more stable the conjugate base with the lone pair is, the weaker the base will be
- the lower the pKa, the stronger the acid and the weaker the conjugate base
During a reaction with HBr, _______ alcohols react with Br- via SN1, and _______ alcohols react via SN2
secondary and tertiary, primary
steps of an SN1 mechanism for alcohol + H-Br
- protonation (-OH -> (O)+H2 and H-Br -> Br-)
- formation of a carbocation (H2O breaks off, and the carbon that it was attached to becomes positive). if rearrangement occurs, to get to the most stable intermediate, it would happen right after this step.
- nucleophile (Br-) attacks the electrophile (C+)
formation of a carbocation can be problematic because of ______, so to mitigate this issue _______
rearrangement; take into account this rearrangement, and try to get the most stable version of the carbocation through hydride and methyl shifts (want to have low energy in a reaction diagram)
SN2 mechanism for an alcohol and H-Br
concerted step
- -OH is protonated w/ H from H-Br, and Br- is left
- Br- attacks the carbon that -OH2 is on, and at the same time, H2O breaks off.
- INVERSION OF CONFIGURATION OCCURS, so have to take into consideration stereochemistry if asked
sp bond angle
180º
sp2 bond angle
120º
sp3 bond angle
109.5º
sp3d bond angle
120º and 90º
sp3d2 bond angle
90º
chloride is a weaker nucleophile than bromide because _________
it is small and less polarizable
define polarizability
The ability of a bond or molecule to be polarized by distorting its electron cloud. Distortion of a spherical electron cloud.
the greater the number of electrons, polarizability _______ and dispersion forces become _______
increases, stronger
as polarizability increases, reactivity _________
increases
addition of _____, which bonds strongly with O in -OH, promotes a reaction between _____ and an alcohol
ZnCl2, HCl
Lucas test: ZnCl2 in concentrated HCl:
- primary alcohols react _________
- secondary alcohols react _________
- tertiary alcohols react ________
- slowly or not at all
- in 1 - 5 minutes
- in less than 1 minute
ZnCl2 acts like a ______ when paired with HCl
catalyst
primary alcohols react with the Lucas reagent (_________) by the ___ mechanism
HCl and ZnCl2, SN2
- reaction is very slow, it can take from several minutes to several days
- ZnCl2 attaches to O, forming O+(ZnCl)H, this breaks off forming the carbocation. Then, Cl- from H-Cl attaches to the carbocation
secondary and tertiary alcohols react with the Lucas reagent (__________) by the ____ mechanism
ZnCl2 and HCl, SN1
- much quicker
- ZnCl2 bonds to the O, making it O+, before breaking off to form HO-ZnCl2, and Cl- attacks the carbocation in a concerted step.
limitations of HX reactions
- poor yields of alkyl chlorides from primary and secondary alcohols
- elimination competes with substitution, so you might not end up with what you wanted
- carbocation intermediate may undergo a rearrangement
- limited ability to make alkyl halides
use _____ rather than acid catalyzed because _____________
tosylate, less steps and bigger yield
if an environment is highly acidic, do NOT give _____
-OH as it would be neutralized immediately and not react
if an environment is highly basic, do not give ______
H+ or H3O+, as it would be neutralized instead of react
alcohol reactions with phosphorus halides
- P has a partial positive charge, the halide has a partial negative charge
- produces good yields with primary and secondary alcohols
- uses PCl3 for alkyl chlorides (but SOCl2 is better)
- uses PBr3 for alkyl bromides
- PI3 is NOT stable, so have to separately use P and I2 for alkyl iodides
mechanism of an alcohol with PBr3
- displacement of bromide ion from PBr3. O in -OH attacks the PBr2
- H-O+-P(Br)2 is an excellent leaving group - SN2 attack on the alkyl group, Br- attacks the backside
- PBr2O is more stable than PBr3
a positive charge on an O indicates a
GOOD leaving group
reaction of alcohols with thionyl chloride
SOCl2 and heat can be used to convert alcohols into the corresponding alkyl chloride in a simple reaction that produces gaseous HCl and SO2
- S is partial positive, O is partial negative
mechanism of thionyl chloride reaction
- O in -OH attacks the S in SOCl2, the O from the SOCl2 detaches. O in -OH now has a partial positive charge
- a Cl in SOCl2 detaches, and the O reattaches because its still nearby and doesn’t like the negative charge step 1 left it with
3.Cl- attacks the H in -OH, producing chlorosulfite ester and H-Cl - R group detaches, and Cl in the main molecule attacks it (because its still nearby)
- produces R-Cl and gaseous SO2 escapes the area
zaitsev’s rule states that
the major product of an elimination reaction tends to be the more substituted alkene.
dehydration reactions with alcohols uses ______ ; produces an _______
H2SO4 ; alkene
- carbocation intermediate present for secondary and tertiary alcohols
- zaitsev’s rule determines where the double bond will go
- bimolecular dehydration produces ethers.
- low temps (<140ºC) favors ether formation
- high temps ( >180ºC) favors alkene formation
alcohol dehydration utilizes the ____ mechanism
E1 mechanism
- rate of reaction follows the ease of formation of carbocations: 3º>2º>1º
- primary alcohols rearrange, so this is not a good mechanism for converting 1º alcohols into alkenes
dehydration mechanism using E1
- step 1: (protonation) the -OH is protonated, forming -OH2 and a O+
- step 2: (formation of the carbocation) the -OH2 detaches, leaving a carbocation in its place
- methyl or hydride shifts if necessary to form a more stable compound.
- step 3: (loss of a proton forming an alkene) the O in the newly formed H2O attacks a proton from R, creating H3O+ and an alkene
during an E1 reaction, the rate determining step is _______
the formation of the carbocation
bimolecular condensation to form ethers (used industrially)
- a protonated alcohol (electrophile) may be attacked by another molecule of the alcohol (nucleophile) and undergo an SN2 displacement
- the net reaction is a bimolecular dehydration to form an ether
- this is a type of condensation
a diol ________
contains two -OH groups
a vicinal diol contains ___________
two -OH groups, on adjacent carbons of one another
vicinal diols can undergo two reactions
- pinacol rearrangement
- periodic acid cleavage
in a _____ rearrangement, a vicinal diol converts to the ketone (_______) under acidic conditions and heat
pinacol rearrangement, pinacolone
- the reaction is classified as a dehydration since a water molecule is eliminated from the starting material
mechanism of the pinacol rearrangement
- protonation and loss of a water molecule produce a carbocation
- methyl shift forms a resonance-stabilized carbocation, which, upon deprotonation by water, yields the pinacolone product
________ are alcohols with two OH groups on adjacent carbon atoms
glycols
glycols can be oxidatively cleaved by _____ ___ (HIO4) to form corresponding ketones and aldehydes
periodic acid
- its useful for determining the structure of sugars
- the cleavage of a glycol probably involves a cyclic periodate intermediate
esterification is a reaction in which
an alcohol and carboxylic acid forms an ester as the reaction product
types of esters include
tosylate, sulfate, nitrate, phosphate
fischer esterification
- reaction of an alcohol + carboxylic acid -> ester
- sulfuric acid is a catalyst
- the reaction is an equilibrium between starting materials and products, and for this reason the Fischer esterification is seldom used to prepare esters
the esterification reaction achieves better results by reaction the alcohol with an ___ ______
acyl chloride
- the reaction is exothermic and produces the corresponding ester in high yields, with only HCl as a by product
- pyridine is used to neutralize the HCl
the best known nitrate ester is _________, whose systematic name is ______ _______
nitroglycerine, glyceryl trinitrate
glyceryl trinitrate results from the reaction of ____________ with _____________
glycerol (1,2,3-propanetriol) with three molecules of nitric acid
_______ ___ help make up the backbone of DNA
phosphate esters
