Ch 11 Reactions of Alcohols Flashcards
dehydration of an alcohol produces what product(s)?
alkenes
oxidation of an alcohol produces what product(s)?
ketones, aldehydes, acids (ex: carboxylic acid)
substitution of an alcohol produces what product(s)?
halides
(R-X)
reduction of an alcohol produces what product(s)?
alkanes
(R-H)
esterification of an alcohol produces what product(s)?
esters
(R-O-C(=O)-R’)
tosylation of an alcohol produces what product(s)?
tosylate esters
(R-OTs)
(a good leaving group)
deprotination of an alcohol (R-OH) to form an alkoxide and treatment with an alkyl halide (R’-X) produces what product(s)?
ethers
(R-O-R’)
give examples of oxidation based on the change of the formula of the substance:
addition of O or O2; addition of X2 (halogens); loss of H2
give examples of reduction based on the change of the formula of the substance:
addition of H2 (or H-); loss of O or O2; loss of X2
give examples of changes in formula of the substance which are condisered neither oxidation nor reduction:
addition or loss of H+, -OH, H2O, HX
(more options possible)
what does oxidation normally do in terms of bonded atoms to carbon?
generally converts C-H bonds to C-O bonds
what species is more oxidised, an alkane or a carboxylic acid?
carboxylic acid
what species is more oxidised, an alkane or a ketone?
ketone
what species is more oxidised, an alkane or an aldehyde?
aldehyde
what species is more oxidised, an alkane or a primary alcohol?
primary alcohol
what species is more oxidised, an alkane or a secondary alcohol?
what species is more oxidised, a primary alcohol or an aldehyde?
aldehyde
what species is more oxidised, an aldehyde or a carboxylic acid?
carboxylic acid
what species is more oxidised, a secondary alcohol or a ketone?
ketone
what species is more oxidised, a primary alcohol or a carboxylic acid?
carboxylic acid
classify the groups formed form the oxidation of an alkane from most reduced to most oxidised, starting with a 1° carbon
alkane, primary alcohol, aldehyde, carboxylic acid
classify the groups formed form the oxidation of an alkane from most reduced to most oxidised, starting with a 2° carbon
alkane, secondary alcohol, ketone
classify the groups formed form the oxidation of an alkane from most reduced to most oxidised, starting with a 3° carbon
alkane, tertiary alcohol
what do most alcohol oxidising agents have in common, and how do they work?
all have an element (ex: Cr, Cl, I, S) in a high oxidation state bonded to oxygen. The mechanisms are also similar, the first step an intermediate forms in which the oxidant element becomes bound to the alcohol’s oxygen, and after a base removes a proton from the carbinol carbon atom a double bond forms to oxygen, resulting in a oxydised alcohol (a ketone or aldehyde) and a reduced oxidant.
why is it difficult to obtain an aldehyde?
most oxidising agents strong enough to oxidise primary alcohols are also strong enough to oxidise aldehydes. pyridinium chlorochromate (CrO3•pyridine•HCl or pyH+ CrO3Cl- *or * PCC) is a notable exception, capable of oxidising primary alcohols to aldehydes.
under what circumstances can tertiary alcohols be oxidised?
breaking of carbon-carbon bonds is required
in an aqueous reaction, hypochlorous acid (ClOH) acts as an oxidant. what is its final (reduced) form?
hydronium ( H3O+ ) and chloride ion ( Cl-)
chromic acid reagent
Na2Cr2O7 / H2SO4
sodium dichromate / sulfuric acid in aqueous solution
CrO3 / H2SO4
chromium trioxide / sulfuric acid in aqueous solution
what does the chromic acid reagent do to secondary alcohols?
oxidation of secondary alcohols to ketones
the chromic acid (H2CrO4) reagent is used to oxidise secondary alcohols to ketones and primary alcohols to carboxcylic acids
the chromic acid (H2CrO4) reagent is used to oxidise secondary alcohols to ketones and primary alcohols to carboxcylic acids
the chromic acid (H2CrO4) reagent is used to oxidise primary alcohols to carboxylic acids and secondary alcohols to ketones
chromic acid test
the chromic acid reagent does not oxidise teritary alcohols, ketones, or alkenes, as that would require breaking carbon-carbon bonds. the colour change from orange to green/blue indicates the presence of primary and secondary alcohols
what reagent(s) convert(s) primary alcohols to carboxcylic acids?
chromic acid (H2CrO4), sodium hypochlorite (NaOCl)
what reagent(s) convert(s) primary alcohols to aldehydes?
pyridinium chlorochromate (PCC), Swern, DMP
household bleach
sodium hypochlorite (NaOCl), oxidations using sodium hypochlorite involve mildly acidic or basic conditions that may be better than chromic acid for acid-sensitive compounds while accomplishing the same task, oxidation of secondary alcohols to ketones and primary alcohols to caboxcylic acids
NaOCl
sodium hypochlorite (household bleach), oxidations involve mildly acidic or basic conditions that may be better than chromic acid for acid-sensitive compounds while accomplishing the same task, oxidation of secondary alcohols to ketones and primary alcohols to carboxcylic acids
sodium hypochlorite
sodium hypochlorite (NaOCl) (household bleach), oxidations involve mildly acidic or basic conditions that may be better than chromic acid for acid-sensitive compounds while accomplishing the same task, oxidation of secondary alcohols to ketones and primary alcohols to carboxcylic acids
sodium hypochlorate (NaOCl), oxidations involve mildly acidic or basic conditions that may be better than chromic acid for acid-sensitive compounds while accomplishing the same task, oxidation of secondary alcohols to ketones and primary alcohols to carboxcylic acids
Swern
The Swern oxidation uses dimethyl sulfoxide (DMSO) as the oxidizing agent to convert alcohols to ketones and aldehydes. DMSO and oxalyl chloride ((COCl)2) are added to the alcohol at low temperature, followed by a hindered base such as triethylamine
DMSO
The Swern oxidation uses dimethyl sulfoxide (DMSO) as the oxidizing agent to convert alcohols to ketones and aldehydes. DMSO and oxalyl chloride ((COCl)2) are added to the alcohol at low temperature, followed by a hindered base such as triethylamine
The Swern oxidation uses dimethyl sulfoxide (DMSO) as the oxidizing agent to convert alcohols to ketones and aldehydes. DMSO and oxalyl chloride ((COCl)2) are added to the alcohol at low temperature, followed by a hindered base such as triethylamine
why are alcohols such versatile chemical intermediates?
they react as both nucleophiles and electrophiles
explain this generic alcohol reaction
alcohol reacting as a weak nucleophile, bonding to a strong electrophile (the carbocation)
what is the purpose of this reaction of alcohol?
an alcohol (a weak nucleophile) is easily converted to a strong nucleophile by forming its alkoxide ion, so the alkoxide ion can attack a weaker electrophile, such as an alkyl halide
in terms of bond cleavage, what is the difference between alcohol reacting as a nucleophile or electrophile?
The O-H bond is broken when alcohols react as nucleophiles, both when an alcohol reacts as a weak nucleophile, or when an alcohol is converted to its alkoxide that then reacts as a strong nucleophile. In contrast, when an alcohol reacts as an electrophile, the C-O bond is broken.
what is the drawback of protonation of an alcohol to form a better electrophile?
The disadvantage of using a protonated alcohol is that a strongly acidic solution is required to protonate the alcohol. Although halide ions are stable in acid, few other good nucleophiles are stable in strongly acidic solutions. Most strong nucleophiles are also basic and will abstract a proton in acid. Once protonated, the reagent is no longer nucleophilic. For example, an acetylide ion would instantly become protonated if it were added to a protonated alcohol.
R-OH + TsOH ->
R-OTs + H2O
describe the process(es) capable of performing this reaction:
We can reduce an alcohol in two steps, by dehydrating it to an alkene, then hydrogenating the alkene (shown).
Or, convert the alcohol to the tosylate ester, then use a hydride reducing agent to displace the tosylate leaving group (works with most primary and secondary alcohols).
describe an alcohol in acid
In acidic solution, an alcohol is in equilibrium with its protonated form. Protonation converts the hydroxyl group from a poor leaving group (-OH) to a good leaving group (H2O). Once the alcohol is protonated, all the usual substitution and elimination reactions are feasible, depending on the structure (1°, 2°, 3°) of the alcohol.
what is unique about halide ions as nucelophiles?
Most good nucleophiles are basic, becoming protonated and losing their nucleophilicity in acidic solutions. Halide ions are exceptions, however. Halides are anions of strong acids, so they are weak bases. Solutions of HBr, HCl, or HI contain nucleophilic Br-, Cl-, or I- ions. These acids are commonly used to convert alcohols to the corresponding alkyl halides.
how would you convert a tertiary alcohol to a tertiary alkyl halide?
Via SN1. Because alkyl halides are strong nucelophiles but also stable in acid (because they are the weak bases (X-) of strong acids (HX)), protonation of the alcohol forms the leaving group, and carbocation forms (SN1). Halide ion attacks the carbocation. Shifts possible, the carbocation will form on the most substituted carbon.
how would you convert a primary alcohol to a primary alkyl halide?
Via SN2. Because alkyl halides are strong nucelophiles but also stable in acid (because they are the weak bases (X-) of strong acids (HX)), protonation of the alcohol forms the leaving group, which is displaced in a concerted mechanism by the halide with inversion of stereochemistry at the alcohol carbon.
which is a stronger nucleophile, chloride ion or bromide ion, and why?
Chloride ion is a weaker nucleophile than bromide ion, because it is smaller and less polarisable. An additional Lewis acid, such as zinc chloride (ZnCl2), is sometimes necessary to promote the reaction of HCl with primary and secondary alcohols. Zinc chloride coordinates with the oxygen of the alcohol in the same way a proton does— except that zinc chloride coordinates more strongly.
The reagent composed of HCl and ZnCl2 is called the Lucas reagent. Secondary and tertiary alcohols react with the Lucas reagent by the SN1 mechanism.
The reactions of alcohols with hydrohalic acids do not always give good yields of the expected alkyl halides. Why?
- Poor yields of alkyl chlorides from primary and secondary alcohols. Primary and secondary alcohols react with HCl much more slowly than tertiary alcohols, even with zinc chloride added. Under these conditions, side reactions may prevent good yields of the alkyl halides.
- Eliminations. Heating an alcohol in a concentrated acid such as HCl or HBr often leads to elimination. Once the hydroxyl group of the alcohol has been protonated and converted to a good leaving group, it becomes a candidate for both substitution and elimination.
- Rearrangements. Carbocation intermediates are always prone to rearrangements. We have seen that hydrogen atoms and alkyl groups can migrate from one carbon atom to another to form a more stable carbocation. This rearrangement may occur as the leaving group leaves, or it may occur once the cation has formed.
- Limited ability to make alkyl iodides. Many alcohols do not react with HI to give acceptable yields of alkyl iodides. Alkyl iodides are valuable intermediates, however, because iodides are the most reactive of the alkyl halides. Instead, several phosphorus halides are useful for converting alcohols to alkyl halides: Phosphorus tribromide (PBr3), phosphorus trichloride (PCl3), and phosphorus pentachloride (PCl5).
What is the purpose of the phosphorous halide reagent?
To convert primary and secondary alchols to alkyl halides via SN2 (inversion of stereochemistry), also works with iodine, unlike hydrohalic acids (R-OH + HX -> R-X + H2O). Does not work with tertiary alcohols.
what mechanism do alcohol dehydrations generally take place via?
Alcohol dehydrations generally take place through the E1 mechanism. In the acid-catalysed dehydration of an alcohol, protonation of the hydroxyl group converts it to a good leaving group. Water leaves, forming a carbocation. Loss of a proton gives the alkene.
what is the rate limiting step in the acid-catalysed dehydration of an alcohol?
describe the acid-catalysed dehydration of a primary alcohol
With primary alcohols, rearrangement and isomerization of the products are so common that acid-catalysed dehydration is rarely a good method for converting them to alkenes. The following mechanism shows how butan-1-ol undergoes dehydration with rearrangement to give a mixture of but-1-ene and but-2-ene. The more highly substituted product, but-2-ene, is the major product, in accordance with the Zaitsev rule.
outline the guidelines for predicting products from of acid-catalysed dehydration.
- Dehydration usually goes by the E1 mechanism. Rearrangements may occur to form more stable carbocations.
- Dehydration works best with tertiary alcohols and almost as well with secondary alcohols. Rearrangements and poor yields are common with primary alcohols.
- (Zaitsev’s rule) If two or more alkenes might be formed by deprotonation of the carbocation, the most substituted alkene usually predominates.
osmium tetroxide (OsO4) and peroxides (H2O2) do what to alkenes?
convert them to 1,2-diols (glycols)
periodic acid (HIO4) added to a 1,2-diol (glycol) produces what?
ketones and aldehydes
how would one break an to alkene double bond into two carbonyl groups?
1) osmium tetroxide (OsO4) and peroxides (H2O2) to form the 1,2-diol (glycol)
2) periodic acid (HIO4) to produce ketones/aldehydes
converting an alcohol and an acid into an ester and water is called what?
a dehydration condensation called the Fischer esterification that takes place with an acid catalyst such as sulfuric acid (H2SO4)
how does the tosylate group (Ts) relate to esters?
In addition to forming esters with carboxylic acids, alcohols form inorganic esters with inorganic acids such as nitric acid, sulfuric acid, and phosphoric acid. In each type of ester, the alkoxy (-OR) group of the alcohol replaces a hydroxyl group of the acid, with loss of water. We have already studied tosylate esters, composed of para-toluenesulfonic acid and alcohols (but made using tosyl chloride). Tosylate esters are analogous to sulfate esters, which are composed of sulfuric acid and alcohols.
This reaction generates a sodium or potassium salt of an alkoxide ion and hydrogen gas.
The reactivity of alcohols toward sodium and potassium decreases in the order: methyl > 1° > 2° > 3°. Sodium reacts quickly with primary alcohols and some secondary alcohols. Potassium is more reactive than sodium and is commonly used with tertiary alcohols and some secondary alcohols.
Some alcohols react sluggishly with both sodium and potassium. In these cases, a useful alternative is sodium hydride, usually in tetrahydrofuran solution. Sodium hydride reacts quickly to form the alkoxide, even with difficult compounds.
explain how you would convert an alcohol to an alkoxide?
This reaction generates a sodium or potassium salt of an alkoxide ion and hydrogen gas.
The reactivity of alcohols toward sodium and potassium decreases in the order: methyl > 1° > 2° > 3°. Sodium reacts quickly with primary alcohols and some secondary alcohols. Potassium is more reactive than sodium and is commonly used with tertiary alcohols and some secondary alcohols.
Some alcohols react sluggishly with both sodium and potassium. In these cases, a useful alternative is sodium hydride, usually in tetrahydrofuran solution. Sodium hydride reacts quickly to form the alkoxide, even with difficult compounds.
describe the Williamson ether synthesis
Step 1: Form the alkoxide of the alcohol having the more hindered group.
Step 2: The alkoxide displaces the leaving group of a good SN2 substrate (such as a primary halide or tosylate).
