Hydroxy derivatives of hydrocarbons (alcohols,

phenols, ethers) and sulfur analogues:

Bonding system characterization. Physical properties. Acid-

base properties, the structural determinants of acidity. Theirs

reactions connected with their nucleophilic properties

(alkylation, acylation, sulphonic acid, producing inorganic

esters), alcohols, acid-catalyzed conversion. Oxidation of

alcohols and phenols. Ethers properties, cleaved of ethers.

Special bonding systems of ethers (epoxides and hemiacetals,

acetals and enol ethers) and their chemical reactions. Their

synthesis.

Grouping of compounds with C-OH, C-O-C, C-SH and C-S-C bonds

Starting point: classical valence theory:

according to the hybrid status of the pillar carbon:alcohols (R-OH): sp3 carbon phenols, enols (Ar-OH, C = C-OH): sp2 carbon

- not arbitrary, different bonding!

according to the order of sp3 carbon atoms (alcohols): primary (1°), secondary (2°), tertiary (3°) similarity to the halogen derivatives

according to the number of hydroxyl groups (diol, triol, polyol) in case of diols: according to their position to each other: geminal, vicinal, disjunct

according to the nature of the hydrocarbon group:saturated / unsaturated / acyclic / cyclic

n 1

Formally - a water/a hydrogen sulphide is

substituted with hydrocarbon radicals

BUT! for sulphur empty d orbitals, S = O bond is

formed ("four and six valence" sulphur!)

1-C-OH bonded compounds (alcohols, phenols, enols)

ethanol phenol vinyl alcohol

NomenclatureFunctional class nomenclature

Functional class names of alcohols are derived by naming the alkyl group that bears the hydroxylsubstituent (-OH) and then adding alcohol as a separate word. The chain is always numbered beginning at the carbon to which the hydroxyl group is attached.

Substitutive nomenclatureSubstitutive names of alcohols are developed by identifying the longest continuous chain that bears the hydroxyl group and replacing the -e ending of the (pentane) corresponding alkane by the suffix -ol. The position of the hydroxyl group is indicated by number, choosing the sequence that assigns the lower locant to the carbon that bears the hydroxyl group.

Hydroxyl groups take precedence over (“outrank”) alkyl groups and halogen substituents in determining the direction in which a carbon chain is numbered.

Trivial names (common names)

Several alcohols are commonplace substances, well known by common names that reflecttheir origin (wood alcohol, grain alcohol) or use (rubbing alcohol).Wood alcohol is methanol (methyl alcohol, CH3OH), grain alcohol is ethanol (ethyl alcohol, CH3CH2OH), and rubbing alcohol is 2-propanol [isopropyl alcohol, (CH3)2CHOH].

Glycerol (glycerin, propane-1,2,3-triol), glycol (ethylene glycol, ethane-1,2-diol).

Classification of C-OH, C-O-C, C-SH and C-S-C compounds 2.

2. C-O-C compounds (ethers)According to the linked groups: symmetrical and non-symmetrical (mixed) ethers According to the hydrocarbon group

- Aliphatic ethers (R-O-R, R-O-R1) - Aliphatic-aromatic ethers (R-O-Ar) - Aromatic ethers (Ar-O-Ar1 + heteroaromatic analogues) - Enol ethers: specific, different (higher) reactivity [-C = C-OR (Ar)]

Special types of ether

3. C-O-O-H, C-O-O-R compounds

Formally, the alkylated / arylated derivatives of hydrogen peroxide

Cyclic ethers epoxides (oxiranes) hemiacetal acetal orthoester

special compounds: different reactivity than

cyclic ether

Similarity to aldehydes and ketones

Relation to carboxylic acids

Ether derivatives of geminal diols

Nomenclature of ethers

Ethers are named, in substitutive IUPAC nomenclature, as alkoxy derivatives of alkanes.ONLY alkoxy / aryloxy prefix + base carbon chain

Substitutive IUPAC nomenclature

Functional class IUPAC names of ethers are derived by listing the two alkyl groups in the general structure ROR in alphabetical order as separate words, and then adding the word “ether” at the end. When both alkyl groups are the same, the prefix di- precedes the name of the alkyl group.Ethers are described as symmetrical or unsymmetrical depending on whether the twogroups bonded to oxygen are the same or different. Unsymmetrical ethers are also calledmixed ethers. Diethyl ether is a symmetrical ether; ethyl methyl ether is an unsymmetrical ether.

Functional class IUPAC nomenclature

Cyclic ethers have their oxygen as part of a ring—they are heterocyclic compoundsSeveral have specific IUPAC names.

trivial names, additive nomenclature, Hantzsch-Widman nomenclature

(additive nomenclature)

Hantzsch-Widman nomenclature:

(trivial names) (trivial names)

In each case the ring is numbered starting at the oxygen. The IUPAC rules also permit oxirane (without substituents) to be called ethylene oxide. Tetrahydrofuran and tetrahydropyran are acceptable synonyms for oxolane and oxane, respectively.

Many substances have more than one ether linkage. Two such compounds, often used as solvents, are the diethers 1,2-dimethoxyethane and 1,4-dioxane. Diglyme, also a commonly used solvent, is a triether.

Nomenclature of ethers 2.

4. Compounds with C-S-H, C-S-R bonds (sulfur analogs of alcohols , phenols and ethers)

In close analogy to the oxygen-containing analogues - thioalcohols, arenthiols, thioethers

Derivatives with more than two ligands

Relationship with sulfones according to the

binding system, chemically similar to

carboxylic acids

thioalcohol arenthiol sulfide (thioether) disulfide if n>2 polysulfideR1=R2 or R1≠R2 different from oxygen

sulfinyl group sulfonyl group

Thiols are given substitutive IUPAC names by appending the suffix -thiol to the name of the corresponding alkane, numbering the chain in the direction that gives the lower locant to the carbon that bears the ―SH group. The final -e of the alkane name is retained. When the ―SH group is named as a substituent, it is called a mercapto group. It is also often referred to as a sulfhydryl group, but this is a generic term, not used in systematic nomenclature.

Nomenclature of thiols

Substitutive IUPAC names

At one time thiols were named mercaptans. Thus, CH3CH2SH was called “ethyl mercaptan” according to this system. This nomenclature was abandoned beginning with the 1965 revision of the IUPAC rules but is still sometimes encountered, especially in the olderliterature.

aromatics: benzenethiol nomenclature (in the older literature thiophenol name is used)

Hydroxyl groups take precedence

over sulphanyl/mercapto group.

The sulfur analogs (RS―) of alkoxy groups are called alkylthio groups. The first two of the following examples illustrate the use of alkylthio prefixes in substitutive nomenclature of sulfides. Prefixes: alkylthio/alkylsulfanyl, arylthio/arylsulfanyl, alkylpolythio

Substitutive nomenclature of sulfides

Functional class IUPAC names of sulfidesFunctional class IUPAC names of sulfides are derived in exactly the same way as those of ethers but end in the word “sulfide.” hydrocarbon group names + sulfide, disulfide, polysulfide suffix

Sulfur heterocycles have names analogous to their oxygen relatives, except that ox- is replaced by thi-. Thus the sulfur heterocycles containing three-, four-, five-, and six-membered rings are named thiirane, thietane, thiolane, and thiane, respectively.

Nomenclature of sulfides

Substitutive nomenclature:

Functional class IUPAC names:

Substitutive nomenclature

prefix: alkylsulfinyl, arylsulfinyl, alkylsulfonyl, arylsulfonyl

Nomenclature of sulfoxides and sulfones

Functional class nomenclature

hydrocarbon group names + sulfoxide / sulfone suffix

Additionally: Compound Name + S-oxide / S, S-dioxide suffix

Dimethyl sulfoxideMethylsulfinylmethane

Functional class nomenclature:Substitutive nomenclature:

Dimethyl sulfonMethylsulfonylmethane

Dimethyl sulfide S-oxide Dimethyl sulfide S,S-dioxide

Bonding system of alcohols and ethers

Starting point: structure of water - sp3 hybrid state for oxygen (h12h2

2h31h4

1)

Alcohols – C(sp3)-O(sp3) hetero nuclear -bondEthers – two C(sp3)-O(sp3) hetero nuclear -bond

tetrahedral compound but the bond angle is deformed(R,R1 groups have more space demand)

Bond E – both C-O and O-H are strongC-O: 355-380 kJ/mol (compare to: C-C: 345-355 kJ/mol)O-H: 460-465 kJ/mol (compare to: C-H: 400-415 kJ/mol)

Phenols, phenol ethers, enol ethers: shortening bond distance more stronger bond!! (greater bond order)

Reason: interaction between nonbonding e-pair and -e-system (+M effect)

Seven-center bond with eight electrons - electron delocalization!

(parallel PZ orbitals)

Resonance structures:

C-O bond: the increasing double bond character Aromatic ring increased electron density ( OH, OR first order directing groups, activating substituents!)

Bond distance

(sp2 hybrid state

for oxygen)

Electronegativities

ENC = 2.5, ENO = 3.5, ENH = 2.1 polar hetero nuclear bonds, charge separation permanent dipole moment

Tioalcohols and tioethersFormal similarity between O and S BUT in case of sulphur: 3s23p43do

(electon cofiguration of oxygen: 1s22s22p4)

Further differences: S has larger atom radius (rS = 0.102 nm, rC = 0.077 nm, ro = 0.073 nm) longer and weaker bonds compare to oxygen

Non-bonding e-pairs have greater space demand larger deformation compare to oxygen analogues

or

e. g.

Thiophene (aromatic compound)

Physical properties of alcohols, ethers and their thio analogousBoiling point, melting point – Typically, higher than alkanes, and alkyl halides, it has homologous seriesIncreasing length of carbon chain makes it closer to R-Cl, RH characteristics (dispersion forces between the alkyl chains become increasingly dominant)

R-OH R-SH ~ R-OR1 ~ R-Cl R-H

Forces H bond dipole-dipole Induced dipole - Induced dipole

H-OH > Me-OH, Et-OH, Pr-OH worse fit, weakening associationH-OH > H-SH, R-OH > R-SH weakening H-bond (S nonbonding pair is diffuse)

Boiling points (oC)

Melting points of n-alcohols (ROH)

Melting point: minimum curve – longer alkyl group incorporation into the diamond-like H-bond structure of the ice is not occurs completely soIf the alkyl chain is long than „alkane-like” mp can be expected

A dipole–dipole attraction between the positively polarized proton of the OH group ofone ethanol molecule and the negatively polarized oxygen of another. The termhydrogen bonding is used to describe dipole–dipole attractive forces of this type. The proton involved must be bonded to an electronegative element, usually oxygen or nitrogen.Protons in C―H bonds do not participate in hydrogen bonding.

Hydrogen bonding

Hydrogen bonding in ethanolinvolves the oxygen of one molecule and the proton of an ―OH group of another. Hydrogen bonding is muchstronger than most other types of dipole–dipole attractiveforces.

Di- and polyols: highly elevated mp, bp

Reason: intermolecular H-bonds, long chains

Density: 1 (H2O) – alkyl groups makes the molecule „lighter”

Solubility: In Water: H bonds, in low concentrations the solubility is good

(n = 1-3: unlimited!)Ethers: worse solubility in water, BUT S(Et2O) = 8 g/100 ml!!

„one-sided” H bonds, ether only H acceptor!Thiols: weak H bonds weak solubility in water

Preparation of alcohols

1. From alkyl halides by SN reactionProblem: competing elimination (alkene formation) →contaminated product probability R = 1° <2° <3°direction is increasing

2. Hydrolysis of esters

The acidic variant is an equilibrium reaction, reversal of the esterification. Better: alkaline hydrolysis (≥ 1 equiv base.)

Typical: NaOH (KOH)/H2O or NaOH/alcohol, dioxane etc – H2O (solubility!), then H3O

A two-step pathway for avoiding elimination

SN reaction with a less nucleophile partner, easy ester cleavage

Preparation of alcohols3. Hydration of alkenes (formal or actual water addition) 3.1. Acid-catalyzed addition of water

The structure of the major product (regioselectivity) is defined by the Markovnikov’s rule.

3.2. Oxymercuration – demercuration

3.3. Hydroboration

4. Reduction of oxo compounds

Opportunities:1. catalytic reduction (H2/cat., cat. = Pd-C, Pt, PtO2, Raney-Ni, etc.)2. Metal hydrides (NaBH4/R-OH, LiAlH4/Et2O or THF --- H-)3. Dissolving metal reduction (Zn/HCl or NaOH, Na/EtOH, etc. --- formation of H2)

The structure of the major product (regioselectivity) is defined by the Markovnikov’s rule.

The structure of the major product (regioselectivity) is defined by the Markovnikov’s

rule BUT anti-Markovnikov product is formed.

dilute

Preparation of alcohols

5. Reduction of esters

In laboratory: LiAlH4 (LAH)/Et2O;

Industry: catalytic reduction (harshconditions, eg. copper-chromite

(Cu2Cr2O5)/150-400 oC, 100-300 bar)

6. Reactions of oxo comp. / carboxylic acid derivatives and Grignard reagenst

Do you know these reactions ????

Preparation of phenolsIn laboratory: „cooking” of diazonium salts

By-products

Diazonium salt Phenol

Industry: nowadays starting from cumene

The world phenol production:8.9 million tonnes in 2012.The global phenol foreign tradeexceeded USD 3.6 billion in 2012.The world phenol supply is expectedto go beyond the 10.7 million tonnesmark in 2016.

Preparation of ethers

LG = Hlg, OSO2Q, OSO2OR1

Ethers can be synthesized from alcohols or phenols by nucleophylic substitution – This is

Williamson-type ether synthesis

The structure of methylating agents

Alkylating agents:

- Alkyl halide

- Sulphonic acid esters

- Dialkyl sulphates

Some problems:

First:

Second:

Preparation of thiols

Nucleophilic substitution. Disadvantage: symmetrical thioether formation, cause the resultant product is also reactive in nucleophilic reactions so a possible secondaryreaction can take place

A better substitution reaction:

Synthesis of thiols through isothiouronium salt

The most often used method

thiourea

Oxymercuration – demercuration: synthesis of ethers by electrophillic addition of alcohols

The structure of the major product (regioselectivity) is defined by the Markovnikov’s rule.

Preparation of thioethers

In a nucleophilic substitution reaction

Analogy with Williamson’s ether synthesis

Thiols and thiophenols reacts readily,

Reason: the great nucleophilicity of S (+ easy formation of thiolate, thiophenolate)

thiolate thiophenolate

Same problems as in the case of ethers:

First:

Second:

Preparation of benzene thiols (thiophenols)

It can be synthesized from arylsulfonyl chloride by simple reduction or by the reaction of

Grignard reagents with elemental sulphur.

It can be prepared from phenols too, in a three-steps procedure. First, the phenol was

reacted with N,N-dialkyl-tiocarbamoyl-chloride, followed by the Pd catalyzed

rearrangement and hydrolysis .

Chemical properties of alcohols, ethers and thio analogues

Starting point: polar compound, heteroatoms electron excess (greater e- density), H loses e-

Sulphur: polarisable!

1.1. Basicity: non-bonding e-pair/partial negative charge Brönsted base, Lewis base

e. g. BF3Et2O bp: 127 oC, it

can be distilled!

1. Acid-base properties

2.1. Acidity - alcohols (phenols, enols), thiols: strongly polarized H-O bond (requirement for acidity) possible deprotonation, Brönsted acidity

The required base deprotonation strength depends on the acidity of RX-H compound. Acidity depend on the stability of the formed anion during the deprotonation!!

Tendencies:✓ R-OH ~ H2O, depending on the order of alcohols: 1o > 2o > 3o

✓ Ar-OH > R-OH✓ R-SH > R-OH

B: metal or

Acidity of alcohols, phenols Acidity of substituted phenols

deprotonation

Picric acid

Explanation of tendencies of acidity – stability of anions

Phenols: charge delocalisation on the aromatic system (after the deprotonation of phenols)

Phenolate: LCAO-MO: 7 centred bond with 8 electrons greater Ka than alcohols

Resonance structures

G‡

R-OH + B:

Ar-OH + B:

R-O: + HB

Ar-O: + HB

Thiols: After the deprotonation the pairs of electrons distributed in bigger space (cf. larger ion radius of sulphur)

MeO: MeS:

Phenolate anion

Reactions can be derived directly from the bonding system - the nucleophilic character

Differences between alcohols and phenolsPhenols: stronger C-O bond O-H bond cleavage is preferred (weaker bond + the stability of phenolate ion) acid catalysed process (C-O bond cleavage) are rare!

C-O bond cleavage:Initiating step: protonation under

acidic condition

O-H bond cleavage:Initiating step: deprotonation under

neutral or basic condition

Chemical properties of alcohols1. Ether formation

LG = Hlg, OSO2Q, OSO2OR1

e.g. methylating agents

Notes: aryl halides (except if it is actyvated) no reaction alcoholate is better nucleophile strong base necessary for preparing an alcoholate

phenols have greater acidity even aqueous basic solution can used (NaOH, KOH, Na2CO3/H2O)

1.2. Ether synthesis with solvolysisSolvolysis: itself the solvent is the nucleophile

1.3. Ether synthesis under acidic condition (acid catalysed nucleophile substitution)

Importance: the most applied ether synthesis

Acidic activation, alcohol has double role.

Formally: intermolecular water elimination

Synthetic importance: symmetrical ethers

Nucleophile substitution (O-nucleophile!)

1.1. Williamson’s synthesis (R1 = alkyl, allyl, benzyl)

Acid catalysed ether synthesis - mechanism: carbocation intermediate

BUT! Competitive reaction with elimination: alkene formation ( elimination)

tendency!

Alkene formation: Zaitsev’s rule (more stable alkene is formed)

Chemical properties of alcohols

Ether formation is favoured if: 1o or 2o alcohol large ROH concentration cat. amount H

lower temperature

2. Ester formation

General:

Esters of inorganic acids

Carboxylic acid esters

Acid catalysed acylation (3 mechanism)Equilibrium!!

In practice an important step: acylation

Most important acylating agents:

Important biological role: DNA, RNA: nucleotide, nucleic acid (Organic chemistry III.)

Chemical properties of alcohols

Phosphoric acid esters

Trialkyl phosphate

AdN + E mechanism

NO Equilibrium!!!

Sulfonate ester derivatives:

Importance: sulfonate esters are good leaving groups (as sulfonate anion: R1SO2O: ), SN

reactions!! To replace OH group with other substituent: first transform OH to sulfonateester then do the substitutive reaction

Hydrogen halides: alkyl halides

Acid catalysed SN, waterelimination!

General condition: cc. HHlg/Δ. In case of 3o alcohols even at room temperature

Chemical properties of alcohols

OH group badleaving group

The oxidation states above alcohol levels: aldehyde / ketone; acid possible oxidation products. The structure of the product and the required conditions (reactivity) depends on the structure of the starting alcohol.

RCHO easy oxidizability ; partial oxidation requires special reagents and conditions: Cr (VI), or removal of aldehyde

Industry: catalysts for dehydrogenation (CuO-Cu/300 oC). Important reaction: EtOH → MeCHO

2. 2o Alcohols

Chemical properties of alcohols - OXIDATION

Mixture of carboxylic acids

harsh oxidation

Up to ketone the oxidation takes place readily

Oxidizing agents: CrO3/H2SO4 (Jones reagent), CrO3*2Py/DCM (Collins reagent), K2Cr2O7/H2OCr(VI) (orange)→ Cr(III) (green)

BUT, KMnO4/H+ or KMnO4/H2O chain cleavage

Cr(VI)

1. 1o Alcohols

3. 3o Alcohols

Difference: there is no opportunity for dehydrogenation in alkaline or neutral medium, no reaction.

BUT! In acidic medium: first dehydratation then alkene chain cleavage

Note: the biological oxidation of alcohols is also possible.

For example: The oxidation of ethanol to acetaldehyde with the help of dehydrogenase enzyme

Chemical properties of alcohols - OXIDATION

Chemical properties of phenols

Easy deprotonation – potential O-nucleophile acylation (ester formation) sulfonylation (sulfonate ester formation) alkylation (ether formation)

Oxidation of phenols – takes place easily

Phenol

OH groups with acidic H can be alkylated with

diazoalkanes

Alkylation:ethers Acylation:

esters

Sulfonylation: sulfonate ester

or

During storage it gets coloured since the OH group has high +M effectthat results large e-density in the aromatic ringoxidation is easy1,2-(OH)2 and 1,4-(OH)2 benzenes

1,2-benzoquinone 1,4-benzoquinone

Aromatic electrophilic substitution of phenols – the OH group will not react but it has directing effect

Use of salicylic acid: production of Aspirin®

Chemical properties of phenols

Kolbe reaction: electrophile: O=C=O

effect

Highly activated and very reactive aromatic ring

picric acid

The reaction occurs in aqueous solution without

a catalyst!!!Polyhalogenation

Dilute HNO3

phenol

willow bark ( natural source of salicylic acid) can ease pain and reduce fevers

Phenol-formaldehyde resins

Crosslinkedpolycondensationplastic: bakelite

Baekeland (inventor)

Chemical properties of phenolsHydroxy-methylation

Importance

C-O-C highly polarized but strong bond

Based on binding system may be a direct SN reaction... But! Alkoxy group is a bad leaving group because the weak stabilization no bond cleavage

Consequence:Ethers are slightly reactive, no reaction in neutral and basic medium, inert to the alkali and alkaline earth metals, organometallic compounds and dilute (!) acids

Ideal solvents (e.g. Grignard reaction), extraction agents

Possible reactions: based on Brönsted / Lewis basicity: protonation, coordination Lewis acids (for ACTIVATION ...)

Activation: Protonation - strong acids, strong acidic conditions

Question: what is the nucleophile ?? A typical solution is concentrated HHlg / Δ

Because of the secondary reaction -- small synthetic application: mixture of alkyl halides...BUT! For phenol ethers selective cleavage of due to the different binding energies of C-O.Furthermore, there is no secondary reaction due to the strong Ar-O bond. (Protective Group!!!)

Chemical properties of ethers

Good leaving group

Cleavage of acetals, enol ethers - much easier than "simple" ethers - with dilute acidic medium

Reversible equilibrium reaction - the same mechanism in both directions. Reverse direction: Synthesis of acetals from oxo compounds

Reaction of epoxides

Chemical properties of ethers

Typical reaction: ring opening preparation of 1,2-disubstituted systems (alcohols)

Three-membered strained ring:• Large Bayer – strain (Angle strain, The 60o bond angles are much smaller

than the optimum 109.5 o angles of a normal tetrahedral carbon atom)• Large Pitzer - strain (eclipsed groups) → high reactivity

Nu attack

protonation

more stable tautomer(constitutional isomer)

Baeyer suggested that three- and four-membered rings suffer from what we now callangle strain. Angle strain is the strain a molecule has because one or more of its bondangles deviate from the ideal value; in the case of alkanes the ideal value is 109.5°.

Angle strain: destabilization that results from distortion of bond angles from theirnormal values

Torsional strain: destabilization that results from the eclipsing of bonds on adjacentatoms

Chemical properties of ethers - ring-opening of epoxides

Ring opening in neutral or alkaline medium - nucleophile attack of the epoxy carbon atoms.An ether functional group substitution by nucleophile, different reactivity than simple ethers due to the ring strain!

Ring opening in acidic medium - nucleophile attack on the epoxy protonated carbons

O-nucleophile → C-O bond

N-nucleophile → C-N bond

C-nucleophile→ C-C bond

Antiperiplanar (trans) OH and Nu

Solvents, paint and varnish industry

Ethylene glycolbond

Ethylene glycol

monoethyl ether

Chemical properties of ethers - Oligo-and polyethylene glycols, crown ethers

Diethylene glycol Triethylene glycol

Good solvatation of cations

High boiling point, good solventsReactions with metal salts at high T

Cyclic derivatives: crown ethers

12-crown-4 18-crown-6 15-crown-5

Complex formation according to the size of metal salts Li+ --- 12-crown-4 Na+ --- 15-crown-5 K+ --- 18-crown-6

Use:➢ Crown ethers are used in the laboratory as phase transfer catalysts➢ Medical use: remove metal ions from living body

Ethylene oxide as starting material

Polyethylene glycol

In chemistry, a phase-transfer catalyst or PTC is a catalyst that facilitates the migrationof a reactant from one phase into another phase where reaction occurs. Phase-transfercatalysis is a special form of heterogeneous catalysis.Ionic reactants are often soluble in an aqueous phase but insoluble in an organic phasein the absence of the phase-transfer catalyst. The catalyst functions like a detergent forsolubilizing the salts into the organic phase.Phase-transfer catalysis refers to the acceleration of the reaction upon the addition ofthe phase-transfer catalyst. By using a PTC process, one can achieve faster reactions,obtain higher conversions or yields, make fewer byproducts, eliminate the need forexpensive or dangerous solvents that will dissolve all the reactants in one phase,eliminate the need for expensive raw materials and/or minimize waste problems.Phase-transfer catalysts are especially useful in green chemistry—by allowing the use ofwater, the need for organic solvents is reduced.

Chemical properties of thiols and thioethers

Chemical properties of thiols - starting point: considerable acidity, RS: easy generation

RS: excellent nucleophilethiols readily can be acylated, alkylated, etc.. - The similarity to alcohol!

Difference: oxidation reactions (compared to alcohol - more possibility)

Reaction with Csp3 electrophiles

Reaction with Csp2 electrophiles

Acid cat. AdNC=O

Acyl SN (AdN+ E)

Mild oxidation or or weak base (in cat. amount)

Harsh oxidation

Significance of sulfonic acids:Detergents, pharmaceutical

Oxidizing agents:

Biological importance:

thioether

thioester

thioacetal

disulfide

sulfonic acid

Alkylation – S as nucleophile

Oxidation - Preparation of sulfoxides, sulfones with electrophilic oxidizing agents

Chemical properties of thiols and thioethers

Chemical properties of thioethers

Sulfonium salts

Stable, solid compoundscan be chiral if R =R1=R2

Oxidizing agents:

difficult

Prep. of sulfoxides with oxidation is not easy:• Requires mild reaction conditions (0-25 oC)• 1 equiv. oxidizing agents