Alkyl Halides, Aromatic Hydrocarbons, Alcohols, Phenols, Ethers, and Thiols Lecture Notes

Flashcards based on lecture notes about Alkyl Halides, Aromatic Hydrocarbons, Alcohols, Phenols, Ethers, and Thiols.

Alkyl Halides

AKA halogenated HCs; Lipid-soluble; Common reactions are Nucleophilic substitution & Dehydrohalogenation; Stable on the shelf but not readily metabolized in vivo.

IUPAC Naming Three Portions:

Substituents, Prefix, Suffix

Identifying the Main Chain:

Longest chain of bonded carbon atoms.

Main Chain with Rings

If a ring has more carbons in it than in an attached carbon chain, the ring is the main chain; If the ring has fewer carbons, then the ring is a substituent and the main chain is the carbon chain.

Naming Substituents

Carbon-containing substituents are named as alkyl groups; Halide groups are named as halo substituents; sec- and tert- are not alphabetized

Numbering the Chain

Open chain compounds are numbered so that the first substituent on either end receives the lowest number.

Numbering Cycloalkanes

If there are only two substituents on the ring, the carbon in the ring that has the substituent first in the alphabet = position #1 (Ignore di, tri, tetra, sec-, and tert-)

IUPAC name for Alkyl Halides

Haloalkane

Common name for Alkyl Halides

Alkyl halide

Functional Class Nomenclature of Alkyl Halides (Common Name)

The alkyl group and the halide are listed separately in the name. The alkyl group is the longest chain starting at the carbon that has the halogen attached. Other alkyl groups are listed as substituents.

Substitutive Nomenclature of Alkyl Halides (IUPAC name)

Alkyl halides have a halo (fluoro-, chloro-, bromo- and iodo-) substituents on an alkane chain. The halogen is treated as a substituent. The carbon chain is numbered from the side closest the substituent as before.

Classification of Alkyl Halides

Primary: the carbon that the halogen is attached to is directly attached to one other carbon.
Secondary: the carbon that the halogen is attached to is directly attached to two carbons.
Tertiary: the carbon with the halogen attached is directly attached to three other carbons.

Bonding in Alkyl Halides

The halogen is connected to the carbon with a s bond. C-F < C-Cl < C-Br < C-I

Boiling Points (Alkyl Halides)

Increasing the number of halogens (Cl, Br or I) also increases the induced dipole-induced dipole attractive forces and therefore also the boiling point.

Boiling Points (Fluorine)

Fluorine has very low polarizability and the boiling points do not increase with increasing numbers of fluorine atoms.

Solubility in Water

Alkyl halides are insoluble in water whereas the solubility of alcohols in water is directly related to the size of the alkyl group the OH is attached to.

Density (Alkyl Halides)

Alkyl fluorides and chlorides are less dense, and alkyl bromides and iodides more dense, than water. Increasing halogenation increases density so CH2Cl2 is more dense than water.

Uses and General Characteristics of Alkyl Halides

Bond dipole moments increase as C—I < C—Br < C—F < C—Cl.
Common uses: solvents, anesthetics, freons (refrigerants), pesticides.

Preparation of Alkyl Halides

Reaction of alcohols with hydrogen halides yields alkyl halides.

Rate of Reaction (Alcohols and Alkyl Halides)

Tertiary alcohols react fastest at low temperature and primary slowest needing higher temperatures.

Preparation of alkyl & allylic halides

Free radical halogenation of alkanes

Nucleophilic Substitution (SN) Components:

Substrate, Reagent/Nucleophile (Nuc), Leaving Group (LG), Solvent/Reaction Conditions

Substitution Mechanisms

Methyl, 1º & unhindered 2º - SN2
3º, hindered 2º - SN1

Bimolecular (SN2) Nucleophilic Substitution

Concerted reaction; Nuc attacks, LG leaves; Pentacoordinate carbon in transition state; Rate depends on conc. of both reactants

SN2 Reaction Stereospecificity

100% inversion of configuration

Factors that Affect SN2 Reaction Rates - Nucleophile Strength

Species with negative charge is a stronger nuc than an analogous neutral species (e.g. -OH > H2O; -NH2 > NH3).
Nucleophilicity increases from left to right across the periodic chart (e.g. -OH > -F).
Nucleophilicity increased down the periodic table (I- > Br- > Cl- > F-) or (-SeH > -SH > -OH).
Polar protic solvents (e.g. ethanol, ammonia decrease nucleophilicity. Polar aprotic solvents e.g. (acetonitrile, DMSO, acetone) increase nucleophilicity.

Steric Effects (SN2 Reaction Rates)

When bulky groups interfere with a rxn. because of their size, this is called steric hindrance. Steric hindrance affects nucleophilicity, not basicity.

Leaving Group (SN2 Reaction Rates)

The substrate should have a good leaving group. A good leaving group should be electron withdrawing, relatively stable, and polarizable. They are weak bases.

Unimolecular (SN1) Nucleophilic Substitution

Two-step reaction; LG leaves, then Nuc: attacks; Tricoordinate carbocation intermediate; Solvolysis (when solvent is also the nucleophile = SN1 reaction; Rate depends on substrate conc. only

SN1 Reaction Stereoselectivity

Racemization - not always exactly 50/50. Carbocation can be attacked from the top or bottom face giving both enantiomers. Longer-lived carbocations give more racemization, shorter-lived give more inversion

Factors Influencing SN1 Reaction Rates

Carbocations are stabilized by alkyl groups (through hyperconjugation and the inductive effect) and by resonance.
Leaving group stability: the better the leaving group, the faster the reaction.
Solvent polarity: the reaction is favored in polar protic solvents.

Elimination Reactions

May proceed by a unimolecular (E1) or bimolecular (E2) mechanism. If the halide ion leaves with H+, the reaction is called a dehydrohalogenation.

Elimination Mechanisms

E2: 2º, hindered 1º, or bulky strong base
E1: 3º, B-branched 2º

E2 Stereospecificity

Anti-coplanar elimination of H and LG

Seytzeff Product in E2 Reactions

Most substituted; Major with small base, i.e., ethoxide, small LG

Halogenation of Alkanes

Overall reaction equation: RH + X2  RX + HX (X=F, Cl, Br or I)
For F2 the reaction is explosive; For I2 the reaction is endothermic and not feasible. The reaction is exothermic and useful for Cl2 and Br2

Chlorination of Methane

Reaction has free radicals as intermediates.

Alkyl Halides of Pharmaceutical Importance

Chloral hydrate, Halothane, Enflurane, Desflurane, Isoflurane, Thyroid hormones, Chloromethane, Clindamycin, Corticosteroids, Pimecrolimus, Sucralose

Alkyl Halides and the Environment

Ozone Depletion, Persistence & Bioaccumulation, Toxicity, Industrial Pollution

Aromatic Hydrocarbons

Based on benzene and exhibit multicenter bonding which confers unique chemical properties; Lipid-soluble; Common reactions are electrophilic aromatic substitution

Discovery of Benzene

Isolated in 1825 by Michael Faraday Synthesized in 1834 by Eilhard Mitscherlich Other related compounds with low C:H ratios had a pleasant smell, so they were classified as aromatic.

Benzene Structures

Proposed in 1866 by Friedrich Kekulé Failed to explain existence of only one isomer of 1,2-dichlorobenzene.

Benzene Structures (Modern)

Each sp2 hybridized C in the ring has an unhybridized p orbital perpendicular to the ring which overlaps around the ring. Resonance Structure

Other Conjugated Hydrocarbon Rings - Annulenes

Cyclobutadiene, benzene, cyclooctatetraene, cyclodecapentaene

Annulenes (Reactivity)

All cyclic conjugated hydrocarbons were proposed to be aromatic. However, cyclobutadiene is so reactive that it dimerizes before it can be isolated. And cyclooctatetraene adds Br2 readily.

What Does It Take to Be Aromatic?

It must be cyclic and planar; Alternating double and single bonds; A magic number of pi electrons; Resonance structures must be able to move the pi electrons in a circular manner; Non-bonding electrons can also participate in the resonance structures.

Hückel’s Rule

If the compound has a continuous ring of overlapping p orbitals and has 4N + 2 pi electrons, it is aromatic. If the compound has a continuous ring of overlapping p orbitals and has 4N electrons, it is antiaromatic. N is any integer, starting at zero

Huckel's Rule: The 4n+2p Electron Rule

Planar monocyclic rings with a continuous system of p orbitals and 4n + 2p electrons are aromatic (n = 0, 1, 2, 3 etc)
Aromatic compounds have substantial resonance stabilization
Benzene is aromatic: it is planar, cyclic, has a p orbital at every carbon, and 6 p electrons (n=1)

Benzene and Bonding Orbitals

Benzene has 3 bonding and 3 antibonding orbitals; All the bonding orbitals are full and there are no electrons in antibonding orbitals; benzene has a closed shell of delocalized electrons and is very stable

The Annulenes

Annulenes are monocyclic compounds with alternating double and single bonds
An annulene is aromatic if it has 4n+2p electrons and a planar carbon skeleton

Aromatic, Antiaromatic, and Nonaromatic Compounds

Benzene and cylcopentadientl anion are aromatic Cyclobutadiene is antiaromatic Cyclooctatetraene, if it were planar, would be antiaromatic

Benzenoid Aromatic Compounds

Polycyclic benzenoid aromatic compounds have two or more benzene rings fused together

Nonbenzenoid Aromatic Compounds

Nonbenzenoid aromatic compounds do not contain benzene rings

Fullerenes

Buckminsterfullerene is a C60 compound shaped like a soccer ball with interconnecting pentagons and hexagons.
Each carbon is sp2 hybridized and has bonds to 3 other carbons.
Buckminsterfullerene is aromatic

Heterocyclic Aromatic Compounds

Heterocyclic compounds have an element other than carbon as a member of the ring

Kekulé Benzene

Formula of benzene is C6H6

Structural features of benzene

All of the carbon-carbon bonds are 140 pm. In between the Csp2-Csp2 single bond length of 146 pm and the Csp2-Csp2 double bond length of 134 pm.
All carbons are sp2 hybrids bond Ð = 120°

Molecular Orbital Description of Benzene

The 6 p-orbitals combine to give Three bonding orbitals with 6 p electrons; Three unoccupied antibonding orbitals
Benezene has a closed-shell π electron configuration

In-vivo Aromatic Hydrocarbons

Aromatic HCs undergo Hydroxylation, Epoxidation, Diol formation

Nomenclature of Benzene Derivatives

Benzene is the parent name for some monosubstituted benzenes; the substituent name is added as a prefix

Disubstituted Benzenes

When two substituents are present their position may be indicated by the prefixes ortho, meta, and para (o, m and p) or by the corresponding numerical positions

Numbers must be used as locants when more than two substituents are present

If one of the substituents defines a parent other than benzene, this substituent defines the parent name and should be designated position 1

The C6H5- group

Called phenyl when it is a substituent. A hydrocarbon with a saturated chain and a benzene ring is named by choosing the larger structural unit as the parent. If the chain is unsaturated then it must be the parent and the benzene is then a phenyl substituent.

Reactions of Benzene - Electrophilic aromatic substitution

Another atom, or group of atoms, replaces a hydrogen atom on the benzene ring, and the product retains the stable aromatic ring.

Electrophilic Aromatic substitution Mechanism

Attack on the electrophile forms the sigma complex. Loss of a proton gives the substitution product.

Bromination of Benzene

Require a stronger electrophile than Br2. Use a strong Lewis acid catalyst, FeBr3.

Chlorination and Iodination of Benzene

Chlorination is similar to bromination. Use AlCl3 as the Lewis acid catalyst
Iodination requires an acidic oxidizing agent, like nitric acid, which oxidizes the iodine to an iodonium ion.

Nitration of Benzene

Use sulfuric acid with nitric acid to form the nitronium ion electrophile.

Activating, O-, P-Directing Substituents

Alkyl groups stabilize the sigma complex by induction, donating electron density through the sigma bond.
Substituents with a lone pair of electrons stabilize the sigma complex by resonance.

The Amino Group

Aniline, like anisole, reacts with bromine water (without a catalyst) to yield the tribromide.
Sodium bicarbonate is added to neutralize the HBr that’s also formed

Deactivating Meta-Directing Substituents

Electrophilic substitution reactions for nitrobenzene are 100,000 times slower than for benzene. Meta-directors deactivate all positions on the ring, but the meta position is less deactivated. Deactivators – Nitro, carbonyl grp etc.. = favored meta; Halogens = favored O/P

Structure of Meta-Directing Deactivators

The atom attached to the aromatic ring will have a partial positive charge. Electron density is withdrawn inductively along the sigma bond, so the ring is less electron-rich than benzene.

Halobenzenes

Halogens are deactivating toward electrophilic substitution, but are ortho, para -directing!
Since halogens are very electronegative, they withdraw electron density from the ring inductively along the sigma bond.
But halogens have lone pairs of electrons that can stabilize the sigma complex by resonance.

Friedel-Crafts Alkylation

Synthesis of alkyl benzenes from alkyl halides and a Lewis acid, usually AlCl3. Reactions of alkyl halide with Lewis acid produces a carbocation which is the electrophile.

Friedel-Crafts Acylation

Acyl chloride is used in place of alkyl chloride. The acylium ion intermediate is resonance stabilized and does not rearrange like a carbocation. The product is a phenyl ketone that is less reactive than benzene.

Catalytic Hydrogenation

Elevated heat and pressure are required. Possible catalysts: Pt, Pd, Ni, Ru, Rh.

Side-Chain Oxidation

Alkylbenzenes are oxidized to benzoic acid by hot KMnO4 or Na2Cr2O7/H2SO4.

Side-Chain Halogenation

Benzylic position is the most reactive. Chlorination is not as selective as bromination, results in mixtures. Br2 reacts only at the benzylic position.

Alcohols, Phenols, and Ethers

Hydroxy group – the –OH functional group; An alcohol has an –OH group attached to an aliphatic carbon; A phenol has an –OH group on a benzene ring; An ether has the functional group: R-O-R’

Naming Alcohols

Name the longest chain to which the –OH group is attached. Use the hydrocarbon name of the chain, drop the final –e, and replace it with –ol; Number the longest chain to give the lowest number to the carbon with the attached –OH; Locate the –OH position; Locate and name any other groups attached to the longest chain; Combine the name and location of other groups, the location of the –OH, and the longest chain into the final name

Diols and Triols

Alcohols containing two –OH groups are diols, three –OH groups are triols. The IUPAC names for these compounds have endings of –diol and –triol rather than –ol

Naming Phenols

Substituted phenols are usually named as derivatives of the parent compound phenol.

Physical Properties of Alcohols

The –OH group is polar and capable of hydrogen bonding; This makes low molecular weight alcohols highly soluble in water.

Alcohols and Water Solubility

Larger alkanes have greater hydrophobic regions and are less soluble or insoluble in water

Boiling Points of Alcohols

The –OH group can hydrogen bond between alcohol molecules leading to relatively high boiling points.

Alcohol Reactions - Dehydration

The removal of water (dehydration) from an alcohol at 180°C is an elimination reaction that produces an alkene.

Alcohol Reactions - Ether Creation

Under slightly different conditions (140°C) , a dehydration reaction can occur between two alcohol molecules to produce an ether.

Alcohol Reactions - Oxidation

Removal of hydrogen atoms; Primary alcohols become aldehydes then carboxylic acids. Secondary alcohols becomes ketones and Tertiary alcohols do not readily react.

Important Alcohols - Methanol

Production: useful as a solvent and industrial starting material but highly toxic, if taken internally causes blindness and/or death

Important Alcohols - Ethanol

Ethylene Biological fermentation of hydrates Solvent, starting material, fuel alcoholic beverages Moderately toxic

Important Alcohols - 2-propanol

Main component of rubbing alcohol

Important Alcohols - 1,2,3-propanetriol

Non-toxic food moistening agent with soothing qualities

Phenols

Behaves as a weak acid in water and can react with bases to form salt.

Uses of Phenols

In a dilute solution, used as a disinfectant. Derivatives used as disinfectants or antioxidants in food.

Properties of Ethers

Much less polar than alcohols; More soluble in water than alkanes, but less soluble than alcohols; Low boiling and melting points.

Nomenclature (IUPAC) Ethers

Naming Alkoxyalkanes or Dialkyl ethers

Cyclic Ethers

Cyclic ethers contain ether functional group as part of a ring system.

Cyclic Ethers - THF and Dioxane

Low reactivity used as solvents

Cyclic Ethers: Ethylene oxide, Oxirane, or Epoxide

Very reactive O Ethylene oxide O Oxirane or epoxide

Thiols

Most distinguishing characteristic is their strong and offensive odor