Organic Functional Groups: Alkyl Halides, Alcohols, Carbonyls

Posted on Feb 17, 2026 in Chemistry

FGI: Functional Group Interconversions

Alkyl Halides

Alkyl halides (haloalkanes)

• Alkyl halide or haloalkanes.
• Compounds with a halogen atom bonded to a saturated sp3-hybridized carbon atom.
• Halogen atomic radius increases down the periodic table.
• Lengths of corresponding carbon–halogen bonds increase accordingly, while C–X bond strengths decrease going down the periodic table.
• The carbon–halogen bond of alkyl halides is polarized: the carbon atom bears a slight positive charge (δ+), and the halogen a slight negative charge (δ-).
• The alkyl halide C–X carbon atom behaves as an electrophile in polar reactions.

Alcohols, Phenols, Ethers and Sulfur Analogues

• Alcohols, phenols, and ethers are organic derivatives of water in which one or both of the water hydrogens is replaced by an organic group: H–O–H versus R–O–H, Ar–O–H, and R–O–R′.
• Thiols and sulfides are the corresponding sulfur analogues, R–S–H and R–S–R′.
• The names alcohol and thiol are restricted to compounds that have their –OH or –SH group bonded to a saturated, sp3-hybridized carbon atom.
• Phenols and thiophenols have their –OH or –SH bonded to an aromatic ring.
• Enols and enethiols have the –OH or –SH bonded to a vinylic, sp2-hybridized carbon.
• The word “phenol” is the name both of a specific compound and of a class of compounds.
• Alcohols and phenols have nearly the same geometry around the oxygen atom as water.
• The C–O–H bond angle is approximately tetrahedral (108.5° in methanol).
• Thiols have a more compressed C–S–H bond angle (96.5° in methanethiol).
• The oxygen atom is sp3-hybridized in alcohols.
• Alcohols and phenols, like water, have higher boiling points than might be expected because of hydrogen bonding.
• Thiols do not typically form hydrogen bonds because sulfur is not sufficiently electronegative.
• Alcohol classifications:
  • Primary (1° alcohol): 1 R
  • Secondary (2° alcohol): 2 R
  • Tertiary (3° alcohol): 3 R

Carbonyls

(See carboxylic acids and derivatives below.)

Carboxylic Acids

• Carboxylic acids (-C(=O)OH) are present in most biological pathways and are the biological starting materials from which other acyl derivatives are made.
• Common derivatives include:
  • Acid chloride (-C(=O)Cl)
  • Ester (-C(=O)OR’)
  • Amide (-C(=O)NH2)

Naming Alkyl Halides

1. Find the longest chain, and name it as the parent.
   • If a double or triple bond is present, it must be included in the parent chain.
2. Number the carbons of the parent chain beginning at the end nearer the first substituent, whether alkyl or halo.
   • Assign each substituent a number according to its position on the chain.
   • If different halogens are present, number all and list them in alphabetical order when writing the name.
   • e.g. 5-Bromo-2,4-dimethylheptane; 2-Bromo-4,5-dimethylheptane; 1-Bromo-3-chloro-4-methylpentane.
3. If the parent chain can be properly numbered from either end by step 2, begin at the end nearer the substituent that has alphabetical precedence.
   • e.g. 2-Bromo-5-methylhexane (not 5-bromo-2-methylhexane).

• Many simple alkyl halides are also named by identifying first the alkyl group and then the halogen.
  • CH3I can either be called iodomethane or methyl iodide.
  • 2-Chloropropane (or isopropyl chloride), bromocyclohexane (or cyclohexyl bromide).
  • Names shown in parentheses will not be used in this discussion; therefore refrain from using them to avoid confusion.

Naming of RX and ROH

General Properties

• Alcohols and phenols, like water, are both weakly basic and weakly acidic.
• As weak bases they are reversibly protonated by strong acids to yield oxonium ions, ROH2+.
  • ROH + HX <-> ROH2+ : X-
• As weak acids they dissociate slightly in dilute aqueous solution, donating a proton to water and generating H3O+ and an alkoxide ion (RO-) or a phenoxide ion (ArO-).
  • ROH + H2O <-> RO- + H3O+
• Alcohols are weak acids.
  • Do not react with weak bases such as amines or bicarbonate ion.
  • React only to a limited extent with metal hydroxides such as NaOH.
  • React with alkali metals and with strong bases such as sodium hydride (NaH) and sodium amide (NaNH2).
  • Alkoxides are bases that are used as reagents in organic chemistry.
• Carboxylic acids:
  • Carboxyl carbon is sp2-hybridized.
  • Carboxylic acids are strongly associated because of hydrogen bonding, which significantly increases boiling point.
  • Most carboxylic acids exist as cyclic dimers.
  • Carboxylic acids react with bases to give metal (M+) carboxylate salts, RCO2–M+.
  • Carboxylic acids slightly ionize in water.
  • Carboxylic acid (water-insoluble) + NaOH → Carboxylic acid salt (water-soluble) + H2O [H2O].

Interconversion Reactions

• Alcohols (ROH) can be prepared from many other kinds of compounds including:
  • RX (alkyl halide). — Substitution.
  • RC(=O)OR’ (ester). — Esterification.
  • RC(=O)OH (carboxylic acid). ROH <- oxidation / > reduction.
  • RC(=O)H (aldehyde). ROH <- oxidation / > reduction.
  • RC(=O)R’ (ketone). ROH <- oxidation / > reduction.
  • RRC=CRR (alkene). — Hydration (addition) / Dehydration (elimination).
• Reactions of carboxylic acids can be grouped into:
  • RC(=O)O- — Deprotonation [B-].
  • CHHOH — Reduction.
  • RC(=O)Y — Nucleophilic acyl substitution.
• Nucleophilic acyl substitution reactions (RC(=O)Y):
  • RC(=O)OH → hydrolysis [H2O].
  • RC(=O)OR’ → alcoholysis (esterification) [R’OH].
  • RC(=O)NH2 → aminolysis [NH3].
  • RC(=O)H → reduction [H-].

Preparing Alkyl Halides from Alkenes

• Recall reactions of HX and X2 with alkenes in electrophilic addition reactions.
• The hydrogen halides HCl, HBr, and HI react with alkenes by a polar mechanism to give the product of Markovnikov addition.
• Bromine and chlorine undergo anti addition through a halonium ion intermediate to give 1,2-dihalogenated products.
• Alkyl halides are electrophiles that react with nucleophiles / Lewis bases in one of two ways:
  • Undergo substitution of the X-group by the nucleophile (X = Cl, Br, I). Example: R–X + Nu:- → R–Nu + X:-.
  • Undergo elimination of HX to yield an alkene.
• Example illustrations (formal representations):
  • H..C–C..Br + OH- <-> H..C–COH.. + Br- (<- HBr)
  • H..C–C..Br + OH- <-> ..C=C.. + H2O + Br- (<- HBr addition)

Nucleophilic Substitution Reactions

• One of the most common and versatile reaction types in organic chemistry.
• General: R–X + Nu:- → R–Nu + X:-
• Example: nucleophilic substitution of (R)-1-bromo-1-phenylethane with cyanide ion, –C≡N.
• (R)-1-bromo-1-phenylethane → (S)-2-Phenylpropanenitrile [–C≡N] (example transformation).

Predicting the Mechanism of a Nucleophilic Substitution Reaction

1. 1-chloropropanebenzene (Cl replaced with OAc, where OAc = CH3COO- (acetate / ethanoate)) [CH3CO2-Na+, CH3CO2H, H2O].
2. 3-bromopropanebenzene (Br replaced with OAc) [CH3CO2-Na+, DMF].

Elimination Reactions (Zaitsev’s Rule)

• Elimination reactions almost always give mixtures of alkene products.
• Formulated in 1875 by Alexander Zaitsev; used to predict major products.
• In the elimination of HX from an alkyl halide, the more highly substituted alkene product predominates.
• Examples:
  • 2-Bromobutane → But-2-ene (81%) + But-1-ene (19%) [CH3CO2-Na+ (sodium ethoxide is a strong base), CH3CH2OH].
  • 2-Bromo-2-methylbutane → 2-Methylbut-2-ene (70%) + 2-Methylbut-1-ene (30%) [CH3CH2O-Na+, CH3CH2OH].

Predicting Product of an Elimination Reaction

• Question: What product(s) would you expect from the elimination reaction of 1-chloro-1-methylcyclohexane with tBuOK in ethanol?
• tBuOK = potassium tert-butoxide.
• It is sometimes used in place of KOH; its steric bulk makes it less likely to act as a nucleophile.
• Strategy:
  • Treatment of an alkyl halide with a strong base such as tBuOK yields an alkene.
  • To find the products, locate the hydrogen atoms on each carbon adjacent to the leaving group and then generate potential alkene products by removing HX in as many ways as possible.
  • The major product will be the one that has the most highly substituted double bond.
  • Example: 1-chloro-1-methylcyclohexane → 1-methylcyclohexene (major) + methylenecyclohexane (minor) [tBuOK, ethanol].

Preparing Alkyl Halides from Alcohols (Substitution)

• Treat the 3° alcohol with HCl, HBr, or HI — simplest method.
• The reaction works best with tertiary alcohols, R3COH.
• Primary and secondary alcohols react slowly and at higher temperatures.
• The reaction of HX with a tertiary alcohol is often so rapid that it can be carried out by bubbling the pure HCl or HBr gas into a cold ether solution of the alcohol.
• Example: …COH → …CX + H2O [H–X].
• Example: 1-methylcyclohexanol → 1-chloro-1-methylcyclohexane (90%) + H2O [HCl (gas), ether, 0°C].

Preparing Alkyl Halides from Primary and Secondary Alcohols

• 1° and 2° alcohols are best converted into alkyl halides by treatment with thionyl chloride (SOCl2), phosphorus tri-/pentachloride (PCl3/PCl5), or phosphorus tribromide (PBr3).
• Reactions normally take place readily under mild conditions.
• These reactions are less acidic and less likely to cause acid-catalyzed rearrangements than the HX method.
• Example: Butan-2-ol → 2-bromobutane (86%) + H3PO3 [PBr3, ether, 35°C].

Dehydration of Alcohols

• Dehydration gives alkenes (and water).
• Important in both the laboratory and in biological pathways.
• Acid-catalyzed elimination reaction; works well for tertiary alcohols.
• Follows Zaitsev’s rule and yields the more stable alkene as the major product.
• Example: 2-methylbutan-2-ol → 2-methylbut-2-ene (trisubstituted, major) + 2-methylbut-1-ene (disubstituted, minor) [H3O+, THF (conc. H2SO4 or H3PO4), 25°C].

Oxidation of Alcohols

• Primary alcohols yield aldehydes or carboxylic acids depending on oxidant and conditions.
  • RC(OH)HH → RC(=O)H (aldehyde) [O]. RC(=O)OH (carboxylic acid) [O].
  • Dess–Martin periodinane (DMP) in dichloromethane is used in the laboratory to prepare an aldehyde from a primary alcohol.
  • Strong oxidizing agents such as chromium trioxide (CrO3) in aqueous acid oxidize primary alcohols directly to carboxylic acids.
• Secondary alcohols yield ketones.
  • RR’C(OH)H → RC(=O)R’ [O].
  • Na2Cr2O7 in aqueous acetic acid is used for large-scale oxidations.
  • Example: 4-tert-butylcyclohexanol → 4-tert-butylcyclohexanone (91%) [Na2Cr2O7, H2O, CH3CO2H, heat].
• Tertiary alcohols do not normally react with most oxidizing agents (no reaction) [O].
• Aldehydes are easily oxidized to carboxylic acids, but ketones are relatively inert toward oxidation.
• –CHO hydrogen is abstracted during oxidation; CrO3 is the most common oxidizing agent. KMnO4 and hot HNO3 are occasionally used.
• Example: Hexanal → hexanoic acid (85%) [CrO3, H3O+, acetone, 0°C].

Preparing Aldehydes and Ketones

• Preparing aldehydes:
  • Aldehydes from reduction of carboxylic esters using diisobutylaluminum hydride (DIBAH). (Note: RCOOH is typically too unreactive for direct transformation.)
  • Example: Methyl dodecanoate CH3(CH2)10C(=O)OCH3 → dodecanal CH3(CH2)10C(=O)H (88%) [DIBAH, toluene, −78°C, H3O+].
• Preparing ketones:
  • Secondary alcohols are oxidized by chromium-based reagents to give ketones.
  • Example: 4-tert-butylcyclohexanol → 4-tert-butylcyclohexanone (90%) [CrO3, CH2Cl2].

Reduction of Carboxylic Acids and Esters

• Carboxylic acids and esters are reduced to give primary alcohols.
• These slow reactions are usually carried out with LiAlH4.
• Two hydrogens become bonded to the former carbonyl carbon during carboxylic acid and ester reductions.
• Example: Octadec-9-enoic acid (oleic acid) → Octadec-9-en-1-ol (87%) [LiAlH4, ether, H3O+].
• Example: Methyl pent-2-enoate → pent-2-en-1-ol (91%) + CH3OH [LiAlH4, ether, H3O+].
• NaBH4 is a weaker reducing agent than LiAlH4.
• Aldehyde CHO → alcohol CH2OH [NaBH4 / LiAlH4, H3O+].
• Ester CO2CH3 → alcohol [LiAlH4, H3O+].
• Carboxylic acid CO2H → alcohol [LiAlH4, H3O+].

Reduction to Alcohols from Acyl Chlorides and Acids

• From RCOCl:
  • Acid chlorides are reduced by LiAlH4 to yield primary alcohols.
  • Reduction occurs through an aldehyde intermediate, which is immediately reduced in a second step to yield the primary alcohol.
  • Example: Benzoyl chloride → benzyl alcohol [LiAlH4, ether, H3O+].
• From RCOOH:
  • Carboxylic acids are reduced by LiAlH4 to give primary alcohols by nucleophilic acyl substitution of –H for –OH.
  • Hydride ion is a base and a nucleophile; reaction proceeds through a reactive aldehyde intermediate which is not isolated.
  • Carboxylic acid → 1° alcohol [H-, LiAlH4].

Reduction of Aldehydes and Ketones

• Aldehydes are reduced to give primary alcohols; ketones are reduced to give secondary alcohols.
• Sodium borohydride (NaBH4) is usually used to reduce aldehydes and ketones because it is easy and safe to use.
• NaBH4 is a white, crystalline solid that can be weighed in the open atmosphere and used in either water or alcohol solution.
• Lithium aluminium hydride (LiAlH4) is used in the reduction of aldehydes and ketones; it is a greyish powder soluble in ether and THF.
• LiAlH4 is much more reactive than NaBH4 but also more dangerous — it reacts violently with water and decomposes explosively when heated above 120°C.

Conversion of Alcohols into Esters (Esterification)

• Alcohols react with carboxylic acids to give esters (esterification).
• Reaction is common in the laboratory and in living organisms.
• In the laboratory the reaction can be carried out in a single step if a strong acid is used as catalyst.
• Reactivity of the carboxylic acid can be enhanced by converting it into a carboxylic acid chloride, which then reacts with the alcohol.

Carboxylic Acid Derivatives

• Compounds in which an acyl group is bonded to an electronegative atom or substituent that can act as a leaving group.
• They can be converted to the parent carboxylic acid by hydrolysis; chemistry of all carboxylic derivatives is similar.
• All undergo nucleophilic acyl substitution reactions.

Nucleophilic Acyl Substitution Reactions and Relative Reactivity

• Relative reactivity of carboxylic acid derivatives depends on both addition and elimination steps; addition is generally rate-limiting due to steric and electronic factors.
• Sterically unhindered acid derivatives are more accessible to an approaching nucleophile.
• It is usually possible to convert more reactive acid derivatives to less reactive ones.
• Acid halides and acid anhydrides do not persist in living organisms because they react rapidly with water.
• Acid derivative RC(=O)Y reactions:
  • RC(=O)OH [H2O] — hydrolysis.
  • RC(=O)OR’ [R’OH] — alcoholysis (esterification).
  • RC(=O)NH2 [NH3] — aminolysis.
  • RC(=O)H [H-] — reduction; RCHHOH [H-] — reduction.
• Direct nucleophilic acyl substitution of a carboxylic acid is difficult because the –OH group is a poor leaving group.
• Reactivity is enhanced by:
  • Protonating the carbonyl oxygen of the carboxyl group, making the carbonyl carbon atom more electrophilic.
  • Converting –OH into a better leaving group.

Conversions of Carboxylic Acids Into More Reactive Derivatives

1. Conversion of carboxylic acids into acid halides (RCO2H → RCOX).
   • Conversion is accomplished by treatment of carboxylic acid with thionyl chloride (SOCl2) or PBr3.
2. Conversion of carboxylic acids into acid anhydrides (RCO2H → RCO2COR′).
   • Two molecules of carboxylic acid will lose 1 equivalent of water by heating.
   • Preparation is uncommon due to the high temperatures required for dehydration.
3. Conversion of carboxylic acids into esters (RCO2H → RCO2R′).
   • Most useful reaction of carboxylic acids.
   • Several methods for accomplishing transformation:
     • Reaction of carboxylate anion with a primary alkyl halide, usually in the presence of base.
     • Fischer esterification: acid-catalyzed nucleophilic acyl substitution of a carboxylic acid with an alcohol.
     • The need to use an excess of liquid alcohol as solvent limits Fischer esterification to the synthesis of methyl, ethyl, propyl, and butyl esters.

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