§3 · Grignard from Dihalides
1,2 → Alkene (β-elimination) |
1,3 → Stable diGrignard → Cyclopropane |
1,4 → Cyclobutane tendency |
1,5 → Cyclopentane tendency
1,2-Dihalo (VICINAL)
Br–CH₂–CH₂–Br + Mg
→ CH₂=CH₂ + MgBr₂
β-ELIMINATION, NOT diGrignard
1,3-Dihalo
Br(CH₂)₃Br + Mg
→ BrMg(CH₂)₃MgBr
Stable diGrignard ✓
1,4 & 1,5-Dihalo
Stable diGrignard formed
Intramolecular Wurtz → cyclobutane / cyclopentane
gem-Dihalides do NOT form stable diGrignard; carbene formation or elimination predominates.
§7 · All Reactions of RMgX
7.1 · With HCHO → 1° Alcohol
R–MgX + HCHO → [R–CH₂–OMgX] ──H₃O⁺──→ R–CH₂–OH
Chain extended by +1C as primary alcohol
CH₃MgBr + HCHO ──Et₂O──→ CH₃CH₂OH (ethanol — primary)
7.2 · With RCHO → 2° Alcohol
R–MgX + R'CHO → R–CHOH–R'
One new C–C bond formed at carbonyl carbon
C₂H₅MgBr + CH₃CHO ──H₃O⁺──→ CH₃CH(OH)C₂H₅ (2-butanol — secondary)
7.3 · With Ketone → 3° Alcohol
R–MgX + R'COR'' → R–C(OH)R'R''
Tertiary alcohol; both R' and R'' from ketone retained
CH₃MgBr + (CH₃)₂CO ──H₃O⁺──→ (CH₃)₃COH (t-butanol — tertiary)
7.4 · With Ester (2 equiv) → 3° Alcohol
2 R–MgX + R'COOR'' → R'CR₂–OH (3° alcohol)
Ketone intermediate reacts with 2nd Grignard · 2 equivalents consumed
2 CH₃MgBr + CH₃COOEt ──H₃O⁺──→ (CH₃)₃COH (t-butanol)
Formate ester exception: HCOOR + 2RMgX → R₂CHOH (secondary alcohol)
7.5 · With Acid Chloride → Ketone (then 3° if excess)
RMgX + R'COCl → R'COR (ketone) ──excess RMgX──→ 3° alcohol
Hard to stop at ketone · Use Gilman (R₂CuLi) to stop at ketone
CH₃MgBr + C₂H₅COCl → CH₃COC₂H₅ (methyl ethyl ketone, if controlled)
──excess CH₃MgBr──→ CH₃C(OH)(C₂H₅)CH₃ (3° alcohol)
7.6 · With CO₂ → Carboxylic Acid (+1C as COOH)
R–MgX + CO₂ → R–COOMgX ──H₃O⁺──→ R–COOH
C₂H₅MgBr + CO₂ ──H₃O⁺──→ C₂H₅COOH (propanoic acid)
7.7 · With Ethylene Oxide → 1° Alcohol (+2C)
R–MgX + CH₂–CH₂(O) → R–CH₂–CH₂–OH
SN₂ at less hindered C · 2-carbon chain extension
CH₃MgBr + ethylene oxide ──H₃O⁺──→ CH₃CH₂CH₂OH (propan-1-ol, +2C)
7.8 · With Substituted Epoxide → 2° Alcohol
Attack at less hindered C (SN₂) · Inversion at attacked carbon
C₂H₅MgBr + propylene oxide (CH₃–CHCH₂–O)
──H₃O⁺──→ C₂H₅–CH₂–CHOH–CH₃ (attack at C1, less hindered)
7.9 · With Nitrile → Ketone
R–MgX + R'C≡N → R'C(=NMgX)R ──H₃O⁺──→ R'COR (ketone)
Only ONE addition; imine intermediate less electrophilic
C₂H₅MgBr + CH₃C≡N ──H₃O⁺──→ CH₃CO–C₂H₅ (methyl ethyl ketone)
7.10 · With DMF → Aldehyde
R–MgX + HCONMe₂ → [R–CH(OMgX)NMe₂] ──H₃O⁺──→ R–CHO
Excellent method for one-carbon homologated aldehyde
C₆H₅MgBr + DMF ──H₃O⁺──→ C₆H₅CHO (benzaldehyde)
7.11 · With H₂O / D₂O → Alkane (Protonolysis)
R–MgX + H₂O → R–H + HOMgX
R–MgX + D₂O → R–D + DOMgX (deuterium labelling)
C₂H₅MgBr + D₂O → C₂H₅D + BrMgOD
7.12 · With α,β-Unsaturated Carbonyl: 1,2 vs 1,4
RMgX → 1,2-addition (kinetic; hard nucleophile → hard carbonyl C)
R₂CuLi (Gilman) → 1,4-addition (soft-soft; conjugate addition)
CH₃MgBr + CH₂=CHCHO → 1,2-product: CH₂=CHCH(OH)CH₃ (major)
(CH₃)₂CuLi + CH₂=CHCHO → 1,4-product: CH₃CH₂CHO (major)
7.13 · Kumada Coupling (Pd / Ni catalyst)
R–MgX + R'–X ──Pd or Ni──→ R–R' + MgX₂
New C–C bond · Couples Grignard with aryl/vinyl halide
7.14 · With O₂ → Alcohol (via peroxide)
R–MgX + O₂ → R–O–OMgX ──H₃O⁺──→ R–OH
Free radical chain; avoid air during Grignard reactions
7.15 · With Br₂ → Alkyl Bromide
R–MgX + Br₂ → R–Br + MgXBr (halodemetalation)
7.16 · With SO₂ → Sulfinic Acid
R–MgX + SO₂ → RSO₂MgX ──H₃O⁺──→ RSO₂H
§9 · Numerical Concepts & Mole Rules
HCHO
1 eq. RMgX
→ 1° alcohol
RCHO
1 eq. RMgX
→ 2° alcohol
R₂CO
1 eq. RMgX
→ 3° alcohol
Ester
2 eq. RMgX
→ 3° alcohol
Nitrile
1 eq. RMgX
→ Ketone
Ethylene Oxide
1 eq. RMgX
→ 1° alcohol (+2C)
H₂O
1 eq. RMgX
→ R–H (destroyed)
HC≡CH
2 eq. RMgX
→ 2 R–H (2 acidic H)
Carbon Chain Extension Rules:
+ HCHO → +1C (1°) | + RCHO → +1C (2°) | + CO₂ → +1C as –COOH
+ Ethylene oxide → +2C (1°) | + R'CN → +1C (ketone)
Multiple acidic H — total RMgX consumed per mole:
NH₃ → 3 eq. | H₂O → 2 eq. | HC≡CH → 2 eq. |
RC≡CH → 1 eq. | R₂NH → 1 eq. | HO–R–NH₂ → 2 eq.
In numericals: always check (1) number of labile H before counting RMgX moles, (2) 1,2 vs 1,4 addition question (RMgX = 1,2; Gilman = 1,4), (3) epoxide opening = inversion at attacked C.