GRIGNARD REAGENTS ORGANOMETALLICS FROM DIVALENT METALS DIVALENT METALS

This reaction was discovered by the Frenchman, Victor Grignard -- Nobel Prize in 1912 Formation of Grignard Reagents

HALIDE REACTIVITIES R-I > R-Br > R-Cl expensive, not readily available RX + Mg R-Mg-X less reactive, but easy to prepare or buy good compromise RELATIVE RATES : FAST SLOW

FORMATION OF A GRIGNARD REAGENT Ethers are obligatory solvents for the Grignard Reaction. The reaction doesn’t work without an ether solvent. Typical ether solvents are: Diethyl ether (b.p. 35 o C) Tetrahydrofuran (b.p. 65 o C) Dioxane (b.p. 101 o C) ether + THF

Consider two different leaving groups: The second reaction is too slow at 35 °C, Why might you need different solvents? Bromine is more reactive than chlorine. therefore we use a higher boiling solvent.

Formation of this complex is exothermic; the reaction is sufficiently exothermic to boil the solution without having to add external heat! Ethers stabilize the Grignard Complex

Mg:[Ne]3s 2 3s3p3s3p Mg.. 3s3p R-Mg-X RX.. +RX two ethers coordinate ETHERS COORDINATE INTO EMPTY 3p ORBITALS two bonds form promotion

RMgX O Et.. O Et.. : ether molecules coordinate into empty 3p orbitals on magnesium THE GRIGNARD COMPLEX Ethers stabilize the Grignard Complex

The complete structure of the Grignard reagent is quite complex. It is probably an equilibrium mixture of the type: While this complex picture may be more correct, it is easier to treat the Grignard reagent as if it were simply R-Mg-X, which is what we shall do in this course. R-Mg-X IS A USEFUL SIMPLICATION ….. and the actual reactive species may be a complex dimer. CHEMISTS HAVE BEEN ARGUING ABOUT THE STRUCTURE OF THE GRIGNARD REAGENT FOR YEARS AND STILL CANNOT AGREE

We can view the Grignard as a hybrid reagent. RMgX is a source of a carbanion ( R: - ) just like RLi. Therefore we expect Grignard reagents to be both a strong base and good nucleophile.

+ : - covalentionic PERCENT IONIC CHARACTER carbanion -- ++ C-K51 C-Na47 C-Li43 C-Mg35 C-Zn18 C-Cd15 C-Cu 9 strongest base best nucleophile percent ionicbond most reactive least reactive Less ionic character than organolithium compounds. More covalent.

Grignard Reagents give all the same reactions as alkyllthium compounds. R-Mg-XR-Li

Grignard reagents are strong bases and react readily with any slightly acidic hydrogen ( compare R-Li). Any source of H + will bring about this reaction: water acids alcohols aminesalkynes carboxylic acids atmosperic moisture Any -O- H, -S- H, or -N- H bonds are sufficiently acidic to react.

This is not a stereospecific synthetic method. A DELIBERATE SOURCE OF PROTONS OR DEUTERIUM ( or H 2 O) R R+S

C A B C : Grignard reagents lose stereochemistry (racemize) when made from an enantiomerically pure alkyl halide. INVERSIONS OF THE GRIGNARD REAGENT Organolithium compounds also usually loose stereochemistry, however, some RLi compounds retain configuration at low temp- eratures (-60 o C or below), where the rate of inversion is slow. C A B C : MgX + A C B C X * chiral halide scrambles stereochemistry

SYNTHESIS OF ALCOHOLS AND CARBOXYLIC ACIDS CARBOXYLIC ACIDS

Reaction with Carbonyl Compounds Just as with alkyllithiums ( RLi ): formaldehyde primary alcohols other aldehydes secondary alcohols ketones tertiary alcohols carbon dioxide carboxylic acids Read the following section only from Chap 16 (16.7)

REACTION WITH CARBON DIOXIDE R-Mg-X + O=C=O R-C-O - MgX + O R-COOH H3O+H3O+ ether Mg 1) CO 2 2) H 3 O + ether (s)(s)

STARTING HALIDES YOU CANNOT USE YOU CANNOT USE

NOTE TO STUDENTS CAUTION Most Grignard and Alkyllithium compounds are not stable compounds. You cannot buy them, and you must make them and use them immediately. Therefore, I will expect you to show the reaction that forms these reagents in any synthesis problem. Do not “pull a Grignard or Alkyllithium out of your hat” you must show how it is made from a halide. RXRMgX Mg ether (CH 3 ) 2 C=O Also ….. do not forget the hydrolysis step with H 3 O + etc

THESE REACTIONS DON’T WORK …. WHY NOT? Mg ether INTERFERING GROUPS !