INORGANIC REAGENTS FOR ORGANIC SYNTHESIS.pptx

All about inorganic reagents used in organic chemistry

1. B.Sc. Sem-V Organic Chemistry (Che-301) Presentation By Dr. Nandan C. Pomal Assistant Professor, Faculty Of Science, Sigma University, Vadodara, Gujarat Unit-II (A) Inorganic Reagents For Organic Synthesis

2. ALUMINIUM ISOPROPOXIDE Aluminium Isopropoxide [(CH3) 2 CHO - ] 3 Al 3+ It is used as catalysts and an intermediates in a different reactions. They belong to aluminum alkoxide groups. Widely used as a selective reducing agent for aldehydes and ketones. It is an inexpensive and also easy to handle among the other aluminum alkoxides.

3. ALTERNATIVE NAMES Triisopropoxyaluminium Aluminiumisopropanolate 2-Propanol aluminium salt AIP

4. STRUCTURE OF ALUMINIUM ISOPROPOXIDE The central Aluminium is octahedral surrounded by three bidentate (O- iPr ) 3 ligands, each featuring tetrahedral Al.

5. PHYSICAL PROPERTY More soluble in benzene and less soluble in alcohols White solid Boiling point : 140.5 C Melting point : 128 -133 C It decomposes in presence of water

6. HANDLING, STORAGE, AND PRECAUTIONS The dry solid is corrosive Moisture sensitive Flammable An irritant Used in a fume hood

7. PREPARATION It is prepared by the reaction between isopropyl alcohol and aluminium metal, or aluminium trichloride: 2 Al + 6 iPrOH → 2 Al(O- i -Pr)3 + 3 H2 AlCl3 + 3 iPrOH → Al(O- i -Pr)3 + 3 HCl

8. SYNTHETIC APPLICATION MEERWEIN-PONNDORF-VERLEY (MPV) REDUCTIONS Carbonyl compound are reduced to the respective alcohol in the presence of aluminium isopropoxide solution. The acetone, so formed, is removed by slow distillation and hence the reaction proceeds only in the desired direction.

9. Reaction

10. Mechanism STEP (1) The aluminium alkoxide 1, reacted with a carbonyl oxygen to form tetra coordinated aluminium intermediate 2 STEP (2) The intermediates 2 transfer hydride to the carbonyl group from the alkoxy ligand to form an another intermediate 3 STEP (3) The intermediate 3 eliminate a new carbonyl group and gives a tricoordinate aluminium species 4. STEP (4) Alcohol is formed and the catalyst 1 is regenerated.

11. Example ii) Reduction of o- nitrobenzaldehyde to o- nitrobenzyl alcohol a) Reduction of aldehyde i ) Reduction of crotonaldehyde to crotyl alcohol

12. b) Reduction of ketone i) Synthesis of oestradiol from oestrone

13. OPPENAUER OXIDATION It is an oxidation reaction of alcohol to ketone in presence of aluminium isopropoxide.

14. Example: Cholestenone is prepared by oxidation of cholesterol in toluene solution with aluminum isopropoxide as catalyst and cyclohexanone as hydrogen acceptor.

15. • Conversion of carvone to carveol

16. HYDROLYSIS OF OXIMES Oximes can be converted into parent carbonyl compounds by aluminum isopropoxide followed by acid hydrolysis.

17. Lithium aluminium hydride (LIALH 4 )

18. Lithium Aluminium Hydride LiAlH 4 is a reducing agent . More specifically, nucleophilic reducing agent and used to reduce polar multiple bonds like C=O. There is a tetrahedral arrangement of hydrogens around Al 3+ in aluminium hydride, AlH 4- ion. The hybridization in central Al is sp 3 . LiAlH 4

19. Lithium Aluminium Hydride : Physical Property Reacts with water, soluble in THF and miscible with diethyl ether White crystals solid (pure samples) appearance grey powder (commercial material) hygroscopic Boiling point : 184 ° C, Melting point : 150 ° C Density: 0.917 g/cm 3 (solid) It is odourless

20. Lithium Aluminium Hydride: Preparation LAH is prepared by the reaction between Lithium Hydride and Aluminium Chloride . LiAlH 4

21. Lithium aluminium hydride: Chemical Properties LiAlH 4 It reacts violently with water by producing hydrogen gas and therefore it should not be exposed to moisture and the reactions are performed in inert and dry atmosphere. ( anhydrous non-protic solvents ) 2. As far as the preference of solvent is concerned, it is highly soluble in diethyl ether. However it may spontaneously decompose in it due to presence of catalytic impurities. Therefore the  preferred solvent for LAH is THF despite the low solubility.

22. Lithium Aluminium Hydride: Mechanism of reduction The reduction of a carbonyl group by LiAlH 4 is initiated by the attack of nucleophilic hydride ion on the carbonyl carbon to give a tetrahedral intermediate. LiAlH 4 is a nucleophilic reducing agent since the hydride transfer to the carbonyl carbon occurs prior to the coordination to the carbonyl oxygen. It reacts faster with electron deficient carbonyl groups. The reactivity of carbonyl compounds with this reagent follows the order: LiAlH 4 Aldehydes > Ketones > Ester > Amide > Carboxylic acid