Claisen condensation

1. Carbonyl compounds - reaction of the aldol type Claisen condensation reaction proceeds between aldehyd and an ester under base catalysis the base is usually the alcoholate of alcohol bound in ester after reaction when acidified very often observe formation of a,b-unsaturated ester the more is the product after dehydratation conjugated, the more difficult is to isolate molecule with hydroxy group

2. Carbonyl compounds - reaction of the aldol type PERKIN synthesis Aromatic aldehydes and acetanhydride under base catalysis

3. Carbonyl compounds - reaction of the aldol type Knoevenagel condensation Reaction of aldehydes or ketones with compounds having acidic methylene X, Y = CN, COOR, NO2, COR, CHO

4. Aldolisation and aldol condensation– catalysed by a base Acidity constants of various compounds compound structure

5. Reactions of carbonyl compounds Darzen reaction Reaction of aldehydes with a-halogenesters

6. Reactions of carbonyl compounds Mannich reaction Reaction of aldehyde (ketone) in acidic medium with Mannich reagent ( formed from formaldehyde and sec. amine) Mannich reagent the starting compound has to have enolisable structure Reaction leads to N,N-dialkylaminomethyl carbonyl compounds Příprava N,N-dialkylaminomethylkarbonylových sloučenin

7. Reactions of carbonyl compounds without a-hydrogens They cannot under treatment of base undergo aldolisation and aldol condensation Cannizar reaction (disproporcionation): from aldehyde alcohol and carboxylic acid are prepared beside benzaldehyde react this way also alifatic compounds with fully substituted a-carbon atom and also other aromatic compounds:.

8. Reaction of carbonyl compounds Wittig reaction Introduction of double C=C bond instead C=O bond

9. Oxidation of carbonyl compounds Aldehydes are easily oxidable to carboxylic acids even by gentle oxidation reagents Proof of aldehyde group by Tollens reagent Proof by Fehling reagent before reaction Fehling I and Fehlingem II are mixed together Fehling I = aqueous solution of CuSO4 Fehling II = aqueous solution of salt C4H4O6 Na K + NaOH

10. Oxidation of carbonyl compounds oxidation of aldehydes and ketones by peroxyacids to esters Baeyer – Villiger oxidation Ability of migration is dependent upon the type of substitution: H Ph t-alkyl sek.alkyl prim.alkyl methyl > > > > >

11. Reactions at carbon atom in the neigbourhood of carbonyl Hydrogen atoms in the neigbourhood of carbonyl are acidic aldolisation and other reactions Halogenation in acidic medium: Because halogen by its acceptor effect makes hydrogen atom in the neigbourhood acidic, the halogenation to further steps is easier than to the first step, we are faced formation of more halogenated products.

12. Reactions at carbon atom in the neigbourhood of carbonyl Haloform reaction bromoform • Generally haloform is formed – compound with characteristic smell: chloroform- liquid • jodoform and bromoform -crystalinic

13. Reactions at carbon atom in the neigbourhood of carbonyl Nitrosation to a-position treatment by alkaline nitrite nitroso oximo (isonitroso) tautomerie For the reaction is possible to use also aldehydes or ketones with a longer chain

14. Reactions at carbon atom in the neigbourhood of carbonyl Methyl or methylene group next to carbonyl is sensitive to oxidation, leading to dialdehydes, diketones or aldehydketones oxidation agent is SeO2 Conditions: dioxane (water), SeO2, 50 – 100 oC 1,2-diketones R, R1 = Ph = benzil = CH3 = diacetyl 1,2-aldoketones 1,2-dialdehydes 1,2-dioxoderivatives is possible to prepared by oxidation of acyloins by Cu2+ acetate

15. 1,3-diketones and 1,3-dioxo compounds Claisenova kondenzace Reaction of aldehydes and ketones with esters Reaction of ketones with esters leads to 1,3-diketones Reaction of aldehydes with esters leads to 1,3-ketoaldehydes Condensation of esters leads to 1,3-ketoesters (b-ketoesters) Catalyst are chosen according with acidity of substrates: alcoholates, sodium amide, or sodium

16. Acyloin condensation reaction of aldehydes without a- hydrogen atoms (mostly aromatic) during reaction are prepared acyloines (a-hydroxyketones) benzoin condensation catalyst is cyanide anion

17. 1,2-Dicarbonyl compounds dialdehydes methylglyoxal diacetyl

18. 1,3-diketones and 1,3-dioxo compounds Generaly the equilibrium between keto and enol form is shifted to more stabil keto form; at 1,3-dicarbonyl compounds we meet in dependence upon the solvent also enolform. Its existence is explained by possible formation of stabil cyclic structures. H2O 84% 16% Hexan 8% 92%

19. 1,3-diketones and 1,3-dioxo compounds 1,3-dioxo compounds can form by treatment of bases ambident anions. These react wíth an agents according its properties obeying Kornblum rules. Polar solvent SN2 SN1

20. Conjugated additions to a,b-unsaturated carbonyl compounds Reactions proseed at systems, where carbonyl is member of the group –CHO, - COR, -COOR, CONH2 or where instead it is -CN, - NO2, -SOR or SO2Rgroup. These are nucleophilic additions, which may be sometimes, mainly at nitriles, complicated by 1,2-addition

21. Conjugated additions to a,b-unsaturated carbonyl compounds

22. Conjugated additions to a,b-unsaturated carbonyl compounds 1,4-addition proceeds with compounds with acidic hydrogen atom Substrates are a,b-unsaturated ketones, esters, nitriles Michael addition

23. Ketenes very reactive carbonyl species (more reactive than aldehydes and ketones) Csp2 Csp Osp2 Preparation : „keten lamp “

24. Ketenes