This document discusses nucleophilic addition reactions to carbonyl groups such as aldehydes and ketones. It explains that the carbonyl carbon is electrophilic and susceptible to attack by nucleophiles such as water, alcohols, cyanide, and organometallic reagents. The addition reactions can proceed through acid or base catalysis. Products like hydrates, hemiacetals, and acetals can form depending on the nucleophile and conditions. Carbohydrates exist as cyclic hemiacetals called pyranoses and furanoses, which have alpha and beta anomers.

1. ADISI NUKLEOFILIK

2. Aldehyde Ketone STRUCTURE

3. GUGUS KARBONIL elektrofilik Di atom Karbon nukleofilik di oksigen Nu: nukleofil Menyerang disini H + atau E + Elektrofil mengadisi disini .. :  +  - .. : : - +

4. C O .. .. . . GUGUS CARBONIL = PLANAR (HIBRIDIASASI SP 2 ) Nukleofil bisa menyerang dari atas atau bawah Nu: Nu:

5. ADISI NUKLEOFILIK KE C=O MEKANISME DALAM ASAM DAN DALAM BASA

6. Adisi Nukleofilik ke Karbonil Larutan Basa atau Netral Suatu ion alkoksida LARUTAN BASA Nuklofil baik Dan basa kuat (biasanya bermuatan) - or on adding acid

7. Adisi Nukleofilik ke Karbonil katalisis Asam Acid catalysis speeds the rate of addition of weak nucleophiles and weak bases (usually uncharged). Lebih reaktif untuk mengadisi daripada prekusor takterprotonasi LARUTN ASAM (+) pH 5-6 Asam lebih kuat Memprotonasi nukleofil

8. Adisi Sianida Buffer pH 6-8 Dalam larutan asam dengan sedikit CN - , dan HCN (g) merupakan suatu masalah (beracun). Suatu sianohidrin :C N:

9. HYDROLYSIS OF THE NITRILE GROUP

10. (R-Li) Addition of Organometallic Reagents ether workup step alcohol :R - Synthesis of Alcohols These reagents cannot exist in acid solution

11. hydrates are unstable and cannot be isolated in most cases Adisi oleh Air most hydrates revert to an aldehyde or ketone as soon as they form aldehyde or ketone favored

12. .. : : + + .. KatalisisAsam + .. : :Nu Acid catalysis enhances the reactivity of the carbonyl group - nucleophilic addition proceeds more easily. weak nucleophiles can react RECALL Water is a weak nucleophile.

13. .. .. .. .. .. .. .. .. .. .. : : : : : + + + a hydrate WATER ADDS TO THE CARBONYL GROUP OF ALDEHYDES AND KETONES TO FORM HYDRATES catalyzed by a trace of acid In a reaction where all steps are reversible, the steps in the reverse reaction are the same as those in the forward reaction, reversed! MICROREVERSIBILITY: .. + for most compounds the equilibrium favors the starting materials and you cannot isolate the hydrate

14. ACETALS AND HEMIACETALS

15. .. : : + + .. ACID CATALYSIS + .. : :Nu Acid catalysis enhances the reactivity of the carbonyl group - nucleophilic addition proceeds more easily. weak nucleophiles can react RECALL Alcohols are weak nucleophiles.

16. Addition of Alcohols addition of one mole addition of second mole hemiacetal an acetal H + H + TWO MOLES OF ALCOHOL WILL ADD The equilibria normally favor the aldehyde or ketone starting material, but we will show how they can be made.

17. aldehyde ketone hemiacetal acetal (ketal)* (hemiketal)* ACETALS AND HEMIACETALS *older term *older term

18. hemiacetal .. .. .. .. .. .. .. .. .. : : : : : : + + + H 2 SO 4 ACID CATALYZED FORMATION OF A HEMIACETAL + + .. + Normally the starting material is favored - but a second molecule of alcohol can react if in excess (next slide) Like a hydronium ion first addition C O R R H O R H C O R R H O H R C O R R H R H O C O R R H R O HO 3 SO .. -

19. acetal : .. .. .. .. .. : : : : .. .. .. .. .. .. .. .. : : : : : : : + + + + + + FORMATION OF THE ACETAL ( from the hemiacetal ) Resonance stabilized carbocation S N 1 second addition hemiacetal remove

20. CYCLIC ACETALS

21. Dry acid = HCl gas HCl in methanol HOTs Formation of 2,2-Dimethoxypropane dry acid = HCl gas or p -toluenesulfonic acid remove H 2 O THIS IS A NON-CYCLIC ACETAL (TsOH) mp 106 o C

22. CARBOHYDRATES AND SUGARS

23. Cyclization of Monosaccharides glucose glucopyranose a hemiacetal only sugars seem to make stable hemiacetals

24. a pyranose ring a furanose ring 6 5 two anomers are possible in each case FURANOSE AND PYRANOSE RINGS for clarity no hydroxyl groups are shown on the chains or rings 1 2 3 4 5 1 2 3 4 furan pyran

25. ANOMERS for clarity hydroxyl groups on the chain are not shown anomeric carbon (hemiacetal) anomers differ in configuration at the anomeric carbon

26. Glucose hemiacetals 66% 34% open chain < 0.001%

27. HAWORTH PROJECTIONS It is convenient to view the cyclic sugars (glucopyranoses) as a “Haworth Projection”, where the ring is flattened. upper-right back This orientation is always used for a Haworth Projection  -D-(+)-glucopyranose HAWORTH PROJECTION Standard Position

28. D-(+)-glucose L-(-)-glucose GLUCOSE ENANTIOMERS HAWORTH FISCHER WE WILL LEARN HOW TO CONVERT FISCHER PROJECTIONS TO HAWORTH PROJECTIONS OF EITHER ANOMER

29. H 2 O hydrate hemiacetal acetal R-O-H H 2 O R-O-H ADDITION OF WATER AND ALCOHOLS WATER ALCOHOLS no reaction NaOH H 2 O H 2 O H + acetals are stable to base but not to aqueous acid

30. cyclic hemiacetal R-O-H H 2 O cyclic acetal cyclic acetal H 2 O OFTEN USED AS A PROTECTIVE GROUP STABLE IF FORMED FROM A CARBOHYDRATE A STARCH OR “ POLYSACCHARIDE” IF FORMED FROM CARBOHYDRATES CYCLIZATIONS