Paper No and Title 14: Organic Chemistry IV (Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic rings)

Transcription

1 Subject Chemistry Paper No and Title 14: Organic Chemistry IV (Advance Organic Synthesis and Supramolecular Chemistry and carbocyclic Module No and 5: C-C disconnections of alcohols Title Module Tag CHE_P14_M5

2 TABLE OF CONTENTS 1. Learning outcomes 2. Introduction 3. Synthesis of alcoholic compounds by 1,1 C-C disconnections 4. Synthesis of alcoholic compounds by 1,2 C-C disconnections 5. Summary

3 1. Learning Outcomes After studying this module, you shall be able to Know the importance of alcohol compounds Design the synthesis of carbonyl compounds using 1,1 C-C disconnection approach Understand the synthetic pathways of alcohols using aldehyde or ketone and Grignard reagent Design the synthesis of carbonyl compounds using 1,2 C-C disconnection approach 2. Introduction Alcohol compounds are an important class of compounds in organic chemistry. Any compounds possessing the group R-OH, where R is alkyl group comes under the category of alcoholic compounds or its derivatives. The different kind of alcohols includes primary alcohols, secondary alcohols and tertiary alcohols (Figure 1). Alcohols have wide applicability in our daily life. They are useful as synthetic intermediates, cleansers, cosmetics, fuels, alcoholic beverages, etc. The synthetic and retrosynthetic analysis of alcoholic compounds are required for their utility. Figure 1

4 The C-C disconnections of alcohols are more challenging because of their vast numbers and it becomes very difficult to identify, which C-C bond to disconnect for carbocation and carboanion. However, there are reagents available for the generation of carbanion like RMgX and carbocation like RBr. 3. Synthesis of alcoholic compounds by 1,1 C-C disconnections Any compound bearing an alcoholic group can be disconnected at the C-C bond adjacent to oxygen. The starting materials for these types of compounds are an aldehyde or ketone and Grignard reagent (Figure 2). Figure 2

5 For example, 2-methyl-2-propanol (1) can be made from acetone (4) and methyl magnesium bromide (5). Retrosynthetic analysis: The retrosynthetic pathway of 2-methyl-2-propanol (1) is given in figure 3. The C-C bond adjacent to oxygen has been disconnected to give cation (2) and anion (3) as synthons. The reagent for the cation (2) is acetone (4) and reagent for carbanion 3 is Grignard reagent, methyl magnesium bromide (5). Figure 3 Synthesis: The synthetic pathway of 2-methyl-2-propanol (1) is given in figure 4. The reaction of methyl bromide (6) with magnesium in the presence of dry ether gives Grignard reagent, methyl magnesium bromide (5). The reaction of methyl magnesium bromide (5) with acetone (4) gives the target molecule (1).

6 Figure Synthesis of branched side chain alcohol Retrosynthetic analysis: The retrosynthetic pathway of branched side chain alcohol, 2,3-dimethylbutan-2-ol (7) is given in (Figure 5). The C-C bond adjacent to oxygen has been disconnected to give cation (8) and anion (3) as synthons. The reagent for the cation (8) is 3-methylbutan-2-one (9) and reagent for carbanion (3) is Grignard reagent, methyl magnesium bromide (5), through path a. An alternative and more popular is through pathway b.

7 Figure 5 Synthesis: The synthetic pathway of 2,3-dimethylbutan-2-ol (7) is given in (Figure 6). The reaction of methyl bromide (6) with magnesium in the presence of dry ether gives Grignard reagent, methyl magnesium bromide (5) (Figure 4). The reaction of methyl magnesium bromide (5) with 3-methylbutan-2-one (9) gives the target molecule (7). The synthetic method through pathway b disconnection approach is given in (Figure 7).

8 Figure 6 Figure Synthesis of unbranched side chain alcohol Retrosynthetic analysis: The retrosynthetic pathway of unbranched side chain alcohol, 2-methylpentan-2-ol (10) is given in figure 7. Two pathways for the disconnection approach have been shown. The pathway b is more favoured. The C-C bond adjacent to oxygen has been disconnected to give cation 2

9 and anion (12) as synthons. The reagent for the cation (2) is acetone (4) and reagent for carbanion (12) is Grignard reagent, (13). Figure 8 Synthesis: The synthetic pathway of 2-methylpentan-2-ol (10) is given in figure 9. The reaction of propylbromide with magnesium in the presence of dry ether gives Grignard reagent, propylmagnesium bromide (13) (Figure 9). The reaction of propylmagnesium bromide (13) with acetone (4) gives the target molecule (10).

10 Figure 9 4. Synthesis of alcoholic compounds by 1,2 C-C disconnections Any compound bearing an alcoholic group can also be disconnected at the C-C bond next to the adjacent bond to the oxygen atom. The retrosynthetic analysis in (Figure 10) shows the C- C disconnection. The starting materials for these types of compounds are epoxide and Grignard reagent (Figure 11). Figure 10

11 Figure 11 Let us consider an example, 1-phenyl-2-butanol (14) can be made from 2-ethyloxirane (15) and phenyl magnesium bromide. Retrosynthetic analysis: The retrosynthetic analysis of 1-phenyl-2-butanol (14) is given in figure 12. Figure 12

12 Synthesis Using the above disconnection approach synthesis of 1-phenyl-2-butanol (14) is given in figure 13. The reaction of 1-butene (but-1-ene, 16) with peracid leads to the formation of epoxide at the position of double bond, known as 2-ethyloxirane (15). The reaction of 2-ethyloxirane (15) with phenyl magnesium bromide gives the target molecule (14). 5. Summary Figure 13 Any compounds possessing the group R-OH, where R is alkyl group comes under the category of alcoholic compounds or its derivatives. The C-C disconnections are more challenging because of their numbers in organic molecules. Any compound bearing an alcoholic group can be disconnected at the C-C bond adjacent to oxygen. 2-Methyl-2-propanol can be made from acetone and methyl magnesium bromide. Synthesis of branched side chain and unbranched side chain alcohol has been explained. Any compound bearing an alcoholic group can also be disconnected at the C-C bond next to the adjacent bond to the oxygen atom. This is known by 1,2 C-C disconnections.