1
Reactivity of α,β-unsaturated carbonyl compounds towards nucleophilic addition reaction: a local hard–soft acid–base approach

Type: Goal | Advantage: None | Novelty: None | ConceptID: Goa1

2
The Fukui function fk+ and local softness sk+ are assigned as reactivity parameters for nucleophilic addition reaction in acrolein, methylacrylate, methylmethacrylate, acryloylchloride, cinnamaldehyde and cinnamoylchloride.

Type: Method | Advantage: None | Novelty: New | ConceptID: Met1

3
All calculations were performed at the HF level of theory using 6-31G, 6-31G** and TZV basis sets.

Type: Model | Advantage: None | Novelty: None | ConceptID: Mod1

4
The condensed local softness calculated using a Löwdin population is compared with the local softness calculated from a Mulliken population.

Type: Goal | Advantage: None | Novelty: None | ConceptID: Goa2

5
The most probable sites for nucleophilic attack on the α,β-unsaturated carbonyl compounds are determined from local reactivity descriptors: they are quite reliable to predict the reactivity relative to atomic charges.

Type: Conclusion | Advantage: None | Novelty: None | ConceptID: Con1

Introduction

6
The chemical reactivity of a molecule is often interpreted in terms of charge distribution of its atoms.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac1

7
Atomic charges are used to indicate the preferred direction for a reagent to approach a substrate.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac2

8
Although the chemists have an intuitive feeling for the reactivity based on charge distribution, assigning precise reactivity from atomic charge failed in several cases.1,2

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac3

9
In recent years, reactivity descriptors3–7 such as hardness, softness, Fukui function etc. have emerged as powerful tools in predicting the reactive sites of molecules.

Type: Model | Advantage: None | Novelty: None | ConceptID: Mod2

10
These reactivity descriptors are derived from density functional theory.

Type: Model | Advantage: None | Novelty: None | ConceptID: Mod2

11
Global hardness and global softness8–12 represent the reactivity of a molecule as a whole.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac4

12
On the other hand, the Fukui function13 defines the reactivity of an atom in a molecule and it is a local property.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac5

13
Fukui function and local softness, which is closely related, are suited to describe the relative reactivity of different substrates.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac6

14
Pearson's hard–soft acid–base (HSAB) 12,14–16 principle suggested that hard–hard and soft–soft interactions are favorable over hard–soft interactions.17–19

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac7

15
Again it has been found that soft–soft interactions are preferred in the site of the maximum Fukui function, i.e. frontier control,20–22 but on the other hand, hard–hard interactions are preferred in the site of the minimum Fukui function,23,24i.e. charge control.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac8

16
In this paper we have presented the reactivity parameters, the local softness sk+ and sk− and Fukui functions fk+ and fk− of α,β-unsaturated carbonyl compounds, namely acrolein (H2CCHCHO), methylacrylate (H2CCHCOOCH3), methylmethacrylate (H2CC(CH3)COOCH3), cinnamaldehyde (C6H5CHCHCHO), cinnamoylchloride (C6H5CHCHCOCl) and acryloylchloride (H2CCHCOCl), and the most reactive sites of nucleophilic attack were derived.

Type: Goal | Advantage: None | Novelty: None | ConceptID: Goa1

17
In these compounds the carbonyl carbon is slightly positive, due to mesomeric and resonance effects.

Type: Model | Advantage: None | Novelty: None | ConceptID: Mod3

18
The β-carbon, which is conjugated with the carbonyl carbon develops partial positive charge.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac9

19
Experimentally it has been found that a nucleophile attacks at the β-carbon atom of α,β-unsaturated carbonyl compounds.25

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac10

20
Here we have investigated the reactive sites of these carbonyl compounds towards a nucleophile using a local hard–soft acid–base approach.

Type: Goal | Advantage: None | Novelty: None | ConceptID: Goa3

Theoretical aspects

21
Within the framework of density functional theory (DFT) 3 the global hardness (η) 9–12 of an N electron system is defined as: where E, N, μ and v(r⃑) are the energy, number of electrons, chemical potential and external potential, respectively.

Type: Model | Advantage: None | Novelty: None | ConceptID: Mod4

22
Again, the inverse of global hardness with a factor of ½ is defined as global softness (S),The local property, Fukui function4f(r) is defined as the derivative of electron density, ρ(r⃑), with respect to the number of electrons at a constant external potential, v(r⃑).

Type: Model | Advantage: None | Novelty: None | ConceptID: Mod5

23
Similarly local softness, s(r⃑), is defined as the derivative of electron density, ρ(r⃑), with respect to the chemical potential, μ, at constant external potential,Applying the finite difference approximation, three types of condensed Fukui functions23 are found from electronic population analyses26.where, qk(N), qk(N + 1) and qk(N − 1) are atomic charges for atom k in the N, (N + 1) and (N − 1)-electron systems.

Type: Model | Advantage: None | Novelty: None | ConceptID: Mod6

24
The Fukui functions fk+ and fk− and local softness sk+ and sk− are calculated from SCF calculation using 6-31G, 6-31G** and TZV basis sets27,28 and all these calculations are performed with the program GAMESS29.

Type: Model | Advantage: None | Novelty: None | ConceptID: Mod7

Results and discussion

25
The α,β-unsaturated carbonyl compounds contain two reactive sites, the carbonyl group site and the carbon–carbon double bond site.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac11

26
Hence, two types of nucleophilic addition reaction can be assigned as the direct addition reaction and conjugated addition reaction.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac12

27
However, to what extent a given nucleophile undergoes the direct addition and conjugated addition is dependent on the steric and electronic factors.

Type: Model | Advantage: None | Novelty: None | ConceptID: Mod8

28
If the carbonyl carbon is more sterically congested and weakly electrophilic, the conjugated addition will occur more readily than the direct addition, on the other hand if the β-carbon is more sterically congested the direct addition will take place predominantly.

Type: Model | Advantage: None | Novelty: None | ConceptID: Mod8

29
Thus the nucleophilic reagents add to the conjugated system in such a way so as to form the most stable intermediate anion.30

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac13

30
The tendency of the α,β-unsaturated carbonyl compounds to undergo nucleophilic addition is not simply due to the electron withdrawing ability of the carbonyl group, but to the existence of a conjugated system that permits the formation of the resonance stabilized anion.

Type: Model | Advantage: None | Novelty: None | ConceptID: Mod9

31
Theoretically atomic charges, Fukui functions and local softness values can be calculated for each atom in the molecule and they provide an insight in directing the incoming nucleophiles for the attack on the carbon atoms of the α,β-unsaturated carbonyl compounds.

Type: Model | Advantage: None | Novelty: None | ConceptID: Mod10

Atomic charges

32
The atomic charges derived from Mulliken population analysis (MPA) and Löwdin population analysis (LPA) for Cα, Cβ and Ccarbonyl atoms of α,β-unsaturated carbonyl compounds are given in Table 1.

Type: Observation | Advantage: None | Novelty: None | ConceptID: Obs1

33
It is seen from Table 1 that both MPA and LPA derived charges have negative values for Cα and Cβ atoms.

Type: Observation | Advantage: None | Novelty: None | ConceptID: Obs1

34
Since the charges of the Ccarbonyl atoms are positive, a nucleophile should attack at the carbonyl atoms.

Type: Result | Advantage: None | Novelty: None | ConceptID: Res1

35
However, experimentally it has been found that in most of the cases the nucleophilic addition takes place at the β-carbon atom.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac14

36
Hence it is difficult to predict the reactive sites of these compounds from atomic charge values.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac15

37
In our recent studies,31,33 Fukui function and local softness appear to be better reactivity descriptors for studying the acidity and basicity of zeolites.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac16

38
Roy et al32. used the reactivity descriptors to study the most preferable protonation sites in aniline and substituted anilines in the gas phase.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac17

39
Thus, the Fukui function and the local softness are found to be superior to atomic charges in determining the reactive sites in molecules.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac18

Fukui function

40
The Fukui function values for the Cα, Cβ and Ccarbonyl atoms are presented in Table 2.

Type: Observation | Advantage: None | Novelty: None | ConceptID: Obs2

41
Both MPA and LPA derived Fukui functions for the Cβ and Ccarbonyl atoms are positive.

Type: Observation | Advantage: None | Novelty: None | ConceptID: Obs2

42
The negative Fukui function is observed for the Cα atom in acrolein and acryloyl chloride.

Type: Observation | Advantage: None | Novelty: None | ConceptID: Obs2

43
The negative values of Fukui functions indicate a very low probability for nucleophilic attack to take place at those sites.

Type: Result | Advantage: None | Novelty: None | ConceptID: Res2

44
Recently, Hirao and co-workers,31,32 suggested that the Fukui function of an atom should be always positive.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac19

45
They found that the Fukui function calculated using Hirshfeld population analysis become positive although MPA derived Fukui function for some atoms become negative in the same calculation.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac19

46
In our present study, the LPA derived Fukui functions are found to be positive for all the atoms.

Type: Conclusion | Advantage: None | Novelty: None | ConceptID: Con2

47
While comparing the Fukui function values calculated using 6-31G, 6-31G** and TZV basis sets, it appears that the β-carbon of each of the molecule has maximum values.

Type: Observation | Advantage: None | Novelty: None | ConceptID: Obs3

48
This indicates that the incoming nucleophile will preferably attack the β-carbon atom which is in agreement with the experimental results.25

Type: Result | Advantage: None | Novelty: None | ConceptID: Res3

49
Moreover, the Fukui function values for β-carbon with less bulky groups at α and β positions are more than those of the molecules where more bulky groups are present at α and β positions.

Type: Observation | Advantage: None | Novelty: None | ConceptID: Obs4

50
For all the molecules the reactivity of the atoms for nucleophilic attack decreases in the order: Cβ > Ccarbonyl > Cα while considering the MPA derived Fukui functions.

Type: Conclusion | Advantage: None | Novelty: None | ConceptID: Con3

51
The LPA derived Fukui functions also predict the same trend bearing a disorder in case of methylacrylate.

Type: Conclusion | Advantage: None | Novelty: None | ConceptID: Con4

Local softness

52
The local softness values of all the molecules calculated with different basis sets such as 6-31G, 6-31G** and TZV are given in Table 3.

Type: Observation | Advantage: None | Novelty: None | ConceptID: Obs5

53
Like Fukui functions, local softness values predict the similar trend of reactivity.

Type: Result | Advantage: None | Novelty: None | ConceptID: Res4

54
The reactivity of the atoms for nucleophilic attack decreases in the order: Cβ > Ccarbonyl > Cα bearing slight disorder for LPA derived softness values.

Type: Result | Advantage: None | Novelty: None | ConceptID: Res4

55
From the softness values a reactivity order for molecules could be derived.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac20

56
From Table 2 and Table 3 it is seen that Fukui function and local softness values are more at the β-carbon atoms in the molecules with less bulky groups.

Type: Result | Advantage: None | Novelty: None | ConceptID: Res5

57
Hence, β-carbon atoms of α,β-unsaturated carbonyl compounds are more reactive and prone for nucleophilic attacks when less bulky groups are present.

Type: Conclusion | Advantage: None | Novelty: None | ConceptID: Con5

Conclusions

58
Local reactivity descriptors are shown to be very powerful in predicting the reactivity of α,β-unsaturated compounds.

Type: Conclusion | Advantage: None | Novelty: None | ConceptID: Con6

59
From the Fukui functions and local softness values it is concluded that the β-carbon atoms of the α,β-unsaturated carbonyl compounds are more reactive towards a nucleophile.

Type: Conclusion | Advantage: None | Novelty: None | ConceptID: Con3

60
The reactivities of the three types of carbon atoms are found to decrease in the order: Cβ > Ccarbonyl > Cα in all of the molecules.

Type: Conclusion | Advantage: None | Novelty: None | ConceptID: Con3

61
The local softness values are dependent on the substituents present at the β-carbon atoms.

Type: Conclusion | Advantage: None | Novelty: None | ConceptID: Con7

62
The local softness values of β-carbon atoms with less bulky groups are greater than those with more bulky groups.

Type: Conclusion | Advantage: None | Novelty: None | ConceptID: Con5

63
These results provide an insight in comparing the intermolecular reactivities of various α,β-unsaturated carbonyl compounds.

Type: Background | Advantage: None | Novelty: None | ConceptID: Bac21