This thesis entitled “Organic Transformations in Water: Synthetic and Mechanistic Studies towards Green Methodologies” is in two parts. Part-I describes various synthetic studies aimed at developing improved methodologies; Part-II describes certain mechanistic studies directed towards an improved understanding of phase transfer catalysis and the hydrophobic effect.
Water is uniquely advantageous as a solvent. It is environmentally benign, non-flammable, liquid over a wide temperature range and possesses a high heat capacity that makes it inherently safe. Water also catalyses chemical transformations between insoluble organic reactants. Water thus serves as a reaction medium, a product partitioner and a reaction catalyst.1
Part-I:- Reactions in Water under both Microwave and Ambient Conditions
Part-I is further divided into three chapters.
Chapter II deals with reactions of 2-nitroalcohols (2NAs), and is divided into three sections. Section A describes the synthesis of nitroalkanes via the microwave-assisted, water-mediated chemoselective reduction of 2NAs using tributyltin hydride (Bu Scheme 1 ). The 2NAs, synthesized from nitromethane and aldehydes (aliphatic, alicyclic, heterocyclic or m- & p-substituted aromatic aldehydes), were converted into corresponding nitroalkanes in excellent yields. The 2NAs derived either from substituted nitromethane [nitroethane, (nitromethyl)benzene, etc.] or bulky aldehydes (o-substituted aromatic aldehydes), however, failed to furnish nitroalkanes under these conditions. Also a major solvent effect was observed: the extent of conversion was greater in water than in water-polar 3SnH) as reducing agent. The chemoselective reduction of 2NAs to nitroalkanes was observed accidentally while trying to remove the nitro group of 2NAs in a Bu3SnH-AIBN-water system under microwave conditions. When equimolar quantities of 2NA and Bu3SnH were added to water, microwave irradiation led to nitroalkanes (protic solvent mixtures and the reaction did not occur either in aprotic polar or non-polar solvents.
Scheme 1. Microwave assisted chemoselective reduction of 2NAs to nitroalkanes in Bu3SnH-water
In Section B, the microwave assisted synthesis of nitroalkanes from nitroalkenes has been described. Equimolar quantities of nitroalkene and Bu Scheme 2 ). The nitroalkenes substituted even by bulky groups at C-1 & C-2 were converted into corresponding nitroalkanes. Hence the drawback of the method described in Section A was overcome by employing nitroalkenes as starting materials. 3SnH in water under microwave irradiation, led to excellent yields of corresponding nitroalkanes (Scheme 2). The nitroalkenes substituted even by bulky groups at C-1 & C-2 were converted into corresponding nitroalkanes. Hence the drawback of the method described in Section A was overcome by employing nitroalkenes as starting materials.
Scheme 2. Microwave assisted reduction of nitroalkenes to nitroalkanes in Bu3SnH-water
In Section C, the synthesis of nitroalkenes via dehydration of 2NAs in a K Scheme 3 ). Thus, the dehydration of 2NAs has been accomplished under relatively mild conditions. (It was observed that the 2NAs bearing bulky groups underwent the retro-Henry reaction rather than dehydration.) 2CO3-water system has been described. This conversion was accomplished at 0-5 °C in 5-30 minutes, the nitroalkenes being isolated in good yields (Scheme 3). Thus, the dehydration of 2NAs has been accomplished under relatively mild conditions. (It was observed that the 2NAs bearing bulky groups underwent the retro-Henry reaction rather than dehydration.)
Scheme 3. Dehydration of 2-NAs in aqueous K2CO3 solution
Chapter III describes the chemoselective reduction of ketoaldehydes. This was serendipitously discovered during attempted enantioselective reduction of prochiral ketones using amino acid-NaBH Scheme 4 ). The method provides a mild and efficient route for the chemoselective reduction of aldehydes under aqueous basic conditions. 4-Na2CO3 in water. When equimolar quantities of aldehyde and ketone were added to a solution NaBH4 in aqueous Na2CO3 at ambient temperature, the aldehydes were selectively reduced. Good yields of primary alcohols were generally observed with excellent chemoselectivities. Extension of this study to the selective reduction of ketoaldehydes under the above reaction conditions furnished ketoalcohols in > 70% yields with > 80% chemoselectivities (Scheme 4). The method provides a mild and efficient route for the chemoselective reduction of aldehydes under aqueous basic conditions.
Scheme 4. Chemoselective reduction of ketoaldehydes with NaBH4-Na2CO3 in water
Chapter IV deals with deprotection of various acetals, thioacetals and tetrahydropyranyl (THP) ethers in hexane under ambient conditions, by employing chloral hydrate as reagent. Chloral hydrate is a crystalline solid with pK2 When a a 9.66.stirred suspension of excess chloral hydrate in hexane was treated with the acetal, thioacetal or THP ether, the corresponding aldehyde, ketone and alcohol were obtained in good to excellent yields (stirred suspension of excess chloral hydrate in hexane was treated with the acetal, thioacetal or THP ether, the corresponding aldehyde, ketone and alcohol were obtained in good to excellent yields (stirred suspension of excess chloral hydrate in hexane was treated with the acetal, thioacetal or THP ether, the corresponding aldehyde, ketone and alcohol were obtained in good to excellent yields (
Scheme 5. Chloral hydrate catalyzed hydrolysis of acetals, thioacetals including THP ethers
Part-II:- Mechanistic Studies on Phase Transfer Catalysis and The Hydrophobic Effect
Part-II is in two chapters.
Chapter V describes a study of the mechanism of the phase transfer catalyzed (PTC) nucleophilic reaction of cyanide ion with alkyl halides in decane ( Scheme 7 ). In the extraction mechanism proposed earlier,3 the PTC forms the mixed species, tributylhexadecylphosphonium cyanide (THPB), which is believed to be more soluble in decane than is the starting cyanide. A problem with this explanation is that the positive free energy of transfer of the cyanide ion from the aqueous to the organic phase, which is unlikely to be offset by solvation energy of the hexadecyl and butyl groups.
Scheme 6. Cyanide displacement reaction of 1-chloro octane3
The present studies explore the possibility that the reaction occurs via the formation of aggregates resembling reverse micelles ( Figure 1 ). In these, the hydrocarbon residues point outwards, with the ionic species ensconced in a deeply embedded interior along with a certain number of water molecules. Thus, the ionic species are not only shielded from the organic medium, but also stabilized in a relatively polar micro-environment (largely via dipolar interactions and hydrogen bonding). It is assumed that this stabilization energy surpasses the positive free energy of transfer of cyanide ion from aqueous to the organic phase.
Figure 1. Typical representation of cyanide displacement reaction in THPB-decane-water micellar pool
In fact, NMR studies on the structural dynamics of THPB in solution offered evidence of aggregation. Also, a correlation between the structures of catalyst and reactant was observed in studies with various other PTC’s.
Chapter VI deals with the mechanism of the Diels-Alder reaction (DAR) in water. The concept of the hydrophobic effect (HE)4 and preferential hydrogen bonding of water with the polarized transition state5 have been invoked to explain the apparent acceleration of Diels-Alder reactions in water.
The present studies explore the possibility that the highly polar water microenvironment stabilizes the transition state. Semi-quantitative rate studies of DAR involving water soluble reactants indicate that the possible role of solvation and hydrogen bonding on the polarized transition state as the key factor in the rate enhancement of water mediated DAR. The DAR in the presence of a catalytic amount of water along with the organic solvent catalyzed the reaction more efficiently, as compared to the reaction in pure organic solvent. It was also observed that there was a prominent effect of traces of water on the rate in solvent-free conditions.
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| Identifer | oai:union.ndltd.org:IISc/oai:etd.iisc.ernet.in:2005/3391 |
| Date | January 2013 |
| Creators | Shrinidhi, Annadka |
| Contributors | Chandrasekhar, Sosale |
| Source Sets | India Institute of Science |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
| Relation | G25852 |
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