मैं उनकी थीसिस "बहुघटक प्रतिक्रियाओं (एमसीआर) का उपयोग करके कार्बनिक सल्फर युक्त यौगिकों का संश्लेषण: उनके जैविक और फोटोफिजिकल अध्ययन" शीर्षक से अग्रेषित कर रहा हूं, जिसे उन्होंने पीएचडी के लिए प्रस्तुत किया था। विज्ञान की) इस संस्थान की डिग्री। मैं आईआईटीजी के अपने सभी दोस्तों (डॉ. जहीर भाई, डॉ. जिया भाई, डॉ. पंकज, पलाशुदीन, समीर हुसैन, अख्तर हुसैन, वाजिद अली, शाहनवाज, क्रापा, शाद, आदिल, कफील, अशरफुल, जुल्फिकार, डॉ. सोमू) को धन्यवाद देता हूं। और एएमयू से डॉ.
Introduction
Development of MCRs
Brief literature review of sulfur containing organic compounds
While quetiapine, 23f an antipsychotic drug, is used for the treatment of schizophrenia, bipolar disorder, and also as an antidepressant to treat major depressive disorders 23g (Figure 1.4). Significant progress for the construction of new C−S effects, mainly involving addition and substitution strategies, has been made.
MCR Based Carbon−Sulfur Bond-Forming Reactions
This 4CR is one of the only new MCRs that uses four independently variable components to form multiple stereogenic centers (Scheme 1.4).56. The preparation of 2-oxopyrrolidine (γ-lactam), a natural product, also relied on a diastereoselective one-pot four-component reaction (4CR) for the assembly of the core structure (Scheme 1.5).57.
Sulfa-Michael Additions (SMA) of Thiols
Wang and co-workers developed a highly efficient asymmetric SMA of a wide range of thiols with various hexafluoroisopropyl α,β-unsaturated esters catalyzed by the amine-thiourea-sulfonamide catalyst in high yields and with excellent enantioselectivities (Scheme 1.17) . This process provided a facile access to the γ-thioether-substituted enoates in moderate to good yields and very good enantioselectivities (Scheme 1.25).77.
Ring-Opening of Epoxides, Aziridines, and Azlactones with Thiols
Wu et al reported a quinine-catalyzed asymmetric desymmetrization of N-protected meso -aziridines with aryl thiols to afford β-amino sulfides in low to good yields and low to moderate enantioselectivities as shown in Scheme 1.28. 80. Lattanzi and Sala identified α,α-diphenyl-L-prolinol, an efficient catalyst for the desymmetrization of meso -N-acylaziridines with aryl thiols to provide aminothiols in low to good yields and poor to moderate enantioselectivities ( Scheme 1). 81.
Results and Discussion
Scheme 2.1. Synthesis of sulfides through MCR strategy and their oxidation into corresponding sulfones
The reactions of 1,3-diphenylpropane-1,3-dione (1b), benzaldehyde (2a) with benzylthiol (3c) or various aromatic thiols (3) were investigated under. Similarly, the reactions of 1,3-diphenylpropane-1,3-dione (1b), aromatic aldehydes containing various electron-donating or -withdrawing substituents at the para or meta position of the benzene ring, with varied aromatic thiols ( 3) performed. carried out.
Plausible mechanism for the formation of unsymmetrical sulfide
Experimental Section
The receptor grid generation panel within the Glide suite was used to set up the receptor network for the prepared structures. Three-dimensional structures of these compounds were then prepared using the LigPrep maestro module implementing the OPLS_2005 force field, and ionic states were generated for the ligands at pH values of 7.0 ± 2.0. Piperidine (0.1 mmol) and aldehyde (1 mmol) were successively added to a mixed solution of 1,3-diketone (1 mmol) in 3 mL of ethanol, and the reaction mixture was allowed to stir for 5-10 minutes at room temperature.
Thiol (1.2 mmol) was then added to the reaction mixture directly, if it is a solid, or dropwise through a syringe. The following work-up procedure was followed for products such as 4aaa to 4aac, 4abc, 4ape, 4aqe, 4ase, 4ate, 4bac, 5cac and 5cbc because the solid precipitate did not come out during the reaction time. It was then concentrated in a rotary evaporator and the crude residue was passed through a silica gel column (60-120 mesh) to give the desired pure product.
The reaction mixture was then slowly brought to room temperature and stirred for another 2 hours. Finally, the organic layer was dried over anhydrous Na2SO4 and concentrated in a rotary evaporator. Complete crystallographic data of 4aac, 5cad, 6c and 7a for structural analysis have been deposited at the Cambridge Crystallographic Data Centre, CCDC No.
Results and Discussion
Synthesis of 3-(alkyl/aryl(alkyl/arylthio)methyl) substituted 4-hydroxy coumarins
Ethanethiol, propanethiol, benzylthiol and 2-chlorobenzylthiol produced the desired products in comparable yields (9aaa-9aaj), however the yield decreased in the case of 2-mercaptoethanol. Similar yields were obtained, but thiols with electron-donating functionality react slightly faster than the electron-withdrawing counterparts (Table 3.2, entries 6–10). 2-Naphthalenethiol also underwent the transformation smoothly to produce the expected product (9aah) in good yield (Table 3.2, entry 11).
Furthermore, 2,4-dimethoxybenzaldehyde was also found to produce the desired product in good yield (9awe). Notably, 2-naphthyldehyde also reacted smoothly to produce the desired product (9ale) in good yield (Table 3.2, entry 26). In the presence of 4-halo-substituted thiols, 4-methoxybenzaldehyde and 4-cyanobenzaldehyde reacted with similar efficiency (9abg and 9aif), although the yield was slightly higher in the latter case (Table 3.2, entries 27-28).
Heterocyclic aldehydes also performed well to produce the desired products (9auc and 9ata) in good yields (Table 3.2, entries 29-30).
Entry 4-Hydroxycoumarin Aldehyde Thiol Product Yield (%) b
After examining the aliphatic thiols, we turned our attention to aromatic thiols, leaving all other reactants unchanged. After observing the effect of different thiols, we focused on investigating the effect of substituents on the aldehyde. Aromatic aldehydes produced better yields than the aliphatic aldehydes due to the relative instability of aliphatic aldehydes.
It was found that the electronic factor of the substituents on the aldehyde did not play a prominent role, but the steric factor. Para-substituted derivatives gave much better yields (9aae-9ahe) than ortho-substituted derivatives (9aoe and 9ame). The reaction of 4-hydroxycoumarin with an aromatic aldehyde gave a Knoevenagel intermediate in the presence of an L-proline catalyst.
Nucleophilic addition of the Knoevenagel intermediate via conjugate addition to the α,β-unsaturated carbonyl group from substituted thiols affords the final product.
A Plausible Reaction Mechanism
Experimental Section
Where, 'σ' indicates the standard deviation for the solvation intensity of the 9ata ligand in the absence of Co2+/Ni2+ and 'K' represents the slope of the curve. Job9 plot analysis was performed to determine the stoichiometry between the 9ata ligand and Co2+/Ni2+. The similar method can be used to calculate the complex ratio 'a' for the 9ata ligand and Ni2+.
The following work-up procedure was followed for the products in case the solid precipitate did not come out during the reaction time. The resulting solution was allowed to stir for 10 min at room temperature and then filtered. Complete crystallographic data for 9aif, Co-Complex and Ni-Complex for the structural analysis have been deposited with the Cambridge Crystallographic Data Centre, CCDC No.
Crystal data and structure refinement for the compound 9aif for atomic coordinates, equivalent isotropic displacement parameters and bond angles, check the CIF.
Results and Discussion
One-pot three-component reaction for the synthesis of unsymmetrical sulfides
It was noticed that the combination of 2-naphthol, aldehyde, thiol and TBATB in the ratio resp. gave the best result. Interestingly, no product was formed in the absence of catalyst, giving a clear indication that TBATB plays a significant role in the formation of the product. After optimizing the reaction conditions, the similar kind of reactions were carried out with different aromatic aldehydes with substituents such as Cl, Br, OMe, OH and NO2 at the different positions of the aromatic ring with different thiols in the presence of TBATB at room temperature under identical reaction conditions and the successful results is summarized in table 4.2.
The desired unsymmetrical sulfides 11aaa-11ama were obtained in fairly good to high yields, except in a few cases such as entries 7, 12, 21, and 22. It was observed that aromatic aldehydes containing electron-withdrawing groups reacted faster compared to the electron. It was observed that 2-naphthol, 2-nitrobenzaldehyde and ethanethiol gave only 20% yield (Table 4.2, entry 22) under similar reaction conditions, which may be due to the steric hindrance of the nitro group at the ortho position.
Entry 2-Naphthol Aldehyde (2) Thiol (3) Product (11) Yield (%) b
Plausible Mechanism for the formation of unsymmetrical sulfides
Experimental Section
All reagents and solvents were purchased from Aldrich Chemicals (India), Merck (India) or Ranbaxy (India) and were used as received. An aqueous solution of the ligand (11aa) (13 µM in 25 mM PBS solution) was placed in a quartz cell and UV-vis and fluorescence spectra were recorded for increasing concentrations of metal salts up to 13 µM. After completion of the reaction as indicated by TLC, the ethanol was removed on a rotary evaporator and the crude residue was extracted with dichloromethane (3 × 20 mL).
The organic extract was dried over anhydrous sodium sulfate and the solvent was removed on a rotary evaporator.
Results and Discussion
Synthesis of 3-[(alkyl/arylthio)(aryl)methyl]-1H-indoles
After optimization of the reaction conditions, indole, benzaldehyde and ethanethiol were reacted to give the desired product 13aaa in 70% yield. It was observed that aromatic aldehydes containing electron-withdrawing groups in the ring gave better yields compared to the aldehydes with electron-donating substituent. We have also investigated the reactions of various aliphatic thiols, namely propanethiol, benzylthiol and 2-mercaptoethanol with indole and various aromatic aldehydes under similar reaction conditions, and we have isolated the desired products 13aab-13aam in moderate to good yields (Table 5.2, entries 9- 13).
However, when the reactions were carried out with indole, benzaldehyde with p-methylthiophenol or p-methoxythiophenol, it gave the desired products (13aae and 13aai) in 64% and 67%. It is worth mentioning that the protocol also provided the desired product (13aan), albeit in low yield with an aromatic thiol-containing electron-withdrawing group (Table 5.2, entry 17). Likewise, the desired product (13ale) was obtained from indole, 2-naphthylaldehyde and 4-methylthiophenol under identical conditions.
Apart from indole, the reaction was carried out using 5-bromoindole, p-chlorobenzaldehyde and ethanethiol under the experimental reaction conditions, the desired product (13 bea) was obtained in 69% yield (Table 5.2, entry 26).
Plausible mechanism for the formation of the product 13
Experimental Section
Hydrated ferrous sulfate (0.042 g, 0.1 mmol) was added to a stirred mixture of indole (1 mmol) and aldehyde (1 mmol) in 3 mL of ethanol at room temperature. After completion of the reaction as monitored by TLC, ethanol was removed in a rotary evaporator and the crude residue was extracted with dichloromethane (2 x 15 mL). Finally, the crude residue was passed through a silica gel column to obtain the desired pure product.
All the desired products were eluted with ethyl acetate:hexane (1:9) mixture during column chromatography except the compound 13aam and 13ahn were eluted with 1:1 mixture of the same solvent system. For recovery of the catalyst, the reaction was carried out in 3 mmol scale in ethanol. Complete crystallographic data of 13aha for the structural analysis are available at the Cambridge Crystallographic Data Centre, CCDC No.
Copies of this information may be obtained free of charge from the Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK, (fax e-mail: . [email protected] or via: www.ccdc. cam.ac.uk).
