Abstract: In this invention, DESs an anticancer activity compound has been synthesized by 3-(4-(4-(bis(2chloroethyl)amino)phenyl)butanoyloxy)-N,N,N-trimethylpropane-1-aminium chloride (CABAL), and citric acid (CA) which is a good transparent liquid. It has been analyzed by density study. Treatment of (DESs) derivatives of ε-caprolactone in 100°C temperature resulted in colorless good yield (carboxylic substituted ε-caprolactone), which has been characterized by UV. The absorbance of carboxylic substituted ε-caprolactone was observed at 290 and 470 nm. The biodegradable of carboxylic substituted ε-caprolactone was analyzed by swelling behavior at pH 2.2, suggesting that- carboxylic substituted ε-caprolactone may be preferred for drug carrier applications. 3 Claims & 4 Figures
Claims:The following claims specify the scope of the invention:
Claim:
1. The derivative of developing carboxylic substituted ε-caprolactone using DESs comprising the following steps:
a) The density range of novel DESs is highlighted as well as recorded and the analysis of DES in its authentic form and various available brands.
b) The validation of all parameters pertaining to ICH guidelines is performed and the developed analogy is precise, accurate, selective, and robust.
c) The absorbance of wavelength in derivatives of ε-caprolactone in 290 and 470 nm and the ratio variation testing is being passed for synthesis polymer reaction.
2. According to claim 1, the stoichiometric between HBA and HBD compounds is 1:3 and the chlorambucil is the derivative of carboxylic substituted ε-caprolactone from DESs.
3. According to claim 1, the enhancement in swelling nature is supported by drug carrier applications. Swelling happened with increase in acidity that resulted from the breakage of ester and acid bonds in the carboxylic substituted ε-caprolactone. , Description:Field of invention
The present invention is related with the synthesis and characterization of a new green solvents from this compounds CABAL (3-(4-(4-(bis(2chloroethyl)amino)phenyl)butanoyloxy)-N,N,N-trimethylpropane-1-aminium chloride and citric acid (CA). This invention is further extended to synthesis and derivatives ε-caprolactone.
Background of the Invention
The Structure of the simple compounds, Chlorambucil (Benoît Joseph et al., 2002, Ulrich Beyer et al., 1998, Diana Florea-Wang et al., 2004, Melissa Millard et al., 2013) in which three functional groups attached to the central aromatic ring were studied by NMR. A synthesis number of novel class compounds have been functionalized of heterocyclic compounds and ligands to the functional groups (BeataMiksa et a., 2005, Bing-YenWang et al., 2020, IrinaYu. Strobykina et al., 2021). Meanwhile, attention has been forced to functionalize the polymers with substituent functional groups (Biswajit Saha et al., 2019, Amrita Chaudhuri et al., 2018, Lei Tao et al., 2009., Chenyao Nie et al., 2013) that were determined by NMR stduesis well. Therefore, the structures of the related synthesis of Peptide-Cbl conjugate (Sonali B. Fonseca et al., 2011), could then be determined and studied by NMR studies.
Moreover, chlorambucil is being increasingly used in organic chemistry (US3046301A) Often supplies unusual properties due to the alkaline agent (Leroy A Shervington et al., 2009). Thus, it was of interest to synthesis the derivative of quaternary ammonium compounds and examine whether it would have an even greater bulk as expected.
Chemists are largely motivated by the challenges in synthesizing quaternary ammonium compounds tag with chlorambucil and exploring their application in novel ε-caprolactone synthesis under the reaction carry out by DESs. Keep this in view, there is still in need to develop some rational approach towards the synthesis and characterization of a new family carboxylic substituted ε-caprolactone under reaction condition is the DESs; which is a play of crosslink agents and donors for polymer reactions.
There is distinct sparsity in the activity of DESs containing CABAL acceptors, therefore the objective of the invention is to understand the unusual structures and reactivity pattern of this new family of carboxylic substituted ε-caprolactone under reaction condition is the DESs.
Summary of the invention
The current creation gives the synthesizing quaternary ammonium compounds tag with chlorambucil whose density analysis; suggest a good hydrogen acceptor for derivatives of the ε-caprolactone.
In another aspect, the current invention gives a method for the novel derivatives of the carboxylic substituted ε-caprolactone. The method comprises the steps of reacting with CA in the presence of the solvent at RT (room temperature).
Brief description of Drawing
The figure illustrates the exemplary embodiment of the invention.
Figure 1 Schematic representation of the derivative of Chlorambucil, and Synthesis of the deep eutectic solvent.
Figure 2 Derivatives of carboxylic substituted ε-caprolactone by DESs
Figure 3 UV spectra of the carboxylic substituted ε-caprolactone and 4-(2-hydroxyethyl) cyclohexanol at 290 and 470 nm.
Figure 4 Swelling nature of carboxylic substituted ε-caprolactone and 4-(2-hydroxyethyl) cyclohexanol in solution of pH level: 2.2.
Detailed description of the invention
The current innovation at first provides the synthesis of carboxylic substituted ε-caprolactone under the DESs which was then characterised by density analysis, UV-Visible spectral studies.
All the reactions were carried out under an N2 atm and compounds were the use of dean stark apparatus. The reaction is carried by only DESs, not organic solvents. The solvent of ratio (1:3) of CABAL) and CA is transparent liquid because, the molar proportion of the eutectic parts in a twofold framework ought to be close to solidarity, because the lattice binding of a solitary compound depends on the contribution with different compounds of the lattice. Also, the proportion of hydrogen-bonding acceptors and donors is one more factor that infers solidarity proportion standards of the synthesis of polymer responses.
Chlorambucil is a one of the quaternary ammonium compound, chlorambucil (I) was synthesized by a two-step reaction procedure. Forward from the initial step of the reaction, the essential hydroxyl group of dimethylaminopropanol (II) was permitted to react with a free acid group of chlorambucil to get compound III. Compound III was then treated with methyl chloride to frame the quaternary ammonium salt IV. In addition to that, QAC was expected to form a hydrogen bond with the acceptor compound, which was then used to set up the deep eutectic solvent V was affirmed by density.
The invention will be further illustrated by the preparation of the following precursors. A combination of CPL (0.0032 mmol) and DAP (0.3392 mmol) in 15 mL of chloroform was included a 100 mL round base flask. (ACS Med. Chem. Lett. 2011, 2, 6, 419–423) Following this, Methanesulfonic acid (0.2 mL) was added drop-wise, and the response blend was refluxed at 0°C for 24 h with consistent mixing and evacuation of water and afterward response part was kept up with at 27°C; thusly, it was washed with 1N Sodium bicarbonate and water. The organic layer was removed by Magnesium sulfate and isolated. Filtration was done to eliminate the side-products. Eventually, the crude product was acquired, which was then dried in vacuum.
Chlorambucil, conjugated by DAP (1g) and Methyl Iodide (0.059 mL) in C2H5OH (5 mL), was mixed for 6 h under N2 atm at 27°C. The organic solvent was evaporated, then, at that point, a precipitate was melted in Methanol (10 mL), and the arrangement along these lines framed was added with Et2OH (5 mL). The last precipitates were sifted at room temperature. Moreover, the synthetic chemical structure of the 3-(4-(4-(bis (2chloroethyl) amino)phenyl)butanoyloxy)- N,N,N-trimethyl propane-1-aminium chloride (CABAL) was affirmed by FT-IR examination (ACS Appl. Bio Mater. 2018, 1, 6, 2094–2109)
The DES was ready as per the recently revealed protocol.34 In brief; CABAL and CA were blended in different stoichiometric proportions of 1:1, 1:2, 1:3, and 2:1at room temperature (27°C). The reaction blends were unsettled utilizing magnetic stirrers until clear homogenous fluids (solution) were gotten. The proportion, 1:3 framed clear fluids, however fluids with the 1:1, 1:2, and 2:1 proportions were seen to be crystalline, semi-crystalline, or solid at the reaction conditions. Synthetic communications and physicochemical characterization (density) were affirmed for the 1:3 DESs solvents. The density of DESs assumes a primary role in its chemical reactions and is one of the significant physical properties of the solvents. Specifically, it plays essential for the synthesis of polymer response with DES for the development of drug transporter (carrier) applications. The densities of the DES-1:3 solvents are introduced in Table 1. The density of these DESs was in the range of 0.621 to 0.853 g/cm−3 at room temperature (27 °C). The DES-1:3 (Transparent liquid) had the most elevated density (0.853 g/cm−3) when contrasted with other DES-1:1 (0.621 g/cm3- More viscous), 1:2 (0.826 g/cm3- Little bit homogeneous liquid) and 2:1 (0.701 g/cm3- More viscous) at 27 °C. This is because of the expanded concentration of the citric acid compound that may increase the kinetic energy of the atoms, and along these lines, the atoms in the blend vibrate more.
The carboxylic substituted ε-caprolactone was prepared by standard methods. Typically; Monomer unit of 4-(2-hydroxyethyl) cyclohexanol (one equivalent weight) was dissolved in DES (1:3 ratio) and the solution mixture was stirred for 30 min at 27 °C. The dissolved KOtBu, PCC, m-CPBA (one equivalent weight) was then added drop-wise-to ε-caprolactone with DESs (10 ml) and the reaction solution was stirred for 34, 7, 3, and 1 hours at different temperature. The reaction solution was maintained at RT °C. After 3 h, the carboxylic substituted ε-caprolactone were obtained and dissolved in acetone solvent. Finally, the carboxylic substituted ε-caprolactone final product was dried in a vacuum; it is used for drug carrier studies. Chemical interaction characterization (UV and swelling nature) was confirmed for the carboxylic substituted ε-caprolactone.
UV-Visible: The derivative for the carboxylic substituted ε-caprolactone was investigated by UV-Visible spectroscopy. The UV-Visible spectra of the 4-(2-hydroxyethyl) cyclohexanol and carboxylic substituted ε-caprolactone are presented in Figure 1. The spectrum of the 4-(2-hydroxyethyl) cyclohexanol, which is the monomer unit, contains a band at 290 and 470 nm. The spectrum of carboxylic substituted ε-caprolactone showed an intense absorption intensity completely reduced, which is indicative of completely change from starting unit to final product of carboxylic substituted ε-caprolactone (Figure 3). Swelling Nature: The swelling behavior of the 4-(2-hydroxyethyl) cyclohexanol and carboxylic substituted ε-caprolactone was tried in arrangements of pH levels: 2.2 the results are introduced in Figure 2. The swelling behavior of the carboxylic substituted ε-caprolactone at pH 2.2 was more critical in contrast with expanding in other unit of 4-(2-hydroxyethyl) cyclohexanol. This swelling happened because of the increase in acidity that resulted from the breakage of ester and acid bonds in the carboxylic substituted ε-caprolactone (Figure 4).
3 Claims & 4 Figures
| # | Name | Date |
|---|---|---|
| 1 | 202141059983-REQUEST FOR EARLY PUBLICATION(FORM-9) [22-12-2021(online)].pdf | 2021-12-22 |
| 2 | 202141059983-FORM-9 [22-12-2021(online)].pdf | 2021-12-22 |
| 3 | 202141059983-FORM FOR SMALL ENTITY(FORM-28) [22-12-2021(online)].pdf | 2021-12-22 |
| 4 | 202141059983-FORM FOR SMALL ENTITY [22-12-2021(online)].pdf | 2021-12-22 |
| 5 | 202141059983-FORM 1 [22-12-2021(online)].pdf | 2021-12-22 |
| 6 | 202141059983-EVIDENCE FOR REGISTRATION UNDER SSI(FORM-28) [22-12-2021(online)].pdf | 2021-12-22 |
| 7 | 202141059983-EVIDENCE FOR REGISTRATION UNDER SSI [22-12-2021(online)].pdf | 2021-12-22 |
| 8 | 202141059983-EDUCATIONAL INSTITUTION(S) [22-12-2021(online)].pdf | 2021-12-22 |
| 9 | 202141059983-DRAWINGS [22-12-2021(online)].pdf | 2021-12-22 |
| 10 | 202141059983-COMPLETE SPECIFICATION [22-12-2021(online)].pdf | 2021-12-22 |