The present invention relates Synthesis of N-Mannich Bases of 3,4 Dihydropyrimidin-2(1H)-ones by using Fe3O4@SiO2@Et-PhSO3H as magnetically retrievable nanocatalysts.

Prior Art:

Nanoscience is the study of phenomena on a nanometer scale. Atoms are a few tenths of a nanometer in diameter and molecules are typically a few nanometers in size. The smallest structures humans have made have dimensions of a few nanometers and the smallest structures will have the dimensions of a few nanometers. This is because as soon as a few atoms are placed next to each other, the resulting structure is a few nanometers in size. The smallest transistors, memory elements, light sources, motors, sensors, lasers, and pumps are all just a few nanometers in size like carbon nanotubes, grapheme etc.

Recently, nanotechnology processes have positively activated changing developments in environmental science, medicine and catalysis. Nanocatalysis is a rapidly growing field which involves the use of nanomaterials as catalysts for a variety of homogeneous and heterogeneous catalysis applications.
Accordingly, nanocatalysis has become a key area to achieve sustainability and generate various efficient catalytic processes. Thus nanocatalysis has been highlighted as a non-segregate part of nanotechnology. With an elevated speed the nano building blocks are discovered and are becoming the constructive part for the new commercial products and consumer material.

Due to the various interesting characteristics, nanocatalysts are highlighted as an important member amongst various nanomaterial’s (NPs). In recent years, bimembered core-shell (NPs) are very well explored arena in wide range of applications, however trimembered core-shell NPs having synergistic effect are largely untapped. The use of principles of sustainable chemistry is in practice for chemical developments in the new millennium to meet the challenges of protecting the environment and human health while maintaining commercial sustainability, which includes the reduction of the use of toxic initiator or not to generate hazardous substances in the design, manufacture, and application of chemical products.

As nanoparticles possess large surface area to volume ratio, become responsible for their widespread advantageous use in catalysis. The nanomaterial which acts as catalyst differentiates itself from others on the basis of structural and electronics changes. The amazing results were observed in case of nanocatalysts, when the combined with the concept of multi metallic nature, use of support and core shell mechanism. In catalysis, the production of engineered nanomaterials is an interesting task. The development of pathway for production of eco-friendly strategies to generate these nanomaterials that use benign reagents rather than the hazardous substances for conventional use is the aim of people working for sustainable chemistry. Such type of simple protocol and synthetic methods form bulk quantities of nano-catalysts without the need for large amounts of insoluble contents and have found novel applicability in catalysis.

The synthetic modifications in which highly functionalized organic molecules can be produced from easily available substrates via atom efficient reactions are of great importance for organic chemists. The expeditious domino and multicomponent reactions (MCRs) are examples of such types of organic transformations. A special class of tandem sequential reactions represents the MCRs.

MCRs are defined as one-pot reactions in which more than two components are combine to form a new product, incorporating essentially most of moieties from all components. Usual organic synthesis involves formation of individual bonds in a stepwise manner. This generally contains isolation and purification of intermediates and diversion of reaction conditions for consequent step. Whenever ideal case is considered, a target molecule is prepared from readily available starting raw materials. The desirable things for such type of preparations are simplicity, safety, eco-friendly conditions, time economy and considerable yields.

Any chemical entity providing support or serving as an aid in organic synthesis can be viewed as a ‘novel chemical species’. The useful chemical moiety should display several featuresand it should be readily introduced at the beginning of primary steps, and it is remain stable during various synthetic operations and preferably, exert an activating influence on biotic systems. One of the novel chemical species contributing to most of the above characteristics is dihydropyrimidinone.

In 1893, the Italian chemist Pietro Biginelli for the first time reported an acid catalyzed cyclo condensation reaction of ethylacetoacetate, benzaldehyde and urea. Since that time, dihyrdopyrimidinones (DHPMs) have proven to a highly valuable synthetic community.

Diversely functionalized 3,4–dihydropyrimidin-2-(1H)-ones (DHPMs) synthesized by way of the one-pot Biginelli three component condensation have attracted considerable interest in industry as well as in academia because of their wide scope of promising pharmacological activities, such as calcium channel blockers, antihypertensive, antifungal, antiviral, antibacterial, anti-inflammatory, analgesic and anticancer drugs. Hence, they are classified as one of the most important groups of drug like scaffolds.

The recent emphasis in this perspective has been given to the identification of the structurally simple DHPM derivative viz., Monastrol as a mitotic Kinesin Eg 5 motor protein inhibitor for the development of anticancer drugs. The great potential of DHPMs in biological and pharmaceutical fields has accordingly triggered growing interest in their synthetic study. The synthesis of natural molecules, pharmaceuticals and other nitrogenous biologically active compound has long been the significant branch of organic synthesis.

As there is a growing demand for the development of organic reactions in presence of benign media providing high yield of novel products; synthetic manipulations have to be made to develop combinatorial chemistry. Therefore the present invention provides for benign synthesis of N-Mannich bases of 3, 4-dihydropyrimidin-2(1H)-ones by using Fe3O4@SiO2@Et-PhSO3H as magnetically recyclable nanocatalyst.

The present disclosure addresses problems associated with existing benign synthesis of N-Mannich bases of 3, 4-dihydropyrimidin-2(1H)-ones methods, including those mentioned above, and provides a level of transparency and economic advantage. For this reason, it is believed to constitute progress in science and the useful acts, for which Patent are hereby expressly requested.

Objective of the invention

The primary object of the present invention is to Synthesis of N-Mannich Bases of 3,4 Dihydropyrimidin-2(1H)-ones by using Fe3O4@SiO2@Et-PhSO3H as magnetically retrievable nanocatalysts.

Summary of the invention:

Accordingly following invention Synthesis of N-Mannich Bases of 3,4 Dihydropyrimidin-2(1H)-ones by using Fe3O4@SiO2@Et-PhSO3H as magnetically retrievable nanocatalysts.

Detailed description of invention:

The following description includes the preferred best mode of one embodiment of the present invention. It will be clear from this description of the invention that the invention is not limited to these illustrated embodiments but that the invention also includes a variety of modifications and embodiments thereto. Therefore, the present description should be seen as illustrative and not limiting. While the invention is susceptible to various modifications and alternative constructions, it should be understood, that there is no intention to limit the invention to the specific form disclosed, but, on the contrary, the invention is to cover all modifications, alternative constructions, and equivalents falling within the spirit and scope of the invention as defined in the claims.

In any embodiment described herein, the open-ended terms "comprising," "comprises,” and the like (which are synonymous with "including," "having” and "characterized by") may be replaced by the respective partially closed phrases "consisting essentially of," consists essentially of," and the like or the respective closed phrases "consisting of," "consists of, the like.

Accordingly following invention relates to method for the synthesis of N-Mannich bases of 3,4 dihydropyrimidin-2(1H)-ones by using magnetically retrievable nanocatalysts Fe3O4@SiO2@Et-PhSO3H. The synthetic modifications in which highly functionalized organic molecules can be produced from easily available substrates via atom efficient reactions are of great importance for organic chemists. The expeditious domino and multicomponent reactions (MCRs) are examples of such types of organic transformations. A special class of tandem sequential reactions represents the MCRs. MCRs are defined as one-pot reactions in which more than two components are combine to form a new product, incorporating essentially most of moieties from all components. The present invention provides for the industrially feasible process for the preparation of N-Mannich bases of 3, 4-ddihydropyrimidin-2(1H)-ones. Process for preparation of 3, 4- dihydropyrimidin-2(1H)-ones is done by using Biginelli protocol. One embodiment of the invention comprises reacting compound of formula (2) with formaldehyde and secondary amine in presence of synthesized core-shell catalyst Fe3O4@SiO2@Et-PhSO3H.

The preparation of N-Mannich Bases of 3, 4- dihydropyrimidin-2(1H)-ones comprises following four steps-

Step I: Preparation of Fe3O4@SiO2
This procedure involved a synthetic strategy based on the hydrolysis and condensation of tetraethoxysilane on the surface of Fe3O4 magnetic NPs. In a typical preparation procedure, ferric chloride hexahydrate FeCl3.6H2O (11.0 g, 40.7 mmol) and ferrous chloride tetrahydrate FeCl2.4H2O (4.0 g, 20.1 mmol) are dissolved in deionized water (250 mL) under nitrogen atmosphere with mechanical stirrer at 90 °C. The pH value of the solution is adjusted to 9-11 using aqueous NH3 (30 %). After continuous stirring for 4 h, the magnetite precipitates are washed with distilled water until the neutral pH value is obtained. The black precipitate (Fe3O4) is collected with a permanent magnet at the bottom of the reaction flask. The silica coated core–shell magnetic NPs (Fe3O4/SiO2 MNPs) is prepared by an ultrasonic pre-mixing of a dispersion of the above black precipitate (2.0 g) with ethanol (400 mL) for approximately 25 min at room temperature. Then, aqueous NH3 (30 %, 12 mL) and TEOS (4.0 mL) were slowly added successively. The resulting solution is mechanically stirred continuously for 20 h. further the obtained black precipitate product (Fe3O4@SiO2) is collected by magnetic separation and washed with ethanol (3 × 15 mL) and dried under vacuum overnight at room temperature.

Step II: Preparation of Fe3O4@SiO2@Et-PhSO3H
The surface functionalization of the silica-coated magnetic NPs with sulfonyl groups is carried out by adding 2-(4-chlorosulfonylphenyl) ethyltrimethoxysilane to dry toluene (50 mL) containing silica-coated magnetic nanoparticles (3.0 g). The resulting mixture is stirred for 24 h and then washed with toluene (2 × 15 mL) and distilled water. Finally the solid is suspended in H2SO4 (2.5 M) solution for 2.5 h, washed several times with water and dried at room temperature under vacuum overnight to give the corresponding Fe3O4@SiO2@Et-PhSO3H.

Step III: Preparation of Dihydropyrimidinones (Biginelli Protocol)
A mixture of aldehyde (2 mmol), urea/thiourea (2.4 mmol) and catalyst (10 weight % with respect to aldehyde) (in the case of thiourea, 15 weight % of the catalyst is used) is stirred at 100-200 °C for an appropriate time under solvent-free condition. The progress of the reaction is monitored by TLC. After completion of the reaction, the mixture is washed with water. Finally, the mixture is dissolved in hot EtOH and the catalyst is separated by magnetic decantation. The crude product is either recrystallized from EtOH or subjected to preparative thin layer chromatography (silica gel) for further purification.

Step IV: Procedure for the preparation of N-Mannich bases
To a solution of DHPM (0.5 mol) in DMF, formaldehyde (0.10 mol) is added under stirring in presence of catalyst (30 weight % with respect to DHPM). The reaction mixture will be stirred at room temperature for certain time to complete the reaction of formaldehyde and to obtain methylol derivative of DHPM. To this reaction mixture, secondary amines (0.4 mol) in DMF is added drop wise and would be refluxed for certain time. The reaction mixture is poured into cold water. Finally, it is dried and purified by recrystallization from chloroform to give N-Mannich base.

We Claim:

1. A process for synthesis of N-Mannich bases of 3,4 dihydropyrimidin-2(1H)-ones by using magnetically retrievable nanocatalysts Fe3O4@SiO2@Et-PhSO3H means N-Mannich bases of 3, 4-ddihydropyrimidin-2(1H)-ones wherein the process for preparation of 3, 4- dihydropyrimidin-2(1H)-ones is done by using Biginelli protocol.