Synthesis of derivatives of 2-3-indolyl)(phenylmethyl)indandiones

Dissertation for M.Sc.

Field: Chemistry Major: Organic

Abstract

1,3-indandione and its derivatives are of great interest due to their importance in organic chemistry. Many products, which are a sub-branch of 3,1-indandione, show useful and diverse biological activities such as antibacterial properties, blood anticoagulant, mouse death, painkiller, pesticide and anti-infection. A very valuable method for the synthesis of 3,1-indanediones is the Novenagel condensation of benzaldehydes with an active alpha carbon compound.

In this research, the experimental results of the synthesis of indolyl methanes, using the reaction between aldehydes, 3,1-indanedione and indole, are reported.

Use and importance of indanedione

Indonedione is an important compound and has many chemical and biological properties and applications. In addition to anticoagulant effects[1], these compounds have strong metabolic activity[2], anti-parasitic effects[3], mouse death[4], analgesic[5], antibacterial[6] and anti-pulmonary inflammation [1-6][.

Indandione derivatives have many therapeutic properties. Some of them can also be used as useful materials in the field of optics. In addition, 1,3-indandiones are used in the first stage of identification in forensic medicine and are also widely used in the paper industry.

Some of the medicinal properties of indanedione derivatives have been tested on laboratory animals, and its antitussive effect in mice can be mentioned. Unfortunately, many of these molecules have damaging effects. This fact has a negative effect on the medicinal use of indonediones derivatives.

2,1- Indonediones are used for fluorescent fingerprinting of cellulosic materials such as paper. These substances react with amino acids to highlight the fluorescent fingerprint.

A group of these drugs called anticoagulants can be used to treat thrombosis and muscle cramps. Some anticoagulant drugs are used in medical equipment such as test tubes, blood transfusion bags and kidney dialysis equipment.

For example, anisidion [7] (1) acts as a blood thinner and prevents the formation of blood clots.

Also, phenindione [8] (2), as a blood anticoagulant whose activity is anti-vitamin K, is one of the derivatives of other indonediones

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Compound (3) Chlorophacinone[9] is also an anticoagulant that is used as a mouse killer (Figure 1-2).

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Fredricamycin[10](4) is known as an antitumor compound with antibacterial properties (Figure 1-3)]7[.

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Biphenyl-spirocyclic ketones[11] (5) are widely used as anticancer[12] (Figure 1-4) [8[.

Spiroheterocyclic dihydropyrrolo]2,1-[aisoquinolines have potential pharmacological effects including sedation (analgesia), lowering blood pressure and stopping muscle nerve activity (Figure 5-1)]9[.

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1-2- Multicomponent reactions[13]

The use of multicomponent reactions (MCR) has gained increasing importance in the synthesis of organic compounds because the multicomponent strategy has many advantages over linear reactions.For this reason, this method is widely used in synthetic chemistry and medicinal chemistry. Usually, the MCR strategy has advantages such as less time, higher reaction efficiency, preventing unwanted condensation of several molecules, creating an active intermediate. This method has significant advantages such as flexibility and the possibility of forming an effective bond. Easing the purification process, saving solvent, materials, reagents, convergence characteristics, simplicity of implementation, structural diversity and abundance of products are other advantages of this method. MCR was used for the first time in 1850 as Strecker synthesis to make ?-amino acids [10-16].

This method was successfully used in Hantsch's synthesis of 4,1-dihydropyridines in 1882 [17], Bigenelli's synthesis of 4,3-dihydropyrimidine-2-ones in 1891. [18], Mannich's synthesis of ?-aminocarbonyl compounds in 1912 [19], Robinson's synthesis of alkaloid terpinones in 1917 [20], Passerini's synthesis of ?-acyloxycarboxamide in 1921 [21], Bucherer-Berges synthesis of hydantoins in 1934 [22] and It was used.

1-3- Preparation and synthesis of indonediones and its derivatives

1-3-1- Natural preparation

Anticoagulants are naturally present in the body of leeches and insects such as mosquitoes that feed on the blood of other creatures. Researchers have experienced the therapeutic effects of leech through repeated experiments. There is a chapter about leeches and the symptoms of poisonous leeches and useful leeches in Bu Ali Sina's law. Professor Meyer[14], Smith[15] and Horner[16] believe that by putting two leeches behind the ears, incurable brain diseases, cerebral vascular occlusion, Alzheimer's and epilepsy can be treated.

The anti-coagulant substance present in the leech's saliva called "Hirudin" [17] causes the blood to be diluted, the closed vessels open, thereby increasing blood supply and local oxygenation (Figure 6-1).

Figure 1-6- The structure of Hirudin

1-3-2- Laboratory synthesis methods

1-3-2-1- Preparation of 3,1-indanediones through decarboxylation of 2-ethoxycarbonyl sodium salt

Indanedione can be produced by decarboxylation of sodium salt of 2-ethoxycarbonyl-1,3-indanedione, which itself is obtained by condensation of Claisen ethyl acetate and dimethyl phthalate. (Scheme 1-1)]9[.

Scheme 1-1: Preparation of 1,3-indanediones through decarboxylation of sodium 2-ethoxycarbonyl salt

1-3-2-2-Synthesis of 1,3-indanedione derivatives

In 2009, Anife Ahmadova[18] and her colleagues presented a method for the synthesis of new 1,3-indanediones derivatives through the condensation between 2AID and p-(N,N-dimethylamino)benzaldehyde in pypyridine (Scheme 1-2)]23[.

2AID = 2-(1-Hydroxy-ethylid ene)-indan-1,3-dione.

1-3-2-3- Synthesis of stable organophosphine/phosphite silver complexes with 2-acetyl-1,3-indandione ligand with crystal structure [Ph3P.AgC11H7O3]

In 2010, Ning Wang[19] and his co-workers synthesized a series of new stable silver phosphine/phosphate complexes with 2-acetyl-1,3-indandione ligand with crystal structure [Ph3P.AgC11H7O3].

The above complexes using Ph3P/(MeO)3 reaction P/(EtO)3P with C11H7O3] - [Ag in dichloromethane at 0°C have been synthesized with high efficiency (Scheme A-3) [24]. Indane dione with crystal structure [Ph3P.