Word Files
Reference for Downloading Educational Files
  2. Chemical - Petrochemical Engineering
  3. Studying the reactions of 4, 5, 5-trimethyl-4, 5-dihydropyrrolo]1, 2, 3 [hi-indole-1 and 2-dione with aromatic amine derivatives and ketones

Studying the reactions of 4, 5, 5-trimethyl-4, 5-dihydropyrrolo]1, 2, 3 [hi-indole-1 and 2-dione with aromatic amine derivatives and ketones

Number of pages: 103 File Format: word File Code: 31876
Year: 2014 University Degree: Master's degree Category: Chemical - Petrochemical Engineering
Tags/Keywords: Aromatic amines - Arylamine - Dion - Hydrazine - Spiro compounds - Synthesis of indoline
  • Part of the Content
  • Contents & Resources

  • Summary of Studying the reactions of 4, 5, 5-trimethyl-4, 5-dihydropyrrolo]1, 2, 3 [hi-indole-1 and 2-dione with aromatic amine derivatives and ketones

    Dissertation for Master's Degree in Organic Chemistry

    Abstract The research conducted in this thesis consists of two parts, the first part includes the one-pot synthesis of new spiro compounds using 4,5,5-trimethyl 4,5-dihydropyrrolo{1,2,3-hi}indole. 1 and 2-dione are reported with aromatic amines of vectors.         

    The second part includes the synthesis of new derivatives of spiro compounds using 5,6-dihydro1H pyrrolo{3,2,1-ij}quinoline 1,2(4H)dione, acetophenone and hydrazine hydrate in the presence of Et3N catalyst in ethanol solvent.

    Structure of new synthesized compounds with spectral data 1HNMR, 13CNMR and IR have been identified.

    Key words: dione, 3-partial spiro compounds, arylamine, hydrazine,.

    Introduction

    1-1) Synthesis methods of indolines

    Indolins are important compounds in pharmacology that are biologically active and effective on the central nervous system. Considering the similarity and proximity of indolins to indoles and the wide role of indoles in pharmaceuticals, it seems that there is a clear horizon for indolins from the field of pharmaceuticals. Also, the indoline ring is of great value to chemists because it is a good key for the synthesis of various organic substances.

    General theory of Fischer's mechanism

    The cyclization of arylhydrazones to indole derivatives in the presence of acid was discovered by Fischer [1] in 1883, which today is the general method of synthesis It is mostly indoles and indolines, which is one of the most diverse and broad reactions in organic chemistry. Along with the many synthetic applications of this reaction, finding its mechanism is of great interest, until the general accepted mechanism for Fischer indole synthesis was proposed by Robinson [2], [3] and completed by Allen and Wilson [4], Karlin and Fischer [5], Arbozo and Kitaif [6] and Savaro [7]. It seems that the details of the reaction depend on the reaction conditions and the nature of the hydrazone, so it is doubtful that a definitive mechanism applies to the entire reaction. In fact, several studies have been conducted and it has been confirmed that the mechanism changes in different conditions. For example, in many indolization reactions, it is felt that N-hydrazine formation or [3,3] rearrangement is rate-determining. However, Douglas observed the formation of an imine intermediate by N15 and C13 after [3,3] rearrangement in a specific type that replaced the nitrogen of an acyl group. Since the amide formed after the rearrangement is a weak nucleophile, the closing of the five-membered ring will be rate-determining.

    According to Robinson's mechanism, the reaction proceeds through the following main steps (Scheme 1-1). rtl;">2-Formation of carbon-carbon bond (III?II)

    3-Cyclization with removal of ammonia and formation of indole structure

     

     

    (Formulas are available in the main file)

    Synthesindoline and its derivatives, the most important step of this reaction is the formation of the carbon-carbon bond (II) ? (III), which is caused by the intramolecular electrophilic attack of the enamine component [8-11] Further studies have shown that in Fischer synthesis, if strong acids such as HCl, H2SO4 and PPA (polyphosphoric acid) are used [12], a mixture of indole (2) and indoline (3) is obtained, which Indole is the preferred product, and if weak acids such as acetic acid are used, only indoline will be the reaction product. (Scheme 1-2)

     

     

    (Formulas are available in the main file)

     

    Two theories have been presented to change the selection region.Lyle Vascarlos have proposed that the steric interaction in the transition state (TS) controls the regioselectivity of the reaction. With small catalysts such as protons, steric interactions at least at TS lead to cyclization from N-hydrazine with less hindrance. With larger catalysts such as Lewis acid, steric hindrance prevents cyclization from N-hydrazine with lower hindrance. Therefore, cyclization occurs from branched N-hydrazine to provide thermodynamic stability. This proposal cannot explain the differences in the selective region observed when the acid concentration is different [13].

    Another proposal was made by Palmer and McIntyre. In this theory, it was suggested that monoprotonation (protonation of imine hydrogen) occurs in dilute acid and diprotonation (protonation on two nitrogens) occurs in strong acids. According to this theory, the formation of N-hydrazine is the rate-determining step in weak acid. This problem leads to the formation of a TS similar to the reaction product E1, which will form the N-hydrazine product with a double bond with high substitution. On the other hand, diprotonation in high acidity solutions will lead to the formation of hydrazine which is more similar to the E2 reaction product, and therefore N-hydrazine with a double bond with less substitution is formed]14, [15] style="direction: rtl;"> 

    (Formulas are available in the main file)

    In the presence of EtOH-HCl and at a temperature of 110 °C, the following indoline is synthesized with an efficiency of 26% [16] (Scheme 1-4).

    (Formulas are available in the main file )

    Next studies showed that using acetic acid as a weak and bulky acid works well for a higher percentage of indoline (3) (Scheme 1-5).

    Scheme 1-5

    1-2) Indoline synthesis methods 1-2-1) Efficient synthesis of indoline compounds from picolinamide (PA)-?-arylethylamine using palladium catalyst through intramolecular amination of C(SP2)-H bonds with high yield, minimal use of catalyst, mild reaction conditions and using cheap reagent]17[(Shemai 1-6)

    (Formulas available in the main file)

    1-2-2) Hydrogenation of indole derivatives with Hanes dihydropyridine (diethyl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) as a hydrogen source and a Br?nsted acid as a catalyst is an effective way to synthesize optically active indolines [18] (Shemai 1-7).

    (formulas are available in the main file)

     

    1-2-3) Intramolecular amination of arenes with palladium catalyst using Ce(SO4)2 and also one or N-fluoro-2,4,6-trimethylpyridinium triflate as a two-electron oxidant can also be used in the synthesis of derivatives Indolines and indoles are useful]19[(Shemai 1-8)

    Abstract

    The new work described in this thesis involves two parts.

    The first part discusses one-pot sequential reaction of dione, arylamine and acetone, and as efficient procedure. for the synthesis of new spiro derivatives. identified by 1H-NMR, 13C-NMR and FT-IR spectral data.

    Keywords:

    Dione, Spiro Three Compounds, Arylanims, Hydrazine.

  • Contents & References of Studying the reactions of 4, 5, 5-trimethyl-4, 5-dihydropyrrolo]1, 2, 3 [hi-indole-1 and 2-dione with aromatic amine derivatives and ketones

    List:

    Abstract..1

    Chapter One: Generalities. 2

    1) Introduction. 2

    1-1) Synthesis methods of indolines. 2

    1-1-1) General theory of Fisher mechanism. 2

    1-2) Synthesis of indolines 6

    1-2-1) Synthesis of indolines with picolinamide (PA)-?-arylethylamine using palladium catalyst. 6

    1-2-2) Synthesis of indolines Hanz dihydropyridine (diethyl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) 6

    1-2-3) Synthesis of indolines with N-fluoro-2,4,6-trimethylpyridinium triflate. 6

    1-3) Synthesis of quinolines 7

    1-4) Introduction of pyrazoles. 8

    1-4-1) General method of synthesis of pyrazoles 9

    1-4-1-1) Use of 1-3 diketones and hydrazine derivatives 9

    1-4-1-2) Use of 1-3 dipoles and derivatives Hydrazine 10

             1-4-1-3) Use of mononitrile and hydrazine. 11

    1-5) Multicomponent reactions 12

    1-6) One-pot reactions. spiro..14

    1-8) spiro-oxo-indole ring system. 15

    1-9) Synthesis of spiro-oxo-indole compounds from isatin. 16

    1-10) Synthesis of spiro compounds from starting materials other than isatin. 22

    1-11) Synthesis of di-spiro compounds from isatin. 23

    1-12) Synthesis of three spiro compounds from isatin. 25

    1-13) Objective of research work..26

    Chapter Two: Experimental part..27

    2) Experimental part. 28

    2-1) Experimental methods. 28

    2-2) Synthetic methods used: 28

    2-2-1) Synthesis of 4,5,5-trimethyl-4,5-dihydropyrrolo]3,2,1-[hiindole-1,2-dione. 28

    2-2-1-1) Synthesis of 2,3,3-trimethyl-3H-indole: 29

    2-2-1-2) Synthesis of 2,3,3-trimethylindoline: 29

    2-2-1-3) Synthesis of 2-(2,3,3-trimethylindolin-1-yl)-2-oxoacetyl Chloride: 30

    2-2-1-4) synthesis of 4,5,5-trimethyl-4,5-dihydropyrrolo]3,2,1[hi-indole-1,2-dione. 30

    2-3) synthetic methods used for tetrahydroquinoline. 31

              2-3-1) Synthesis of 5,6-dihydro H1-pyrrolo]3, 2, 1-ij [quinoline-1,2(H4)-dione.31

              2-3-1-1) Synthesis of 2-(3,4-dihydroquinolin-1(H2)-yl)-2-oxoacetylchloride. 31

           2-3-1-2) Synthesis of 5 and 6-dihydro H1-pyrrolo]3, 2, 1-[ijquinoline-1 and 2(H4)-dione. 32

    2-4) General method of synthesis of spiro compounds. 33

    2-4-1) Spectral characteristics of spiro compounds. 34

    2-5) Synthesis method of spiro compounds including ring Pyrazoly. 35

    2-5-1) Spectral characteristics of spiro compounds including pyrazoly ring. 38

    Chapter 3: Results and discussion. Synthesis of 4,5,5-trimethyl-4,5-dihydropyrrolo[3,2,1-hi]indole-1,2-dione.43

    3-1-2-1) Synthesis of 2,3,3-trimethyl-3H-indole.43

    3-1-2-2) Synthesis of 2,3,3-trimethylindoline.44

    3-1-2-3) Synthesis of 2-(2,3,3-trimethylindolin-1-yl)-2-oxoacetyl chloride. 45

    3-1-2-4) Synthesis of 4,5,5-trimethyl-4,5-dihydropyrrolo[3,2,1-hi]indole-1,2-dione.45

    3-1-3) General method Synthesis of spiro compounds.45

    3-1-4) General mechanism of synthesis of spiro compounds.45

    3-1-5) Identification of spiro compounds..47

    3-1-5-1) ',5',4'-trimethyl-1-phenyl 5-(5,5,4-trimethyl-2-oxo-1,2,4,5-tetrahydro) Pyrrolo1,2,4,5-tetrahydropyrrolo]3,2,1-[hi dihydro4',5'indole-1yl-'H 2spiro]pyrrolidine-2,'1-pyrrolo]3,2,1-[hi indole-'2,3-dione..47

    3-1-5-2) 5',5',4'-trimethyl 1-(para-toluidine) 5-(5,5,4-trimethyl-2-oxo-1,2,4,5-tetrahydropyrrolo1,2,4,5-tetrahydropyrrolo]3,2,1-[hi dihydro4',5'indol-1yl-'H 2spiro]pyrrolidine-2,'1-pyrrolo]3,2,1-[hi indole-'2,3-dione..48

    3-1-5-3) 5',5',4'-trimethyl-(4-methoxyphenyl) 5-(5,5,4-trimethyl-2-oxo-1,2,4,5-tetrahydropyrrolo1,2,4,5-tetrahydropyrrolo]3,2,1-[hi dihydro4',5'indole-1yl-'H2spiro]pyrrolidine-2,'1- Pyrrolo]3,2,1-[hi indole-'2,3-dione..49

    3-1-5-4)',5',4'-trimethyl-(4-chlorophenyl) 5-(5,5,4-trimethyl-2-oxo-1,2,4,5-tetrahydropyrrolo1,2,4,5-tetrahydropyrrolo]3,2,1-[hi dione Hydro4',5'indole-1yl-'H 2spiro]pyrrolidine-2,'1-pyrrolo]3,2,1-[hi indole-'2,3-49

    3-2) Synthesis of spiro compounds including pyrazole ring.50

    3-2-1) General.50

    3-2-2) Synthesis of 5-6-dihydro H1-pyrrolo]3, 2, 1-ij [quinoline-1-2(H4)-dione.50

    3-2-2-1) Synthesis of 2-(3,4-dihydroquinolin-1(H2)-yl)-2-oxoacetyl chloride.50

    3-2-2-2) Synthesis of 5,6-dihydro H1-pyrrolo]3, 2,1-[ijquinoline-1,2(H4)-dione.51

    3-2-3) General method of synthesis of spiroquinolinic compounds.51

    3-2-4) general mechanism of synthesis of spiro compounds.52

    3-2-5) identification of spiro compounds.

    3-2-5-1) 5-phenyl-2,4,5',6'-tetrahydro 'H2,'H4-spiropyrazole-1,3'-pyrrolo]1,2,3-[ij quinoline-2'-one.53

    3-2-5-2) 5-(4-nitrophenyl)-2,4,5',6'-tetrahydro 'H2,'H4-spiropyrazole-1,3'-pyrrolo]1,2,3-[ij quinoline-2'-one.55

    3-2-5-3)5-(3-nitrophenyl)- 2,4,5',6'-tetrahydro 'H2,'H4-spiropyrazole-1,3'-pyrrolo]1,2,3-[ij quinoline-2'-one.56

    3-2-5-4)5-(4-bromophenyl)-2,4,5',6'-tetrahydro 'H2,'H4-spiropyrazole-1,3'-pyrrolo]1,2,3-[ij quinoline-2'-one.57

    3-2-5-5)5-(4-fluorophenyl)-2,4,5',6'-tetrahydro 'H2,'H4-spiropyrazol-1,3'-pyrrolo]1,2,3-[ij quinoline-2'-one.59

    3-2-5-6)5-(4-chlorophenyl)- 2,4,5',6'-tetrahydro 'H2,'H4-spiropyrazole-1,3'-pyrrolo]1,2,3-[ij quinoline-2'-one.60

    3-2-5-7) 5-(3-methoxyphenyl)- 2,4,5',6'-tetrahydro 'H2,'H4-spiropyrazole -1,3'-pyrrolo]1,2,3-[ij quinoline-2'-one. 61

    Chapter four: Appendices and spectra. 63

    4) Appendices and spectra 64

    Sources and sources. 90

    Absterct 95

    Source:

     

    [1]. Fischer, E ; Jourdan, F.Ber ; 1883, 16, 2241.

    [2]. Robinson, G.M.; Robinson, R. J.Chem.Soc; 1924,125,826.

    [3]. Robinson, G. M.; Robinson, R. J. Chem. Society; 1918, 113,639.

    [4]. Allen, G. F. H.; Wilson, C.V. J. Am. Chem. Soc; 1943, 65, 611. [5]. Carlin, R. B; Fischer, E. E. J. Am Chem. Society; 1948, 7, 3421. [6]. Arbuzou, A. E  Kitaev, Yu. P; Zhur.Obshch. khim 1948, 27, 2328. [7]. Suvorov, N.N.; Sorokina, N. P; Sheinker, Y.N.; Zhur. Obshch. Khim; 1958, 28, 1058. [8]. Robinson, B.; Chem, Rev; 1963, 63, 373. [9]. Robinson, B.; Chem, Rev; 1969, 69, 227. [10]. Przhevalskii, N. W; Ph.D Thesis, Timiryazev agriculture academy, Moscow; 1969.

    [11]. Sundberg, R.I.; Organic Chemistry, The Chemistry of Indoles, Academic Press, 1970, 18, 143.

    [12]. Sorokin, V.I.; Ph.D Thesis, Timiryazev Agricultural Academy, Moscow, 1973. [13]. Grandberg, I. I; Belyaeva, L. D.; Dmitriev, L.B. Khim. Geterotskl. Soedin, 1973, 1, 37. [14]. Hugo, I; Lance, F. J. Org. Chem, 1968, 33, 4283. [15]. Franz, R.; Bernd, R., Dietmar, T; Christian, G; Ger. Offer; 1969, 1, 906, 832. [16]. Skrabal, P; Steiger, J; Zollinger, H. Helv. Chem.Acata, 1975, 58, 92.

    [17]. He, G; Lu, C; Zhao, Y; Nack, W. A., Chen, G; Org. Lett; 2012, 14, 2936. [18]. Rueping, M; Brinkmann, C; Antonchick, A. P; Atoresei, I; Org. Lett; 2010, 12, 4604. [19].  Mei, T-S; Wang, X; Yu, J-Q; J. Am. Chem. Society; 2009, 131, 10806. [20]. Schreiber, S. L;  Liu, J;  Albers, M. W.;  Karmacharya, R;  Koh et al., E. Transpl. Proc; 1991, 23, 2839. [21]. Joule, J.A.; Mills, k; Heterocyclic Chemistry, John Wiley Sons., 2013.

    [22].  Moreno-Mafias, M., Sebastion, R.M., Vallribera, A., Piniella, J.F; Alvarez-Larena, A,. Jimeno, M.L.; Elguero, J; New J. Chem, 1889, 25(2), 329.

    [23]. Chauhana, A; Sharma, P; Kushik, N., Kamar, N; Int, J. Pharm Sci; 2011, 3(5), 166.

    [24]. Sehnal, P; Stara, I.G.; Saman, D; Tichy, M; Misek, J; Cvacka, J; Rulisk, L; Chocholousva, J; Vacck, J; Goryl, G, An organometallic route to long hclicenes. Proc. Natl. Acad.Sci U S A. 2009.

    [25]. Ohsumi, K; Umemura, T; Matsueda, H., Hantaka, T; Onuki, A; Maezono, K., Kageyama, Y; Kondo, N; Pyrazole derivatives and diabetic medicine containing them Google Patents; 2004.

    [26]. Kumar, S; Bawa, S;  Drabu, S.

Studying the reactions of 4, 5, 5-trimethyl-4, 5-dihydropyrrolo]1, 2, 3 [hi-indole-1 and 2-dione with aromatic amine derivatives and ketones
How To Access The File
Related Contents:
Number of pages: 80 Category: Chemical - Petrochemical Engineering

Dissertation for Master's Degree in Organic Chemistry. Summary of the research done in this thesis consists of two parts, the first part is the synthesis of the precursor of 4,5-dihydropyrrolo[1,2,3-hi]indole-1,2-dione (compound 1) and one-pot, three-component synthesis of new derivatives of spiro terecates in water-green solvent and in the presence of HMTA catalyst. The second ...

Number of pages: 85 Category: Chemical - Petrochemical Engineering

Dissertation for Master's Degree (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 ...

Number of pages: 91 Category: Chemical - Petrochemical Engineering

Dissertation for Master's Degree in Organic Chemistry Abstract: The new works carried out in this thesis include the condensation reaction of arylglyoxals prepared during the oxidation of acetophenones related to selenium dioxide with 1,2-diaminobenzene, 2,3-diaminomalonitrile, 2,3-diaminopyridine and 4-nitro-1,2-diaminobenzene in order to prepare quinoxalines and the ...

Number of pages: 65 Category: Industrial Engineering

Thesis for the M.Sc degree in wood and paper industry engineering, Mehr 2013 Abstract: In this research, the physical and mechanical properties of nanocomposites obtained from cellulose nanofibers and poly polymers

Number of pages: 71 Category: Chemical - Petrochemical Engineering

Thesis for obtaining a master's degree in organic chemistry. Abstract: Title: Effective three-component synthesis of new 4-aryl-5-(tert-butylamino)-2-(1-methyl-1H-pyrrol-2-yl)furan-3-carbonitrile derivatives. In this research, a direct and efficient method for preparing new 4-aryl-5-aminofuran derivatives through a three-component one-pot reaction ...

Number of pages: 74 Category: Paramedical

Persian summary: Coumarin derivatives are of great interest due to their biological importance and medicinal activities. A number of coumarin derivatives, especially biscoumarins, are known to be anti-inflammatory due to their numerous and prominent features such as anti-blood clots. In this regard, one-pot synthesis of biscoumarin derivatives using aromatic aldehydes, ...

Number of pages: 109 Category: Chemical - Petrochemical Engineering

Master's Thesis, Department of Chemistry, Organic Chemistry, Abstract An effective method for the synthesis of pyrido[3,2-d]pyrimidine derivatives from the three-component condensation of 6-aminouracil, 6-amino2-thiouracil or 6-amino-1,3-dimethyluracil with aryl aldehydes and malononitrile, a class of pyrido[3,2-d]pyrimidine derivatives in the presence of high performance basic ...

Number of pages: 118 Category: Chemical - Petrochemical Engineering

Doctoral thesis in the field of chemical engineering. Abstract The study of the effective parameters in the synthesis of silver nanoparticles by the inverse microemulsion method of metallic silver nanoparticles is of interest due to their use as catalysts, antimicrobial agents and biosensors. The practical use of silver nanoparticles is highly dependent on the size distribution ...

Number of pages: 93 Category: Chemical - Petrochemical Engineering

Dissertation for Master's degree (M.Sc.) Title abstract: One-step synthesis of new thiazole and bisthiazole derivatives with various connections. In this research, the synthesis of new thiazole derivatives and bisthiazoles with different connections was investigated by click chemistry and green chemistry methods. First, the synthesis of bisacetophenones (b3-a3) through

Number of pages: 103 Category: Chemical - Petrochemical Engineering

Chemistry - trend of organic chemistry Abstract Coumarin or (2-H-chromen-2-one) and their derivatives are compounds that are naturally present in many plants, including tonka beans. And they are an important class of the family of benzopyrone compounds. Coumarin and its derivatives are considered essential elements in many bioactive compounds such as anticoagulant, anti-HIV, ...