ES2606724B1 - Synthesis of quinolines using carbon aerogels based catalysts - Google Patents

Abstract

The present invention describes the synthesis and characterization of acidic carbon aerogels doped with Co (0), as an excellent catalyst for the preparation of quinolines by condensation of Friedländer between 2-aminoarylaldehydes and other carbonyl compounds. The catalytic activity that some of these aerogels have in this transformation is greater than that observed for other heterogeneous catalysts previously described; the corresponding quinolines were synthesized with excellent yields during shorter reaction times and considerably minimizing the amount of catalyst used in the process. The procedure described can be carried out in the absence of solvent, minimizing the isolation and purification steps of the quinolines obtained.

Description

DESCRIPTION

SYNTHESIS OF QUINOLINAS USING CARBON AIRCRAFT BASED CATALYSTS

 5

SECTOR OF THE TECHNIQUE

The present invention belongs to the chemical industry sector, which also includes both the pharmacy and its industry - drug synthesis - as well as chemical engineering or process engineering, the latter as the industrial application of chemistry. In particular, a quinoline synthesis procedure is described. 10

STATE OF THE TECHNIQUE

Problems in the synthesis of organic compounds

The main residues generated in the synthesis of organic compounds are inorganic salts, as a direct consequence of the use of stoichiometric amounts of inorganic reagents. To solve this problem it is necessary to replace the methodologies that use large quantities of this type of reagents with other alternatives, such as catalysis.

Thus, catalysis plays a fundamental role in the development of new processes 20 compatible with the environment. The use of catalysts, in particular heterogeneous catalysts, in chemical processes of interest not only reduces the environmental impact, from both an energy and waste generation point of view, but also considerably reduces the cost of processes by simplifying the stages to the maximum of isolation and purification of the 25 reaction products, a fundamental aspect for the industry.

Heterogeneous catalysts

A catalyst is a substance that, added in quantities much lower than the stoichiometric, increases the speed of a certain process; The heterogeneous catalysts are those in which catalyst and reagents are in different phases. In general, a catalyst does not allow thermodynamically unfavorable reactions, does not modify the thermodynamic equilibrium and is not part of the reaction products.

  35

The use of heterogeneous catalysts in industrial processes, replacing homogeneous catalysts that act in solution, has the following advantages:

 ease of separating the catalyst from reagents and products; The catalyst is a solid that can be easily separated from reaction products and / or excess reagents, the latter generally in solution, by a single filtration step.

 greater robustness of the catalyst, withstanding higher temperature and pressure ranges.

 lower corrosive capacity; This allows a longer duration of equipment in the industry.

 lower toxicity. Most of the heterogeneous catalysts are non-volatile and harmless in contact with the skin, which allows to easily comply with the current regulations on safety of use.

 possibility of reusing the same catalyst, which means cost savings and, in many cases, operating time and waste minimization.

On the other hand, the activity of a catalyst must be adequate depending on the reaction to be catalyzed. A low activity would result in poor performance, which translates into low economic profitability or high production times. On the contrary, a very high activity generally causes unwanted reactions leading to contamination of the desired compound with reaction byproducts. twenty

Among the numerous synthesis procedures of this type of catalysts are the methods described in patents ES 2 366 848 and ES 2 369 269.

Quinolines 25

Quinolines are aromatic nitrogen heterocycles present in a large number of natural and synthetic products with interesting pharmacological and physical properties. The simplest quinoline structure, also known as quinoline, is represented by the formula Q1

 30

Naturally, quinoline is found in cocoa, black tea, whiskey and coal. It is a major constituent in cigarette smoke. It has also been found in several plants such as Peganum harmala and Rubus laciniata, as well as several species of the genus Mentha.

Like other organic compounds, their traditional synthesis procedures produce inorganic salts as residues, which are harmful to the environment.

 5

Quinolines have various fields of application among which are medicine, in the treatment of Alzheimer's and Malaria among other diseases, in the food and textile industry, in photography etc; they are also used in the preparation of materials useful in the manufacture of electronic devices and light emitting diodes (OLEDs). 10

There are many products that incorporate quinolines in their structure and that have biological activity; As examples we can mention Camptothecin, a natural product that has anti-cancer activity and quinolines with formula Q2, Q3 and Q4. [Muscia et al. (2006) TetrahedronLett. 47: 8811], all of them synthetic products with antiparasitic activity.

 twenty

Synthesis of quinolines by Friedländer condensation

Among the known procedures for the synthesis of quinolines can be mentioned:

 Synthesis of Combes

 Synthesis of Doebner

 Synthesis of Gould-Jacobs

 25

 Synthesis of Knorr

 Synthesis of Riehm

 Pfitzinger synthesis

 Synthesis of Conrad-Limpach

 Camps synthesis

 30

 Synthesis of Doebner-Miller

; Y

 Friedländer synthesis

The synthesis or condensation of Friedländer is one of the simplest and most effective methods for the synthesis of quinolines; It consists of the condensation of 2-aminoarylcarbonyl compounds, aldehydes or ketones, with carbonyl compounds with enolizable hydrogens, generally in an acid medium.

 5

However, to date, only a few examples of heterogeneous catalysts for the condensation of Friedländer have been described; Among them are Al2O3, H2SO4 / SiO2, NaHSO4 / SiO2, HClO4 / SiO2, phosphomolibed acid / SiO2, propylsulfonic acid / SiO2 and KAl (SO4) 2 • 12H2O / SiO2.

 10

Recently, the synthesis of quinolines / quinolin-2 (H) -ons by condensation of Friedländer, between 2-aminoaryl ketones and ethyl acetylacetate, has been described in a process promoted by acid and / or basic mesoporous aluminosilicates, (Al) SBA- 15, MCM-41 functionalized with amino groups, APS / SBA-15 simultaneously containing amino groups and sulfonic groups, [Cu3 (BTC) 2] (where BTC is benzenetricarboxylic acid 15) and microporous carbon materials [ES 2 395 109], [Domínguez-Fernández et al. (2009) ChemCatChem 1: 241], [López-Sanz et al. (2010) Top. Catal, 53: 1430], [J. López-Sanz et al. (2012) Catal. Today 187: 97], [Pérez-Mayoral and Cejka, (2011) ChemCatChem 3: 157], [E. Pérez-Mayoral et al. (2012) Dalton Trans 41: 4036], [J. López-Sanz et al. (2013) ChemCatChem 5: 3736]. twenty

While condensation catalyzed by acid silicates led to mixtures of the corresponding quinolines and quinolin-2 (H) -ones, in the presence of basic materials, mesoporous silicas functionalized with amino groups, a drastic change in reaction selectivity was observed giving place to the corresponding quinolones with quantitative yield and total selectivity. More recently, the first examples of bifunctional siliceous materials of the T-MCF type functionalized with amino groups (where T is Nb or Al) that efficiently catalyze Friedländer condensation between 2-amino-5-chlorobenzaldehyde and compounds 1,3 have been described -dicarbonyl; The study shows that the most active catalysts are those that contain heteroatoms in their structure. The experimental results obtained suggest that the first stage of the reaction is the condensation of Knoevenagel between the starting reagents. In addition, a computational study on the first stage of the reaction catalyzed by the different solids has been carried out. The theoretical study suggests that the efficacy of the catalysts used is due to cooperative effects between the heteroatoms present in the silica matrix and

the amino groups, both acting as activating agents of the starting reagents and thus decreasing the energy barrier [A. Smuszkiewicz et al (2013) Catal. Today 70: 218], [A. Smuszkiewiczet al. (2013) J. Mol. Catal. A: Chem. 378: 38]. Much more recently, we have conducted a study on the catalytic activity of basic carbon materials in the synthesis of quinolines [Godino et al. (2014) 5 ChemCatChem 6: 3440].

Carbon Materials

Carbon materials can be very diverse due to the wide variety of raw materials and the available synthesis methods. In this sense, 10-carbon gels (including aerogels, xerogels or criogles) are novel materials prepared by sol-gel synthesis methods under very strict controlled conditions that have demonstrated great applicability in adsorption and catalysis processes since both their properties Textural, porosity and surface chemistry can be optimized to suit a specific use. However, 15-carbon aerogels have never been used in the development of heterogeneous catalysts for the synthesis of quinolines.

OBJECT OF THE INVENTION

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The present invention has as its object a quinoline synthesis process, hereinafter "process of the invention", which comprises a Friedländer reaction catalyzed by carbon aerogels.

Another object of the invention relates to catalysts designed to generate about 25 reaction conditions that allow obtaining quinolines with higher yield and a selectivity of 100%, hereinafter "catalysts of the invention".

DESCRIPTION OF THE FIGURES

 30

Figure 1.- Scheme of preparation of the catalysts of the invention in which the airgel is doped with metal.

Figure 2.- Scheme of preparation of the catalysts of the invention in which the metal is supported on the airgel. 35

Figure 3.- Graphical representation of the pore size distribution determined by Hg porosimetry. Graph A) indicates the influence of the catalyst. B) indicates the influence of the carbonization and / or activation treatment on the sample doped with Co.

 5

Figure 4.- DRX of Co catalysts in which the influence of the treatment of doped carbon aerogels RFCoS, RFCo1000 and RFCo500 can be observed. 2 represents the angle of diffraction

Figure 5.- Micrographs of HRTEM a) RFCo500 b) RFCo1000 10

Figure 6.- Determination of oxygenated groups on the surface of aerogels, RFNaS, RFNaSPO and RFNaSPS by DTP. The axis of abscissa represents the temperature in degrees Kelvin and in that of ordinates F represents in number of mmol desorbed of CO or CO2 per gram of sample in a second

Figure 7.- FTIR of functionalized carbon aerogels

Figure 8.- Friedländer reaction between 2-amino-5-chlorobenzaldehyde (1a) and ethyl acetylacetate (2a) catalyzed by carbon aerogels, at 50 ° C, in the absence of solvent. A) shows the temporal evolution of the quinoline 3a yield in the presence of RFCoS, B) the quinoline 3a yield in the presence of RFS, RFNaS and RFCoS at 240 minutes of reaction time and C) the quinoline 3a yield in the presence of MCF, NbMCF and RFCoS at 180 minutes of reaction time.

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Figure 9. Friedländer reaction between 2-amino-5-chlorobenzaldehyde (1) and ethyl acetylacetate (2a) catalyzed by carbon materials treated with oxidizing agents RFSPO, RFSPS, RFNaSPO, RFNaPS , at 50 ° C, in the absence of solvent A) It shows the performance of quinoline 3a in the presence of RFS, RFSPO and RFPS at 240 minutes of reaction time and B) the performance of quinoline 3a in the presence of RFNaS, RFNaSPO at 240 minutes of reaction time.

Figure 10.- Friedländer reaction between 2-amino-5-chlorobenzaldehyde (1) and ethyl acetylacetate (2a) catalyzed by carbon aerogels doped with transition metals, at 50 ° C, in the absence of solvent. A) shows the performance of quinoline 35 3a in the presence of RFCuS, RFNiS, RFPtS at 240 minutes of reaction time,

B) the quinoline 3a yield in the presence of RFCuS, RFCu500, RFCu10001%, RFCu10003% at 240 minutes of reaction time and C) the temporal evolution time evolution of the quinoline 3a yield in the presence of RFCoS and RFCuS,

Figure 11.- Friedländer reaction between 2-amino-5-chlorobenzaldehyde (1) and 5 ethyl acetylacetate (2a) catalyzed by RFCoS, RFCo500 and RFCo1000, at 50 ° C, in the absence of solvent

Figure 12.- Friedländer reaction between 2-amino-5-chlorobenzaldehyde (1) and ethyl acetylacetate (2a) catalyzed by RFCo500, RFNa500, RFNa500Co1, 10 RFNa500Co3 and RFNa500Co5 A) at 50 ° C, B) at 30 ° C, in the absence of solvent at 15 min of reaction time.

Figure 13.- Friedländer reaction between 2-amino-5-chlorobenzaldehyde (1) and ethyl acetylacetate (2a) catalyzed by carbon aerogels containing Co (0) and 15 subsequently treated with oxidizing agents RFCoSPO, RFCoSPS, RFCo500PO, RFCo1000PO , at 50 ° C, in the absence of solvent.

Figure 14.- Friedländer reaction between 2-amino-5-chlorobenzaldehyde (1) and ethyl acetylacetate (2a) catalyzed by carbon poraerogels containing Co (0) and 20 subsequently treated with oxidizing agents RFNa500Co3PO , at 50 ° C, in the absence of solvent.

DETAILED DESCRIPTION OF THE INVENTION

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Definitions

In the present invention, "Friedländer condensation" (or "Friedländer reaction") shall be understood as any condensation of 2-aminoarylcarbonyl compounds, aldehydes or ketones, and other carbonyl compounds, with enolizable hydrogens. 30

"Quinolines" means those chemical compounds of General Formula A:

where,

R1, R2 and R3 can be, interchangeably: 5

 linear or branched hydrocarbon chains, containing aromatic or aliphatic groups, or both, containing or not heteroatoms such as F, Cl, Br, I, N and / or O.

 aromatic groups containing aliphatic chains or not, containing or not heteroatoms such as F, Cl, Br, I, or N and / or O. 10

In particular

 R1 and R2 may be hydrocarbon chains, linear or branched, containing aromatic or aliphatic groups, unsaturated or not, containing or not heteroatoms such as N and / or O; and 15

 R3 is a group that contains heteroatoms such as F, Cl, Br, I, or N and / or O.

"Heterogeneous catalyst" means a substance that, added in quantities much lower than the stoichiometric, increases the speed of a certain process; In the processes of heterogeneous catalysis, catalyst and 20 reagents are in different phases. In particular, a heterogeneous carbon catalyst is a catalyst in which the active phase is dispersed over a coal a, preferably coal airgel.

"Pretreatment" means a process consisting of heating in an inert or reducing atmosphere, depending on the precursor salt of the active phase, and the final oxidation state that is required. It is a common process in the catalyst synthesis process and is performed to decompose a precursor salt and transform it into the desired active phase. In an inert atmosphere some salts decompose oxides, in a reducing atmosphere 30

(H2) is normally brought to zero oxidation (pure metal) and more is done for noble metals (Pt, Pd, Ru, Rh, etc). In the catalysts described and used in the present invention, the reducer is the carbon support itself that transforms transition metals (Co, Ni, Cu) into metals in a state of zero oxidation (for example, Co (0), Ni (0 ) or Cu (0)). 5

Catalysts of the invention

Another object of the invention relates to carbon catalysts, hereinafter "catalysts of the invention", which are useful as heterogeneous catalysts in the Friedländer condensation described previously. That is, catalysts comprising carbon aerogels to catalyze a condensation of Friedländer.

In a particular embodiment, the catalysts are heterogeneous catalysts formed by metals, preferably transition metals, and carbon aerogels.

In a preferred embodiment, the catalysts comprise mesoporous carbon aerogels. twenty

In a particular embodiment, the carbon used in the synthesis of the airgel can be activated.

In a more particular embodiment, the carbon airgel is doped with the 25 metals.

In another more particular embodiment, the metals are supported on the coal airgel.

 30

In another particular embodiment, the catalyst comprises metal particles selected from the group consisting of Co, Ni, Cu and Pt.

In a preferred embodiment the catalyst comprises a carbon airgel, preferably mesoporous, and the active phase is Co (0). More specifically, the catalyst comprises a mesoporous carbon airgel contained when using Na2CO3 as a catalyst, which is impregnated and pretreated to obtain Co (0) as the active phase. 5

In a also preferred embodiment, the metals are in the form of metal nanoparticles.

Method of the invention 10

In this context, the first object of the invention is a quinoline synthesis process, or "process of the invention", which comprises a condensation of catalyzed Friedländer using the catalysts of the invention.

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Specifically, a synthesis of quinolines by reaction of 2-aminoarylaldehydes with other carbonyl compounds, with enolizable hydrogens, is described in the presence of a heterogeneous catalyst comprising a carbon airgel as generally represented in scheme 1.

 twenty

Scheme 1. Friedländer reaction between 2-aminoarylaldehydes and other carbonyl compounds

Together with the high yield, one of the advantages of this process is that it can be performed in the absence of solvent. Therefore, in a particular embodiment, the process of the invention is performed in the absence of solvent.

In a preferred embodiment the process of the invention employs an amount of catalyst less than 10% by weight over the total weight (w / w) of the stoichiometric amounts of the starting reagents. In some specific cases, the

The process only requires amounts of catalyst in amounts not exceeding 5% w / w with respect to the stoichiometric amounts of the starting reagents.

REALIZATION MODES

 5

The synthesis procedures of the catalysts and the corresponding quinolines are detailed below:

General procedure for preparing the catalysts:

All syntheses are based on the polymerization reaction of resorcinol (R) and formaldehyde (F) initially patented by Pekala [Pekala RW. "Lowdensity, resorcinol – formaldehyde aerogels". US 4,873,218; 1989]. More recently, the synthesis of carbon gels doped with metals and some of their applications as catalysts or electrocatalysts have also been patented by the authors [patents ES 2 366 848 and ES 2 369 269]. For this work, the carbon materials under study were synthesized by modifying and optimizing the procedures described in the literature in order to obtain a wide range of materials with various physical-chemical characteristics.

In a typical experiment, a mixture of resorcinol (R) and formaldehyde (F) 20 in water (W) is prepared. The presence or absence of a salt that acts as a polymerization catalyst and / or metal precursor will determine the nature of the heterogeneous catalyst (doped or supported, Scheme 1). Doped materials are obtained, which can be used directly as heterogeneous catalysts, if a precursor salt of the corresponding transition metal 25 is dissolved in the original solution. Alternatively, once a carbon airgel or activated pure carbon airgel is prepared, a salt of the corresponding transition metal is deposited by impregnation on the carbon material and the subsequent thermal treatment leads to the formation of the active phase thus obtaining supported catalysts.

 30

The polymerization took place for one day at 25 ° C, two days at 50 ° C and five days at 80 ° C in a 0.5 cm diameter glass mold; then, the gels thus obtained were cut into 5mm pellets, immersed in acetone for 2 days and dried with supercritical CO2. These polymer gels were subsequently carbonized at different temperatures generating carbon gels. Activated carbon gels were obtained from these carbonized by steam treatment at high temperature (900 ° C).

Its surface chemistry was also adjusted by treatments with various oxidants, results obtained with hydrogen peroxide or ammonium persulfate are presented here. The treatment was carried out using a ratio of 1 g of carbon airgel treated with 10 mL of concentrated H2O2 (9.8 M), for 48 hours, in a bath with continuous stirring at 25 ° C; after this time the sample was washed with plenty of distilled water and dried in an oven at 110 ° C. The treatment with (NH4) 2S2O8 was carried out with a saturated solution of this salt in 1 M sulfuric acid (1 g of coal / 10 mL of solution), for 48 hours, in a bath with continuous stirring at 25 ° C; subsequently the sample was washed with distilled water until the ions (SO4) 2- were removed. 10

The preparation schemes are schematized in Figures 1 and 2, indicating the synthesis variables and the final products.

Table 1 summarizes the R / F molar ratio (where “R” indicates resorcinol and “F” 15 indicates formaldehyde), R / W (where “W” is water), R / C (where “C” is the catalyst used in RF polymerization), "T" indicates the carbonization temperature and also the activation conditions and treatments for the modification of the surface chemistry of the material are detailed. The nomenclature indicates that these are materials obtained from RF, the metal used in the precursor salt, the carbonization temperature, the activation in water vapor (S), and the functionalization treatment with H2O2 (PO) or ( NH4) 2S2O8 (PS). Bibliographic references for previously prepared samples are also included; the rest, were synthesized specifically for the present invention.

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 Catalyst

 R / F R / W R / C C T (° C) Activation with W (g) Functionalization Ref

 RFS

 1/2 1/8 0 - 1000 900 ° C / 2h 1

 RFSPO

 Samples derived from RFS H2O2 -

 RFNaS

 1/2 1/8 800 Na2CO3 1000 900 ° C / 2h 1

 RFNaSPO

 Samples derived from RFNaS H2O2 -

 RFNaSPS

 (NH4) 2S2O8 -

 RFNa500

 1/2 1/15 300 Na2CO3 500 - 2

 RFNa500Co1 RFNa500Co3 RFNa500Co5

 Samples derived from RFNa500 Impregnation with Co (AcO) 2 + T at 350ºC / He -

 RFCo500

 1/2 1/8 1wt% Co (AcO) 2 500 3

 RFCo500PO

 Sample derived from RFCo500 H2O2 -

 RFCo1000

 1/2 1/8 1wt% Co (AcO) 2 1000 3

 RFCo100PO

 Samples derived from RFCo1000 - H2O2 -

 RFCoS

 900 ° C / 2h -

 RFCoSPO

    - H2O2 -

 RFCoSPS

 Samples derived from RFCoS - (NH4) 2S2O8 -

Table 1. Nomenclature and synthesis conditions of carbon aerogels. "Ref" indicates the bibliographic reference describing the synthesis of the airgel: 1: Carbon 37 (1999) 1199, 2: Appl.Catal. B: 75 (2007) 312 and 3: Langmuir, 16 (9), 2000. 4367.

Characterization of catalysts 5

The TG-ATD experiments show that all synthesized solids are stable at approximately 350 ° C in air.

The characterization of the synthesized solids was carried out by determining their textural characteristics  surface area, volume and pore size distribution - by adsorption / desorption of N2 at 77 K and by Hg porosimetry, its chemical composition by elemental analysis and the nature of the oxygenated groups by desorption at programmed temperature (TPD) and Infrared by Fourier transform, FTIR, its crystalline structure by RX diffraction (DRX) and its morphology by electron microscopy.

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Table 2 shows the textural characteristics of some of the synthesized materials:

 Airgel

 SBET (m2 / gr) Sext (m2 / gr) W0 (cm3 / g) L0 (nm) V2 (cm3 / g) V3 (cm3 / g) Metal (%)

 RFS

 1085 35 0.377 1.29 0.035 0.984 0.0

 RFNa500

 641 337 0.19 0.61 1,020 0.997 n.d.

 RFNaS

 1260 322 0.363 1.25 1,113 0.018 n.d.

 RFCoS

 219 88 - - 0.217 0.929 5.3

 RFCo500

 660 132 - - 0.887 0.122 4.2

 RFCo1000

 388 57 - - 0.092 0.995 4.5

Table 2. Textural characterization of synthesized carbon aerogels.

n.d. = not detected, concentration below the detection limit. % Metal obtained from the ash content. twenty

SBET = BET surface, Sext = macro and mesopore surface determined by porosimetry of Hg, W0 and L0 = diameter and volume of micropores determined by adsorption of N2, respectively.

As seen in Table 2, the porosity is greatly influenced by the presence of and the nature of salts in the solution, the carbonization temperature and the activation processes. This is also evident in the distribution of macro and mesopores obtained by mercury porosimetry (Figure 3) for samples doped with Co. By increasing the temperature (T) of carbonization the 5 porosity is widened by the greater weight loss and After activation, both meso and macroporosity develop from the average diameter of the precursor carbonized.

Since in all cases a ratio R / F = ½ has been used, and generally a solution R / W = 1/8, the chemical composition of the organic fraction in the aerogels obtained is approximately constant. During carbonization, the weight loss increases with the treatment temperature, decreasing the content of heteroatoms O, H, and increasing the proportion of C. Both the RF and RFNa sample, charred at 1000 ° C, have a C content = 96% and H = 0.5%, determined by elemental analysis in the doped samples (RFCo), during the carbonization the decomposition of the precursor salt simultaneously occurs; the metal appears, in this case, reduced (peak at 44.12 ° C corresponds to I100 of the metallic Co) (Figure 4). The proportion of metal (Table 2) increases with increasing weight loss in each treatment (gasification of the organic part). twenty

High resolution transmission electron microscopy microphotographs, HRTEM, (Figure 5) show the influence of thermal treatment on the dispersion of the active phase. It is observed how the metal particles are so small, after carbonization at 500 ° C, that they mostly remain below the limit of detection; These results are in agreement with the DRX (Figure 4), where the diffraction peaks of the metal are not observed, indicating that their size is below 4 nm. However, when carbonized at 1000 ° C, Co appears to form a high distribution of nanoparticles of size around 10-15 nm.

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Finally, with respect to the surface chemistry of the catalysts, as mentioned above, the carbonaceous support generally has a low oxygen content. The introduction of oxygenated groups was carried out by treatments with PO and PS and their quantitative analysis was carried out by DTP experiments (Figure 6); Qualitative analysis is performed by analyzing profiles 35 of the DTP curves and by FTIR.

 Sample

 O CO CO2 CO / CO2

 (%) (moles / g)

 RFNaS

 1.7 526 266 1.98

 RFNaSPO

 5.0 1863 640 2.91

 RFNaSPS

 13.7 3933 2319 1.70

 5

Table 3. Composition of the aerogelesRFNaS, RFNaSPO and RFNaSPS.

Figure 6 shows an example of the increase in oxygen content of the supports, in the absence of metal, depending on the oxidation treatment. Table 3 shows the oxygen contents, calculated from the amounts of CO2 and 10 CO2 desorbed, as well as the CO / CO2 ratio. The groups that desorbed as CO2 are the most acidic, mainly carboxylic groups, which decompose below 400 ° C, anhydrides around 450-550 ° C, while lactones have greater thermal stability. The groups that desorb CO are generally less acidic; the appearance of a peak simultaneously with the CO2 peak indicates the presence of anhydrides, the phenols decompose around 700 ° C, while quinones and carbonyls do so at a higher temperature (> 900 ° C). Clearly, treatments with PS introduce a higher concentration of oxygen, specifically carboxylic groups (Figure 6B), which makes the surface simultaneously more acidic and hydrophilic. The FTIR of the samples, both supports and doped catalysts, 20 show after functionalization with PS an intense band at 1720 cm-1 associated with vibration C = O in carboxylic groups, and carbonyl, ketones or aldehydes. This band is not significant after PO treatments (Figure 7).

Synthesis of quinolines 25

In a typical experiment, a corresponding catalyst (25 mg; amount less than 10% by weight) is added to a mixture of 2-amino-5-chlorobenzaldehyde (0.5mmol), ethyl acetylacetate (5 mmol), at 50 ° C with respect to the stoichiometric amounts of the reagents used) and the reaction mixture is kept under stirring for 240 minutes; Samples were taken at 15, 30, 60, 120, 180 and 240 minutes of reaction time. Next, CH2Cl2 (0.5 mL) was added to each sample and the catalyst was removed by filtration. Then, the solvent and excess reagents were removed by evaporation under reduced pressure. The reactions were followed by thin layer chromatography (DC-Aulofolien / Kieselgel 60, F245, Merck) using as solvents mixtures of CH2Cl2 / EtOH, in a ratio of 98: 2. 35

The characterization of the synthesized quinolines was performed by Proton Nuclear Magnetic Resonance, 1 H NMR (Bruker ADVANCE, DPX-300, 300 MHz for 1 H) using DMSO-d6 as solvent and tetramethylsilane as internal reference.

Example 1: Synthesis of ethyl 6-chloro-2-methylquinolin-3-carboxylate (3a). 5

1H NMR (300 MHz, DMSO-d6, 25 ° C, TMS) ,88.84 (s, 1H), 8.27 (d, 3J (H, H) = 2.1 Hz, 1H), 7.99 (d, 3J (H, H) = 9 Hz, 1H), 7.85 (dd, 3J (H, H) = 2.4 Hz, 9 Hz, 1H), 4.38 (q, 3J (H, H) = 7.2 Hz, 2H), 2, 85 (s, 3H), 1.38 (t, 3J (H, H) = 7.2 Hz, 3H).

Example 2: Synthesis of ethyl 6-chloro-2-phenylquinolin-3-carboxylate (3b). 10

1H NMR (300 MHz, DMSO-d6, 25 ° C, TMS)  8.83 (s, 1H), 8.32 (d, 3J (H, H) = 2.4 Hz, 1H), 8.16 (d, 3J ( H, H) = 9 Hz, 1H), 7.9 (dd, 3J (H, H) = 2.4 Hz, 9 Hz, 1H), 7.6 - 7.57 (m, 2H), 7.52 - 7.49 (m, 3H), 4.11 (q, 3J (H, H) = 7.2 Hz, 2H), 1.17 (t, 3J (H, H) = 7.2 Hz, 3H).

Example 3: Synthesis of tert-butyl 6-chloro-2-methylquinolin-3-carboxylate (3c). fifteen

1H NMR (300 MHz, DMSO-d6, 25 ° C, TMS) 8.74 (s, 1H), 8.23 (d, 3J (H, H) = 2.4 Hz, 1H), 7.97 (d, 3J ( H, H) = 9 Hz, 1H), 7.82 (dd, 3J (H, H) = 2.4 Hz, 9 Hz, 1H), 2.82 (s, 3H), 2.15 (s, 9H) .

Figure 8 shows the influence - of the catalysts RFS, RFNaS, RFCoS -, 20 on the preparation of quinoline 3a by means of a Friëdlander condensation between 2-amino-5-chlorobenzaldehyde (1) and ethyl acetylacetate (2a) ( Scheme 2). The RFS and RFNaS samples are pure carbon aerogels with different porosity; The first one is a microporous material (Table 2) while the RFNaS is mesoporous. The comparison between RFNaS and RFCoS, both mesoporous samples, allows us to establish the influence of Co in the quinoline synthesis reaction.

Scheme 2. Friëdlander condensation between 2-amino-5-chlorobenzaldehyde (1) and ethyl acetylacetate (2a).

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As Figure 8 shows, the carbon airgel synthesized from R / F and cobalt acetate, RFCoS, led to quinoline 3a with almost quantitative yield

after 60 min of reaction time; shows a catalytic activity far superior to that presented by the analogue RFS, RFNaS aerogels (Figure 8B). The fundamental differences between these aerogels, RFS, RFNaS and RFCoS, are both the porosity of the materials and their composition; In the case of the most active catalyst, RFCoS, the surface of the carbon material is decorated with metallic nanoparticles of Co. While RFS is a typically microporous carbon, the RFNaS and RFCoS aerogels also have some mesoporosity (Figure 3; Table 2). Additionally, in Figure 8C, the comparison of the catalytic activity of other catalysts, mesoporous silicas in this case doped or not doped with Nb as transition metal for Friedländer condensation is shown; as can be seen, although NbMCF mesoporous silica led to quinoline 3a with high yield (86%; 3 h) [A. Smuszkiewiczet al. (2013) J. Mol. Catal. A: Chem. 378: 38]; The RFCoS airgel, object of the present invention, showed superior activity.

Taking into account the results obtained, everything seems to indicate that porosity 15 has hardly any influence on the catalytic activity. In addition, in view of the functional differences of the surface of the studied aerogels, it can be concluded that the predominant active catalytic species in the RFCoS airgel is Co (0).

Next, the catalytic activity of those 20 aerogels that were treated with oxidizing agents was carried out. In Figure 9 it can be seen that the incorporation of oxygenated groups on the surface of the RFS and RFNaS supports, by treatment with oxidants, resulted, in all cases, to obtain quinoline 3a with greater performance due mainly to the increase in the content of oxygenated surface groups. There is, however, no direct correlation between oxygen content and reaction performance, since similar yields are obtained after functionalization with PO and PS, however their oxygen contents are very different. (Figure 9).

In addition, the concentration of acidic groups in these materials does not seem to significantly affect the catalytic activity observed, since the quinoline 3a yield obtained in the process catalyzed by RFNaSPO and RFNaSPS is about 60% in both cases.

A study was also carried out on the condensation of Friedländer catalyzed by 35 carbon aerogels doped with nanoparticles of other transition metals  RFCuS, RFNiS and RFPtS  and the comparison of their catalytic activity with that of the

Corresponding RFCoS airgel above. As can be seen in Figure 10, in all the cases studied, the corresponding quinoline 3a was obtained with total selectivity, the airgel being doped with Cu nanoparticles showing the highest activity (Figure 10a).

 5

In view of these results, and considering that the airgel with the highest catalytic activity was RFCoS (Figures 8, 10A and 10C), the catalytic activity of other coal aerogels doped with cobalt toRFCo500, RFCo1000 and RFCoS was studied  While the first two were obtained by carbonization at 500 and 1000 ° C, respectively, the RFCoS airgel is obtained by activating the RFCo1000 with water vapor. The use of these materials as catalysts in the synthesis of quinolines, following the experimental protocol described in the present invention, allowed us to analyze the influence of the synthesis conditions of aerogels on their catalytic activity (Scheme 2; Figure 10). Fundamentally these processes change the distribution of pore sizes from meso to macroporous by increasing the 15 T of carbonization, increasing both ranges of porosity with activation.

In Figure 11 it can be seen how the reaction proceeds more efficiently in the case of the RFCo500 catalyst calcined at 500 ° C; probably the greater dispersion of the active phase and the presence of mesoporos induces it to be the most efficient catalyst for the preparation of quinoline 3a at the shortest reaction times; quinoline 3a was obtained with a yield of approximately 60% only 15 min of reaction time. Both the RFCoS and RFCo500 catalyzed process led to quinoline 3a with quantitative yield after 2h of reaction time. The increase in the size of the metal nanoparticles occurs primarily during carbonization at 1000 ° C. After this process, the activation with water vapor opens the porosity and favors the contact of the reagents with the nanoparticles, so that the reactivity varies in the order RFCo500> RFCoS> RFCo1000, depending on the dispersion and accessibility of the metallic phase . From the results obtained, in this case, it can be concluded that the reaction conditions used for the preparation of the airgel significantly influence its catalytic activity. It is important to mention that the Friedländer reaction catalyzed by the carbonized airgel at a higher temperature led to quinoline 3a with a lower yield than the one obtained in the cases described above; although in this case it was also possible to obtain a pure sample of quinoline 3a after 35 hours of reaction time.

In parallel, a similar study was carried out with carbon aerogels doped with Cu (0) nanoparticles (Figure 10B). As can be seen in Figures 10 and 11, in all the cases studied the catalytic activity of carbon aerogels doped with Cu (0) was considerably lower than that obtained for aerogels doped with Co (0). 5

Given that the best quinoline 3a yields were obtained in the RFCo500 catalyzed process, the experiments presented below were performed using this catalyst.

 10

The study of the influence of the amount of catalyst (RFCo500) on the Friedländer condensation between 2-amino-5-chlorobenzaldehyde (1) and ethyl acetylacetate (2a) (Scheme 2) was carried out. As expected, the reaction proceeds more efficiently using larger amounts of catalyst, in this case 50 mg.

 fifteen

In addition, RFCo500 proved to be a fully reusable catalyst in the synthesis of quinoline 3a, at 50 ° C, for at least two consecutive cycles maintaining its total activity; During the third cycle, a 20% decrease in activity was observed.

In order to generalize the reaction, RFCo500 was tested in the Friedländer 20 reaction between 2-amino-5-chlorobenzaldehyde (1) and different 1,3-dicarbonyl compounds 2, at 50 ° C, and in the absence of solvent. Table 4 shows some of the results obtained for the synthesis of quinolines 3.

As shown in Table 4 and Figures 2 and 5, aerogels doped with Co (0), which are described in the present invention, are more efficient catalysts even than the mesoporous silicas described so far for this transformation.

To study the influence of the protocol followed for the incorporation of 30 Co (0) in the carbon material in the catalytic activity, the aerogels RFNa500Co1, RFNa500Co3, RFNa500Co5 prepared from the airgel RFNa500 (Table 1) by impregnation with acetate were studied of 1%, 3% and 5% cobalt and subsequent reduction at 350 ° C, for 2 h, under nitrogen atmosphere.

 35

As can be seen in Figure 12, the most efficient catalysts, in this case, were RFNa500Co aerogels containing Co nanoparticles (0)

supported; even the airgel containing the least amount of Co (0), RFNa500Co1, led to a pure sample of quinoline 3a (Scheme 2) in just 15 min of reaction time when the reaction was carried out at 50 ° C (Figure 12A ). It is important to mention that these catalysts efficiently promote the reaction even at lower temperatures, 30 ° C (Figure 12B); As shown in Figure 5, the higher the Co (0) content of these materials, the higher the quinoline yield obtained.

Scheme 3.- Friedländer reaction between 2-amino-5-chlorobenzaldehyde (1) and 10 different b-ketoesters (2a) catalyzed by carbon aerogels doped with transition metals.

 Catalyst

 R1 R2 Time [min] Performance [%]

 RFCo500

 I OEt 30 (60) 80 (92)

 Ph

 OEt 180 84

 I

 OBut 240 92

 MCFa

 I OEt 180 40

 NbMCFa

 I OEt 180 86

 PET / MAG 30:70

 Me OEt 60b (15) c 71b (99) c

a Look at Smuszkiewiczet al. (2013) J. Mol. Catal. A: Chem. 378: 38. b Ambient temperature. C

Reaction temperature: 50 ° C

(Godino et al (2014)

15 ChemCatChem6: 3440).

Table 4. Synthesis of quinolines 3 catalyzed by RFCo500 (25 mg), at 50 ° C, and in the absence of solvent.

In view of these results it can be concluded that the catalysts of the type RFNa500Co 20 described in the present invention are alternative catalysts for the synthesis of quinolines via Friedländer condensation, even more efficient than the PET / MAG basic carbon materials described very recently in our research group [Godino et al. (2014) ChemCatChem 6: 3440].

 25

Along the same lines, a similar study was carried out with aerogels containing Co (0) and subsequently treated with oxidizing agents (Figures 13 and 14). In general, these aerogels, specifically RFCoSPO, RFCoSPS, RFCo500PO and RFNa500CoPO, proved to be less efficient catalysts in the synthesis of quinoline 3a than their analogs containing exclusively Co (0). However, 5 in the case of RFCo1000PO the trend is the opposite.

In summary, the present invention describes different catalysts based on carbon aerogels with different composition, structure and porosity efficient for the preparation of quinolines by condensation of Friedländer between 2-aminoarylaldehydes 10 and carbonyl compounds with enolizable hydrogens. Some of the solids described here proved to be more efficient and simpler and cheaper to prepare than other heterogeneous acid catalysts, such as MCF and NbMCF mesoporous silicas, and even more active than PET / MAG 30:70 basic carbons recently described by the inventors themselves for this transformation.

Thus, as described in the present invention, the corresponding quinolines were synthesized with excellent yields during shorter reaction times, with the consequent energy savings, and considerably minimizing the amount of catalyst employed in the process.

The process described in the present invention is carried out in the absence of solvent, minimizing the isolation and purification steps of the quinolines obtained, being possible to obtain them as completely pure samples by only slightly increasing the reaction time. Due to the small amounts of catalyst used in the process - in some cases quantities below 5% (w / w) with respect to the stoichiometric amounts of the reagents used - waste generation is minimized as much as possible. The reasons mentioned above guarantee that the procedure described here is, as far as possible, a process compatible with the environment.

Claims (13)

1. Catalyst for synthesizing quinolines by means of a Friedländer condensation comprising a carbon airgel.  5 2. Catalyst according to the preceding claim which further comprises metal particles. 3. Catalyst according to the preceding claim characterized in that the metal particles are transition metal particles. 10 4. Catalyst according to any of the preceding claims characterized in that the carbon airgel is doped with the metal particles. 5. Catalyst according to any of the preceding claims characterized in that the metal particles are supported on the carbon airgel. 6. Catalyst according to any of claims 2 to 5 characterized in that the metal particles are selected from the group consisting of Co, Ni, Cu and Pt. 20 7. Catalyst according to the preceding claim characterized in that the metal particles are Co (0) particles. 8. Catalyst according to any of claims 2 to 7 characterized in that the metal particles are in the form of nanoparticles. 9. Process for obtaining quinolines comprising a condensation of Friedländer catalyzed by a catalyst according to any of the preceding claims. 30 10. Method for obtaining quinolines, according to claim 9, characterized in that it is carried out in the absence of solvent. 11. Method for obtaining quinolines, according to any of the claims 9 or 10, characterized in that it employs a quantity of catalyst less than 10% w / w with respect to stoichiometric amounts of the starting reagents. 12. Method for obtaining quinolines according to any of claims 10 to 12, characterized in that the yield in quinolines is greater than 80%. 13. Method for obtaining quinolines according to any of claims 10 to 12, characterized in that the yield in quinolines is greater than 90%. 10