Simple Preparation of New Potential Bioactive Nitrogen-Containing Molecules and Their Spectroscopy Analysis

The impact of research on the small molecules chemistry is difficult to quantify and currently, it is still one of the most active areas of organic chemistry, medicinal chemistry and lately chemical biology. In recent years, a lot of interest has been shown in the preparation of nitrogen-containing compounds due to their numerous biologically significant activities. But it is the separation and purification process of the new synthetized organic molecules, the ones that take a key role in drug design and development.


Introduction
The impact of research on the small molecules chemistry is difficult to quantify and currently, it is still one of the most active areas of organic chemistry, medicinal chemistry and lately chemical biology. In recent years, a lot of interest has been shown in the preparation of nitrogen-containing compounds due to their numerous biologically significant activities. But it is the separation and purification process of the new synthetized organic molecules, the ones that take a key role in drug design and development.
Many texts about the simple and optimal preparation of bioactive compounds have been published, and in this chapter the multicomponent reactions and efficient linear process, which allow the synthesis of this kind of structures, will be discussed. However, the purpose of this chapter is to reveal those important aspects that finally determined why a molecule can be used and distributed as a drug: their preparation, purification, and characterization.
In almost all organic synthetic methodologies the purification process use simple column chromatography techniques (gravity or external pressure) using different support materials (solid adsorbents) as the stationary phase. Column chromatography is advantageous over most of the other chromatographic techniques because it can be used in both analytical and preparative applications. After the preparation and purification of a new compound has been realized, it becomes the characterization step. New purified molecules must be strongly characterized to determine its structural configuration. Among different analysis techniques, NMR experiments and X-Ray crystallography are the most efficient ways to determine the relative stereochemistry and, in suitable cases, also the absolute configuration of the obtained products.
In the development of our medicinal program directed to small molecules for drug delivery, the strategies for the preparation of nitrogen-containing molecules such as substituted indoles, tetrahydroquinolines, and N-substituted amides of carboxylic acids are illustrated in this chapter as well as their synthetic applications and analytic characterization. The discussion is complemented with a deep explanation of the analytical techniques employed www.intechopen.com for their isolation and purification including the spectroscopic and spectrometric techniques using for the elucidation structure for every new compound.

Simple preparation of new N-aryl-N-(3-indolmethyl) acetamides and their spectroscopic analysis
The vital importance of derivatives like indole-3-acetic acid, as a hormone responsible for the plant growth, and tryptophan, as a constituent of proteins and indispensible precursor of indole alkaloids, enhances the current interest for the design of simple and efficient synthetic routes for the preparation of molecules with the indole skeleton.
The research of the indol chemistry has been and it is still one of the most active areas of heterocyclic chemistry. In the past decades, a lot of interest has been shown in the preparation of substituted indoles due to their numerous biologically significant activities (Gribble, 2003). The derivatives of 3-indolylmethanamine 1 are the important intermediates of natural and natural-like products, such as hydro--carboline and pyrido[4,3-b]indole derivatives (Wynne & Stalick, 2002;Molina et al., 1996). This 3-indolyl methanamine motif is also embedded in numerous indole alkaloids from the simple alkaloid gramine 2 to complex aspidospermine alkaloid 3 (Baxter et al., 1999;Saxton, 1998) (Fig. 1). As a result of their biological and synthetic importance, a variety of methods have been reported for the preparation of 3-substituted indoles, using indol or 3-indolcarboxyaldehyde as starting materials. Generally, the Mannich reaction (Dai et al., 2006) and the catalyzed Friedel-Crafts alkylation reactions of indoles (Ke et al., 2005;Zhao et al., 2006;Jiang et al., 2005;Shirakawa & Kobayashi, 2006) are considered as a powerful carbon-carbon bond process to afford the 3-indolylmethanamine derivatives 1. However, another synthetic route to access to these compounds by using 3-indolcarboxyaldehyde, via its imino derivatives, is valid. This route has been used by our laboratory, which recently started an own medicinal program directed to small molecules for drug delivery. The particular interest in 3indolylmethanamine derivatives molecules, that could serve as useful precursors to many drug-like indolic or quinolinic compounds, is based on the evaluated antiparasitic properties of some analogues (Kouznetsov et al., 2004a, Kouznetsov et al., 2004bVargas et al., 2003). In this novel direction, the simple preparation of new (3-indolmethyl)acetamide and (1-acetylindolmethyl-3)acetamide, regulating only the solvent nature, is the relevant fact that has not been described and it gives the opportunity to prepare more of this kind of compounds.

Synthesis and purification of the new the (3-indolmethyl)acetamide and (1-acetylindolmethyl-3)acetamide
Aldimines are valuable starting materials not only for different N-containing heterocycles but also to diverse secondary heteroaromatic amines (Hutchins & Hutchins, 1991), which represent good candidates for bio-screening with diverse types of activities (Kleemann & Engel, 2005;Evers et al., 2005). Thus, the N-aryl imine 6, the main and value starting, can be prepared from commercially available 3-indolaldehyde 4 and 2-cyanoaniline 5, according to published methods (Colyer et al., 2006). This aldimine is obtained as a white and stable solid after purification by recrystallization in 95 % yield (Fig. 2). The method employed to obtain the precursor 7, is one of the most known procedures to reduce an aldimines with an excess of NaBH 4 in methanol, protocol that is still the reaction of choice to produce secondary amines in reasonably good yield. Thus, N-(2-cyanophenyl)-N-(3-indolylmethyl)amine 7 is prepared as was described and was obtained as white solid in 70 % yield after purification through recrystallization (Bello et al., 2010). This example, in which the main precursor is prepared in a linear process and purified by recrystallization, represents an excellent technique that avoids the loss of value material and it will be increase the global yields of the final product. Besides the efficient preparation and easily purification of compound 7, this amine has interesting structural elements to use in the synthesis of different indolic heterocycles. In this case, the study of its acetylation by acetic anhydride is showed.
First, to a stirred solution of amine 7, using in toluene as solvent due to the insolubility of compound 7 in polar common solvents (CH 3 CN, CH 2 Cl 2 , AcOEt and DMF), it is added Et 3 N and acetic anhydride, the mixture is refluxed for appropriate time to obtain the N-(2cyanophenyl)-N-(3-indolmethyl)acetamide 8 in acceptable yield (50 %) after purification using silica gel 60 Mesh and using a mixture of hexane: ethyl acetate (2:1) as an eluent.
Then, the acetylating reaction described above was performed between the amine and an excess acetic anhydride in the presence of Et 3 N at 100 °C , without the organic solvent (toluene). After the usual workup, the diacetylated indole 9 is obtained in good yield (85 %) using the same parameters employed to the purification of compound 8. This simple change in the reaction conditions could afford different acetamides based on the 3-indolyl methanamine motif (Fig. 3). This finding reveals a selective process to protect different amino groups and represents a good protocol to the synthetic organic chemistry, especially within those processes that require a particular position protection.

Characterization of the N-aryl-N-(3-indolmethyl)acetamides 8 and 9 by spectroscopy and spectrometric techniques
The structures of the C-3 substituted indoles 7-9 were confirmed on the basis of recorded analytical and spectral data and are supported by inverse-detected 2D NMR experiments. The IR spectrum of compound 7 illustrates the characteristic absorption bands at 3402 and 3352 cm -1 assignable to tension vibrations of CH 2 -N-H and N-H indol , respectively. Its 1 H NMR spectrum displays a duplet at  4.56 ppm (J = 4.9 Hz) ppm corresponding to two protons coupling with the neighbor N-H proton (br. s, 4.84 ppm), which suggest the presence of the methylenic unit linked to the N-H function. The peaks find at  7.17-7.3, 7.36-7.40 and 7.63 ppm reveals the presence of aromatic protons of the indole moiety. The 13 C NMR spectra, also showed all expected characteristic peaks at  39.4 (CH 2 ), 117 (CN), and 95.6-150.2 (aromatic carbons).
The mass spectrometric analysis of compound 8 gives a molecular ion peak M +· , at m/z 289, suggesting the molecular formula C 18 H 15 N 3 O, and indicating that the acetyl group is coupling with 7. The acetamide 8 displayed characteristic infrared absorption bands with a single amine absorption band at 3342 cm -1 and with a carbonyl sign at 1701 cm -1 suggesting the acetylation reaction involvement of the CH 2 -N; this is the band appearing at high wave number of the corresponding N-H indol vibration tension in the IR spectrum. Its 1 H NMR spectra analysis showed a singlet at 2.58 ppm corresponding to three protons which belong to the acetyl group and another singlet at 4.55 ppm due to the presence of the methylenic 3-CH 2 -N indolic protons. This signal's multiplicity is explained by assuming the proton N-H next to it, substituted now for the acetyl group, which leaves no possibility to H,H coupling, while it does happen with the amine 7.
The 13 C NMR spectrum of the acetamide 8 displayed characteristic carbonyl signal at 168 ppm, this is strong evidence to the new acetyl group bonded to the molecule; in addition to a signal at 39.3 and 23.9 ppm, showing the presence of CH 2 and CH 3 in the molecule. Introduction of an acetyl group into the molecule affects the chemical shift of the hydrogen bonded to the aromatic carbon close to the acetylatin nitrogen; this appears at 116 ppm for the compound 7 and at 123 ppm for the acetamide 8. The signal at 39.3 ppm for CH 2 -N has been distinguished on the basis of the DEPT-135 experiment. On the basis of these spectral studies, compound 8 was characterized as the N- The new compound 9 gave a molecular ion peak at m/z 331 in the mass spectrometric analysis, corresponding to the molecular formula C 20 H 17 N 3 O 2 as indicated by its EI-MS. The www.intechopen.com loss of 43 units (one acetyl group) generates the same mass spectrum as the acetamide 8. The IR spectrum of this molecule shows bands at 1704 and 1654 cm -1 , assignable to two carbonyl groups while the N-H absorption bands are not observed in the region of 3300-3400 cm -1 . The 1 H NMR spectrum showed, as expected, two singlets at  22.4 and 23.9 ppm, which integrated for three protons each. In the case of the methylenic protons, they appeared to be diasterotopic resonating at the high field frequencies  4.75 and 5.46 ppm with a coupling constant J = 15 Hz, usual constant value to a germinal coupling. Of course, the aromatic protons were also assigned.
The 13 C NMR spectrum showed all expected characteristic peaks at  169.4 (ArN-CO-), 168.5 (Ar indol N-CO-) ppm, in addition to a signal at  117.3 ppm showing the presence of CN in the molecule. Besides, methyl carbons at 23.9 (Ar indol NCO-CH 3 ) and 22.4 (ArNCO-CH 3 ) ppm and the methylene carbon at  42.8 ppm were also displayed in the 13 C NMR.
With respect to the characterization of the diacetamide 9, through X-ray diffraction, the monoclinic system was determined with the compound crystallized at 25ºC from heptaneethyl acetate (2:1) (Fig. 4). The crystallized material has the following cell constants: a = 11.1184(19) Å, b = 8.0048(13) Å, c = 20.534(4) Å and space group P 2 1 /n (Table 1), possessing the different bond lengths of the molecule constituent atoms was also extracted with this technique (Table 1).
From this data, the different bond lengths of the two amide bonds present within the structure were as expected. Even knowing the double bond character of the amide bonds, in this case, the amide bond distance between the aliphatic nitrogen N2 and C12 is 1.364 Å, while the distance between the aromatic nitrogen N1 and C9 is 1.388 Å. From this data, the different bond lengths of the two amide bonds present within the structure were as expected. Even knowing the double bond character of the amide bonds, in this case, the amide bond distance between the aliphatic nitrogen N2 and C12 is 1.364 Å, while the distance between the aromatic nitrogen N1 and C9 is 1.388 Å.
These data correspond with the thought that the amide bond N2-C12 is shorter because of the electron withdrawing inductive effect from the -cyanophenyl substituent and the possibility of the nitrogen non-shared electrons to be delocalized on the amide bond through a mesomeric effect giving this bond a stronger double bond character.
On the other hand, the amide bond N1-C9 is longer because the nitrogen non-shared electrons are compromised with the aromatic system and they are not as available to be delocalized on the amide bond giving it less double bond character (Table 2).

Conclusions
An efficient, economic, and fast synthetic route was designed and its illustrated in this section showing the possible construction of the N-aryl-N-(3-indolmethyl)acetamides with the incorporation of the indolic core as a structural analogues of some alkaloids.
The acylation method is worth as a regioselective process because the conditions variations lead to the mono-or di-acetamide. The characterization of the obtained compounds through different techniques gives evidence enough and strong support with regard to the success of the proposed scheme.

A convenient procedure for the synthesis of new quinoline derivatives and their spectroscopic analysis
Quinoline and tetrahydroquinoline structures are essential feature of many natural products. These heterocycles play a key role in heterocyclic and medicinal chemistry. Their syntheses by various methodologies have been published extensively (Kouznetsov et al, 2005;Kouznetsov et al., 1998;Katrizky et al., 1996;Jones, 1984).
Polyfunctionalized tetrahydroquinolines (THQs) are molecules of great interest in organic synthesis due to the fact that many natural products present this system in their structure, and these compounds exhibit diverse biological activities (Glushenko et al., 2008;Broch et al., 2008;Ichikawa et al., 2004;Morsali, et al., 2004;Chen et al., 2000).
Apart from their marked bioactivities, THQs are also important and reliable precursors in quinoline preparation, another group of heterocyclic molecules that has a great number of pharmacological properties (Trpkovska et al., 2003). An efficient route for the preparation of THQs is the acid-catalyzed Povarov reaction that is classified as imino Diels-Alder cycloaddition (Kouznetsov, 2009;Paazderski et al., 2007;Kouznetsov & Mora, 2006;Youssed et al., 2003) that permits the condensation of anilines, aldehydes, and electron-rich alkenes using acidic catalysts under mild conditions to afford new substituted tetrahydroquinolines.
For any Direct Oriented Synthesis (DOS) methodology towards the synthesis of bioactive substituted tetrahydroquinolines and quinolones, this route represents an easily and scalable approach for the investigations on the synthesis of small drug-like (tetrahydro)quinoline molecules containing C-2 aryl fragment, those synthesis could be accomplished via cycloaddition reactions. In this order, this section explain the simple preparation of new N-(2-nitrophenyl-1,2,3,4-tetrahydroquinolin-4-yl) pyrrolidin-2-ones using BiCl 3 -catalyzed three component Povarov reaction between nitrobenzaldehydes, toluidine and N-vinylpyrrolidin-2-one, and their transformations into potentially bioactive 2-aryltetrahydroquinoline derivatives, N-amidyl substituted at the C-4 position.
These reactions proceeded smoothly in MeCN and at room temperature giving final products, substances easy to purify by column chromatography using silica gel as a support and a mixture of petroleum ether and ethyl acetate (2:1) as an isocratic eluent. The N-(2-nitrophenyl-1,2,3,4-tetrahydroquinolin-4-yl) pyrrolidin-2-ones 14 and 15 can be obtained with good respective yields 95% and 70% (

Characterization of the N-[6-methyl-2-(4´-nitrophenyl)-1,2,3,4-tetrahydroquinolin-4yl] pyrrolidin-2-one 14 by spectroscopy and spectrometric techniques
The structures of the C-2 substituted tetrahydroquinolines 14 and 15 were confirmed on the basis of analytical and spectral data and were supported by inverse-detected 2D NMR experiments. The IR spectrum show the characteristic absorption bands of the compound 14 at 3394 and 1666 cm -1 , assignable to the amine and amide group, respectively, and the nitro group signals at 1512 and 1342 cm -1 . Their mass spectrum showed a molecular ion m/z: 351, it coincided with the molecular weight (351 g/mol). The 1 H NMR spectrum of this compound presented the 4-H proton signal at 5.69 ppm, observed as a double doublet with the coupling constants 6.4 Hz and 11.1 Hz.

This fact suggested axial-axial and axial-equatorial interactions between 4-H and 3-H protons.
On the other hand, the 2-H proton signal was observed at 4.65 ppm with the coupling constants 3.1 Hz and 10.7 Hz that indicated at vicinal axial-axial and axialequatorial interactions (Fig. 6).
The high value of the coupling constant (10.7-11.1Hz) of the 4-H and 2-H protons confirmed the axial proton configurations; therefore, substituents of the C-2 and C-4 positions of tetrahydroquinoline ring have the equatorial disposition, respectively.
However, having a possible mechanism of realized multi-component condensation, we could anticipate the various diastereomers the cis or trans configuration. For these reasons, further structural studies were realized.

X-Ray diffraction single crystal study
Samples crystals of both compounds of interest were growth by slow evaporation in ethanol. However, the difficulty to obtain suitable crystals from compound 15 only allows performing the study for the compound 14. The diffraction data of the compound 14 were collected at 273K using a CCD area detector with graphite-monochromatic Mo K radiation ( = 0.71073 Å).
This data were computed using Bruker-AXS software. For solution and refinement of the structure Shelxs-97 and Shelxl-97 (Sherldrick, 1997a;Sheldrick, 1997b) were used respectively. Molecular and crystal structures were obtained using Mercury software (Allen, 2002).

Conclusions
The synthesis of two new nitro-isomers of N-(tetrahydroquinolinyl) pyrrolidin-2-ones using a versatile and simple methodology called the three component imino Diels-Alder cycloaddition is illustrated as an excellent route for the preparation of novel kind of structures, the spectral analysis showed the 2-H axial , 4-H axial configuration; therefore the diequatorial disposition of the C-2 and C-4 substituent that confirmed the formation of the endo-adduct during a Diels-Alder cycloaddition process.

Convenient and scaleable three-step synthesis of new N-benzyl (pyridyl) cinnamamides from substituted (hetero)aromatic aldehydes
The relatively stable amide bond is not only common in natural-occurring materials like peptides and vitamins, it is also found in many synthetic substances. Among these important and interesting class of organic molecules: N-benzylcinnamides and Nphenylcinnamides have been always the focus of attention of organic, bioorganic and medicinal chemists due to their many useful synthetic applications (Takasu et al., 2003;Bernini et al., 2006;Nair et al., 2007) as well as their diverse (bio)chemical properties (Curtis et al., 2003;Tamiz et al., 1999;Lewis et al., 1991). Moreover, N-amide cinnamic acid derivatives are frequently presented in the nature (Mbaze et al., 2009;Vasques et al., 2002).
Both types of amides could be prepared generally via acylation reactions of the corresponding benzylamines or anilines and cinnamic acid derivatives (anhydrides or acyl halides) that are frequently used in the preparation of drug candidate molecules (Carey et al., 2006). However, the known acylation reactions for N-benzylcinnamides preparation employ hazardous and corrosive reagents (e.g., SOCl 2 , PCl 3 , (COCl) 2 , NEt 3 ) besides the starting functionalized benzylamines are not commercially available products, and almost any of their functional groups needs to be protected to ensure chemoselective amide formation (Nesterenko et al., 2003).
Considering the reported biological properties of certain N-arylcinnamides and Nbenzylcinnamides that have showed in vitro antimycotic activity (Leslie et al., 2010) and the inhibition of the transcription of carcinogenic genes in infected cells (Sienkiewicz et al., 2007). The need of an easy, rapid and "green" protocol for the synthesis of these kind of compounds is necessary to explore new pharmacological targets, and in this order the challenge of the organic chemistry is currently focused on the design of novel methodologies that suppress the use of acyl chloride (including any dangerous reagent required for their synthesis) and promoting the direct condensation between carboxylic acids and amines, coupling that currently is performed using efficient promoters such as N,N'-dicyclohexylcarbodiimide (DCC) (Amma & Mallouk, 2004), (benzotriazol-1yloxy)tripyrrolidinophosphonium hexafluorophosphate (ByPOB) (McCalmont, 2004;Baures et al;2002), triethylamine (Walpole, et al., 1993) and boron-based catalysts like BH 3 . THF (Huang et al., 2007).
The search of bioactive not only requires a good synthetic route, all the reagents must be stable and inexpensive to improve the structural complexity as in the biological properties. In this case, the integrity of most of the benzylamines is compromised when they are exposed to air moisture or even stored at low temperatures for a long period of time (Nazih & Heissler, 2002). A way to prevent this effects is based on choosing an appropriate strategy that enables the preparation of the desired amount benzylamines at lower cost than those acquired commercially, which could be possible by reduction of nitriles (Haddenham et al., 2009) and oximes (Gannett et al., 1988).
The "green" protocol described in this section is directed to enhance the disadvantages already described for the existing methodologies. Considering first the excellent chemical reactivity of aldehyde group against hydroxylamine's nucleophilicity to give oximes, this part was based on the existing methodologies which were improved according to the green chemistry principles with the use of less hazardous Na 2 CO 3 as a base to release the nucleophile (Dallinger & Kappe, 2007;Roberts & Strauss, 2005;Yadav & Meshram, 2001;Varma, 1999). The posterior reduction of the prepared oximes give the functionalized benzylamines (pyridylmethylamines) in quantitative yield, this allows the coupuling of the corresponding amines, without further purification, with cinnamic acid in the presence of boric acid to afford the final products in agreement to our previous experience synthesizing this type of compounds (Hernandez et al., 2008).

Synthesis of new N-benzyl (pyridyl) cinnamamides from substituted (hetero)aromatic aldehydes
The choice of diverse (hetero)aromatic aldehydes 16a-k was motived by the interest in quest for N-hetarylmethyl cinnamamides with antioxidant and anticancer properties. The direct condensation of 16a-k and hydroxylamine in the presence of Na 2 CO 3 is realize in an ethanol/water medium. Thus, a mixture of aldehydes 16a-k, Na 2 CO 3 and hydroxylamine hydrochloride was mixed in deionized water for 5 min. at room temperature, and then a small amount of the respective aldehyde was added for a period of another 5 minutes. The reaction mixture was stirring for 15 min. and after traditional work-up, the pure products, the substituted aldoximes 17a-k were obtained in quantitative yield (Fig. 11). Fig. 11. Preparation of the respective (hetero)benzylamines from the aldehydes 16a-k in a scalable methodology.
Taking into consideration that one of the most "atom-economical" procedures for the preparation of an amine is hydrogenation of an oxime in which the only by-product is water, we addressed also to this approach (Trost, 1995;Trost, 1991). Having in our hands the eleven solid and stable aldoximes 17a-k obtained in first step, each of them was hydrogenated at room temperature overnight under H 2 atmosphere using 10 % palladium on charcoal in ethanol (Fig. 11).
The hydrogenation mixture obtained in the second step is filtered through celite and the filtrate was concentrated to dryness allowing the crude amine 18a-k, which was quickly added, without any further purification, to an anhydrous toluene solution of trans-cinnamic acid 19 in the presence of B(OH) 3 (10 % mol) at 110 ºC for 6-10 h (Fig. 12).
The required workup at the end of the reaction can be perform in two ways: one consist in the precipitation of the product of interest with a solution of NaHCO 3 and their subsequent washing with water or that can be purified with column chromatography depending on the complexity of the final crude. For the second choice, the recommended support is neutral or basic alumina (Al 2 O 3 ) due to the acidity of the trans-cinnamic acid that will remain from the reaction. An acid support like common silica gel (SiO 2 ) will retain both substances (the amide of interest and the residual cinnamic acid). After the method of preference for the purification of the amides has applied, the final products the N-benzylcinamides 20a-k were obtained in excellent yields and with a high purity level (Table 6). Table 6. Synthesized N-benzyl cinnamides 20a-k.
The 1 H NMR spectra of the compounds 20 display a general group of characteristic signals for this series. For example, in the cinnamide 20g spectrum the methylene protons at 4.47 ppm (2H, d, J = 5.7 Hz, -CH 2 ) is the signal that is observed in high fields, signal that is coupling with the N-H signal, observed as a triplet at 5.99 ppm (1H, J = 5.7 Hz, NH). The analysis of olefinic protons indicate the trans configuration of the final products when the high value of the coupling constant observed is compared with the typical value for the cis configuration: in the case of compound 20g, and for the entire 11 synthetized molecules, the assignment of the proton at 6.41 ppm (1H, d, J = 15.7 Hz, =CHCO) and the coupling in trans form with the other olefinic proton, the one that appears at lower fields, at 7.66 ppm (1H, J = 15.7 Hz, =CHPh) confirmed the configuration of all the products (Fig. 13).

Conclusions
The improvement of the existing methodologies for the preparation of benzylamines, is described as protocol that enhances the efficiently, easily, rapidly and safety way in which the oximes can be obtained, leading to explore their synthetic use in the preparation of more complex systems or evaluate their pharmacological properties as a potential reactivators of the acetylcholinesterase enzyme (Sinko et al., 2010) or their allergenic activity (Bergström et al., 2008).
Taking into account that boronic compounds have showed catalytic activity in peptide synthesis, it is demonstrated also that boric acid is a practical and useful catalyst for amidation between cinnamic acid and the prepared benzylamines due to its remarkable catalytic potential. The notable features of this procedure are mild and green reaction conditions, good reaction rates, cleaner reaction profiles and excellent global yields for a linear synthesis of three steps. The recollected spectral data described for N-benzyl cinnamides should be reliable in the structural analysis of natural cinnamides and these substances could serve as a model for small-molecule screening towards new bioactive compounds. www.intechopen.com