PDF superior New approaches to the synthesis of pyridinium N heteroarylaminides

5. (a) Vaquero, J. J.; Alvarez-Builla, J. Advances in Nitrogen Heterocycles; 2000; Vol. 4, pp 159–250; (b) Valenciano, J.; Cuadro, A. M.; Vaquero, J. J.; Alvarez-Builla, J. Tetrahedron Lett. 1999, 40, 763–766; (c) Crabb, D. L.; McCullough, K. J.; Preston, P. N.; Rosair, G. M.; Bishop, B. C.; Wright, S. H. B.; Clegg, W.; Coles, S. J. Chem. Soc., Perkin Trans. 1 1999, 1517–1526; (d) Bishop, B. C.; Marley, H.; Preston, P. N.; Wright, S. H. B. J. Chem. Soc., Perkin Trans. 1 1999, 1527–1532; (e) Schmidt, A.; Martin, N. Heterocycles 2001, 55, 827–834; (f) Butler, N. R.; Wallace, L. M. J. Chem. Soc., Perkin Trans. 1 2001 , 1778–1784; (g) Valenciano, J.; Sanchez-Pavon, E.; Cuadro, A. M.; Vaquero, J. J.; Alvarez-Builla, J. J. Org. Chem. 2001 , 66, 8528– 8536; (h) Schmidt, A. J. Heterocycl. Chem. 2002, 39, 949–956; (i) Kappel, J. C.; Yokum, T. S.; Barany, G. J. Comb. Chem. 2004, 6, 746–752; (j) Dietrich, M.; Matthias, N. Heterocycles 2004, 63, 2605–2614; (k) Butler, R. N.; Fahy, A. M.; Fox, A.; Stephens, J. C.; Cunningham, D.; Ryder, A. J. Org. Chem. 2006, 71, 5679–5687; (l) Moderhack, D.; Noreiks, M. Heterocycles 2006, 68, 2113–2122; (m) Valenciano, J.; Sanchez-Pavon, E.; Cuadro, A. M.; Alvarez-Builla, J.; Vaquero, J. J. Eur. J. Org. Chem. 2007 , 15, 2423–2429.

dimensional H,H and H,C-correlation experiments, COSY, HSQC, HMBC or related spectra. In order to identify the sig- nals in the description of each product, positions of the pyridi- nium ring are not labelled, positions of the azine ring are labelled ( 0 ), positions of the 3-aryl substituent are labelled ( 00 ), positions of the 5-aryl substituent ( 000 ) and positions of the aryl belonging to the aryl ring of the N-benzyl substituent, when present, are labelled ( 0000 ). Elemental analyses were carried out on a Heraeus Rapid CHN analyzer and were within 0.4% of the theoretical values for all the new compounds described. Low resolution mass spectra (MS) were taken on a Hewlette Packard 5988A (70 eV) spectrometer using chemical ionization (CI) or electrospray (ESI) and high resolution analysis (FAB or TOF) was performed on a VG AutoSPEC (Micromass Instru- ment) or on an Agilent 6210 Time-of-flight LC/MS. All re- agents and solvents were obtained from commercial sources, except 3-pyridineboronic acid, 15 and were used without further purification. TLC analyses were performed on silica gel (Kie- selgel 60 F 254 , MachereyeNagel) and spots were visualized un-

increases, longer time was necessary to obtain a similar conversion, and in compounds 9a– f about a 15% of starting aminide 2a was always detected. On the contrary, with short dialkylating agents, like in the synthesis of 12 (Scheme 3) from 1,2-diiodoethane or 1,3-diiodopropane, no bis-alkyl- ation was observed on 2a, probably due to electronic repulsion in the intermediate salt. With diiodoethane, 2a was recovered as hydroiodide, indicating a predominance of the elimination process, while compound 13 was obtained from 1,3-diiodopropane.

4 reaction has not been further used in synthesis in spite of the potential interest in the resulting 2,3- difunctionalized aniline derivatives for the preparation of fluorine-containing indoles. So, first we tried to apply the reported reaction conditions to get 3-fluoro-2-iodotrifluoroacetanilide (3aa) from 1a employing iodine as an electrophile. Thus, using a slight excess of t-BuLi/TMEDA in THF at 78 ºC, we were able to generate the dilithiated species 2a and trap it with iodine, allowing the isolation of 3aa in 63% yield (Scheme 2). We also observed that working at temperatures over ca. 60 ºC a competitive lithium fluoride elimination takes place affording benzyne 19 intermediate 5 that intramolecularly evolve to afford, after electrophilic quenching, the iodinated benzoxazole 4 in moderate yield (Scheme 2). This observation has been previously described by Clark and Caroon in the directed metalation of 3- fluoroaniline bearing pivaloyl, N-Boc, or benzoyl as directing groups. 20 In an analogous way, the addition of bromine or hexachloroethane as electrophilic reagents to 2a afforded the corresponding 3- fluoro-2-halo-trifluoroacetanilides 3ab and 3ac in 45 and 30% yield. Moreover, the basic hydrolysis of some of these trifluoroacetanilides 3 furnished 3-fluoro-2-haloanilines 6aa and 6ab in high yields (Scheme 2).

Method A: To a solution of Pyridinium N-2’-pyridylaminide 1 1 mmol in dichloromethane 5 mL stirred at -20°C a solution of the corresponding NXS 1 mmol in the same solvent 10 mL was added[r]

Method B afforded 2e in a 55% yield the reaction mixture was stirred for 6 h at room temperature Mp 110-112 °C dec yellow powder, EtOAc.. Acknowledgements This research was supported by [r]

During the course of our studies on the intramolecular arylation of 1b, we evaluated the behavior of the pyridyl radical 2 (Scheme 1). The ultimate goal was the preparation of bipyridine 3 by a reaction pathway involving a exo/endo- trig cyclization, followed by N–N bond breaking, as previously described. 3d Compound 3, however, was not detected and instead, the tricyclic derivative 4 was obtained in moderate yield. 4 Following the same target in the development of a preparation of bipyridines and related biaryls by intramolecular radical arylation (i.e., 5, Scheme 1), we decided to prepare salt 6 in order to explore the feasibility of an intramolecular free radical ipso-substitution of the corresponding arenesulfonamides by pyridyl radicals, according to the methodology described by Motherwell and col. 5 This well-established method, based on aryl radical cyclizations, has been applied to the synthesis of biaryls and arylheterocycles. However, to the best of our knowledge, references concerning the use of heteroaryl radicals in such a method have not been published to date. Indeed, from a general point of view, the cyclization of pyridyl radicals has scarcely been exploited in synthesis. 6

A solution of TTMSS (0.248 g, 1 mmol) and AIBN (0.164 g, 1 mmol) in m-xylene (1 mL) and MeCN (9 mL) was added dropwise by a syringe pump, during 13 h, to a stirred solu- tion of the corresponding pyridinium salt 13 (0.5 mmol) in MeCN (2 mL) at 80 C (bath temperature). Stirring was maintained at the same temperature for further 12 h. The so- lution was concentrated and the crude mixture was separated by flash chromatography, yielding the pure compounds 19, 20, and 21. Assignments and analysis of the structures were performed using NOE experiments.

only obtained on using DMF as a solvent, where inter- mediate mono-, di-, and tri-salts were kept in solution and could react to give the final product (Scheme 2). Iso- lation of 5 and 6 was achieved by concentrating the mix- ture to a minimum volume of solvent to keep the products in solution, and subsequently adding the solu- tion dropwise to vigorously stirred AcOEt. This pro- duced precipitation of tetra-salts 5 and 6 while the corresponding N-aminide 4 remained in solution. 20

The synthesis of N-aminide intermediates 5 has been traditionally performed by attack of the corresponding 2-heteroaryl hydrazine 2 to 2,4-dinitrophenyl pyridinium chloride 1 (see Scheme 1) generating the hydrazone 3, which is again closed to a pyridinium derivative by acid catalysis, to produce the salt 4 and from there, by treatment with base, the N-aminides were obtained. This method, adapted from the scheme described by Beyer 11 is suitable

The same scheme was applied to the alkylation of the pyrazine-stabilized aminide 6 (Scheme 6, Table 3) with essentially the same results. The presence of the ring alkyl- ated compounds 20 in roughly 25% yield indicates that also the more p -deficient diazine ring could produce a weaker hydrogen bond, thus facilitating alkylation on the more nucleophilic ring nitrogen. No traces of the 4-N alkylated derivative were detected, indicating that electronic effects are dominant in the process. Again, the final N–N reduction afforded 2-alkylaminopyrazines 12 in good yield.

Motivated by the aforementioned importance of GQFs in communications and signal processing, and taking into account that deriving exact expressions for the distribution of such an intricate variables may pose a challenge from an analytic point of view, this thesis revisits the problem of analyzing non-central GQFs. Along this line, a new method to characterize these variables is proposed, aiming to circumvent the major drawbacks of classical approaches and seeking simple and tractable approximations for the PDF and cumulative density function (CDF) of both real and complex GQFs. The proposed approach is later leveraged to be applied to arbitrary positive random variables, showing the potential of the method and highlighting its main advantage: it ensures, for any level of accuracy, that the resulting expressions represent a valid distribution.

First steps have already been taken in Boophilus ticks, using the tick larval packet test and the adult immersion test, the majority of the work being done by Drs. Kemp and Thullner as members of the FAO/Industry Group and the FAO/Industry Contact Group on Parasite Resistance and consultants to FAO. The larval dispersal test for amidine resistance has been added to the test portfolio. Statistical analysis of test results and supply of actives still need to be addressed.

DISENO DE NUEVOS ACCESOS AL PARQUE OFIMATICO DESDE LA AVENIDA DE ALFONSO MOLINA DESIGN OF NEW APPROACHES TO THE “PARQUE OFIMATICO” FROM ALFONSO MOLINA AVENUE AUTOR DEL PROYECTO: DIMAS RO[r]

The design and synthesis of new chemosensors for the determination of metal cations represent an area of hight interest in supramolecular chemistry. The detection and cuantification is important in many fields of application such as environmental bioinorganic chemistry, developmental biology, clinical toxicology, waste management, and bioremediation of radionuclides and metal ions[1]. Besides, there is a growing concern for determining trivalent metal cations as Fe 3+ , Cr 3+ and Al 3+ which are highly toxic. Classic

the efficiency of the enantiomeric induction. We then turned our attention to evaluate the effect of the substitution at the amino group. For this reason, we evaluated aminoalcohols 6–8a,c and 10a,c with secondary and primary amino groups, structurally related to the most efficient catalysts 5a and 5c containing a tertiary amino group. The reactions catalyzed by these 1,2-amino- alcohols (entries 6–12) afforded the addition product in good to excellent yields. The induction capacities observed were from moderate to low. The comparison of the inductive capacity between all chiral ligands evaluated demonstrates that the most Table 1

In light of this information, it seems that the relationship between Yahweh and Edom, and perhaps, though less explicit, Yahweh and Qos, can be explained in three ways. The first explanation is the idea set forth above, that Yahweh and Qos were both manifestations of the syrian storm deity known from the general milieu of syria-Palestine, who were endowed with traits indigenous to their local worshippers. This is a viable perspective in the sense that the inhabitants of the steppe were dependent on their deities for rain and defense of their territory from enemies, hence the typical role of the storm-god as warrior and bringer of fertility. The southern origin of both Qos and Yahweh warrants an understanding of these deities as storm-gods, though a connection with the northern storm-deity Hadad, or his Canaanite counterpart, Baal, is not necessary. 5

One key area that appears to have been affected is reflection. Reflection is what enables us, according to many theorists, to generalize, as we create “mental models” from our experience. It is, in many ways, the process of “learning from experience.” In our twitch-speed world, there is less and less time and opportunity for reflection, and this development concerns many people. One of the most interesting challenges and opportunities in teaching Digital Natives is to figure out and invent ways to include reflection and critical thinking in the learning (either built into the instruction or through a process of instructor-led debriefing) but still do it in the Digital Native language. We can and must do more in this area.

Attitudinal Loyalty, favorable attitude toward a brand or purchase intention. It is composed of : cognitive aspects that are based on current psychological cogni- tivism, previous knowledge of brand, brand value (Oliver, 1999; Jacoby & Kyner, 1973), emotional states, humor, feelings (Dick & Basu, 1994), impulses, expecta- tions and switching costs (Nath , 2005) purchase intention (Dall'Olmo R., et al., 1997). Social aspects, consumers exhibit loyalty to a brand influenced by the so- cial group to which they belong. Some factors have been studied such as social pressure, social hierarchy (Shouten & McAlexander, 1995) recommendation, so- cial motivation (family, friends, and community) and as a personal effort to be in- tegrated into a community (Oliver, 1999). Behavioral Loyalty has been the pio- neering approach. In early research, loyalty is studied through the “repeat purchase” paradigm (Ehrenberg, et al., 1990). Other studies measure customer loyalty based on market share, sales, etc. (Uncles, et al., 2003). Combination of perspectives (attitudinal and behavioral): favorable attitude toward a brand and repeat purchase. Baldinger & Robinson (1996) y Uncles et al. (2003) were among the first authors to indicate the importance of measuring loyalty as an attitude and behavior at a time. Other researches refer the multidimensional loyalty (Kuo, et al., 2004).

relevant contributions. The new approaches rework and broaden the significance and scope of industrial heritage, giving priority to the interpretation of these assets, not as mere isolated elements, but as part of their territorial context. At the same time, the value of the intangible assets of the industrial culture is stressed, as are the testimonies and memories of work. It is a renewed, integral and geographic vision that gives pride of place to the industrial landscape, identified as the result of a process that configures space in line with the productive needs, creating buildings, artefacts, machines, communication and energy infrastructures, systems and networks of spaces (Humanes, 2011). The landscape is understood and interpreted globally, as a result of a historical process that organises a territory built up of «cultural and natural elements, material and immaterial elements, tangible and intangible elements, whose interrelations determine their character; (…) the spatial structure that springs from this process is a cultural landscape» (Cruz, 2011: 44). In this sense, each productive activity designs specific ways of organising the territory; so the mining valleys, the steelworks, the textile colonies, the shipyards, the workers’ villages, the energy, communications and transport installations, or the railway lines and infrastructures, all acquire the consideration of landscapes of cultural interest that must be interpreted within the framework of complex territorial, heritage systems (Cruz, 2012).