Journal of Molecular Structure 979 (2010) 56–61

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Journal of Molecular Structure

journal homepage: www.elsevier .com/locate /molstruc

Intramolecular hydrogen bond stabilization of hemiaminal structures, precursorsof imidazo[1,2-a]pyridine

Manuel Velázquez a, Héctor Salgado-Zamora a,*, Cuauhtémoc Pérez b, Ma Elena Campos-A a,Patricia Mendoza a, Hugo Jiménez a, Rogelio Jiménez a

a Departamento Química Orgánica, Escuela Nacional Ciencias Biológicas, I.P.N., Prolongación Carpio y Plan de Ayala S/N, México 11340, D.F., Mexicob Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico

a r t i c l e i n f o

Article history:Received 28 October 2009Received in revised form 28 May 2010Accepted 29 May 2010Available online 8 June 2010

Keywords:HemiaminalHydrogen bondIntramolecular interactionAromatic stabilityImidazo[1,2-a]pyridine

0022-2860/$ - see front matter � 2010 Elsevier B.V. Adoi:10.1016/j.molstruc.2010.05.044

* Corresponding author.E-mail address: hsalgado47@hotmail.com (H. Salg

a b s t r a c t

A theoretical study supported by calculations at the B3LYP/6-31+G and B3LYP/6-311++G(d,p) levels dem-onstrated that an attractive interaction involving a hydrogen bond between a hydroxyl group and anacceptor halogen atom (O–H� � �Cl) is present in 2,3-dihydro-2-hydroxy-2-chloromethylimidazo[1,2-a]pyridinium salts, which have an hemiaminal structure. However, the conformers obtained from a dihe-dral angle analysis performed upon these hemiaminal structures showed relatively small differences inenergy among them, indicating that the hydrogen bonding interaction is not entirely responsible forpreventing the aromatization process. Calculations were carried out on the gas phase of the hemiaminalcation 6b and the corresponding fully aromatic heterocycle cation 8b. It was found that the difference inenergy between the two species is rather small, suggesting that other factors must be contributing to thehemiaminal isolation. The fact that a hydrogen bond is a stabilizing element of the hemiaminal suggeststhat the formation process of this compound should be favored in aprotic solvents. Accordingly, the con-densation of several 2-aminopyridines with 3-bromo-1,1,1-trifluoroacetone was revised. The reactionperformed in dry acetone (a non-competing hydrogen bond solvent) proceeded to the hemiaminal deriv-ative, thus confirming the prediction made by theoretical calculations.

� 2010 Elsevier B.V. All rights reserved.

1. Introduction

The imidazo[1,2-a]pyridine nucleus has attracted considerableattention due to the wide variety of pharmacological activitiesexhibited by derivatives of the heterocycle [1]. Therefore it is notsurprising that numerous synthetic routes to this heterocyclicsystem have been developed [2]. The most common approach tothe synthesis of imidazo[1,2-a]pyridines (1) involves the conden-sation of a-halocarbonyl compounds with 2-aminopyridines(Scheme 1) [3,4]. The mechanism of the process has been investi-gated in relation to several parameters that are involved [5]. Theintermediacy of aminals of the type (2) in the synthesis of 1-alky-limidazo[1,2-a]pyridinium salts (3) has been demonstrated [6,7].Brief heating of (2) in 48% hydrobromic acid gave the correspond-ing imidazopyridinium salt (3).

In a detailed mechanistic study [8] based upon the analysis ofspectral (1H NMR) changes at varying times, it was possible todetect the formation of the intermediate salt (4) in equilibriumwith the neutral aminal structure (5), which eventually dehydratedto give the 2-arylimidazo[1,2-a]pyridine system, although none of

ll rights reserved.

ado-Zamora).

the intermediates was isolated. An extended investigation involv-ing the condensation of 2-aminoazines with 1,3-dibromo and1,3-dichloroketones in ethyl acetate, also led to the isolation ofquaternary salts of type 6 [9]. Similarly, the reaction of 2-amino-pyridine with 3-bromo-1,1,1-trifluoroacetone in anhydrous ethylalcohol (at room temperature) produced the hemiaminal deriva-tive (7a) [10]. However, no other hemiaminal derived from othersubstituted 2-aminopyridines was obtained, instead the corre-sponding aromatic 2-trifluromethylimidazo[1,2-a]pyridine wasisolated, a fact that attracted our attention.

Aminals and hemiaminals derived from acetone or electron-withdrawing substituted aryl aldehydes have been detected by nu-clear magnetic resonance [11,12]. Aminals stabilized by verystrong electron-withdrawing groups (such as CF3–) have been iso-lated [13]. Hemiaminals and aminals exist in natural products,sometimes in very crowded environments and the stability ofthese is explained by invoking intramolecular hydrogen bonding,electronic effects and other attractive interactions [14–21]. Thecarbon atom at position 2 of structure (6) carries a chloromethylmoiety and a hydroxyl group, which should give rise to an attrac-tive interaction involving a hydrogen bond. Then, one could spec-ulate whether such an interaction would be sufficient enough tostabilize the hemiaminal structure, preventing the aromatization

N NH2

N

NR1

OH

R2

N

N OH

R1

XCHRCOR1

N

NR2

Br

N

N OH

CF3N

NH OHCl

R

2

5

7 a, R = H6

R1 = AlkylR2 = Ph

N

NR1

R1

48% HBr

3Br

R1

N

NH OH

R1

4

-H2O

R1 = 4-MeC6H4, 4-MeOC6H4,Ph

-H+

H+

+ HX

R

Cl

Scheme 1. Hemiaminals and aminals from imidazo [1,2-a] piridinium. Table 1Preparation of 2,3-dihydro-2-hydroxy-2-chloromethylimidazo[1,2-a]pyridinium salts6.

Compound R Yield (%) m.p. (�C)

6a 6-Br 45 290 dec6b H 65 220–2216c 5-Br 60 290–2926d 6-Br, 8-Me 36 195–197

N

Br

NH2

+ Cl ClO

acetone,rt

N

N OH

Cl

H

Br

N

N

Br

D2O

6a

Cl

(-H2O)

5

78

H

Cl

Cl

N

N OH

Cl

H

Br Cl5

78

8a

Scheme 2. Hemiaminals 6a from the condensation reaction of 2-amino-5-bromo-pyridine and 1,3-dichloroacetone in dry acetone.

M. Velázquez et al. / Journal of Molecular Structure 979 (2010) 56–61 57

process. Accordingly, a theoretical study was launched aimed atdemonstrating the existence of an intramolecular O–H� � �Cl hydro-gen bond in hemiaminal (6) and the extent to which such an inter-action accounts for the stability of cation (6). In addition, acomparison was made between the relative energy of (6) and thatof the corresponding aromatic heterocycle (8). Finally, the reactionof various 2-aminopyridines with 3-bromo-1,1,1-trifluoroacetone(in dry acetone) was re-investigated in order to demonstrate thatavoidance of hydrogen bonding solvents in this type of reactionshould favour the formation of the hemiaminal species.

2. Results and discussion

In a routine experiment, treatment of 2-amino-5-bromopyri-dine with 1,3-dichloroacetone did not afford the expected 2-chlo-romethylimidazo[1,2-a]pyridine derivative. Instead, a compoundwas isolated for which the hemiaminal structure 6a was proposedbased upon the literature [9] and spectroscopic information(Scheme 2). In the 1H NMR spectrum, the isolated product showedthe usual pattern of a pyridinium salt: H-5 appeared as a doublet(J = 1.6 Hz) at d 8.75, H-7 gave a doublet (J = 9.6) at d 8.19, andH-8 resonated at d 7.11 (J = 9.6 Hz). Protons at position 3 weremagnetically non-equivalent and gave a double of doublets at d4.71 and d 4.60 (J = 12 Hz) (cf. the chemical shifts and J values forthe geminal protons in structure 7a, d 5.14 and 4.86, J = 16 Hz[10]). The methylene protons adjacent to the chlorine atom gavean apparent singlet at d 3.89. In the 13C NMR spectrum, the meth-ylene carbons appeared at d 47.93 and 60.17. The signal at d 89.10(a quaternary carbon atom, confirmed by a DEPT experiment) isindicative of a saturated carbon atom attached to two heteroatoms.The reaction was carried out with other substituted 2-aminopyri-dines and afforded products 6b–d in the yields shown in Table 1.The isolated compounds showed NMR spectra similar to that de-scribed for 6a, and only in compound 6d, the methylene protons

adjacent to the chorine atom split into doublets with J = 11.2 Hz.Upon addition of deuterium oxide to the NMR tube, a set ofadditional signals appeared in both 1H and 13C NMR spectra. Thesesignals correspond to the conjugated acid, the fully aromatic imi-dazo[1,2-a]pyridine system, 8a [22]. Integration of the 1H NMRspectrum indicates that in solution both products coexist in a 1:1ratio. The experiment with D2O suggests that the presence of watertriggers aromatization but, on the other hand, the 1:1 ratio may bealso indicative of a similar energy content of the non-aromatizedand the aromatized species. Compound (8a) was also obtained byheating intermediate 6a for a brief period with ethyl alcoholcontaining aqueous HCl.

2.1. Theoretical calculations

An analysis of the dihedral angles of different conformationalarrays involving atoms N1, C2, C3, C10, O11, H16 and Cl16 ofstructure 6b was carried out at a DFT B3LYP/6-31+G level of theory,using the Gaussian 94 package of programs [23], with the supportof GaussView [24] and MOLDEN [25]. Accordingly, the dihedral an-gles (h) comprising the hydroxyl and chloromethyl moieties wererotated simultaneously 360� by 30� increments and plotted againstthe resultant energy of each modified structure. A pair of potentialenergy plots, each one with a fixed dihedral angle in the envelope-shaped five-membered conformer was obtained.

The minimum energy geometries found were re-optimized atthe B3LYP/6-311++G (d,p) DFT level and submitted to frequency

58 M. Velázquez et al. / Journal of Molecular Structure 979 (2010) 56–61

calculations to obtain the zero point energy (ZPE) correction for theelectronic energy. The results obtained confirmed that the set ofconformers are stationary points on the potential energy surface.Fig. 1 shows the seven minima obtained and Table 2 summarizessome relevant geometrical information. From the energy dataand the Boltzmann distribution law, the equilibrium percent pop-ulation of each conformer at 25 �C, was calculated, results are sum-marized in Table 3. The aim of this part of the study was toinvestigate the possible existence of an attractive hydrogen bond-ing interaction that would provide added stability to cation 6b, ascompared to the aromatized conjugated acid, imidazo[1,2-a]pyri-dine 8b.

The geometry of the two lowest-energy minima found (B and C)suggests that a gauche effect may be operating in the array O11–C2–C10–Cl12 of 6b. However, the fact that the gauche conformerF is much less stable than either B or C suggests that the stabilityof the latter two conformations arises essentially from an attractiveinteraction between the hydroxyl hydrogen and the chlorine atom.

Fig. 1. The seven minima (A–G) found for hemiaminal cation 6, B is the global minimumwas used to calculate the interconversion energy barrier.

Then, the corresponding O–H� � �Cl interatomic distances were mea-sured and the values found (Table 4) were shorter than the sum ofthe van der Waals radii (2.95 ÅA

0

) of the atoms involved, suggesting ahydrogen bonding interaction [26,27]. From the same table it isinteresting that the conformer with the shortest interatomic dis-tance is also the one with the lowest energy. In addition, and in or-der to detect the possible existence of bond critical points (BCP)which may be indicative of an electronic density transferencethrough space between the chlorine and hydrogen atoms, an AIManalysis using the wave function generated from Gaussian 94 wascarried out with the AIMAll program [28]. Since no BCP’s werefound, the hypothesis of the electrostatic character of the attractiveinteraction was reinforced.

The kinetic stability of hemiaminal derivatives 6 in aprotic sol-vents cannot be ascribed solely to the hydrogen bonding attraction(cf. stability factors in trans 2-halocyclohexanols [29]) and 2-chlo-roethanol [30–34], despite the strength of this interaction, whichcan be deduced from the gas phase relative energies of the

and C is the conformer with the second lowest energy. Conformational structure H

Table 2Geometrical description of the minima found for the theoretical model of hemiaminalcation 6b.

N

N OH

Cl

H

1

2

34

511

10

12

16

hemiaminal

Conformer (h) (N1–C2–O11–H16)

(h) (N1–C2–C10–Cl12)

(h) (C2–C3–N4–C5)

A 77.7 56.0 350.1B 83.4 292.9 345.9C 160.9 179.3 346.3D 160.3 59.3 350.0E 310.9 58.8 3.6F 293.7 167.9 248.7G 317.0 306.1 7.3

Table 3ZPE-corrected values of electronic energy (B3LYP/6-311++G(d,p)), and equilibriumpopulations at 25 �C (298 K), according to the Boltzmann distribution law. The energyvalues (DE0) are relative to the global minimum.

Conformer DE0 (kcal/mol) Population (%)

A 1.47 5.30Ba 0.00 79.51Ca 1.03 11.83D 2.18 1.43E 2.03 1.88F 4.62 0.02G 4.17 0.04

a Lowest energy conformer.

Table 4Interatomic distances between the chlorine (chloromethyl moiety) and hydrogen(hydroxyl moiety) atoms.

Conformer Interatomicdistance (Å)

Relative energy,DE0 (kcal/mol)

Parameter (sum of vander Waals radii)

B 2.55 0.00 2.95 ÅC 2.59 1.03

M. Velázquez et al. / Journal of Molecular Structure 979 (2010) 56–61 59

conformers of 6b. Or following Sayer and Jencks [34], the mainte-nance of a significant overlap and bonding with the departing oxy-gen and hydrogen in an sp3 hybridized transition state is morethan enough to offset the stabilization provided by the aromaticsystem. However, the relatively small differences in energy be-tween the conformers suggest that the barriers for interconversionbetween them should not be high, meaning that at the tempera-ture of the experiment, elimination to yield the aromatic heterocy-

N NH

Cl

H

O

N N

Cl

H

+ H2O

ΔE0 = 2.1 kcal/mol

8b E = 0.0 kcal/mo

6b

8b

Scheme 3. Relative energies of hemiaminal 6b and t

cle could take place even in some of the more energeticconformations. Therefore, a comparison was carried out betweenthe thermodynamic stability of the global minimum of the hemia-minal cation 6b in equilibrium with the corresponding aromaticspecies 8b (Scheme 3).

The relative energies found indicate that the aromatic heterocy-cle is slightly more stable than the hemiaminal. However, these re-sults correspond to gas phase calculations, and it is more likely for

l

Global minimum of 2-chloromethylimidazo[1,2-a]pyridinium

he fully aromatic imidazo [1,2-a] piridinium 8b.

60 M. Velázquez et al. / Journal of Molecular Structure 979 (2010) 56–61

the energy difference to be smaller in solution, as implied by the1:1 ratio of compounds 6a and 8a observed in the 1H NMR spec-trum upon addition of deuterated water (vide supra). In any event,the theoretical and experimental results support the idea that thestability provided by the aromatization of the fused heterocycle 8is very similar to that provided by the aromaticity of the pyridinering in 6. Thus, the isolation of hemiaminal 6 as the single productin acetone may be attributable to a kinetic barrier for aromatiza-tion. Approximations were made to elucidate the energy barrierbetween conformers: Conformers A and B are related through rota-tion of the C–C bond that connects the five-membered ring withthe chloromethyl moiety, such rotation was taken into accountto estimate the energy barrier of a minimum where an intramolec-ular attraction is present, with another in which such attraction isabsent and therefore the dehydration process should easily occur.Thus, this calculation would open the possibility of knowing thenecessary energy to offset the attractive force. After applying theGaussian QST3 method to optimize transition states and calcula-tions at the DFT/B2LYPS level (basis set 6-311++G(d,p)), the corre-sponding geometry H (Fig. 1) for interconversion of conformer Binto conformer A was found. Geometry H involves a conformer inwhich the C–Cl bond is eclipsed with the C2–N1 bond of thefive-membered ring, it was optimized and subjected to avibrational analysis. Only one imaginary frequency, the vibrationassociated to the interconversion of conformers A and B(�92.50 cm�1) was found and the calculated rotational energybarrier was 6.41 kcal/mol. Thus suggesting that the dehydrationprocess is kinetically controlled.

On the other hand, it would be expected that in polar protic sol-vents, the favored elimination process leading to 8 takes place,probably via protonation of the hydroxyl group. In aprotic solvents,such as acetone or ethyl acetate, such an event does not take place.However, the protonating character of the medium increases whenD2O is added. That is, water may be playing the role of a catalysttriggering the aromatization process.

Finally, the condensation of several 2-aminopyridines with 3-bromo-1,1,1-trifluoroacetone was carried out in the presence of

N NH2

+ BrCF3

O

acetone, rt

N

N OH

CF3

H

7

Br

R

Scheme 4. 2,3-Dihydro-2-hydroxy-6-bromo-2-trifluoromethylimidazo [1,2-a]pyridinium bromide.

Table 5Preparation of 2,3-dihydro-2-hydroxy-2-trifluoromethylimidazo[1,2-a]pyridiniumsalts 7.

Compound R Yield (%) m.p. (�C)

7a H 90 288 deca

7b 6-Br 45 294–2967c 5-Me 70 289–2907d 6-Br, 8-Me 50 268–269

a Lit. [10] m.p. > 270 �C dec.

dry acetone to demonstrate the hypothesis that formation of thehemiaminal should be favored with the use of aprotic solvents. In-deed the corresponding hemiaminal derivatives 7a–d were formed(Scheme 4) and isolated in the yields shown in Table 5, thus sup-porting the aforementioned hypothesis.

3. Conclusion

In agreement with the results obtained from theoretical calcu-lations, a hydrogen bond interaction of the type O–H� � �X existsin hemiaminal structures 6 and 7. However, this attractive interac-tion is only partially responsible of the intermediate hemiaminalstructure that prevents the aromatization process to take place.Additional factors should be contributing to the stabilization ofthe amino-alcohol intermediate such as structural features, thepresence of the pyridine moiety and other electronic attractiveinteractions. The successful condensation reaction of substituted2-amino pyridines with 1,3-dichlororoacetone and with 3-bro-mo-1,1,1-trifluroacetone to give the corresponding 2-hydroxy-2,3-dihydroimidazo[1,2-a]pyridinium salts in dry acetone, showedthat this reaction is favoured in non-protic solvents.

4. Experimental

Melting points were measured on an electrothermal meltingpoint apparatus and are uncorrected. 1H and 13C NMR spectral datawere recorded at 400 and 100 MHz, respectively using a Varian 400BB spectrometer. Chemical shifts (d) are given in parts per milliondownfield from TMS (d = 0).

General procedure for the reaction of 2-aminopyridines with1,3-dichloroacetone and 3-bromo-1,1,1-trifluoroacetone.

Under a nitrogen atmosphere, a solution of 2-aminopyridine(5.3 mmol) in acetone (5 mL) was stirred at room temperature.To this solution, a previously prepared solution of 1,3-dichlotoace-tone or 3-bromo-1,1,1-trifluoroacetone (5.3 mmol) in 5 mL of ace-tone was added. After a period of time (1–12 h) a precipitate wasformed, which was collected by filtration. The solid was washedwith cold acetone (2 � 5 mL) and dried. Re-crystallization from iso-propyl alcohol may be carried out to increase purity of the crudeproduct.

2,3-Dihydro-2-hydroxy-6-bromo-2-chloromethylimidazo[1,2-a]pyridinium chloride, 6a. Isolated as a white powder, mp. 290–292 �C. 1H NMR (DMSO-d6) d: 8.75 (d, 1H, J = 2.0 Hz), 8.18 (dd,1H, J = 2.0 Hz, J = 9.6 Hz), 7.11 (d, 1H, J = 9.6 Hz), 4.71 (d, 1H,J = 14 Hz), 4.60 (d, 1H, J = 14 Hz), 3.96 (s, 2H). 13C NMR d: 152.60,146.87, 137.45, 110.10, 104.73, 89.10, 60.17, 47.93. Anal. Calcd.for C8H9BrCl2N2O: C, 32.00: H, 3.00; N, 9.33. Found: C, 31.64; H,3.37; N, 8.96.

2,3-Dihydro-2-hydroxy-2-chloromethylimidazo[1,2-a]pyridini-um chloride, 6b. Isolated as a whitish powder, m.p. 288 �C. 1H NMR(DMSO-d6) d: 8.39 (d, 1H, J = 8.8 Hz), 8.03 (dt, 1H, J = 2.0, J = 12 Hz),7.14 (dd, 1H, J = 1.2, J = 12 Hz), 7.05 (ddd, 1H, J = 1.2, J = 8.8,J = 12 Hz), 4.76 (d, 1H, J = 18 Hz), 4.66 (d, 1H, J = 18 Hz), 4.00 (s,2H). 13C NMR d: 153.63, 144.77, 137.25, 113.70, 108.80, 88.67,59.87, 48.05. Anal. Calcd. for C8H10Cl2N2O: C, 43.43: H, 4.52; N,12.67. Found: C, 42.89: H, 5.00; N, 12.19.

2,3-Dihydro-2-hydroxy-5-bromo-2-chloromethylimidazo[1,2-a]pyridinium chloride, 6c. Isolated as a light brown powder, m.p.290 �C (dec). 1H NMR (DMSO-d6) d: 7.90 (s, 1H), 7.31 (s, 1H), 7.09(d, 1H, J = 7.6 Hz), 4.71 (d, 1H, J = 12 Hz), 4.60 (d, 1H, J = 12 Hz),3.97 (s, 2H). 13C NMR d: 155.0, 145.27, 128.23, 107.50, 87.68,65.19, 48.07. Anal. Calcd. for C8H9BrCl2N2O: C, 32.00: H, 3.00; N,9.33. Found: C, 32.39; H, 3.41; N, 9.09.

2,3-Dihydro-2-hydroxy-6-bromo-2-chloromethyl-8-methylim-idazo[1,2-a]pyridinium chloride, 6d. Isolated as a whitish powder,

M. Velázquez et al. / Journal of Molecular Structure 979 (2010) 56–61 61

m.p. 195–197 �C. 1H NMR (DMSO-d6) d: 8.59 (s, 1H), 8.13 (s, 1H),4.75 (d, 1H, J = 14 Hz), 4.64 (dd, 1H, J = 14 Hz), 3.97 (d, 1H,J = 11.2), 3.94 (d, 1H, J = 11.2 Hz), 2.24 (s, 3H). 13C NMR d: 152.40,126.26, 114.10, 92, 60, 56, 16.12. Anal. Calcd. for C9H11BrCl2N2O:C, 34.39: H, 3.50; N, 8.91. Found: C, 33.99: H, 3.98; N, 8.56.

6-Bromo-2-chloromethylimidazo[1,2-a]pyridine, 8b. Isolatedas a white powder, m.p. 125–126 �C (lit. [22] m.p. 127.7 �C). 1HNMR (DMSO-d6) d: 8.9 (s, 1H), 7.99 (s, 1H), 7.46 (d, 1H,J = 9.6 Hz), 7.39 (dd, 1H, J = 2.0 Hz, J = 9.6 Hz), 4.86 (s, 1H). 13CNMR d: 142.9, 142.8, 128.1, 127.11, 117.7, 112.3, 105.9, 39.6.

2,3-Dihydro-2-hydroxy-6-bromo-2-trifluoromethylimidazo-[1,2-a]pyridinium bromide, 7b. Isolated as a white powder, m.p.295–297 �C. 1H NMR (DMSO-d6) d: 8.69 (d, 1H, J = 1.2 Hz), 8.0 (dd,1H, J = 2.0 Hz, J = 2.0 Hz), 7.20 (t, 1H, J = 6.0 Hz), 5.22 (d, 1H,J = 15 Hz), 4.86 (d, 1H, J = 15 Hz). 13C NMR d: 153.6, 147.4, 136.7,123.1, 110.9, 107.2, 88.2, 58.5. Anal. Calcd. for C8H7Br2F3N2O: C,26.37; H, 1.92; N, 7.69. Found: C, 25.97; H, 2.20; N, 7.33.

2,3-Dihydro-2-hydroxy-5-methyl-2-trifluoromethylimidazo-[1,2-a]pyridinium bromide, 7c. Isolated as a whitish powder, m.p.290–292 �C. 1H NMR (CDCl3) d: 7.92 (dd, 1H, J = 7.6 Hz,J = 1.2 Hz), 7.06 (d, 1H, J = 8.8 Hz), 6.92 (d, 1H, J = 7.6 Hz), 5.0 (d,1H, J = 14 Hz), 4.83 (d, 1H, J = 14 Hz), 2.63 (s, 3H). 13C NMR d:154.4, 147.4, 144.9, 115.0, 106.6, 94.1, 87.4, 56.37, 19.0. Anal.Calcd. for C9H10BrF3N2O: C, 36.12: H, 3.34; N, 9.37. Found: C,35.78: H, 3.51; N, 9.02.

2,3-Dihydro-2-hydroxy-6-bromo-8-methyl-2-trifluoromethy-limidazo[1,2-a]pyridinium bromide, 7d. Isolated as a beige powder,m.p. 268–269 �C. 1H NMR (DMSO-d6) d: 8.68 (d, 1H, J = 1.2 Hz), 7.91(s, 1H), 7.65 (s, 1H), 5.17 (d, 1H, J = 15 Hz), 4.97 (d, 1H, J = 15 Hz),2.39 (s, 3H). 13C NMR d: 153.7, 146.8, 134.6, 123.73, 122.3, 122.16,107.6, 87.8, 59.1, 17.0. Anal. Calcd. for C9H9Br2F3N2O: C, 28.57; H,2.38; N, 7.40. Found: C, 28.15; H, 2.43; N, 7.07.

Acknowledgment

Financial support from Consejo Nacional de Ciencia y Tec-nología CONACYT MEXICO through Grant No. 49937 is gratefullyacknowledged.

Appendix A. Supplementary data

Supplementary data associated with this article can be found, inthe online version, at doi:10.1016/j.molstruc.2010.05.044.

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