Synthesis of Novel Pyridinium Betaine Precursors ... - IngentaConnect

Letters in Organic Chemistry, 2011, 8, 249-257

249

Synthesis of Novel Pyridinium Betaine Precursors from exo-Norbornene Dicarboximides Julia V. Hernández-Madrigal*,1, Armando Pineda-Contreras1, Oscar F. Vázquez-Vuelvas1, Mikhail A. Tlenkopatchev2, Héctor García-Ortega3, Rubén Gaviño-Ramírez4 and Zeferino Gómez-Sandoval1 1

Facultad de Ciencias Químicas, Universidad de Colima, Km 9 Carretera Colima-Coquimatlán, Apartado Postal 29000. Coquimatlán, Colima, México 2

Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México, Apartado Postal 70360, CU, Coyoacán, México DF 04510, México 3

Facultad de Química, Universidad Nacional Autónoma de México, Apartado Postal 70360, CU, Coyoacán, México DF 04510, México 4

Instituto de Química, Universidad Nacional Autónoma de México, Apartado Postal 70360, CU, Coyoacán, México DF 04510, México Received July 29, 2010: Revised December 09, 2010: Accepted March 14, 2011

Abstract: N-heterocyclic norbornene Dicarboximides were synthesized by reacting the exo-norbornene-5,6-dicarboxylic anhydride with 2-, 3-, and 4-aminopyridine. The amides resulting from 3 and 4-aminopyridine derivatives were converted into the corresponding betaines via Menshutkin reaction using ethyl-bromoacetate. The chemical structures of the obtained products were confirmed by FT-IR and 1H and 13C NMR spectroscopy, EA and MS as well as by calculation of 1 H and 13C NMR chemical shifts using the GIAO method (PW91/6-311G++ (3df, 3pd) approximation by GAUSSIAN and PW91/IGLO-III approximation by deMon2k).

Keywords: Betaine precursors, dicarboximides, Menshutkin reaction, norbornene, pyridinium, zwitterions. INTRODUCTION The pyridine ring plays a key role in several biological processes and many derivatives are used as therapeutic agents, antibacterials, antimicrobial agents, antihistaminic, antihypertensives, for activating potassium channels, and for the treatment of ulcerative colitis [1-5]. Recently, there has been an increasing number of publications dealing with new structures, for instance pyridinium betaines have taste properties, such as bitter inhibitor [6] and taste enhancer [7], among other. Heterocyclic pyridinium betaines have unusually large dipole moments since contain both negatively charged aromatic electron-donating and positively charged aromatic electron-withdrawing groups which satisfy the requirement of a short-range charge transfer for secondorder nonlinear optical applications [8]. Another application of betaines is solvatochromism, in which the standard betaine has been used to introduce spectroscopically an empirical scale of solvent polarity [9]. Norbornene derivatives have been used for the synthesis of high molecular weight polymers with novel versatile and complex molecular architectures. The ring-opening metathesis polymerization (ROMP) of this kind of compounds using *Address correspondence to this author at the Facultad de Ciencias Químicas, Universidad de Colima, Km 9 Carretera Colima-Coquimatlán, Apartado Postal 29000. Coquimatlán, Colima, México; Tel/Fax: 011 52 312 316 1163; E-mail: [email protected]

1570-1786/11 $58.00+.00

both classical and well-defined initiators [10, 11] in aqueous media, is a well established process [12-14]. In this paper, we reported the synthesis and characterization of novel pyridinium betaine precursors by reacting the exoNorbornene-5,6-dicarboxylic anhydride with 2-, 3-, and 4aminopyridines, which were further transformed to a pyridinium zwitterionic. These monomers could undergo ROMP to give linear norbonene based polybetaines using well-defined initiators. EXPERIMENTAL PROCEDURE Techniques 1

H NMR (200, 300 and 400 MHz) and 13C NMR (75 and 100 MHz) spectra were recorded using a Bruker Avance III spectrometer with tetramethylsilane (TMS) as internal standard. IR spectra were recorded with Varian 3100 FT-IR Excalibur Series. Elemental analysis was carried out using Perkin Elmer 2400, Series II CHNS/O Elemental Analyzer, using cystine as standard. Decomposition points were determined using Mettler Toledo TGA/SDTA851 and DSC StarSystem. Gas chromatography-mass spectrometry (GCMS) analysis was performed in a Varian Saturn 2100T GC/MS mass spectrometer interfaced to a Varian 3900 gas chromatograph. equipped with a VF-5ms capillary column (30 m x 0.25 mm).

© 2011 Bentham Science Publishers Ltd.

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Letters in Organic Chemistry, 2011, Vol. 8, No. 4

Reagents All solvents were distilled before using according to general purification procedures. Chlorobenzene was purchased from Riedel-de Haën and 1,2-dichloroethane from Spectrum Chemical Mfg. Corp. All other reagents were acquired from Aldrich and used without further purification. The exo-Norbornene-5,6-dicarboxylic anhydride (1) was prepared according to literature [15]. N-(2-pyridyl)-exo-Norbornene-5,6-dicarboximide (2a) To a solution of 1 (3.12 g, 19.0 mmol) in xylene (29 mL), 2-aminopyridine (1.79 g, 19.0 mmol) was added, the mixture was heated at reflux for 3 h. After cooling the mixture to room temperature, the precipitate was removed by filtration under a vacuum. The collected filtrate was re-crystallized twice from a toluene. The compound 2a was obtained as white crystals in 81% yield (3.70 g, 15.4 mmol). m.p. 189-191 °C, 1H NMR (300 MHz, CDCl3, 298 K) , ppm, 8.65, 7.85, 7.36, 7.28 (Harom), 6.34 (H-C=C, t, 2H), 3.4 (H-C-C=C, s, 2H), 2.8 (H-C-C=O, t, 2H), 1.6 (H-CH, m, 2H). 13C NMR (75 MHz, CDCl3) , ppm, 176.3 (C=O), 149.6, 145.9, 138.2, 123.8, 121.8, (Carom), 137.8 (C=C), 47.9 (Callylic), 45.7 (C), 42.8 (CH2). IR (KBr) 2992 ( C-H), 1760 (as C=O), 1698 (s C=O), 1467-1588 ( C=C, C=N Ar), 1366 ( C-N) cm-1. Anal. Calcd for C14H12N2O2: C, 69.99; H, 5.03; N, 11.66; O, 13.32. Found: 69.845; H, 5.135; N, 11.635. N-(3-pyridyl)-exo-Norbornene-5,6-dicarboximide (2b) To a solution of 1 (3.16 g, 19.3 mmol) in xylene (29 mL), 3-aminopyridine (1.82 g, 19.3 mmol) was added, the mixture was heated at reflux for 2 h. The resulting compound was slurry of amic acid, it was filtered and dried to yield 89% (4.43 g, 17.2 mmol). To a solution of amic acid in acetic anhydride (14.61 mL, 0.15 mmol), anhydrous sodium acetate (0.67 g, 8.11 mmol) was added. The mixture was heated and stirred for 4 h at 85°C and then directly precipitated into iced water. After stirring the mixture for 5 min, the precipitate formed was collected by filtration and washed with cold water. Once the product was dried under reduced pressure, the compound was re-crystallized from toluene twice and the solid was removed by filtration under a vacuum. The compound 2b was obtained as slight yellow hue crystals in 83% yield (3.43 g, 14.3 mmol). m.p. 182-184 °C, 1H NMR (200 MHz, CDCl3/DMSO, 298 K) , ppm, 8.58, 8.50, 7.73, 7.49 (Harom), 6.33 (H-C=C, t, 2H), 3.23 (H-C-C=C, s, 2H), 2.87 (H-C-C=O, s, 2H), 1.48 (H-CH, s, 2H). 13C NMR (75 MHz, CDCl3 /DMSO) , ppm, 174.5 (C=O), 147.2, 145.5, 132.5, 127.1, 121.9 (Carom), 135.9, (C=C), 45.9 (Callylic), 43.2 (C), 41.0 (CH2). IR (KBr) 2967 ( C-H), 1773 (as C=O), 1691 (s C=O) ,15821483 ( C=C, C=N Arom), 1378 ( C-N) cm-1. Anal. Calcd for C14H12N2O2: C, 69.99; H, 5.03; N, 11.66; O, 13.32. Found: C, 69.945; H, 5.120; N, 11.625. N-(4-pyridyl)-exo-Norbornene-5,6-dicarboximide (2c) Compound 2c was prepared in the same manner as 2a, in this time the mixture was heated at reflux for 4 h. The compound was obtained as slight yellow hue crystals in 76% yield (3.75 g, 15.6 mmol).

Hernández-Madrigal et al.

m.p. 158-160 °C, 1H NMR (300 MHz, CDCl3, 298 K) , ppm, 8.72 (Harom, m, 2H), 7.39 (Harom, m, 2H), 6.36 (H-C=C, t, 2H), 3.42 (H-C-C=C, t, 2H), 2.88 (H-C-C=O, d, 2H), 1.63 (H-CH, m, 1H), 1.43 (H-CH, m, 1H). 13C NMR (75 MHz, CDCl3) , ppm, 175.8 (C=O), 150.6, 139.3, 119.8 (Carom), 137.9 (C=C), 47.8 (Callylic), 45.9 (C), 42.9 (CH2). IR (KBr) 2979 ( C-H), 1776 (as C=O), 1699 (s C=O) ,1496-1582 ( C=C, C=N Arom), 1377 ( C-N) cm-1. Anal. Calcd for C14H12N2O2: C, 69.99; H, 5.03; N, 11.66; O, 13.32. Found: C, 69.815; H, 5.145; N, 11.665. N-(ethyl 3-pyridinium acetate bromide)-exo-norbornene5,6-dicarboximide (3b) To a stirring solution of 2b (2.63 g, 11.0 mmol) in chloroform (23 mL), ethyl bromoacetate (1.08 mL, 9.8 mmol) was added. The reaction was conducted at 50-55 °C for 96 h and during this period, the mixture turned yellow. The compound was precipitated with ethyl acetate twice. The solvent was decanted and the solid was dried under a vacuum. Compound 3b was obtained as a pale yellow powder in 65% yield (2.36 g, 5.8 mmol) m.p. 171 °C (dec), 1H NMR (400 MHz, TFA, 298 K) , ppm, 9.03, 8.61, 8.59, 7.97 (Harom), 6. 10 (H-C=C, m, 2H), 5.44 (H-CH-N+, d, 2H), 4.10 (COO-CH2, d, 2H), 3.15 (H-CC=C, d, 2H), 2.85 (H-C-C=O, m, 2H), 1.43 (H-CH, m, 1H), 1.13 (H-CH, m, 1H), 1.02 (H-CH2, m, 3H). 13C NMR (100 MHz, TFA) , ppm, 179.3 (C=O), 167.4 (C=O ester), 145.4, 143.7, 138.2, 133.0, 129.1 (Carom), 143.6 (C=C), 65.8 (N+CH2), 62.3 (O-CH2), 49.1 (CH-C=C), 46.6 (CH-C=O), 43.0 (CH2), 12.6 (CH3). IR (KBr) 2990 ( C-H), 1772 (as C=O), 1699 (s C=O), 1588, 1507 ( C=C, C=N Arom), 1368 ( CN), 1180, 1120 (as,s C-O) cm-1. Anal. Calcd for C18H19BrN2O4: C, 53.08; H, 4.70; Br, 19.62; N, 6.88; O, 15.71. Found: C, 52.887; H, 5.007; N, 6.780. N-(ethyl 4-pyridinium acetate bromide)-exo-norbornene5,6-dicarboximide (3c) The titled compound was prepared in the same manner as 3b, this time 1,2-dichloroethane was used instead of chloroform at 55-60 °C for 72 h. The solvent was removed under reduced pressure at 35°C and the crude material was subjected to purification by silica gel flash column (1,2dichloroethane) and washed with ethyl acetate and then with methanol. The residue was collected and the solvent was removed under reduced pressure at 35°C. Afterwards, the product was precipitated with diethyl ether. The solvent was decanted and the solid dried in vacuo (2 times). The titled compound was obtained as an orange powder in 89% yield (3.97 g, 9.7 mmol). m .p. 181.7 °C (dec), 1H NMR (200 MHz, CDCl3, 298 K) , ppm, 9.36, 8.31 (Harom), 6.29 (H-C=C, d, 2H), 6.05 (H-CHN+, t, 2H), 4.19 (COO-CH2, m, 2H), 3.32 (H-C-C=C, d, 2H), 2.99 (H-C-C=O, d, 2H), 1.52, (syn-H-CH, d, 1H), 1.35, (anti-H-CH, m, 1H), 1.23 (H-CH2, m, 3H). 13C NMR (75 MHz, D2O) , ppm, 175.4 (C=O), 166.0 (C=O ester), 147.4, 147.1, 121.2 (Carom), 138.0 (C=C), 63.2 (N+-CH2), 60.3 (OCH2), 48.2 (CH-C=C), 46.2 (CH-C=O), 43.5 (CH2), 14.0 (CH3). IR (KBr) 2984( C-H), 1778 (as C=O), 1716 (s C=O), 1637, 1514 ( C=C, C=N Arom), 1351 ( C-N), 1214, 1149 (as,s C-O) cm-1. Anal. Calcd for C18H19BrN2O4: C,

Synthesis of Pyridinium Betaine Precursors


251

O O

O

C Amic acid

O

N H

R

Toluene

1

O

+

reflux OH

O Xilene reflux 2a, 2c

R-NH2

(CH3CO)2O

N-R O

a: R=2-pyridyl b: R=3-pyridyl c: R=4-pyridyl

CH3COONa O N-R 2b, 2c

O

Scheme 1. Synthesis of dicarboximides 2a-2c.

53.08; H, 4.70; Br, 19.62; N, 6.88; O, 15.71. Found: C, 52.430; H, 5.035; N, 7.040. Computational Details Full geometry optimizations, without symmetry constraints, for all the N-heterocyclic norbornene dicarboximides, were performed within the density functional theory framework as implemented in Gaussian 03 [16] and deMon2k [17] programs. For Gaussian 03 code, the B3LYP hybrid functional in combination with the 6311G(d,p) [18-25] bases set, was employed. The calculations in the deMon2k program were performed with the local density approximation (LDA) using the Dirac exchange [26] in conjunction with the correlation functional proposed by Vosko, Wilk and Nusair (VWN) [27] employing the double plus valence polarization, DZVP [28], basis set and the A2 auxiliary function set [28] for the variational fitting of the Coulomb potential [29]. In order to discriminate between the minima and transition states of the optimized structures, harmonic frequencies were calculated. The magnetic isotropic shielding tensors were calculated using the standard GIAO/PW91 [30-34]/6-311++G (3df, 3pd) (Gauge-independent atomic orbital) [35] approach with the Gaussian 03 program package and GIAO/PW91/IGLOIII [36] approach with the deMon2k. RESULTS AND DISCUSSION Different methods to prepare norbornene dicarboximides have been reported: via Diels-Alder reaction between Table 1.

cyclopentadiene and N-alkylmaleimide [37], nucleophilic substitution of alkyl halides with norbornene dicarboximide [38, 39] and acylation of amines [39-42], among others. In this regard, norbornene-5,6-dicarboxylic anhydride (1) react readily with amines to the corresponding amic acids which are cyclized to imides using acetic anhydride as dehydrating agent. Therefore, in the present work, we describe the synthesis of exo-N-heterocyclic norbornene dicarboximides 2a-2c by reacting the exo-Norbornene-5,6-dicarboxylic anhydride with 2-, 3-, and 4-aminopyridines, respectively. Both, one and two-steps synthesis fashions were used, depending on the reactions conditions (Scheme 1). Table 1 shows that 2a can be prepared merely in one step fashion either in toluene or xylene, as can be seen xylene is an excellent solvent to prepare dicarboximides in a short reaction time and in a good yield (entry 1 and 2). The compound 2b was synthesized only in two-step fashion, an additional dehydrating step was required (entry 3). 3aminopyridine reacts with 1 to yield the amic acid which was cyclized to the dicarboximide 2b by using acetic anhydride as a dehydrating agent (Scheme 1). Dicarboximide 2c was synthesized by two steps fashion in toluene (entry 4) and by one step fashion with better yield in xylene (entry 5). Since 2- and 4-aminopyridine can exist in amine and imine forms, the nitrogen atom of the amino moiety is rich in electrons and consequently, the reaction can be carried out in one step (Scheme 2). IR, 1H and 13C NMR and DEPT spectra clearly confirmed the structure of the compounds. The IR of dicarboximides 2a-2c exhibit the typical absorption bands due to symmetric and antisymmetric stretching vibrations of

Reaction Conditions for the Synthesis of Dicarboximides 2a-2c

Entry

Compound

Solvent

Amic acid (%)

Yield (%)

Reaction time (hrs)

1

2a

Toluene

-

77

3

2

2a

Xylene

-

81

3

3

2b

Xylene

89

83

4

4

2c

Toluene

92

67

6

5

2c

Xylene

-

76

4

252


N

NH2

N


NH2

N H

NH2

NH2

NH

N

N

N H

NH

Scheme 2. Tautomerism of 2- and 4-aminopyridines.

the carbonyl groups (1691-1699 and 1760-1776 cm-1) and stretching C-N (1366-1378 cm-1). The NMR spectra of dicaboximides are very similar (Fig. 1); however, it is worth noting that the Hsyn and Hanti protons of the methylene bridge in the structure 2a appear as a single signal at higher field, probably because the chemical environment is the same. The spectrum of 2c indicates that these protons are nonequivalent and split in two peaks similar to the corresponding protons in 1 as well as other norbornene derivatives reported [41, 43]. However in compound 2b the 1H chemical shift of methylene bridge in CDCl3 is different with that in DMSO/CDCl3 (Fig. 1). In order to confirm proton assignment, magnetic shielding tensors were calculated by Gaussian03 and deMon2k program packages. Theoretical calculations were performed for lower energy conformations

of 2a and 2a’, 2b and 2b’ and 2c (Fig. 2), the results (Table 2) revealed that the protons of the bridging methylene group show different chemical shifts for each conformer. The prediction shows a single signal for both Hsyn and Hanti of 2a’ conformer, whereas for 2a conformer each hydrogen displays an own signal. In this case, the proton signal located directly above the carbonyl plane, Hsyn, is displaced downfield from Hanti signal, probably due to perturbations of the unshared electrons on the nitrogen on magnetically anisotropic properties of the carbonyl groups. The conformer 2a is approximately 371 cal·mol-1 lower in energy than 2a’ and in experimental conditions the conformers interconvert rapidly is detected by NMR causing that protons of the methylene bridge displayed a single signal in both CDCl3 and DMSO solvents.

Fig. (1). 1H NMR spectra of 2a’, 2b’ and 2c recorded in CDCl3, 2b in CDCl3/DMSO.


Table 2.


253

1 H and 13C Chemical Shifts in the NMR Spectra of Compounds 2a-2c, Calculated by the GIAO Method (PW91/6-311G++ (3df, 3pd) Approximation by GAUSSIAN and PW91/IGLO-III Approximation by deMon2k)

2a Atom

theo*

theo **

1-H

6.74

6.36

1´-H

6.77

6.38

2-H

3.41

3.13

2a' exp 6.34

2b

theo*

theo **

theo*

theo **

6.76

6.36

6.74

6.39

6.73

6.35

6.78

6.36

3.47

3.26

3.45

3.29

3.42 2´-H

3.50

3.26

3-H

2.68

2.58

2.59

2.52

anti 5-H

1.53

1.45

3.49

3.24

3.52

3.17

2.68

2.61

2.71

2.56

1.94

1.83

7-H

7.38

7.53

8-H

7.93

9-H

DMSO

CDCl3

6.33

6.35

2.87 2.74

2.64

2.63

2.61

1.60

1.50

1.59

1.49

1.62 syn 5-H

exp

3.23

2.88 3´-H

exp

2b'

2c

theo*

theo **

6.77

6.38

6.75

6.37

3.49

3.26

3.41

exp 6.36

theo*

theo **

6.75

6.38

6.77

6.37

3.47

3.27

3.49

3.19

2.70

2.56

2.61

2.60

3.42 3.48

3.20

2.67

2.60

2.88

2.88 2.74

2.63

1.62

1.58

1.49

1.63

1.57

1.47

1.46

1.51

1.44

1.43

1.49

1.43

1.48 1.60

1.48

1.57

1.48

7.28

7.47

7.66

8.00

8.60

7.73

7.67

8.05

8.66

7.39

7.87, 7.86

8.73, 8.74

8.49

7.85

7.89

7.48

7.46

7.06

7.49

7.41

7.43

7.05

8.72

9.04, 9.02

8.62, 8.61

7.34

6.94

7.36

7.34

6.93

8.85

8.44

8.50

8.58

8.84

8.44

-

-

-

10-H

8.86

8.49

8.65

8.90

8.51

9.19

9.64

8.58

8.58

9.19

9.68

-

-

-

1-C

147.3

148.3

146.8

147.8

147.0

148.7

146.8

183.9

147.0

148.0

135.9

133.6

146.9

148.1

55.5

53.7

56.0

53.4

55.5

52.6

54.9

53.3

179.6

184.6

179.5

184.4

137.8 1´-C

147.2

180.6

2-C

55.8

53.3

146.7

147.9

146.9

148.7

55.2

52.9

55.3

53.4

47.9 2´-C

56.7

53.4

3-C

55.8

53.7

45.9 55.0

52.6

56.0

53.0

55.3

53.2

55.6

52.4

45.7 3´-C

55.5

52.8

4-C

179.4

182.3

43.2 55.9

53.9

55.0

53.6

179.2

182.7

153.4

182.8

176.3 4´-C

178.3

180.6

5-C

49.3

47.1

6-C

153.9

7-C

174.5 178.3

181.0

153.4

183.7

42.8

49.2

47.8

49.1

47.2

41.0

148.1

145.9

153.9

151.9

178.9

147.9

127.3

126.8

121.8

126.3

125.1

135.7

8-C

139.5

154.4

138.2

139.5

140.0

9-C

126.2

154.4

123.8

125.8

10-C

153.2

151.9

149.6

154.0

137.9 147.0

148.0

55.8

53.0

47.9

47.8 55.3

52.9

55.3

148.7

45.7

45.9 55.2

53.1

153.3

148.6

176.3

175.8 153.4

182.9

43.1

49.1

47.3

42.9

48.9

47.2

127.1

128.4

179.2

134.1

139.3

143.5

144.9

148.1

132.5

133.6

134.5

132.9

150.6

122.7, 121.2

118.8, 119.1

126.4

125.8

121.9

123.6

125.3

125.9

119.8

156.4, 156.5

156.7, 156.6

126.6

179.8

154.3

145.5

147.0

179.7

154.4

-

-

-

154.2

152.0

150.5

147.2

149.2

152.7

150.8

-

-

-

*calculated by GAUSSIAN, calculated by deMon2k.

The compound 2b also has two conformations which are very close in energy, the conformer 2b is only 45 cal·mol-1 more stable than 2b’. The protons predicted theoretically for methylene bridge split in a doublet for 2b’ conformer, the Hsyn signal is displaced upfield from Hanti signal, while for 2b conformer such hydrogens appear as single signal. The difference in the chemical shifts between Hsyn and Hanti decreases in going from 2a to 2b. Experimentally, the spectrum of compound 2b in CDCl3 shows different chemical shifts for Hsyn and Hanti protons; however, these protons have identical chemical shifts in DMSO/CDCl3, these results reveal that in CDCl3 exist solely the conformer 2b’ but conformer 2b in DMSO/CDCl3. The chemical shifts predicted theoretically are in accordance with the values observed experimentally for 2c compound, where the protons of the bridging methylene

group are split in two doublets (Fig. 1) as in the parent anhydride 1. The structures of 2a-2c were also confirmed by mass spectrometry with m/z for 2a-2c determined to be 241.2 (m/z theory: 240.09) for every structure. The quaternary piridiniums are usually obtained via Menshutkin reaction [44]. 2b and 2c react with ethylbromoacetate to obtain pyridinium betaine precursors (Scheme 3). Because of steric hindrance around the nitrogen atom in ortho position of aminopyridin moiety, 3a betaine was not obtained. IR, 1H and 13C NMR and DEPT spectra clearly confirmed the structure of the compounds. Like the parent amides, the IR spectra of 3b and 3c show absorption bands due to symmetric and antisymmetric stretching vibrations of

254



Fig. (2). Lower energy conformations of 2a and 2a’ (-502413.857 and -502413.486 kcal·mol-1), 2b and 2b’ (-502412.137 and -502412.091 kcal·mol-1) and 2c (-502412.571 kcal·mol-1). O

Br- CH2COOC2H5 N+

N O NR

2b, 2c

3b

O BrCH2COOC2H5

O

b: R=3-pyridyl c: R=4-pyridyl

O N

BrN+

CH2COOC2H5

3c

O

Scheme 3. Bromoesterification of 2b and 2c.

the carbonyl groups 1772-1778, 1699-1716 cm-1, respectively; vibrations of the carbonyl ester band are in this same region; and additionally, bands in lower wavenumbers 1180-1214, 1120-1149 cm-1 which correspond to asymmetric and symmetric C-O vibrations, respectively. The 1H and 13C NMR spectra of 3b and 3c were similar to their parent dicarboximides (Figs. 3 and 4); 13C NMR spectrum displayed new signals due to C=O ester in a downfield ( 167.4-166 ppm); the -ammonium and alkoxy methylene carbon atom in a upfield ( 65.8-63.2 and 62.3-60.3 ppm, respectively); the methyl carbon atom is in strongest field ( 12.6-14.0 ppm), because it is protected for adjacent hydrogens (Fig. 4). 1H NMR spectrum displayed also those new signals, protons of methylene between ammonium and carbonyl group appear in a downfield ( 5.86-6.05 ppm); the protons of alkoxy methylene group appear in 4.10-4.19 ppm; and methyl group appear in a strongest field ( 1.021.23 ppm) (Fig. 3). Since, a new bond of the pyridine nitrogen is formed in the betaine 3b the protons of the bridging methylene group were split in Hsyn and Hanti signals, in spite of those protons appear as a single signal in 2b, the latter suggests that lone pair on the nitrogen of a pyridine moiety has perturbations on magnetically anisotropic properties of the carbonyl groups. Protons in bridging methylene group 2c do not suffer any change and appear as two doublet signals after the bromoesterification.

CONCLUSIONS We carried out the synthesis of two new pyridinium betaines from exo-norbornilen dicarboximides via Menschutkin reaction. Dicarboximides 2a y 2c can be obtained under mild conditions in one-step reaction using xylene as a solvent whereas for 2b an additional dehydrating step is required. Experimental 1H-NMR showed different chemical shift for Hanti and Hsyn bridge methylene group for 2c, the spectrum of 2b in CDCl3 shows different chemical shift for those protons but Hanti and Hsyn show a single signal in DMSO/CDCl3. The lone pair on a nitrogen of the pyridine moiety plays an important role in shielding and deshielding of Hsyn, since when is quaternized two different signals are observed as in the starting anhydride. CONFLICT OF INTEREST We thank CONACyT for financial support for this research in the form of a stipend (Contract 201658), and the CGIC-UC, FRABA No. project 462/07. ACKNOWLEDGMENTS Thanks to C. Alejandrina Acosta for supporting with the NMR analysis.



Fig. (3). 1H NMR spectra of 3b recorded in TFA and 3c recorded in CDCl3 with peak assignments.

Fig. (4). 13C NMR spectra of 3b recorded in TFA and 3c recorded in CDCl3 with peak assignments.

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