SUPPORTING INFORMATION

Synthesis of substituted guanidines using Zn-Al Hydrotalcite catalyst

LAKSHMI KANTAM. M,* VENKANNA DUPATI, SWARNA JAYA. V, MANORAMA S V

Inorganic and Physical Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad- 500 007, India

Corresponding address

Tel.: +91-40-27193510; fax: +91-40-27160921;

E-mail address: (M. L. Kantam).

Contents

A) General information S2

B) General procedure S3

C) Analytical Data S4-S6

D) Spectra S7-S18

E) References S19

A) General Information

Catalyst (Zn-Al-HT) was prepared by using chloride salts of zinc and aluminum, in co-precipitation method with NaOH solution. All amines and carbodiimides were purchased from sigma Aldrich, Fluka and SRL, India, and were used without further purification. All the solvents were of analytical grade and used as received. The products were purified by column chromatography using mixture of ethyl acetate and hexane as eluent and neutral-aluminaof(100-200) mesh as stationary phase. The products arewell characterized by 1H NMR, 13C NMR, and Massspectroscopy. Samples were scanned on AVANCE 300MHz and INNOVA 500MHz, using TMS as internal standard,and CDCl3and DMSO as solvents. High-resolution mass spectrometry was performed on QSTARXL (Applied Biosystems/MDSSCiex Foster city, USA). Low resolution mass spectrometry was performed using LCQ iontrap mass spectrometer (Thermo Fisher, San Jose, CA, USA) equipped with an ESI source.The elemental analysis wascarried out by Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) using a Thermo Electron make ICP-OES model IRIS intrepid II XDL.Infrared spectra were recorded on Thermo Nicolet Nexus 670 FT-IR spectrometer as KBr pellets. X-ray powder diffraction (XRD) data werecollected on Siemens/D-5000 difractometer using Cu-K radiation with a scan speed of 2 = 0.045/0.5s in the range of 2-65oat room temperature. TG-DTAanalysis was recorded on a Mettler-Toledo TGA/SDTA 821 instrument in the temperature range of 25 – 1000 C with a heating rate of 10 C/min in nitrogen atmosphere. The Raman spectra of the samples were measured on a HORIBA Jobin Yvon Raman Spectrometer, equipped with an excitation source of He-Ne laser (632.8 nm), CCD camera and a scan resolution held at 2 cm-1. Temperature programmed desorption of ammonia (NH3-TPD) was performed in a laboratory built equipment containing a programmable temperature controller and a gas chromatograph having a with thermal conductivity detector (TCD). About 100 mg of catalyst was taken and pretreated at 300 oC for 1 h in He flow (60 ml/min). Then the catalyst was exposed to 10% NH3 balance He gas for 1 h at 100 oC. The physisorbed NH3 was removed under He flow (60 ml/min) for 50 min at the same temperature. Then the temperature of sample was raised up to 800 oC at a heating rate 10 oC/min. The desorbed NH3 gas was monitored with the gas chromatograph by using TCD.

B) General procedure

1) Preparation of catalyst:The Zn-AlHT (Zn/Al 2:1) was synthesized by co-precipitation method at a constant pH of 9.0.Mixtures of molar ZnCl2 and AlCl3 aqueous solutions were slowly introduced into the reactor, where the metal solution were precipitated by the addition of 1.0 M NaOH solution by maintaining the pH at 9. The resultingslurry was then left under stirring for 24 hours at room temperaturethe precipitate was filtered, washed several times with distilled water and then dried at room temperature.

2) Experimental procedure:In a typical procedure, Zn-Al HT (0.05 g, 20 mol %), aromatic amine (1 mmol) and carbodiimide (1 mmol) were stirred in a 15 mL reaction vessel sealed with a Teflon screw cap using 2 ml toluene at 110 oC for 12 h.After cooling to room temperature, the reaction mixture was filtered and washed with ethyl acetate (EtOAc) or dichloromethane (DCM). The combined organic layers were concentrated underreduced pressure, and the resulting crude product was then subjected tocolumn chromatography on neutral alumina usingmixture of hexane and ethyl acetate (EtOAc) (3:2) as eluent to afford the pure product. The products were characterized by 1H, 13C- NMR,Electron spray Ionization (ESI) and High Resolution Mass Spectrometry (HRMS).

C) Analytical data

1.1,3-dicyclohexyl-2-phenylguanidine(table 2, entry 1)1:White solid,1H NMR (CDCl3):  = 7.19 (t, J=7.55Hz, 2H), 6.86 (t, J=7.55Hz, 1H), 6.76 (d, J=7.55Hz, 2H), 3.55 (br, 4H),3.38 (m, 2H), 2.02-1.02 (m, 20H);13C NMR (CDCl3):  = 154.44, 138.67, 129.40, 124.94, 122.15, 52.56, 32.84, 24.93, 24.84. ESI-MS: (M+H) + 300; HRMS: Expected Mol. Wt.:300.2439amu, Found:300.2432amu.

2. 1,3-diisopropyl-2-phenylguanidine(table 2, entry 2)2:White solid,1H NMR (CDCl3):  = 7.28-7.23 (m, 2H), 7.01-6.92 (m, 3H), 5.27 (br, 2H), 3.79-3.67 (m, 2H), 1.15 (d, J= 6.42 Hz,12H);13C NMR (CDCl3): = 151.13, 146.09, 129.02, 122.72, 122.26, 43.61, 22.75. ESI-MS: (M+H) + 220;HRMS:Expected Mol. Wt. 220.1813amu,Found: 220.1810amu.

3. 1,3-dicyclohexyl-2-(p-tolyl)guanidine(table 2, entry 3)2:White solid, 1H NMR (CDCl3):  =8.59 (br, 2H), 7.32-7.01 (m,4H), 3.39 (t, J=7.10 Hz, 2H), 2.83 (s, 3H), 2.08-1.10 (m, 20H);13C NMR (CDCl3):  = 154.40, 135.65, 134.50, 129.70, 122.05, 52.41, 32.62, 24.74, 23.93,20.72. ESI-MS: (M+H)+ 314;HRMS: Expected Mol. Wt.: 314.2596 amu, Found:314.2609amu.

4. 1,3-diisopropyl-2-(p-tolyl)guanidine(table 2, entry 4)1:White solid,1H NMR (CDCl3):  = 7.00 (d, J=8.21 Hz, 2H), 6.66 (d, J=8.21 Hz, 2H), 3.83-3.70 (m, 2H), 3.56 (br, 2H), 2.28 (s, 3H), 1.17 (d, J=6.57 Hz, 12H);13C NMR (CDCl3) :  = 153.89, 135.85, 134.31, 130.21, 129.76,122.85, 45.35, 22.31, 20.88.ESI-MS: (M+H)+234; HRMS: Expected Mol. Wt.: 234.1970amu; Found:234.1965amu.

5.1,3-dicyclohexyl-2-(2-iodophenyl)guanidine(table 2, entry 5):White solid,1H NMR (CDCl3) :  = 7.81 (d, J=7.54 Hz, 1H), 7.28 (d, J=7.54Hz, 1H), 7.05 (d, J=7.54 Hz, 1H), 6.79 (t, J=7.54 Hz, 1H), 3.47-3.14 (br, 4H), 1.93-1.04 (m, 20H);13C NMR (CDCl3): = 151.29, 149.47, 139.12, 129.08, 123.45, 123.11, 97.09, 50.19, 33.97, 25.61, 24.86.ESI-MS: (M+H)+ 426; HRMS: Expected Mol. Wt.:426.1406amu;Found:426.1399amu.

6. 2-(2-iodophenyl)-1,3-diisopropylguanidine(table 2, entry 6)3:White solid,1H NMR (CDCl3):  = 7.28-7.25 (m, 1H), 7.12-6.93 (m, 2H), 6.83-6.80 (m, 1H),3.14-3.12(m, 4H), 1.24-1.13 (d, J =6.8 Hz,12H);13C NMR (CDCl3):  = 150.64, 149.80, 139.14, 129.11, 123.51, 96.83, 43.34, 41.74, 23.50. ESI-MS: (M+H)+ 346;

7. 1,3-dicyclohexyl-2-(4-nitrophenyl)guanidine(table 2, entry 7)1:Yellow solid,1H NMR (CDCl3):  = 8.36 (d, J=9.06 Hz, 2H), 7.31 (d, J=8.87 Hz, 2H), 3.93(br, 2H), 3.61-3.41 (m, 2H), 2.25-1.33 (m, 20H);13C NMR (CDCl3):  = 160.25, 153.72, 136.55, 125.35, 120.12, 49.65, 32.49, 25.07, 24.46. ESI-MS: (M+H)+345; HRMS: Expected Mol. Wt.: 345.2290amu;Found:345.2287amu.

8. 1,3-diisopropyl-2-(4-nitrophenyl)guanidine(table 2, entry 8)3: Yellow solid,1H NMR (CDCl3) : = 8.15 (d, J=8.87 Hz, 2H), 7.11 (d, J=8.30 Hz, 2H), 5.67 (br, 2H), 3.70-3.56 (m, 2H), 1.23 (d, J=6.42 Hz, 12H);13C NMR (DMSO): =153.39, 152.01, 141.72, 125.43, 121.40, 44.43, 22.93, 22.54.ESI-MS: (M+H)+265; HRMS: Expected Mol. Wt.: 265.1664amu;Found: 265.1677amu.

9. 2-(3-acetylphenyl)-1,3-dicyclohexylguanidine(table 2, entry 9):White solid, 1H NMR (CDCl3):  = 7.8 (d, J=7.74 Hz, 1H),7.39-7.27 (m, 2H),7.02 (d, J=7.74 Hz, 1H), 3.75 (br, 2H), 3.43-3.35 (m,2H), 2.55 (s, 3H), 2.02-1.09 (m, 20H);13C NMR (CDCl3): = 198.63, 150.75, 149.18, 138.27, 129.48, 128.46, 123.43, 121.63, 50.47, 33.66, 26.79, 25.51, 24.84.ESI-MS: (M+H)+342;

10. 2-(4-cyanophenyl)-1,3-dicyclohexylguanidine(table 2, entry 10):White solid, 1H NMR (CDCl3):  = 7.54 (d, J=8.49 Hz, 2H), 7.07 (d, J=8.49 Hz, 2H), 5.30 (br, 1H), 3.45-3.71 (m, 3H), 2.07-1.08 (m,20H);13C NMR (CDCl3): = 152.05, 148.57, 133.47, 122.28, 119.17, 105.47, 51.79, 33.07, 29.63, 25.13, 24.61. ESI-MS: (M+H) +325;

11. 1,3-dicyclohexyl-2-(pyridin-3-yl)guanidine(table 2, entry 11): pale Yellow solid, 1H NMR (CDCl3): = 8.36-8.26 (m, 2H),7.79 (br, 1H), 7.43 (d, J=8.30 Hz, 1H), 7.24-7.21 (m, 1H), 5.38 (br, 1H), 3.36-3.27 (m, 2H), 1.93-1.03 (m, 20H);13C NMR (CDCl3): =153.80, 145.22, 143.70, 137.36, 129.37, 123.99, 52.50, 32.83, 24.96, 24.72. ESI-MS: (M+H)+301; HRMS: Expected Mol. Wt.: 301.2392amu;Found:301.2376amu.

12. 1, 2, 3-tricyclohexylguanidine(table 2, entry 12):White solid, 1H NMR (CDCl3):  =3.16- 3.08 (m, 3H),1.88-1.10 (m, 30H); 13C NMR (CDCl3): =151.14, 52.43, 34.14, 25.66, 25.11, ESI-MS: (M+H)+306;

D) Spectra

1. NMR spectra of 1,3-Dicyclohexyl-2-phenylguanidine

1HNMR

13C NMR

2.NMR spectra of 1,3-diisopropyl-2-phenylguanidine

1HNMR

13C NMR

3. NMR spectra of1,3-dicyclohexyl-2-(p-tolyl)guanidine

1H NMR

13CNMR

4. NMR spectra of1,3-diisopropyl-2-(p-tolyl)guanidine

1H NMR

13C NMR

5. NMR spectra of1,3-dicyclohexyl-2-(2-iodoophenyl)guanidine

1HNMR

13C NMR

6. NMR spectra of1,3-diisopropyl-2-(2-iodoophenyl)guanidine

1HNMR

13C NMR

7. NMR spectra of 1,3-dicyclohexyl-2-(4-nitrophenyl)guanidine

1HNMR

13C NMR

8. NMR spectra of 1,3-diisopropyl-2-(4-nitrophenyl)guanidine

1HNMR

13C NMR

9.NMR spectraof 2-(3-acetylphenyl)-1,3-dicyclohexylguanidine

1HNMR

13C NMR

10. NMR spectra of 2-(4-cyanophenyl)-1,3-dicyclohexylguanidine

1HNMR

13C NMR

11. NMR spectra of 1,3-dicyclohexyl-2-(pyridin-3-yl)guanidine

1HNMR

13C NMR

12. NMR spectra of 1,2,3-tricyclohexylguanidine

1HNMR

13C NMR

E) References

1) Q. Li, S. Wang, S. Zhou, G. Yang, X. Zhu, Y. Liu, 2007J. Org. Chem. 72 6763

2) Lakshmi Kantam M,Priyadarsini S, Amal Joseph P J, Srinivas P, Vinu A, Klabunde K J and

Nishina Y 2012Tetrahedron685730

3) W. Zhang, M. Nishiura, Z. Hou, 2007Chem. –Eur. J. 13 4037

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