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An Expedient Approach for the Regio- and Stereoselective Synthesis of Novel Spiroindolizidines via [3+2] Cycloaddition 
Kamal Alimohammadi, Yaghoub Sarrafi, Bahareh Rajabpour 
Department of Organic Chemistry, Faculty of Chemistry, Mazandaran University, Babolsar, Iran, E-mail: ysarrafi@umz.ac.ir (​mailto:ysarrafi@umz.ac.ir​)
List of contents	Page	List of contents	Page
Title, Author’s name, Address, General 
methods and characterization data	S1- S12	NOE of 7	S33
1H NMR of 4a	S13	1H NMR of 10a	S34
13C NMR of 4a	S14	13C NMR of 10a	S35
1H NMR of 4b	S15	NOE of 10a	S36
13C NMR of 4b	S16	1H NMR of 10b	S37
1H NMR of 4c	S17	13C NMR of 10b	S38
13C NMR of 4c	S18	1H NMR of 10c	S39
1H NMR of 4d	S19	13C NMR of 10c	S40
13C NMR of 4d	S20	1H NMR of 10d	S41
1H NMR of 4e	S21	13C NMR of 10d	S42
13C NMR of 4e	S22	1H NMR of 10e	S43
1H NMR of 4f	S23	13C NMR of 10e	S44
13C NMR of 4f	S24	1H NMR of 10f	S45
1H NMR of 4g	S25	13C NMR of 10f	S46
13C NMR of 4g	S26	1H NMR of 10g	S47
1H NMR of 4h	S27	13C NMR of 10g	S48
13C NMR of 4h	S28	1H NMR of 10h	S49
1H NMR of 4i	S29	13C NMR of 10h	S50
13C NMR of 4i	S30	1H NMR of (E)-12 + (Z)-12	S51
1H NMR of 7	S31	13C NMR of (E)-12 + (Z)-12	S52
13C NMR of 7	S32		

Experimental Section:

General Methods: Melting points were measured on an Electrothermal 9100 apparatus and are uncorrected. 1H and 13C NMR spectra were recorded on a Bruker 400 and 500-MHz instrument in CDCl3 and DMSO-d6 solvents; chemical shifts are in ppm (δ) from SiMe4 (TMS) as internal standard. Infrared spectra were recorded on a Shimadzu IR-8300 series FT-IR spectrophotometer. Elemental analyses were performed using a Heracus CHN rapid analyzer. 
Chemicals: Chemicals were obtained from Fluka and Merck and used without further puriﬁcation. 
Compound 6 was prepared according to the literature.1 Compound 4a synthesized and characterized by comparison of its physical and spectroscopic data with literature.2

References:
(1)	Kawai, Y.; Inaba, Y.; Tokitoh, N. Tetrahedron Asymmetry 2001, 12, 309.
(2)	Poornachandran, M.; Raghunathan R. Synth. Commun. 2007, 37, 2507.

General Procedure for the Synthesis of Compounds of 4, 7 and 10:  
A mixture of ninhydrin (1 mmol) or isatin derivatives (1mmol), 1,2,3,4-tetrahydroisoquinoline (1 mmol) and trans-β-nitrostyrenes (1 mmol) in ethanol (10 mL) was stirred at reflux for 2-3 h. After completion of the reaction, as indicated by TLC, the solid was separated by filtration and the pure cycloadducts were obtained by recrystallization from ethanol.

1'-Nitro-2'-phenyl-2',5',6',10b'-tetrahydro-1'H-spiro[indene-2,3'-pyrrolo[2,1-a]isoquinoline]-1,3-dione (4a)



Yellow solid; mp: 187-189 ˚C; IR (KBr, cm-1)  = 1752, 1708, 1556, 1377; 1H NMR (400 MHz, DMSO-d6) δ: 2.64-2.75 (m, 2H, indolizine), 2.94-3.00 (m, 2H, indolizine), 4.47 (d, 1H, benzylic, J = 5.2 Hz), 5.61 (d, 1H, N-CH, J = 6.8 Hz), 6.56 (dd, 1H, CHNO2, J1 = 7.2 Hz, J2 = 5.2 Hz), 7.16-8.05 (m, 13H, Ar-H); 13C NMR (100 MHz, DMSO-d6) δ: 29.6, 43.5, 57.9, 64.8, 77.8, 92.3, 123.1, 123.8, 125.3, 126.2, 127.4, 128.6, 129.0, 129.2, 129.4, 132.8, 133.8, 134.9, 137.6, 138.0, 141.1, 141.6, 198.3, 201.1; Anal. Calcd for C26H20N2O4: C, 73.57; H, 4.75; N, 6.60; Found: C, 73.68; H, 4.79; N, 6.43.

2'-(4-Nitrophenyl)-1'-nitro-2',5',6',10b'-tetrahydro-1'H-spiro[indene-2,3'-pyrrolo[2,1-a]isoquinoline]-1,3-dione (4b) 



Yellow solid; mp: 190-192 ˚C; IR (KBr, cm-1) = 1752, 1706, 1556, 1518, 1355; 1H NMR (400 MHz, DMSO-d6) δ: 2.64-2.73 (m, 2H, indolizine), 2.93-2.99 (m, 2H, indolizine), 4.71 (d, 1H, benzylic, J = 4.8 Hz), 5.59 (d, 1H, N-CH, J = 7.2 Hz), 6.67 (dd, 1H, CHNO2, J1 = 6.8 Hz, J2 = 4.8 Hz), 7.14-8.08 (m, 12H, Ar-H); 13C NMR (100 MHz, DMSO-d6) δ: 29.5, 43.5, 56.4, 65.0, 77.6, 92.0, 123.3, 123.9, 124.0, 125.6, 126.2, 127.5, 129.4, 130.8, 132.4, 134.9, 137.9, 138.2, 140.9, 141.6, 141.7, 147.5, 197.6, 200.4; Anal. Calcd for C26H19N3O6: C, 66.52; H, 4.08; N, 8.95; Found: C, 66.43; H, 4.01; N, 9.04.

2'-(3-Methoxyphenyl)-1'-nitro-2',5',6',10b'-tetrahydro-1'H-spiro[indene-2,3'-pyrrolo[2,1-a]isoquinoline]-1,3-dione (4c)

Yellow solid; mp: 193-195 ˚C; IR (KBr, cm-1)  = 1746, 1698, 1561, 1344; 1H NMR (400 MHz, DMSO-d6) δ: 2.64-2.75 (m, 2H, indolizine), 2.94-3.00 (m, 2H, indolizine), 3.60 (s, 3H, OMe), 4.44 (d, 1H, benzylic, J = 5.2  Hz), 5.59 (d, 1H, N-CH, J = 6.8 Hz), 6.58 (dd, 1H, CHNO2, J1 = 7.2 Hz, J2 = 5.2 Hz), 6.68-8.06 (m, 12H, Ar-H); 13C NMR (100 MHz, DMSO-d6) δ: 29.6, 43.5, 55.5, 57.8, 64.7, 77.7, 92.2, 114.1, 114.9, 121.2, 123.2, 123.8, 125.3, 126.2, 127.4, 129.4, 130.1, 132.8, 134.9, 135.3, 137.6, 138.0, 141.1, 141.7, 159.5, 198.3, 201.0; Anal. Calcd for C27H22N2O5: C, 71.35; H, 4.88; N, 6.16; Found: C, 71.34; H, 4.84; N, 6.23.

2'-(4-Methoxyphenyl)-1'-nitro-2',5',6',10b'-tetrahydro-1'H-spiro[indene-2,3'-pyrrolo[2,1-a]isoquinoline]-1,3-dione (4d)

Yellow solid; mp: 193-195 ˚C; IR (KBr, cm-1)  = 1746, 1703, 1556, 1260; 1H NMR (400 MHz, DMSO-d6) δ: 2.64-2.74 (m, 2H, indolizine), 2.94-2.99 (m, 2H, indolizine), 3.62 (s, 1H, OMe), 4.41 (d, 1H, benzylic, J = 5.6 Hz), 5.58 (d, 1H, N-CH, J = 6.8 Hz), 6.50 (dd, 1H, CHNO2, J1 = 7.2 Hz, J2 = 5.6 Hz), 7.11-8.04 (m, 12H, Ar-H); 13C NMR (100 MHz, DMSO-d6) δ: 29.5, 43.6, 55.5, 57.4, 64.6, 77.7, 92.8, 114.4, 123.2, 123.8, 125.2, 125.5, 126.2, 127.4, 129.4, 130.5, 132.9, 134.9, 137.6, 138.0, 141.1, 141.7, 159.3, 198.4, 201.3; Anal. Calcd for C27H22N2O5: C, 71.35; H, 4.88; N, 6.16; Found: C, 71.47; H, 4.96; N, 6.06.

2'-(4-Methylphenyl)-1'-nitro-2',5',6',10b'-tetrahydro-1'H-spiro[indene-2,3'-pyrrolo[2,1-a]isoquinoline]-1,3-dione (4e)

Yellow solid; mp: 189-191 ˚C; IR (KBr, cm-1)  = 1743, 1706, 1552, 1345; 1H NMR (400 MHz, DMSO-d6) δ: 2.14 (s, 1H, Me), 2.64-2.73 (m, 2H, indolizine), 2.94-3.01 (m, 2H, indolizine), 4.43 (d, 1H, benzylic, J = 5.6 Hz), 5.58 (d, 1H, N-CH, J = 7.2 Hz), 6.53 (t, 1H, CHNO2, J = 6.2 Hz), 6.97-8.05 (m, 12H, Ar-H). 13C NMR (100 MHz, DMSO-d6) δ: 20.9, 29.5, 43.5, 57.6, 64.7, 77.6, 92.6, 123.2, 123.8, 125.2, 126.2, 127.4, 129.0, 129.4, 129.6, 130.7, 132.9, 134.9, 137.7, 137.9, 138.0, 141.1, 141.7, 198.4, 201.1; Anal. Calcd for C27H22N2O4: C, 73.96; H, 5.06; N, 6.39; Found: C, 73.82; H, 5.15; N, 6.52.

2'-(2-Chloro-5-nitrophenyl)-1'-nitro-2',5',6',10b'-tetrahydro-1'H-spiro[indene-2,3'-pyrrolo[2,1-a]isoquinoline]-1,3-dione (4f)


Yellow solid; mp: 180-182 ˚C; IR (KBr, cm-1)  = 1746, 1709, 1529, 1350; 1H NMR (400 MHz, DMSO-d6) δ: 2.64-2.75 (m, 2H, indolizine), 2.89-3.02 (m, 2H, indolizine), 5.09 (d, 1H, benzylic, J = 3.2 Hz), 5.58 (d, 1H, N-CH, J = 6.4 Hz), 6.56 (dd, 1H, CHNO2, J1 = 6.4 Hz, J2 = 3.6Hz), 7.15-8.54 (m, 11H, Ar-H); 13C NMR (100 MHz, DMSO-d6) δ: 29.7, 43.3, 52.8, 65.3, 76.6, 92.0, 123.0, 123.9, 125.0, 126.0, 126.4, 126.9, 127.5, 129.4, 131.0, 132.2, 134.6, 135.2, 137.9, 138.0, 140.2, 140.6, 141.9, 147.0, 197.6, 201.5; Anal. Calcd for C26H18ClN3O6: C, 61.97; H, 3.60; N, 8.34; Found: C, 62.11; H, 3.53; N, 8.25.

2'-(4-Fluorophenyl)-1'-nitro-2',5',6',10b'-tetrahydro-1'H-spiro[indene-2,3'-pyrrolo[2,1-a]isoquinoline]-1,3-dione (4g)

Yellow solid; mp: 193-195 ˚C; IR (KBr, cm-1)  = 1746, 1698, 1556, 1360; 1H NMR (400 MHz, DMSO-d6) δ: 2.64-2.75(m, 2H, indolizine), 2.93-3.01(m, 2H, indolizine), 4.50 (d, 1H, benzylic, J = 4.8 Hz), 5.60 (d, 1H, N-CH, J = 6.8 Hz), 6.56 (dd, 1H, CHNO2, J1 = 6.8 Hz, J2 = 4.8 Hz,), 6.99-8.05 (m, 12H, Ar-H); 13C NMR (100 MHz, DMSO-d6) δ: 29.6, 43.5, 57.0, 64.8, 77.8, 92.4, 115.7, 115.9, 123.4 (J = 73 Hz), 125.7 (J = 88 Hz), 127.4, 129.4, 130.2 (J = 3 Hz), 131.4, 131.5, 132.8, 135.0, 137.7, 139.5 (J = 297 Hz), 141.6, 160.9, 163.3, 198.1, 201.2; Anal. Calcd for C26H19FN2O4: C, 70.58; H, 4.33; N, 6.33; Found: C, 70.72; H, 4.29; N, 6.23.

2'-(4-Chlorophenyl)-1'-nitro-2',5',6',10b'-tetrahydro-1'H-spiro[indene-2,3'-pyrrolo[2,1-a]isoquinoline]-1,3-dione (4h)

Yellow solid; mp: 190-192 ˚C; IR (KBr, cm-1)  = 1746, 1707, 1554, 1362; 1H NMR (400 MHz, DMSO-d6) δ: 2.64-2.74 (m, 2H, indolizine), 2.94-2.99 (m, 2H, indolizine), 4.51 (d, 1H, benzylic, J = 4.8 Hz), 5.58 (d, 1H, N-CH, J = 7.2 Hz), 6.56 (dd, 1H, CHNO2, J1 = 6.8 Hz, J2 = 4.8 Hz), 7.14-8.06 (m, 12H, Ar-H); 13C NMR (100 MHz, DMSO-d6) δ: 29.5, 43.5, 56.8, 64.8, 77.6, 92.2, 123.2, 123.9, 125.4, 126.2, 127.4, 128.9, 129.4, 131.1, 132.7, 133.0, 133.4, 134.9, 137.8, 138.1, 141.0, 141.6, 198.0, 200.9; Anal. Calcd for C26H19ClN2O4: C, 68.05; H, 4.17; N, 6.10; Found: C, 68.20; H, 4.11; N, 5.98.

2'-(4-Cyanophenyl)-1'-nitro-2',5',6',10b'-tetrahydro-1'H-spiro[indene-2,3'-pyrrolo[2,1-a]isoquinoline]-1,3-dione (4i)

Yellow solid; mp: 183-185 ˚C; IR (KBr, cm-1)  = 2234, 1705, 1552, 1367; 1H NMR (400 MHz, DMSO-d6) δ: 2.64-2.72 (m, 2H, indolizine), 2.93-2.99 (m, 2H, indolizine), 4.63 (d, 1H, benzylic, J = 4.0 Hz), 5.59 (d, 1H, N-CH, J = 4.0 Hz), 6.64 (dd, 1H, CHNO2, J1 = 8.0Hz, J2 = 4.0Hz), 7.14-8.07 (m, 12H, Ar-H); 13C NMR (100 MHz, DMSO-d6) δ: 29.5, 43.4, 56.8, 64.9, 77.6, 91.6, 111.4, 118.6, 123.2, 123.9, 125.5, 126.2, 127.4, 129.4, 130.4, 132.5, 132.7, 134.9, 137.9, 138.2, 140.8, 141.5, 197.7, 200.6; Anal. Calcd for C27H19N3O4: C, 72.15; H, 4.26; N, 9.35; Found: C, 72.18; H, 4.34; N, 9.25.

1'-Methyl-1'-nitro-2'-phenyl-2',5',6',10b'-tetrahydro-1'H-spiro[indene-2,3'-pyrrolo[2,1-a]isoquinoline]-1,3-dione (7)

Yellow solid; mp: 181-183 ˚C; IR (KBr, cm-1)  = 1747, 1706, 1536, 1348; 1H NMR (400 MHz, DMSO-d6) δ: 1.87 (s, 3H, CH3NO2), 2.62-2.68 (m, 2H, indolizine), 2.95-3.01 (m, 2H, indolizine), 4.82 (s, 1H, benzylic), 5.14 (s, 1H, N-CH), 6.92-8.11 (m, 13H, Ar-H); 13C NMR (100 MHz, DMSO-d6) δ: 24.1, 29.5, 43.3, 62.7, 70.6, 75.5, 98.1, 123.1, 123.8, 124.1, 126.3, 127.5, 129.2, 129.4, 129.7, 130.3, 131.7, 133.5, 134.7, 138.1, 138.5, 141.4, 141.5, 197.7, 202.6; Anal. Calcd for C27H22N2O4: C, 73.96; H, 5.06; N, 6.39; Found: C, 74.09; H, 4.97; N, 6.34. 

1'-nitro-2'-phenyl-2',5',6',10b'-tetrahydro-1'H-spiro[indoline-3,3'-pyrrolo[2,1-a]isoquinolin]-2-one (10a) 

Cream solid; mp: 203-204 oC; IR (KBr, cm-1)  = 3316, 1720, 1552, 1322; 1H NMR (400 MHz, CDCl3) : 2.66 – 2.81 (m, 3H, indolizine), 3.14 (m, 1H, indolizine), 4.52 (d, 1H, J = 4.8 Hz, benzylic), 5.86 (d, 1H, J = 6.8 Hz, N-CH), 6.14 (dd, 1H, J = 7.2, 4.8 Hz, CHNO2), 6.72 (d, 1H, J = 8 Hz, Ar-H), 7.06 – 7.34 (m, 11H, Ar-H), 7.72 (d, 1H, J = 7.2 Hz, Ar-H), 10.18 (s, 1H, NH); 13C NMR (100 MHz, CDCl3) : 29.9, 42.5, 60.3, 63.6, 75.6, 91.7, 109.7, 123.6, 124.5, 124.9, 126.1, 127.1, 127.3, 128.1, 128.4, 128.6, 129.3, 130.0, 132.7, 133.7, 135.1, 141.4, 176.8; Anal. Calcd for C25H21N3O3: C, 72.98; H, 5.14; N, 10.21; Found: C, 73.09; H, 5.06; N, 10.27. 

5-bromo-1'-nitro-2'-phenyl-2',5',6',10b'-tetrahydro-1'H-spiro[indoline-3,3'-pyrrolo[2,1-a]isoquinolin]-2-one (10b) 

Cream solid; mp: 200-202 oC; IR (KBr, cm-1)  = 3308, 1716, 1552, 1316; 1H NMR (400 MHz, DMSO-d6) : 2.65 (m, 3H, indolizine), 2.93 (m, 1H, indolizine), 4.45 (d, 1H, J = 4.8 Hz, benzylic), 5.68 (d, 1H, J = 6.2 Hz, N-CH), 6.47 (t, 1H, J = 5.6 Hz, CHNO2), 6.69 (d, 1H, J = 8 Hz, Ar-H), 7.15 – 7.30 (m, 9H, Ar-H), 7.48 (d, 1H, J = 8 Hz, Ar-H), 7.67 (s, 1H, Ar-H), 10.33 (s, 1H, NH); 13C NMR (100 MHz, DMSO-d6) : 29.8, 42.7, 59.6, 63.7, 75.6, 91.2, 112.0, 114.6, 125.3, 126.1, 127.2, 127.7, 128.3, 128.7, 129.1, 129.4, 130.2, 133.2, 133.4, 134.7, 135.2, 142.7, 175.9; Anal. Calcd for C25H20BrN3O3: C, 61.24; H, 4.11; N, 8.57; Found: C, 61.33; H, 4.17; N, 8.49.

1-methyl-1'-nitro-2'-phenyl-2',5',6',10b'-tetrahydro-1'H-spiro[indoline-3,3'-pyrrolo[2,1-a]isoquinolin]-2-one (10c)

Cream solid; mp: 207-209 oC; IR (KBr, cm-1)  = 1709, 1557, 1345; 1H NMR (500 MHz, DMSO-d6) :  2.50 – 2.68 (m, 3H, indolizine), 2.75 (s, 3H, N-CH3), 2.90 (m, 1H, indolizine), 4.40 (d, 1H, J = 4.1 Hz, benzylic), 5.75 (d, 1H, J = 6.4 Hz, N-CH), 6.45 (t, 1H, J = 5.3 Hz, CHNO2), 6.92 (d, 1H, J = 7.5 Hz, Ar-H), 7.07 – 7.40 (m, 11H, Ar-H), 7.61(d, 1H, J = 7 Hz, Ar-H); 13C NMR (125 MHz, DMSO-d6) : 26.2, 30.2, 43.1, 60.6, 64.1, 75.9, 91.8, 109.4, 124.1, 124.9, 125.7, 126.5, 127.1, 127.6, 128.7, 129.0, 129.1, 129.8, 130.9, 133.9, 134.9, 135.7, 145.2, 174.8; Anal. Calcd for C26H23N3O3: C, 73.39; H, 5.45; N, 9.88; Found: C, 73.28; H, 5.52; N, 10.02.

1-benzyl-1'-nitro-2'-phenyl-2',5',6',10b'-tetrahydro-1'H-spiro[indoline-3,3'-pyrrolo[2,1-a]isoquinolin]-2-one (10d) 

Cream solid; mp: 210-211 oC; IR (KBr, cm-1)  = 1707, 1555, 1344; 1H NMR (500 MHz, DMSO-d6) : 2.61 – 2.69 (m, 3H, indolizine); 2.91 (m, 1H, indolizine), 4.36 (d, 1H, J = 15.9, N-CH2), 4.47 (bs, 1H, benzylic), 4.84 (d, 1H, J = 15.9, N-CH2), 5.80 (pseudo d, 1H, N-CH), 6.48 (d, 2H, J = 6.7, Ar-H), 6.54 (bs, 1H, CHNO2), 6.60 (d, 1H, J = 7.1 Hz, Ar-H), 7.08 – 7.35 (m, 16H, Ar-H), 7.63 (d, 1H, J = 6.9, Ar-H); 13C NMR (125 MHz, DMSO-d6) : 30.2, 42.9, 43.1, 60.6, 64.2, 75.9, 91.9, 110.1, 124.2, 125.2, 125.7, 126.6, 127.3, 127.6, 127.9, 129.0, 129.3, 129.7, 129.8, 130.8, 133.9, 134.8, 135.7, 136.2, 144.2, 174.7; MS: m/z = 455 (M+ - NO2); Anal. Calcd for C32H27N3O3: C, 76.63; H, 5.43; N, 8.38; Found: C, 76.57; H, 5.46; N, 8.47.

1'-methyl-1'-nitro-2'-phenyl-2',5',6',10b'-tetrahydro-1'H-spiro[indoline-3,3'-pyrrolo[2,1-a]isoquinolin]-2-one (10e)

Cream solid; mp: IR (KBr, cm-1)  = 3323, 1698, 1554, 1335; 1H NMR (400 MHz, CDCl3) : 1.85 (s, 3H, CH3NO2), 2.49 – 2.68 (m, 3H, indolizine); 2.88-2.92 (m, 1H, indolizine), 4.68 (s, 1H, benzylic), 5.29 (s, 1H, N-CH), 6.76 (d, 1H, J = 7.6 Hz, Ar-H), 6.99 – 7.29 (m, 11H, Ar-H), 7.41 (d, 1H, J = 7.2 Hz, Ar-H), 10.78 (s, 1H, NH); 13C NMR (100 MHz, CDCl3) : 24.2 , 29.7, 42.2, 64.8, 68.9, 73.6, 97.2, 110.3, 122.6, 123.0, 124.4, 126.3, 127.0, 127.1, 128.8, 129.1, 129.8, 130.4, 132.9, 134.6, 135.0, 143,2, 177.8; Anal. Calcd for C26H23N3O3: C, 73.39; H, 5.45; N, 9.88; Found: C, 73.47; H, 5.31; N, 9.97.

5-bromo-1'-methyl-1'-nitro-2'-phenyl-2',5',6',10b'-tetrahydro-1'H-spiro[indoline-3,3'-pyrrolo[2,1-a]isoquinolin]-2-one (10f) 

Cream solid; mp: 204-206 oC ; IR (KBr, cm-1)  = 3394, 1700, 1541, 1339; 1H NMR (500 MHz, DMSO-d6) : 1.83 (s, 3H, CH3NO2), 2.59 – 2.69 (m, 3H, indolizine), 2.96 (m, 1H, indolizine), 4.66 (s, 1H, benzylic), 5.27 (s, 1H, N-CH), 6.73 (d, 1H, J = 8, Ar-H), 7.00 (d, 1H, J = 6.5, Ar-H), 7.14 – 7.28 (m, 9H, Ar-H), 7.41 (d, 1H, J = 7.9, Ar-H), 7.56 (s, 1H, Ar-H), 10.88 (s, 1H, NH); 13C NMR (125 MHz, DMSO-d6) : 24.2, 29.8, 42.4, 64.6, 69.1, 73.9, 97.0, 112.4, 114.8, 122.7, 126.3, 127.2, 127.3, 128.9, 129.2, 129.6, 129.9, 130.6, 132.7, 133.3, 134.5, 135.1, 142.7, 177.4; Anal. Calcd for C26H22BrN3O3: C, 61.91; H, 4.40; N, 8.33; Found: C, 61.77; H, 4.49; N, 8.41.

1,1'-dimethyl-1'-nitro-2'-phenyl-2',5',6',10b'-tetrahydro-1'H-spiro[indoline-3,3'-pyrrolo[2,1-a]isoquinolin]-2-one (10g) 

Cream solid; mp: 179-182 oC; IR (KBr, cm-1)  = 1706, 1541, 1345; 1H NMR (500 MHz, DMSO-d6) : 1.86 (s, 3H, CH3NO2); 2.52 – 2.95 (m, 4H, indolizine), 3.14 (s, 3H, N-CH3), 4.71 (s, 1H, benzylic ), 5.32 (s, 1H, N-CH), 6.97 (d, 1H, J = 7.5 Hz, Ar-H), 7.00 – 7.33 (m, 11H, Ar-H), 7.47 (d, 1H, J = 7.5 Hz, Ar-H), 13C NMR (125 MHz, DMSO-d6) : 24.6, 26.7, 30.1, 42.7, 65.5, 69.6, 73.9, 97.6, 109.8, 123.1, 124.2, 124.5, 126.7, 127.6, 129.3, 129.6, 130.3, 130.7,130.9, 131.2, 133.0, 135.0, 135.5, 145.1, 176.2; MS: m/z = 439 (M+); Anal. Calcd for C27H25N3O3: C, 73.78; H, 5.73; N, 9.56; Found: C, 73.83; H, 5.65; N, 9.64.

1-benzyl-1'-methyl-1'-nitro-2'-phenyl-2',5',6',10b'-tetrahydro-1'H-spiro[indoline-3,3'-pyrrolo[2,1-a]isoquinolin]-2-one (10h) 

Cream solid; mp: 198-200 oC; IR (KBr, cm-1)  = 1700, 1544, 1342; 1H NMR (400 MHz, DMSO-d6) : 1.90 (s, 3H, CH3NO2), 2.56 – 2.96 (m, 4H, indolizine), 4.75 (s, 1H, benzylic), 4.87 (1/2 of AB quartet, 1H, J = 15.6 Hz, N-CH2), 4.98 (1/2 of AB quartet, 1H, J = 15.6 Hz, N-CH2), 5.36 (s, 1H, N-CH), 6.90 (d, 1H, J = 8.0 Hz, Ar-H), 7.03 – 7.32 (m, 16H, Ar-H), 7.51(d, 1H, J = 7.6, Ar-H); 13C NMR (100 MHz, DMSO-d6) : 24.3, 29.8, 42.3, 43.2, 64.9, 69.2, 73.6, 97.2, 110.0, 122.8, 123.9, 124.4, 126.3, 126.4, 127.2, 128.0, 128.9, 129.1, 129.2, 129.9, 130.5,130.6, 132.5, 134.5, 135.0, 136.3, 143.8, 175.7; Anal. Calcd for C33H29N3O3: C, 76.87; H, 5.67; N, 8.15; Found: C, 76.71; H, 5.75; N, 8.27.

(Z) and (E)-2-(2-oxoindolin-3-ylidene)-1, 2, 3, 4-tetrahydroisoquinolinium 

Yellow solid; mp: 184-186 oC; IR (KBr, cm-1)  = 3475, 3363, 1634, 1619, 1554, 1329; 1H NMR (400 MHz, CDCl3) : 2.94 (t, 2H, J= 5.8 Hz, indolizine), 3.07 (t, 2H, J = 6 Hz, indolizine), 3.66 (t, 2H, J = 5.8 Hz, indolizine), 4.05 (t, 2H, J = 6 Hz, indolizine), 4.57 (s, 2H, indolizine), 4.96 (s, 2H, indolizine), 6.76 (m, 2H, Ar-H), 6.98 (d, 1H, J = 7.6 Hz, Ar-H), 7.15 – 7.27 (m, 8H, Ar-H), 8.15 (dd, 1H, J= 9.2, 2.8 Hz, Ar-H), 8.21 (dd, 1H, J = 9.2, 2.8 Hz, Ar-H ), 8.44 (d, 1H, J = 2.8 Hz, Ar-H), 8.52(d, 1H, J = 2.8 Hz, Ar-H); 13C NMR (100 MHz, CDCl3) : 28.2, 29.3, 39.7, 43.7, 43.8, 47.6, 112.6, 112.7, 117.2, 117.3, 125.9, 126.7, 126.8, 126.9, 127.0, 127.4, 128.8, 129.2, 130.6, 130.7, 131.2, 131.6, 133.3, 134.2, 137.4, 155.4, 164.7, 192.7, 192.9; MS: m/z = 325 (M+).




















































	















S1





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The effect of copper content on the reactivity of Cu/Co6Al2 solids in the catalytic steam reforming of methane reaction

Dmitry Yu. Murzin

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C. R. Chimie 17 (2014) 612–614
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volution of heterogeneous catalytic reactions kinetics
ith time§
mitry Yu. Murzin
oratory of Industrial Chemistry and Reaction Engineering, Process Chemistry Centre, Åbo Akademi University, 20500 Åbo/Turku,
land
Catalysis by its very definition is a kinetic process; thus
liable kinetic models describing the rate of catalytic
actions are a vital part of any catalytic research either
cused on the understanding of reactions on a molecular
el or on more engineering aspects such as design and
tensification of chemical processes [1–10].
It is even possible to say that reaction kinetics is the
nslation of our understanding of the chemical processes
to a mathematical rate expression. The tradition of
netic modelling is very long. For practical purposes in the
st, power-law models have been used, although their
plicability is limited as they do not predict reaction rates,
ncentration and temperature dependences outside the
nge of the studied experimental conditions.
Mechanistic models based on the knowledge of
mentary processes (adsorption, desorption, surface
actions) provide reliable extrapolation outside the
died interval, making a particular reaction intellectually
tter understood.
Quite a number of textbooks on catalysis and chemical
gineering contain ‘‘ready-to-use’’ equations, while few
[6,11] go in more depth on the principles of derivation of
kinetic equations, using for example a theory of complex
reactions [10,11].
The current trend is to utilize the so-called microkinetic
approach [4,9] bringing physicochemical understanding of
elementary steps into kinetic modelling, which helps
dramatically in case of complex multistep reactions.
Without such analysis, which in fact dates back to the
development of the first computer programs for numerical
data fitting of kinetic data in the 1970s, parameter
estimation becomes extremely challenging, not resulting
in reliable values of parameters.
Even if there is a long tradition in kinetic modelling in
current-day catalytic research, one could see a clear
decline in the utilization of the kinetic approach, mostly
because it is time consuming. The second reason is that in
the recent years many new experimental and theoretical
tools have appeared, including various characterization
methods and computer programs for quantum chemical
calculations. Kinetic research, which used to be one of the
few or maybe the only one method available, is not in
fashion anymore. As a result, very often developed
mechanistic concepts, based for example on spectroscopy
and density functional calculations, are not tested against
available kinetic data.
R T I C L E I N F O
icle history:
ceived 25 September 2013
cepted after revision 3 December 2013
ailable online 28 March 2014
ywords:
etics
noclusters
crokinetic modelling
activation
A B S T R A C T
An overview of development of heterogeneous catalytic kinetic concepts is presented. An
emphasis is made on the application of mechanistically sound models, which are needed
as a part of the understanding of catalytic reactions on a molecular level as well as of the
design and the intensification of chemical processes. Such models should include among
other parameters the size and geometry of reacting molecules, size of nanoclusters and
deactivation as a part of the reaction mechanism.
 2013 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Thematic issue dedicated to François Garin.
Email address: dmurzin@abo.fi.
Contents lists available at ScienceDirect
Comptes Rendus Chimie
w ww.s c ien ced i rec t . c o m31-0748/$ – see front matter  2013 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.
p://dx.doi.org/10.1016/j.crci.2013.12.002
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D. Yu. Murzin / C. R. Chimie 17 (2014) 612–614 613Certainly kinetic modelling cannot be a final proof of
ny mechanism, as particular kinetic models could
orrespond not to a single mechanism. However, kinetic
nalysis can be used to differentiate between rival
echanisms and eliminate incorrect mechanistic propo-
als.
The latter approach is particularly lacking in organic
atalysis when rather complicated mechanisms with one
r several catalytic cycles and a myriad of catalytic species
re proposed without any derivation of kinetic equations
nd even qualitative analysis of the reaction kinetics.
Besides this obvious need for more widespread kinetic
nalysis of complex reactions, there are also some other
reas where kinetic studies could essentially contribute,
ddressing the current needs of research in heterogeneous
atalysis. Such contribution should be based on the
resent-day understanding of catalytic chemistry. Let us
onsider in detail few particular issues.
First is the size and geometry of reacting molecules. For
ery many years, in kinetic modelling, simple or rather
imple kinetic models were based on the so-called
angmuir–Hinshelwood and Eley–Rideal mechanisms
ssuming one adsorbed site for the reactants, indepen-
ently of their complexity and size.
In catalytic reactions involving organic molecules, the
ize of the latter can be ca. 0.5–1 nm, which means that the
ulti-centered nature of adsorption and differences in size
f the reacting species should be taken into account in
inetic modelling. Few examples from the literature where
uch approach was considered could be mentioned [12–
0]. Moreover, in kinetic models for catalytic reactions
volving complex organic molecules with different
nctional groups, the mode of adsorption, requiring
ifferent numbers of catalytic sites, is important and
hould be reflected in kinetic modelling [1].
Such reactant sizes as mentioned above are in fact in the
ame range as the size of nanoclusters, imposing a severe
estriction on the number of adsorbed molecules per
luster, as only few molecules could be adsorbed on the
urface. Theoretical analysis of such cases was reported
1].
Even if it was realized a very long time ago [22] that the
ctivity in the cluster size domain of 2–20 nm could be
ependent on cluster size, incorporation of the cluster size
 kinetic equations giving a quantitative explanation of
tructure sensitivity has started to be applied in kinetics
esearch only very recently [23–34].
Another important issue worth mentioning in this short
verview is the explosion of research devoted to trans-
rmations of (ligno)cellulosic biomass. Although some
eactions of biomass processing are similar to those used in
onventional refining and chemical industries such as
ydrogenation or oxidation, there are also fundamental
ifferences associated with the large number of functional
roups (hydroxyls) present in biomass.
Apparently there would be a need for studying in the
ture kinetics of such reactions as aqueous phase
eforming, catalytic pyrolysis, hydrolysis of poly- and
ligosaccharides, ketonization, decarboxylation, aldol con-
ensation, dehydration, etc. In some cases, for example
queous phase reforming, kinetic modelling can be very
challenging, since quite a number of intermediates and
products are formed. A recent paper on kinetic modelling
[35] of this reaction represents a first attempt, which was
however substantially limited only to gas-phase products.
Kinetic analysis of such complex reactions would
require a special attention towards selectivity, which
should be properly analyzed. Such analysis (for example
one product vs. another one, selectivity vs. conversion) can
significantly help in constructing the correct reaction
network as well as diminishing the number of parameters
to be determined by data fitting. Some computer programs
could even nowadays have a possibility to combine
differential (dc/dt) equations with algebraic ones (i.e.
selectivity vs. conversion).
Another complication in studying lignocellulosic feed-
stock is the presence of impurities, which can vary
depending on the feedstock type and origin.
Typically deactivation is incorporated in the kinetic
modelling of continuous processes in oil refining and other
process industries through a time-dependent catalyst
activity factor, even if time is not a true variable.
Deactivation, however, should be considered as a part of
the reaction mechanism and there are already examples of
this approach available in the literature [36,37].
It should be also mentioned that heterogeneous
catalysts can undergo transformations during catalytic
reactions (changes in morphology, phase transformations,
sintering, etc.). Such changes are yet to be considered in
kinetic analysis, even if there are already some examples
when for example sintering is quantitatively described
[38].
Kinetic analysis discussed above was mainly related to
catalysis by supported metals. Oxide catalysts have
recently been considered as a modern alternative to
noble-metal catalysts, leading to different selectivity
behavior compared to noble-metals, for example in ring
opening of methylcyclopentane [39–41]. Such difference
can be ascribed to different compartment and should be
then properly reflected in reaction kinetics.
Few final words could be related to methodological
aspects of kinetic measurements in catalysis.
First experimental data that are thought to be
important and relevant should be collected in the broad
range of parameters followed by regression analysis,
estimation of rate constants, and evaluation of the model
adequacy.
Among the tools which appeared rather recently, one
should mention micro-(micro-structured, microchannel)
reactors with the size of channels typically ca. 10 mm–
2 mm, allowing to conduct reactions in a small scale.
Microreactors can easily provide short residence time,
provide or remove the heat and allow sufficient mass
transfer. Such reactors are also suitable for acquisition of
kinetic data for gas–solid catalytic reactions, as illustrated
recently [42,43], even if there are still challenges
associated with the deposition of catalytic layers in
microreactors.
In this short account, it was not possible to consider in
detail all aspects of catalytic kinetics and thus only few
topics were selected, mainly reflecting the personal view
and experience of the author.
Re
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