苯肼和醛2

Mohammad Reza Mohammadizadeh · Fatemeh Basti

Received: 13 August 2014 / Accepted: 17 December 2014 / Published online: 31 December 2014 © Iranian Chemical Society 2014

Abstract This paper reports a new and simple procedure for the synthesis of 3H-spiro[isobenzofuran-1,3′-pyrazole] derivatives by reacting 1-benzylidene-2-phenylhydra-zine derivatives with ninhydrin in acetic acid medium at room temperature followed by oxidative cleavage of their corresponding dihydroindeno[1,2-c]pyrazoles. 1-Ben-zylidene-2-phenylhydrazine derivatives were prepared via the reaction between phenylhydrazine and benzaldehyde derivatives. Easy procedure, mild reaction conditions, high yields in short reaction times, availability of starting mate-rials, and no formation of by-product are the advantages of this approach.

Keywords 3H-spiro[isobenzofuran-1,3′-pyrazole] · Ninhydrin · 1-Benzylidene-2-phenylhydrazine · Dihydroindeno[1,2-c]pyrazole

Introduction

Synthesis of compounds with specific chemical structures and biological properties may be important and has always been considered by chemists. Many efforts have been made to provide the efficient ways to produce a wide range of derivatives in each series. One of these compounds which has always been the focus of attention for various research groups is phthalide[1(3H)-isobenzofuranone] frameworks, a bunch of natural products possessing bio-logical activity as well as synthetic goals [1–3]. 3-Substi-tuted spiro-type phthalides are especially very important

M. R. Mohammadizadeh (*) · F. Basti

Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran

e-mail: mrmohamadizadeh@pgu.ac.ir

molecules as they possess antiepileptic, antibiotic and anti-depressant activities as well as their presence in biologi-cally active molecules [4–7]. On the other hand, pyrazole and its derivatives have also been focus of considerable attention due to their broad variety of properties. There is large variety of compounds having the pyrazole core struc-ture that are of importance in agrochemical and pharma-ceutical activities [8].

While isobenzofuranone and pyrazole derivatives have attracted significant attention, the preparation of spiro-heterocyclic compounds incorporating isobenzofuranone and pyrazole motifs has not been the subject of much research.

We have been synthesizing numerous novel spiro-type molecules that have isobenzofuranone moiety through an oxidative cleavage strategy [9–11]. Herein, we apply this strategy to the synthesis of new spirocyclic compounds containing isobenzofuranone and pyrazole skeleton named 3H-spiro[isobenzofuran-1,3′-pyrazole].

ExperimentalGeneral

Melting points were measured on an Electrothermal 9100 apparatus. IR spectra were recorded on A Jasco IR-460 Plus spectrometer. Mass spectra were recorded on an Agi-lent 8430 mass spectrometer operating at an ionization potential of 70 eV. 1H and 13C-NMR spectra were recorded at 500.1, 400.2 and 125.7, 100.6 MHz, respectively, on a BRUKER DRX 500 and 400-AVANCE FT-NMR instru-ment with CDCl3 and DMSO as solvent. The reagents and solvents used in this work were obtained from Fluka, Merck and Aldrich companies and used without further

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1172purification. The reaction monitoring was accomplished by TLC on silica gel PolyGram SILG/UV254 plates.General procedure for the preparation

of 1-benzylidene-2-phenylhydrazine derivatives (3a‑j)To a mixture of phenylhydrazine (1 mmol) in ethanol (5 mL) aldehyde was added followed by some drops of acetic acid. The resulting mixture was disrupted under reflux conditions for 15 min using a magnetic stirrer. The reaction progress was looked for by TLC using a mixture of ethyl acetate/n-hexane (1:10). After completion of the reaction and cooling to room temperature, water (5 mL) was added. Pure product was obtained after filtration and washing with n-hexane (3 × 5 mL). All compounds were known and identified by comparison of their melting points with previously reported values [12–14].

General procedure for the preparation of 3H-spiro[isobenzofuran-1,3′-pyrazole] derivatives in AcOH mediumA mixture of 1-benzylidene-2-phenylhydrazine 3 (1 mmol), and ninhydrin 4 (1 mmol) in acetic acid (3 mL), was stirred at room temperature for 3 h. Then, a solution of Pb(OAc)4 (1 mmol) in acetic acid (2 mL) was added and the resulting mixture was allowed to rotate for additional 40 min at room temperature. After completion, confirmed by TLC, water (5 mL) was added to the reaction mixture and pure product was obtained after filtration and washing with a mixture of EtOAc/n-hexane (1:10, 3 × 5 mL).

5′‑(4‑Chlorophenyl)‑2′‑phenyl‑3H‑ spiro[isobenzofuran‑1,3′‑pyrazole]‑3,4′(2′H)‑dione (5a)

Red powder; mp: 161–1 °C; IR (KBr), (ῡmax, cm−1): 1,7, 1,737, 1,597, 1,516, 1,497; 1H-NMR (400 MHz, CDClCH of Ar), 7.49 (d, 3), δ 7.07–7.11 (m, 3H, CH of Ar), 7.22–7.25 (m, 3H, 3J = 8.6 Hz, 2H, CH of Ar), 7.65–7.23 (m, 2H, CH of Ar), 8.06 (dd, 3J1 = 6.2 Hz, 3J2 = 1.9 Hz, 1H, CH of Ar), 8.16 (d, 3J = 8.7 Hz, 2H, CH of Ar); 13C-NMR (100 MHz, CDCl126.6, 126.9, 127.1, 127.3, 129.2, 129.4, 131.7, 135.5, 3), δ 90.6, 117.2, 122.0, 124.8, 136.0, 139.5, 139.9, 141.9, 167.0, 191.7. Anal. Calcd. for CC 67.93, H 3.33, N 7.16. MS, 22H13ClN2O3 (388.80): C 67.96, H 3.37, N 7.21; Found: m/z (%): 390 ([M+2]+, 20), 3 ([M+1]+, 15), 388 ([M]+, 66), 372 (14), 223 (98), 209 (96), 179 (base peak), 105 (99), 91 (43), 77 (61), 76 (29).5′‑(4‑Nitrophenyl)‑2′‑phenyl‑3H‑ spiro[isobenzofuran‑1,3′‑pyrazole]‑3,4′(2′H)‑dione (5b)

Red powder; mp: 214–217 °C; IR (KBr), (ῡ1max, cm−1): 1,790, 1,732, 1,596, 1,523, 1,497; H-NMR (400 MHz,

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J IRAN CHEM SOC (2015) 12:1171–1176

CDCl3), 7.12–7.17 (m, 3H, CH of Ar), 7.25–7.29 (m, 2H, CH of Ar), 7.30–7.31 (m, 1H, CH of Ar), 7.68–7.76 (m, 2H, CH of Ar), 8.12–8.14 (m, 1H, CH of Ar), 8.35–8.41 (m, 4H, CH of Ar); 13C-NMR (100 MHz, CDCl3), δ 90.8, 117.6, 121.9, 124.2, 125.6, 126.4, 126.9, 127.1, 129.6, 131.9, 134.3, 135.7, 138.1, 139.5, 141.6, 148.1, 166.8, 191.0. Anal. Calcd. for C22H13N3O3.28, N 10.52; Found: C 66.13, H 3.25, N 10.49. MS 5 (399.36): C 66.17, H m/z (%): 400 ([M+1]+, 1), 399 ([M]+, 3), 383 (20), 223 (43), 179 (base peak), 104 (39), 91 (40), 77 (86), 76 (66).5′‑(4‑Fluorophenyl)‑2′‑phenyl‑3H‑spiro[isobenzofuran‑1,3′‑ pyrazole]‑3,4′(2′H)‑dione (5c)

Red powder; mp: 200–203 °C; IR (KBr), (ῡmax, cm−1): 1,794, 1,739, 1,597, 1,531, 1,496; 1H-NMR (400 MHz, CDCl3): δ 7.10–7.15 (m, 3H, CH of Ar), 7.23–7.30 (m, 3H, CH of Ar), 7.67–7.75 (m, 2H, CH of Ar), 7.78 (d, 3

J = 8.8 Hz, 2H, CH of Ar), 8.12 (d, 3J = 6.4 Hz, 1H, CH of Ar), 8.33 (d, 3J = 8.4 Hz, 2H, CH of Ar); 13C-NMR (100 MHz, CDCl125.5, 126.2, 126.9, 127.0, 129.6, 131.9, 132.5, 132.7, 3), 90.7, 112.9, 117.5, 118.6, 121.9, 135.6, 138.4, 139.5, 141.7, 166.8, 191.1. Anal. Calcd. for C22H13FN2O3 (372.35): C 70.96, H 3.52, N 7.52; Found C 70.93, H 3.48, N 7.47. MS: m/z(%): 373 ([M+1]+, 22), 372 ([M]+, 98), 356 (16), 179 (99), 104 (73), 91 (37), 77 (88), 76 (base peak).

5′‑(4‑Bromophenyl)‑2′‑phenyl‑3H‑spiro[isobenzofuran‑1,3′‑ pyrazole]‑3,4′(2′H)‑dione (5d)

Red powder; mp: 158–161 °C; IR (KBr), (ῡmax, cm−1): 1,788, 1,737, 1,596, 1,514, 1,497; 1H-NMR (400 MHz, CDCl3), δ 7.08–7.11 (m, 3H, CH of Ar), 7.22–7.26 (m, 3H, CH of Ar), 7.65 (d, 3J = 8.6 Hz, 2H, CH of Ar), 7.68–7.73 (m, 2H, CH of Ar), 8.08–8.12 (m, 3H, CH of Ar); 13C-NMR (100 MHz, CDCl3), δ 90.6, 117.2, 122.0, 124.4, 124.8, 126.9, 127.0, 127.1, 127.5, 129.4, 131.7, 132.2, 135.5, 139.6, 139.9, 141.9, 167.0, 191.6. Anal. Calcd. for CC 60.95, H 2.99, N 6.45. MS, 22H13BrN2O3 (433.25): C 60.99, H 3.02, N 6.47; Found: m/z (%): 435 ([M+2]+, 4), 434 ([M+1]+, 20), 433 ([M]+, 4), 416 (6), 223 (base peak), 179 (98), 104 (56), 91 (27), 77 (54), 76 (78).

4‑(3,4′‑Dioxo‑2′‑phenyl‑2′,4′‑dihydro‑3H‑ spiro[isobenzofuran‑1,3′‑pyrazole]‑5′‑yl)benzonitrile (5e)

Red powder; mp: 159–162 °C; IR (KBr), (ῡmax, cm−1): 2,222, 1,786, 1,746, 1,597, 1,526, 1,497; 1H-NMR (400 MHz, CDCl3), δ 7.00–7.09 (m, 3H, CH of Ar), 7.16–7.29 (m, 5H, CH of Ar), 7.55–7.72 (m, 2H, CH of Ar), 8.10–8.12 (m, 1H, CH of Ar), 8.19–8.23 (m, 2H, CH of Ar); 13C-NMR (100 MHz, CDCl3), δ 90.6, 117.2, 122.0,

J IRAN CHEM SOC (2015) 12:1171–1176 124.3, 124.4, 124.6, 126.9, 127.1, 128.1, 128.2, 129.4, 131.6, 135.5, 139.7, 140.0, 142.0, 162.6, 167.1, 191.9. Anal. Calcd. for C23H13N11.08; Found: C 72.79, H 3.43, N 11.06. MS 3O3 (379.37): C 72.82, H 3.45, N m/z (%): 380 ([M+1]+, 3), 379 ([M]+, 11), 363 (26), 223 (61), 179 (base peak), 104 (24), 91 (11), 77 (54), 76 (45).

5′‑(4‑Methoxyphenyl)‑2′‑phenyl‑3H‑spiro[isobenzofuran‑1, 3′‑pyrazole]‑3,4′(2′H)‑dione (5f)

Red powder; mp: 148–151 °C; IR (KBr), (ῡH-NMR (400 MHz, max, cm−1): 1,784, 1,745, 1,608, 1,578, 1,497; 1CDCl7.21–7.29 (m, 3H, CH of Ar), 7.–7.71 (m, 2H, CH of 3), δ 3.91 (s, 3H, CH3), 7.03–7.09 (m, 5H, CH of Ar), Ar), 8.09 (dd, 3J8.16 (d, 31 = 6.2 Hz, 3J2 = 1.6 Hz, 1H, CH of Ar), J = 9.2 Hz, 2H, CH of Ar); 13C-NMR (100 MHz, CDCl3), δ 55.4, 90.5, 114.4, 116.9, 120.6, 122.0, 124.0, 126.8, 127.2, 127.8, 129.3, 131.5, 135.4, 140.3, 140.6, 142.3, 161.2, 167.3, 192.3. Anal. Calcd. for C23H16N2O4 (384.38): C 71.87, H 4.20, N 7.29; Found: C 71.84, H 4.17, N 7.26. MS: m/z (%): 385 ([M+1]+, 4), 384 ([M]+, 16), 368 (16), 301 (29), 223 (33), 179 (62), 104 (63), 90 (50), 77 (55), 76 (base peak).

2′‑Phenyl‑5′‑(p‑tolyl)‑3H‑spiro[isobenzofuran‑1,3′‑pyrazole]‑3,4′(2′H)‑dione (5g)

Red powder; mp: 158–161 °C; IR (KBr), (ῡ−1

1,787, 1,748, 1,596, 1,541,1,497; 1H-NMR (400 MHz, max, cm): CDCl3), δ 2.5 (s, 3H, CH7.21–7.28 (m, 3H, CH of Ar), 7.31–7.34 (m, 2H, CH of 3), 7.04–7.10 (m, 3H, CH of Ar), Ar), 7.-7.71 (m, 2H, CH of Ar), 8.08–8.13 (m, 3H, CH of Ar), 13C-NMR (100 MHz, CDCl3), δ 21.6, 90.6, 117.1, 122.0, 124.4, 125.3, 126.1, 126.8, 127.2, 129.4, 129.7, 131.5, 135.4, 140.2, 140.4, 140.7, 142.2, 167.2, 192.1. Anal. Calcd. for C23H16N2O3 (368.38): C 74.99, H 4.38, N 7.60; Found: C 74.95, H 4.36, N 7.58. MS: m/z(%): 369 ([M+1]+, 18), 368 ([M]+, 79), 352 (17), 223 (base peak), 179 (99), 104 (55), 91 (36), 77 (67), 76 (81).

2′,5′‑Diphenyl‑3H‑spiro[isobenzofuran‑1,3′‑pyrazole]‑3,4′(2′H)‑dione (5 h)

Red powder; mp: 150–153 °C; IR (KBr), (ῡmax, cm−1): 1,786, 1,730, 1,599, 1,526,1,494; 1H-NMR (400 MHz, CDCl3), δ 7.06–7.11 (m, 3H, CH of Ar), 7.22–7.27 (m, 3H, CH of Ar), 7.47-7.55 (m, 3H, CH of Ar), 7.65–7.72 (m, 2H, CH of Ar), 8.09–8.12 (m, 1H, CH of Ar), 8.21 (dd, 3J1 = 7.8 Hz, 3J2 = 1.6 Hz, 2H, CH of Ar); 13C-NMR (100 MHz, CDCl3), δ 90.6, 117.1, 122.0, 124.6, 126.0, 126.8, 127.1, 128.1, 128.9, 129.4, 130.1, 131.6, 135.4, 140.1, 140.5, 142.2, 167.2, 191.9. Anal. Calcd. for C22H14N2O3 (354.36): C 74.57, H 3.98, N 7.91; Found: C

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74.52, H 3.94, N 7.87. MS: m/z (%): 355 ([M+1]+, 4), 354 ([M]+, 19), 338 (7), 223 (88), 179 (base peak), 104 (27), 91 (17), 77 (40), 76 (50).

2′‑(4‑Bromophenyl)‑5′‑(4‑methoxyphenyl)‑3H‑spiro[isobenzofuran‑1,3′‑pyrazole]‑3,4′(2′H)‑dione (5i)

Red powder; mp: 167–169 °C; IR (KBr), (ῡmax, cm−1): 1,783, 1,746, 1,606, 1,536, 1,487; 1H-NMR (400 MHz, CDCl3), δ 3.91 (s, 3H, CH3), 6.93 (dd, 3J = 2.6 Hz, 1H, CH of 1 = 3J32 = 2.6 Hz, 1H, CH of Ar), 6.95 (dd, JAr), 7.02 (dd, 31 = 3J2J31 = 3J2 = 2.4 Hz, 1H, CH of Ar), 7.05 (dd, J1H, CH of Ar), 7.33 (dd, 1 = 3J2 = 2.4 Hz, 1H, CH of Ar), 7.19–7.22 (m, 3J1 = 3JAr), 7.35 (dd, 32 = 2.6 Hz, 1H, CH of J7.73 (m, 2H, CH of Ar), 8.09–8.12 (m, 1H, CH of Ar), 1 = 3J2 = 2.6 Hz, 1H, CH of Ar), 7.66–8.13 (dd, 3J3

1 = 3J2 = 2.4 Hz, 1H, CH of Ar); 8.16 (dd, J1 = 3J2 = 2.4 Hz, 1H, CH of Ar); 13C-NMR (100 MHz, CDCl3), δ 55.5, 90.3, 114.5, 117.0, 118.3, 120.3, 122.0, 126.9, 127.1, 127.9, 131.7, 132.3, 135.5, 139.4, 140.9, 141.9, 161.4, 166.9, 192.1. Anal. Calcd. for C(463.28): C 59.63, H 3.26, N 6.05; Found: C 59.60, H 3.24, 23H15BrN2O4 N 6.02. MS, m/z (%): 465 ([M+2]+, 8), 4 ([M+1]+, 35), 463 ([M]+, 8), 446 (20), 301 (97), 257 (49), 178 (46), 104 (68), 90 (56), 76 (base peak).

2′‑(4‑Bromophenyl)‑5′‑(p‑tolyl)‑3H‑spiro[isobenzofuran‑1,3′‑pyrazole]‑3,4′(2′H)‑dione (5j)

Red powder; mp: 1–192 °C; IR (KBr), (ῡmax, cm−1): 1,799, 1,747, 1,588, 1,535, 1,487; 1H-NMR (400 MHz, CDCl3), δ 2.43 (s, 3H, CH6.96–7.18 (m, 2H, CH of Ar), 7.26–7.31 (m, 3H, CH of 3), 6.92–6.94 (m, 2H, CH of Ar), Ar), 7.67–7.78 (m, 2H, CH of Ar), 8.05–8.07 (m, 3H, CH of Ar); 13C-NMR (100 MHz, CDCl118.3, 119.5, 123.1, 125.1, 126.0, 127.3, 128.0, 130.8, 3), δ 22.7, 90.4, 114.6, 132.8, 133.4, 135.1, 136.6, 140.1, 141.9, 1.9, 192.1. Anal. Calcd. for C23H15BrN2O3 (447.28): C 61.76, H 3.38, N 6.26; Found: C 61.73, H 3.34, N 6.22. MS, m/z (%): 449 ([M+2]+, 5), 448 ([M+1]+, 19), 447 ([M]+, 5), 432 (14), 301 (58), 257 (36), 178 (49), 104 (66), 90 (36), 76 (base peak).

Results and discussion

The synthesis of 3H-spiro[isobenzofuran-1,3′-pyrazole] derivatives from the reaction between 1-benzylidene-2-phenylhydrazine derivatives and ninhydrin followed by oxidative cleavage of their corresponding product was stud-ied (Scheme 1).

As can be seen in Scheme 1, initially according to the previously reported procedure, the derivatives of

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Scheme 1 Total path-way for the synthesis of 3H-spiro[isobenzofuran-1,3′-J IRAN CHEM SOC (2015) 12:1171–1176

NHNH2OHEtOHHOOHpyrazole] derivatives

+R2R112Table 1 Synthesis of new derivatives of 3H-spiro[isobenzofuran-1,3′-pyrazole] 5a‑j

5R1R2Yield (%)aaClH94bNO2H97cFH95dBrH93eCNH94fOCH3H91gCH3H91hHH92iOCH3Brj

CH3

Br

a

Refers to isolated pure products

1-benzylidene-2-phenylhydrazine were prepared by the condensation reaction between phenylhydrazine and benza-ldehyde derivatives (3a‑j). These known compounds were identified by comparing their melting points with previ-ously reported values. The reaction of these compounds with ninhydrin in acetic acid medium at room temperature

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R2NHNCR1+OHO3a-j41)AcOHPb(OA, r.t.c),3h2)4,40 minOR1OONNR25a-jfollowed by oxidative cleavage of their corresponding prod-uct by Pb(OAc)-pyrazole] (Table 4 was resulted in 3H-spiro[isobenzofuran-1,3′1). The results show that the desired products were obtained in excellent yields and substituted groups on aromatic rings did not have any profound influ-ence on the reactivity. Yet, oxidative cleavage step was very fast and clean and the pure products were precipitated at the end and extra action was not required for purification. Note that when periodic acid was used as oxidizing agent in the oxidative cleavage of vicinal diol 6a, the product 5a was obtained in only 55 % yield.

The molecular structures of all products 5a‑j were iden-tified from their mass spectrometric analyses, IR, 1H-NMR, 13

C-NMR spectra and elemental analyses. Spectral data of compound 5a, for instance, are as follows: The mass spec-trum of 5a displayed the molecular ion peak at m/z 372, which is in agreement with the proposed structure. The IR spectrum of this compound showed absorption bands due to the carbonyl groups of the lactone and ketone at 1,794, 1,739 cm−1, respectively, and at 1,597, 1,531, 1,496 cm−1 for C=N, C=C and C–N bonds. The 1H-NMR spectrum of this compound shows 12 protons in the aromatic region that correspond well with the structure of this compound. The 1

H-decoupled 13C-NMR spectrum of 5a showed 19 distinct resonances in agreement with the suggested structure.

For more information about the mechanism, in the syn-thesis of compound 5a, the reaction was stopped before adding the Pb(OAc)4 and the product was isolated and identified on the basis of their IR, 1H-NMR, 13C-NMR data and elemental analyses. Spectral data confirmed a vicinal cyclic diol structure in this step (Scheme 2).

The 1H-NMR spectrum of 6a in CDCl3 exhibited two single sharp signals at 3.58 and 4.19 ppm due to the hydroxyl protons, together with aromatic protons which

J IRAN CHEM SOC (2015) 12:1171–1176 Scheme 2 Synthesis of vicinal diol 6a by reaction of com-pound 3a with ninhydrin

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HNHNC3aOCl+O4OHOHAcOHr.t.3hOOHClOHNN6aScheme 3 Proposed mecha-nism for the formation of compounds 5a‑j

O+R2R1OEtOH- HO2R2HNHNCR1+OHOHO4NHNH2H12OOHR13a-jOOHNNHR1AcOH- HO2BOB = H2OorCH3CO2HNNO7R2R28R2OAcOAcPbOONNO- 2 Pb(OAc)2OOHR1NOHNPb(OAc)4,AOcHR26a-jR1ONδOH2ONδOOHOHOR1ONN9R1OON- H2OONR210R211R2R15a-jwere resonated as multiplets in the region at δ = 7.13–3, due to the presence of nitrogen containing free electron

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7.98 ppm. The H decoupled C-NMR spectrum of 6a pair conjugated with carbon–nitrogen double bond. This showed distinct signals in agreement with the proposed carbon is bearing some negative charge and nucleophilic structure. (see Supplementary data).attacks are firstly made through the carbon [16, 17]. There-A plausible mechanism for the synthesis of fore, 1-benzylidene-2-phenylhydrazines 3 attack the nin-3H-spiro[isobenzofuran-1,3′-pyrazole] derivatives is hydrin and after passing the intermediate 8 followed by depicted in Scheme 3. At first, from the condensation reac-intramolecular attack of nitrogen to other carbonyl group of

tion between phenylhydrazine and benzaldehyde derivatives, ninhydrin, dihydroindeno[1,2-c]pyrazole compounds 6a–j the corresponding 1-benzylidene-2-phenylhydrazines are are synthesized. Then, the oxidative cleavage of these cyclic obtained [15]. The 1-benzylidene-2-phenylhydrazine deriva-diols by Pb(OAc)4 produces the orthogonal intermediate 10

tives (phenylhydrazones) 3 act as enamines. In compound through intermediate 9. Because of the strong intramolecular

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1176interactions between the nitrogen and the carbonyl group next to it in such rings [18], a large positive charge assem-bled on the nitrogen in the intermediate 10. Hydrolysis of this intermediate produces the compound 11 which forms the final product by intramolecular sterification reaction.

ConclusionIn conclusion, this work described a novel method for the preparation of a wide variety of new spirocyclic com-pounds containing isobenzofuranone and pyrazole moi-eties, named 3H-spiro[isobenzofuran-1,3′-pyrazole] by oxidative cleavage of dihydroindeno[1,2-c]pyrazoles. This

one-pot and simple procedure can be a convenient and effective method for the synthesis of a wide range of novel drug-like spiroindolines.

Acknowledgments The authors would like to acknowledge finan-cial support provided by Persian Gulf University for carrying out this

research.

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