A new and a convenient route to enaminones and pyrazoles

Abstract

A new method has been developed for the regioselective preparation of enaminones and pyrazoles from 1,3-diketonatoboron difluorides. The reactions proceed smoothly under mild reaction conditions, producing enaminones and pyrazoles in high yields.

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Enaminones and related compounds, possessing the structural unit N–C[double bond, length half m-dash]C–Z (Z = COR, CO₂R, CN, etc.), are versatile synthetic intermediates in the construction of heterocycles.¹ Pyrroles, oxazoles, pyridinones, quinolines, dibenzodiazepines, tetrahydrobenzoxazines, tetronic acids, and aza steroids have been prepared from enaminones.^1,2 Enaminones are also valuable precursors for α-iodo enaminones,³ 3-amino sugar derivatives,⁴ azo compounds,⁵β-aminoketones,⁶ as well as tetrahydropentalenes, tetrahydroindenes, and hexahydroazulenes.⁷ In addition, some of these compounds are pharmaceuticals possessing anticonvulsant^8a–c and analeptic^8d activity, combined with low toxicity.

Enaminones are commonly prepared from amines and 1,3-diketones. The procedure leads to a single product if symmetrical 1,3-diketones⁹ or compounds containing two carbonyl groups of substantially different reactivity are employed,¹⁰ otherwise mixtures are obtained that are often difficult to separate. There is also a great variety of other methods for the preparation of unsymmetrical acyclic or cyclic enaminones.¹¹ These methods involve several reaction steps, but they also suffer from the availability of the starting materials and, when 1,3-diketones and primary or secondary amines are used, they require prolonged heating at high temperatures and the azeotropic removal of water. A few years ago we have described a new synthetic route to pyrimidine N-oxides, starting from 1,3-diketones and carboxamide oximes.¹² We found that reactions catalysed with BF₃ · OEt₂ gave pyrimidine N-oxides in low yields. Later on we discovered that low yields were due to the formation of 1,3-diketonatoboron difluorides. 1,3-Diketonatoboron difluorides, first described by Morgan and Tunstall,¹³ are known as valuable intermediates in organic synthesis.¹⁴ They can also be considered as protected 1,3-diketones.¹⁵

Herein we wish to report our preliminary results on the use of 1,3-diketonatoboron difluorides as starting materials for the regioselective synthesis of unsymmetrical enaminones and substituted pyrazoles. Initially, 1,3-diketonatoboron difluorides 1a–d were prepared in good yields by treatment of the corresponding 1,3-diketones with BF₃ · OEt₂ at room temperature (Table 1). Reactions of 1a–d with amino compounds afforded the products 2–5. The processes are highly regioselective and the products are formed in high yields.

Table 1 Preparation of 1,3-diketonatoboron difluorides

Product	R	Reaction time/h	Yield (%)^a	mp/°C
a Isolated yields are given. b Ethyl acetate. c Lit.^16a mp 158–160 °C. d Lit.^16b mp 189–190 °C. e Toluene. f Lit.^16c mp 163 °C. g Hexane.
1a	Me	6	92	157–159^b^c
1b	Ph	8	89	190–191^b^d
1c	—	72	88	161–162^e^f
1d	—	24	95	58–60^g

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The reactions of 2,2-difluoro-4-methylnaphtho[1,2-e]-1,3,2-dioxaborin and its [2,1-e] isomer with aniline have been reported.¹⁷ They give rise to the formation of the corresponding oxazaborines and not to the enaminones as described herein.

When we performed reactions with 1 or 2 equiv. of an amine, completion was not achieved within several hours. Under these conditions a small amount of the corresponding 1,3-diketones were detected in the reaction mixture. We found that at least 3 equiv. of the amine were required to avoid any side products. The above observation suggests that the coordination of boron in 1,3-diketonatoboron difluoride with an amine also plays a part in the successful termination of the reaction.

Benzoylacetonatoboron difluoride 1a was treated with ammonia, methylamine, isopropylamine, cysteamine, 3-picolylamine, and 3-amino-2,2-dimethylethanol to afford enaminones 2a–f (Table 2). It is worth mentioning that even cysteamine reacted with 1a to yield only the enaminone 2d. Comparable results were obtained employing difluorides 1b–c and the appropriate amines.

Table 2 Preparation of enaminones

Product	R	R^1	Reaction time/h	Yield (%)^a	mp/°C
a Isolated yields are given. b Toluene. c Lit.^18a mp 144–145 °C. d Lit.^18b mp 45–47 °C. e Lit.^18c mp 56–58 °C. f Diethyl ether. g Hexane–ethyl acetate. h Hexane–diethyl ether. i Diethyl ether.
2a	Me	H	0.25	99	143–145^b^c
2b	Me	Me	0.25	99	68–69^b^d
2c	Me	i-Pr	0.5	98	57–58^b^e
2d	Me	CH2CH2SH	0.5	98	Oil
2e	Me	3-PyCH2	0.5	96	Oil
2f	Me	C(Me)2CH2OH	0.5	79	Oil
3a	Ph	i-Pr	0.5	91	Oil^18d
3b	Ph	CH2CH2SH	0.5	88	Oil
3c	Ph	3-PyCH2	1	95	85–86^f
4a	—	H	0.25	98	117–118^g
4b	—	Me	0.25	99	53–54^g
4c	—	i-Pr	1.5	99	Oil
4d	—	CH2CH2SH	1.5	81	Oil
4e	—	3-PyCH2	0.5	97	84–86^h
5a	—	H	0.25	99	73–75^i
5b	—	Me	0.25	99	Oil
5c	—	i-Pr	0.25	95	Oil
5d	—	CH2CH2SH	0.25	83	44–45^i
5e	—	3-PyCH2	0.25	97	Oil

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The problems associated with the use of low boiling amines have been overcome by the utilisation of a Lewis acid–amine complex.⁹ However, these reactions required prolonged heating in toluene and the removal of water. Furthermore, application of an excess of Lewis acid often resulted in the formation of a mixture of enaminones. In our procedure, ammonia or methylamine was passed over the stirred solution of 1,3-diketonatoboron difluoride for 5 min and the reaction was completed after an additional 15 min, giving only one regioisomer in excellent yield.

Our attention was then directed towards hydrazino compounds as nitrogen nucleophiles. Reaction of unsymmetrical 1,3-diketones with monosubstituted hydrazines can yield isomeric pyrazoles. It is known that benzoylacetone gives both 1,3-dimethyl-5-phenylpyrazole and 1,5-dimethyl-3-phenylpyrazole on reaction with methylhydrazine.¹⁹ There is also a report on pyrazole ring closure with methylhydrazine and phenylhydrazine, starting from benzoylacetone in heterogeneous media that resulted in a mixture of pyrazoles.²⁰ When we reacted 1a with 3 equiv. of methylhydrazine we isolated only 1,3-dimethyl-5-phenylpyrazole (6a) in high yield. Similarly, phenylhydrazine furnished 1,5-diphenyl-3-methylpyrazole (6b). In addition, 1,3-diketonatoboron difluorides 1b–d reacted smoothly with hydrazines to offer a single regioisomer of 7–9Table 3.

Table 3 Preparation of pyrazoles

Product	R	R^2	Reaction time/h	Yield (%)^a	mp/°C
a Isolated yields are given. b Lit.^21a mp 22 °C. c Hexane–diethyl ether. d Lit.^21c mp 59–60 °C. e Ethanol. f Lit.^21d mp 138–139 °C. g Diethyl ether. h Toluene.
6a	Me	Me	0.5	95	Oil^b
6b	Me	Ph	2	83	Oil^21b
7a	Ph	Me	0.5	84	59–61^c^d
7b	Ph	Ph	2	89	138–140^e^f
8a	—	Me	0.5	88	165–167^g
8b	—	Ph	0.5	91	87–89^h
9a	—	Me	0.5	91	97–99^h
9b	—	Ph	0.5	95	48–50^c

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The structure elucidation of the enaminones and pyrazoles obtained was established by spectroscopic analyses, ¹H, ¹³C NMR, HMQC, HMBC and NOESY spectra. The ¹H-¹³C HMBC correlation and 2D NOE cross peaks clearly confirm the assigned regioisomers. The structure of compound 8b was also confirmed by an X-ray analysis (not reported).

In conclusion, we have described an efficient and regioselective approach to enaminones and pyrazoles. This methodology is of particular use, especially when one has to deal with a low boiling amine or an amine containing other nucleophilic functional groups (OH, SH). The reactions terminate under mild conditions in a short time with the formation of a single product that is easily isolable in high yields.

Experimental

General methods

Solvents and starting compounds were obtained from commercial sources (Fluka, Sigma and Aldrich). NMR spectra were recorded on a Bruker Avance 300 DPX spectrometer at 302 K. The HMBC spectra were obtained with 512 time increments and 32 scans per t₁ increment. NOESY studies were acquired using the noesytp program on the DPX spectrometer. The mixing time was 100 ms and 32 accumulations were collected. Chemical shifts are reported relative to internal standard Me₄Si. IR spectra were taken on BioRed FTS 3000MX instrument. Melting points were determined on a hot stage and are uncorrected. Microanalysis were performed on a Perkin-Elmer 2400 CHN Analyser. Mass spectra and high resolution mass measurements were acquired on a VG-Analytical Autospec EQ instrument.

General procedure for the preparation of 1,3-diketonatoboron difluorides 1a–d

To a solution of the corresponding 1,3-diketone (1 equiv.) in toluene or dichloromethane (3 mL), boron trifluoride etherate (3 equiv.) was added at room temperature. The reaction mixture was allowed to stand at room temperature for the time noted in Table 1. Afterwards the reaction mixture was evaporated and the residue suspended in water (10 mL). Solid material was filtered off and recrystallised from toluene.

2-Acetyl-3,4-dihydro-1(2H)-naphthalenolatoboron difluoride (1c). IR (KBr, ν cm⁻¹): 2943, 1608, 1506, 1347, 1274, 1216, 1033, 802, 745. ¹H NMR (300 MHz, CDCl₃): δ 2.39 (s, 3H), 2.71 (t, 2H, J = 7.4 Hz), 2.98 (t, 2H, J = 7.4 Hz), 7.28 (d, 1H, J = 7.5 Hz), 7.38 (dd, 1H, J₁ = J₂ = 7.5 Hz), 7.56 (ddd, 1H, J₁ = J₂ = 7.5 Hz, J₃ = 1.3 Hz), 8.11 (d, 1H, J = 7.5 Hz). ¹³C NMR (75 MHz, CDCl₃): δ 21.6, 22.3, 27.5, 107.2, 127.6, 128.0, 128.3, 135.4, 143.5, 177.9, 189.59, 189.61. MS (EI, 70 eV, m/z (%) 236 (M⁺, 100), 221 (91), 215 (55), 193 (65), 127 (58). HRMS (EI) m/z calcd for C₁₂H₁₁BF₂O₂ : 235.0857, found 235.0866. Anal. calcd. for C₁₂H₁₁BF₂O₂ : C, 61.07; H, 4.70; found: C, 60.71; H, 4.50.

2-Acetylcyclopentanolatoboron difluoride (1d). IR (KBr, ν cm⁻¹): 2970, 1606, 1549, 1383, 1348, 1310, 1195, 1154, 1027, 968. ¹H NMR (300 MHz, CDCl₃): δ 2.10 (dd, 2H, J₁ = J₂ = 7.8 Hz), 2.27 (s, 3H), 2.67–2.78 (m, 4H).¹³C NMR (75 MHz, CDCl₃): δ 20.1, 22.3, 25.2, 34.6, 113.0, 187.1, 199.3. MS (EI, 70 eV) m/z (%) 173 (M⁺, 23), 159 (100), 118 (42), 79 (35). HRMS (EI) m/z calcd for C₇H₉BF₂O₂ : 173.0700, found 173.0707. Anal. calcd. for C₇H₉BF₂O₂ : C, 48.33; H, 5.21; found: C, 48.08; H, 5.26.

General procedure for the synthesis of enaminones

To a stirred solution of a boron complex (1 equiv.) in acetonitrile (8 mL), amine (3 equiv.) was added at room temperature. In the case of ammonia or methylamine, the amine was passed over the stirred solution of a boron complex for 5 min at room temperature. The reaction mixture was stirred at room temperature for 0.25–1.5 h (see Table 2) and then evaporated to dryness. The residue was dissolved in dichloromethane (30 mL), washed with water (2 × 10 mL), dried over magnesium sulfate and evaporated to dryness. Products were purified in some cases by flash chromatography.

(2Z)-1-Phenyl-3-[(2-sulfanylethyl)amino]-2-buten-1-one (2d). Colourless oil. IR (NaCl plates, ν cm⁻¹): 3058, 2930, 2554, 1598, 1545, 1438, 1373, 1321, 1291, 1177, 1087, 1065, 1027, 739. ¹H NMR (300 MHz, CDCl₃): δ 1.60 (t, 1H, J = 8.5 Hz), 2.07 (s, 3H), 2.67–2.74 (m, 2H), 3.46–3.52 (m, 2H), 5.69 (s, 1H), 7.34–7.42 (m, 3H), 7.83–7.86 (m, 2H), 11.55 (br s, 1H). ¹³C NMR (75 MHz, CDCl₃): δ 19.4, 25.0, 46.2, 92.6, 126.8, 128.1, 130.5, 140.1, 164.4, 187.9. MS (EI, 70 eV) m/z (%) 221 (M⁺, 42), 188 (69), 174 (76), 105 (100), 91 (77), 77 (67). HRMS (EI) m/z calcd for C₁₂H₁₅NOS: 221.0874, found 221.0882.

(2Z)-1-Phenyl-3-[(3-pyridinylmethyl)amino]-2-buten-1-one (2e). The colourless oil obtained on work-up was subjected to flash chromatography (5 : 3 petroleum ether–ethyl acetate elution). IR (NaCl plates, ν cm⁻¹): 3058, 1601, 1543, 1435, 1319, 1295, 1065, 742. ¹H NMR (300 MHz, CDCl₃): δ 1.95 (s, 3H), 4.54 (d, 2H, J = 6.4 Hz), 5.69 (s, 1H), 7.04–7.32 (m, 5H), 7.50–7.56 (m, 1H), 7.80–7.84 (m, 2H), 8.48 (d, 1H, J = 3.4 Hz), 11.80 (br s, 1H). ¹³C NMR (75 MHz, CDCl₃): δ 19.6, 48.6, 92.9, 121.1, 122.5, 127.0, 128.2, 130.6, 137.1, 140.3, 149.5, 157.2, 164.9, 188.1. MS (EI, 70 eV) m/z (%) 252 (M⁺, 37), 147 (100), 133 (72), 105 (52), 92 (50), 77 (55).

(2Z)-3-[(2-Hydroxy-1,1-dimethylethyl)amino]-1-phenyl-2-buten-1-one (2f). Colourless oil. IR (NaCl plates, ν cm⁻¹): 3367, 2972, 2931, 1596, 1549, 1338, 1067, 740. ¹H NMR (300 MHz, CDCl₃): δ 1.40 (s, 6H), 2.13 (s, 3H), 3.61 (s, 2H), 3.83 (br s, 1H), 5.57 (s, 1H), 7.35–7.40 (m, 3H), 7.80–7.84 (m, 2H), 11.90 (br s, 1H). MS (EI, 70 eV) m/z (%) 233 (M⁺, 18), 202 (100), 184 (25), 162 (27), 105 (37). HRMS (EI) m/z calcd for C₁₄H₁₉NO₂ : 233.1416, found 233.1424.

(2Z)-1,3-Diphenyl-3-[(2-sulfanylethyl)amino]-2-propen-1-one (3b). Colourless oil. IR (NaCl plates, ν cm⁻¹): 3058, 1594, 1566, 1480, 1331, 1058, 750. NMR (300 MHz, CDCl₃): δ 1.49 (t, 1H, J = 8.5 Hz), 2.59–2.67 (m, 2H), 3.37–3.44 (m, 2H), 5.80 (s, 1H), 7.38–7.46 (m, 8H), 7.88–7.91 (m, 2H), 11.45 (br s, 1H). ¹³C NMR (75 MHz, CDCl₃): δ 25.6, 47.7, 94.2, 127.2, 127.8, 128.3, 128.7, 129.7, 130.9, 135.5, 140.2, 166.6, 188.9. MS (EI, 70 eV) m/z (%) 283 (M⁺, 27), 250 (100), 236 (82), 105 (36). HRMS (EI) m/z calcd for C₁₇H₁₇NOS: 283.1031, found 283.1041.

(2Z)-1,3-Diphenyl-3-[(3-pyridinylmethyl)amino]-2-propen-1-one (3c). The colourless oil obtained on work-up was subjected to flash chromatography (5 : 3 petroleum ether–ethyl acetate elution). IR (NaCl plates, ν cm⁻¹): 3059, 2927, 1593, 1566, 1480, 1331, 1226, 1057, 1025, 752. ¹H NMR (300 MHz, CDCl₃): δ 4.38 (d, 2H, J = 6.6 Hz), 5.87 (s, 1H), 7.18–7.22 (m, 1H), 7.33–7.53 (m, 8H), 7.53–7.57 (m, 1H), 7.87–7.90 (m, 2H), 8.36 (d, 1H, J = 1.8 Hz), 8.46–8.49 (m, 1H), 11.68 (br s, 1H). ¹³C NMR (75 MHz, CDCl₃): δ 45.9, 94.5, 123.6, 127.1, 127.7, 128.3, 128.7, 129.8, 131.0, 134.1, 134.7, 135.1, 139.9, 148.6, 148.8, 166.6, 189.0. MS (EI, 70 eV) m/z (%) 314 (M⁺, 39), 223 (95), 149 (75), 105 (100), 77 (97). HRMS (EI) m/z: calcd for C₂₁H₁₈N₂O: 314.1419, found 314.1426.

(2Z)-2-(1-Aminoethylidene)-3,4-dihydro-1(2H)-naphthalenone (4a). IR (KBr, ν cm⁻¹): 3289, 2888, 2831, 1591, 1487, 1359, 1308, 1146, 1032, 986, 901, 847, 777, 743. ¹H NMR (300 MHz, CDCl₃): δ 2.07 (s, 3H), 2.60 (t, 2H, J = 7.2 Hz), 2.84 (t, 2H, J = 7.2 Hz), 5.10 (br s, 1H), 7.15–7.37 (m, 3H), 7.99–8.02 (m, 1H), 10.88 (br s, 1H). ¹³C NMR (75 MHz, CDCl₃): δ 21.6, 25.0, 29.6, 101.3, 126.9 (2C), 127.6, 131.3, 136.2, 142.0, 160.7, 186.1. MS (EI, 70 eV) m/z (%) 187 (M⁺, 100), 172 (14), 97 (13), 69 (15). HRMS (EI) m/z calcd for C₁₂H₁₃NO: 187.0997, found 187.1005.

(2Z)-2-[1-(Methylamino)ethylidene]-3,4-dihydro-1(2H)-naphthalenone (4b). IR (KBr, ν cm⁻¹): 2929, 2830, 1594, 1547, 1476, 1318, 1252, 1182, 1062, 899, 785, 743. ¹H NMR (300 MHz, CDCl₃): δ 2.02, (s, 3H), 2.57 (t, 2H, J = 6.4 Hz), 2.80 (t, 2H, J = 6.4 Hz), 2.98 (d, 3H, J = 5.1 Hz), 7.12–7.15 (m, 1H), 7.25–7.32 (m, 2H), 7.97–8.01 (m, 1H), 12.52 (br s, 1H). ¹³C NMR (75 MHz, CDCl₃): δ 14.63, 25.0, 29.6, 30.2, 100.5, 126.3, 126.7, 127.2, 130.5, 136.5, 141.1, 164.7, 183.3. MS (EI, 70 eV) m/z (%) 201 (M⁺, 100), 186 (52), 56 (97). HRMS (EI) m/z calcd for C₁₃H₁₅NO: 201.1154, found 201.1160.

(2Z)-2-[1-(Isopropylamino)ethylidene]-3,4-dihydro-1(2H)-naphthalenone (4c). Colourless oil. IR (NaCl plates, ν cm⁻¹): 2970, 2930, 1591, 1553, 1469, 1314, 1254, 1156, 1119, 743. ¹H NMR (300 MHz, CDCl₃): δ 1.30 (d, 6H, J = 6.1 Hz), 2.06 (s, 3H), 2.56 (t, 2H, J = 7.6 Hz), 2.80 (t, 2H, J = 7.6 Hz), 3.75–3.86 (m, 1H), 7.12–7.32 (m, 3H), 8.00–8.10 (m, 1H), 12.74 (br s, 1H). ¹³C NMR (75 MHz, CDCl₃): δ 14.8, 24.1, 24.8, 29.5, 45.2, 100.1, 126.2, 126.6, 127.1, 130.4, 136.5, 140.9, 162.6, 183.0. MS (EI, 70 eV) m/z (%) 229 (M⁺, 100), 212 (70), 186 (86), 145 (40), 69 (85). HRMS (EI) m/z calcd for C₁₅H₁₉NO: 229.1467, found 229.1475.

(2Z)-2-{1-[(2-Sulfanylethyl)amino]ethylidene}-3,4-dihydro-1(2H)-naphthalenone (4d). Yellow oil. IR (NaCl plates, ν cm⁻¹): 2930, 2834, 2556, 1589, 1466, 1319, 1252, 1173, 1065, 744. ¹H NMR (300 MHz, CDCl₃): δ 1.60 (t, 1H, J = 6.5 Hz), 2.02 (s, 3H), 2.56 (t, 2H, J = 7.8 Hz), 2.67–2.81 (m, 4H), 3.49 (t, 2H, J = 6.5 Hz), 7.11–7.14 (m, 1H), 7.26–7.30 (m, 2H), 7.97–8.00 (m, 1H), 12.70 (br s, 1H). ¹³C NMR (75 MHz, CDCl₃): δ 14.4, 24.4, 24.7, 28.9, 46.3, 100.5, 125.9, 126.1, 126.7, 130.2, 135.7, 140.6, 162.4, 183.5. MS (EI, 70 eV) m/z (%) 247 (M⁺, 46), 214 (58), 200 (100), 102 (49). HRMS (EI) m/z calcd for C₁₄H₁₇NOS: 247.1031, found 247.1037.

(2Z)-2-{1-[(3-Pyridinylmethyl)amino]ethylidene}-3,4-dihydro-1(2H)-naphthalenone (4e). IR (KBr, ν cm⁻¹): 2989, 1586, 1545, 1466, 1423, 1366, 1310, 1287, 1248, 1173, 1063, 1016, 815, 733, 710. ¹H NMR (300 MHz, CDCl₃): δ 2.05 (s, 3H), 2.61 (t, 2H, J = 6.3 Hz), 2.83 (t, 2H, J = 6.3 Hz), 4.56 (d, 2H, J = 6.0 Hz), 7.14–7.36 (m, 4H), 7.65–7.68 (m, 1H), 7.97–8.00 (m, 1H), 8.52–8.57 (m, 2H), 12.88 (br s, 1H). ¹³C NMR (75 MHz, CDCl₃): δ 14.9, 24.8, 29.3, 44.9, 101.5, 123.8, 126.3, 126.6, 127.1, 130.8, 133.9, 134.7, 135.9, 144.1, 148.7, 149.0, 162.6, 184.5. MS (EI, 70 eV) m/z (%) 278 (M⁺, 87), 261 (70), 186 (77), 92 (100), 65 (54). HRMS (EI) m/z calcd for C₁₈H₁₈N₂O: 278.1419, found 278.1420.

2-[(Z)-1-Aminoethylidene]-1-cyclopentanone (5a). IR (KBr, ν cm⁻¹): 3304, 3156, 2956, 2914, 1627, 1509, 1256, 1045, 913, 633. ¹H NMR (300 MHz, CDCl₃): δ 1.85 (dd, 2H, J₁ = J₂ = 7.2 Hz), 1.91 (s, 3H), 2.30 (d, 2H, J = 7.2 Hz), 2.51 (d, 2H, J = 7.2 Hz), 5.13 (br s, 1H), 9.23 (br s, 1H). ¹³C NMR (75 MHz, CDCl₃): δ 20.4, 20.6, 27.2, 39.0, 103.4, 155.8, 203.9. MS (EI, 70 eV) m/z (%) 125 (M⁺, 92), 97 (33), 82 (40), 69 (100). HRMS (EI) m/z calcd for C₇H₁₁NO: 125.0841, found 125.0846.

(2Z)-2-[1-(Methylamino)ethylidene]cyclopentanone (5b). Colourless oil. IR (NaCl plates, ν cm⁻¹): 2949, 1628, 1584, 1487, 1341, 1258, 1065, 747. ¹H NMR (300 MHz, CDCl₃): δ 1.78–1.88 (m, 2H), 1.93 (s, 3H), 2.31 (t, 2H, J = 7.2 Hz), 2.53 (t, 2H, J = 7.2 Hz), 2.93 (d, 3H, J = 5.0 Hz), 10.26 (br s, 1H). ¹³C NMR (75 MHz, CDCl₃): δ 15.6, 20.4, 27.9, 29.5, 39.0, 102.3, 159.5, 201.4. MS (EI, 70 eV) m/z (%) 139 (M⁺, 98), 124 (38), 82 (66), 61 (100). HRMS (EI) m/z calcd for C₈H₁₃NO: 139.0997, found 139.0997.

(2Z)-2-[1-(Isopropylamino)ethylidene]cyclopentanone (5c). Colourless oil. IR (NaCl plates, ν cm⁻¹): 2967, 2876, 1628, 1586, 1477, 1449, 1368, 1330, 1256, 1186, 1121. ¹H NMR (300 MHz, CDCl₃): δ 1.23 (d, 6H, J = 6.3 Hz), 1.82 (tt, 2H, J₁ = J₂ = 7.8 Hz), 1.96 (s, 3H), 2.31 (t, 2H, J = 7.8 Hz), 2.51 (t, 2H, J = 7.8 Hz), 3.73 (sep, 1H, J = 6.3 Hz), 10.36 (br s, 1H).¹³C NMR (75 MHz, CDCl₃): δ 15.7, 20.3, 23.9, 28.0, 39.1, 44.5, 101.9, 157.6, 201.1. MS (EI, 70 eV) m/z (%) 167 (M⁺, 24), 105 (37), 69 (100). HRMS (EI) m/z calcd for C₁₀H₁₇NO: 167.1310, found 167.1316.

(2Z)-2-{1-[(2-Sulfanylethyl)amino]ethylidene}cyclopentanone (5d). IR (KBr, ν cm⁻¹): 2943, 2840, 1630, 1583, 1474, 1335, 1248, 1128, 1067, 776. ¹H NMR (300 MHz, CDCl₃): δ 1.54 (t, 1H, J = 8.7 Hz), 1.79–1.89 (m, 2H), 1.96 (s, 3H), 2.33 (t, 2H, J = 7.8 Hz), 2.53 (t, 2H, J = 7.8 Hz), 2.64–2.71 (m, 2H), 3.44 (dt, 2H, J₁ = J₂ = 6.6 Hz), 10.47 (br s, 1H). ¹³C NMR (75 MHz, CDCl₃): δ 15.9, 20.4, 25.3, 27.9, 39.1, 46.0, 103.2, 157.7, 202.4. MS (EI, 70 eV) m/z (%) 185 (M⁺, 25), 152 (45), 138 (100), 61 (32). HRMS (EI) m/z calcd for C₉H₁₅NOS: 185.0874, found 185.0875.

(2Z)-2-{1-[(3-Pyridinylmethyl)amino]ethylidene}cyclopentanone (5e). Colourless oil. IR (NaCl plates, ν cm⁻¹): 3259, 2951, 1623, 1574, 1477, 1427, 1249, 712. ¹H NMR (300 MHz, CDCl₃): δ 1.86 (tt, 2H, J₁ = J₂ = 7.3 Hz), 1.92 (s, 3H), 2.35 (t, 2H, J = 7.3 Hz), 2.55 (t, 2H, J = 7.3 Hz), 4.47 (d, 2H, J = 6.6 Hz), 7.27–7.31 (m, 1H), 7.61–7.64 (m, 1H), 8.52–8.55 (m, 2H), 10.67 (br s, 1H).¹³C NMR (75 MHz, CDCl₃): δ 16.0, 20.4, 27.9, 39.2, 44.3, 103.9, 123.8, 134.2, 134.6, 148.5, 148.9, 157.6, 203.0. MS (EI, 70 eV) m/z (%) 216 (M⁺, 94), 159 (57), 124 (65), 107 (43), 92 (100). HRMS (EI) m/z calcd for C₁₃H₁₆N₂O: 216.1263, found 216.1271.

General procedure for the preparation of pyrazoles

To a stirred solution of a boron complex (1 mmol) in acetonitrile (5 mL), methylhydrazine or phenylhydrazine (3 mmol) was added at room temperature. The reaction mixture was stirred at room temperature for the time mentioned in Table 3 and then evaporated to dryness. The residue was treated with ice-cold water (15 mL), then the solid material was filtered off and rinsed with water, yielding pure pyrazoles.

1,3-Dimethyl-4,5-dihydro-1H-benzo[g]indazole (8a). IR (KBr, ν cm⁻¹): 2529, 1594, 1485, 1314, 774, 725. ¹H NMR (300 MHz, CDCl₃): δ 2.45 (s, 3H), 2.66 (t, 2H, J = 6.9 Hz), 2.98 (t, 2H, J = 6.9 Hz), 4.40 (s, 3H), 7.28–7.40 (m, 2H), 7.60–7.63 (m, 2H). ¹³C NMR (75 MHz, CDCl₃): δ 10.2, 18.4, 30.2, 38.4, 117.6, 124.0, 124.2, 127.9, 130.0, 130.9, 139.3, 141.0, 141.7. MS (EI, 70 eV) m/z (%) 198 (M⁺, 100), 183 (45), 115 (22). HRMS (EI) m/z calcd for C₁₃H₁₄N₂O: 198.1157, found 198.1162.

3-Methyl-1-phenyl-4,5-dihydro-1H-benzo[g]indazole (8b). IR (KBr, ν cm⁻¹): 3051, 2936, 1595, 1504, 1424, 1370, 1132, 1067, 965, 760, 731, 689. ¹H NMR (300 MHz, CDCl₃): δ 2.31 (s, 3H), 2.66 (t, 2H, J = 6.9 Hz), 2.97 (t, 2H, J = 6.9 Hz), 6.83 (dd, 1H, J₁ = 7.8 Hz, J₂ = 1.2 Hz), 6.96 (ddd, 1H, J₁ = J₂ = 7.8 Hz, J₃ = 1.2 Hz), 7.08 (ddd, 1H, J₁ = J₂ = 7.8 Hz, J₃ = 1.2 Hz), 7.11–7.14 (m, 1H), 7.23–7.50 (m, 5H). ¹³C NMR (75 MHz, CDCl₃): δ 11.7, 19.3, 30.7, 118.6, 123.1, 125.6, 126.3, 127.1, 127.4, 127.9, 128.6, 129.3, 137.2, 138.2, 140.9, 146.0. MS (EI, 70 eV) m/z (%) 260 (M⁺, 100), 245 (32), 218 (35), 115 (10). HRMS (EI) m/z calcd for C₁₈H₁₆N₂ : 260.1314, found 260.1308.

1,3-Dimethyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazole (9a). IR (KBr, ν cm⁻¹): 2925, 2862, 1543, 1475, 1429, 1367, 1281, 1182, 1113, 1046, 1000, 786, 677. ¹H NMR (300 MHz, CDCl₃): δ 2.15 (s, 3H), 2.50–2.65 (m, 6H), 3.67 (s, 3H). ¹³C NMR (75 MHz, CDCl₃): δ 12.7, 23.1, 23.8, 31.2, 36.7, 125.1, 141.7, 150.9. MS (EI, 70 eV) m/z (%) 136 (M⁺, 100), 121 (42), 94 (31), 67 (43). HRMS (EI) m/z calcd for C₈H₁₂N₂ : 136.1001, found 136.1007.

3-Methyl-1-phenyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazole (9b). IR (KBr, ν cm⁻¹): 2913, 2853, 1597, 1514, 1439, 1378, 1294, 893, 758, 691. ¹H NMR (300 MHz, CDCl₃): δ 2.27 (s, 3H), 2.56–2.59 (m, 4H), 2.95 (t, 2H, J = 1.8 Hz), 7.15–7.20 (m, 1H), 7.35–7.41 (m, 2H), 7.57–7.60 (m, 2H). ¹³C NMR (75 MHz, CDCl₃): δ 12.7, 22.4, 26.9, 31.0, 118.9, 125.3, 128.4, 129.3, 140.3, 143.9, 149.2. MS (EI, 70 eV) m/z (%) 198 (M⁺, 100), 156 (30), 77 (53). HRMS (EI) m/z calcd for C₁₃H₁₄N₂ : 198.1157, found 198.1162.

Acknowledgements

The authors thank Dr Bogdan Kralj and Dr Dušan Žigon (Mass Spectrometry Centre, Jožef Stefan Institute, Ljubljana, Slovenia) for mass measurements. The Ministry of Education, Science and Sport of Slovenia (PO-0503-0103) is gratefully acknowledged for financial support.

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