A new facile way for the preparation of 3-formylcoumarins

Andrei Y. Bochkov; Igor O. Akchurin; Valerii F. Traven

doi:10.1515/hc-2017-0038

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A new facile way for the preparation of 3-formylcoumarins

Andrei Y. Bochkov , Igor O. Akchurin and Valerii F. Traven

Published/Copyright: March 28, 2017

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From the journal Heterocyclic Communications Volume 23 Issue 2

Abstract

3-Formylcoumarins 2 are formed as single products in high yields upon reduction of 3-cyanocoumarins 1 with Raney nickel in formic acid. The starting materials 1 are easily accessible by Knoevenagel condensation of commercially available salicylaldehydes.

Keywords: 3-cyanocoumarins; 3-formylcoumarins; Raney nickel; reduction

3-Formylcoumarins are important building blocks for synthesis of various coumarin derivatives including materials for dye-sensitized solar cells [1], light-harvesting arrays [2], [3], fluorescent labels [4] and sensors [5], [6], [7], [8]. Methods for preparation of 3-formylcoumarins are limited in scope. Due to the electron-withdrawing nature of a lactone moiety, position 3 in coumarin is deactivated towards electrophilic attack, for example, by Vilsmeier reagent, unless strongly electron-donating substituent is attached to the benzene moiety. In practice, only 7-dialkyl- and diarylaminocoumarins react readily to give 3-formyl derivatives upon treatment with DMF/POCl₃ [9]. Some reported methods involve transformations of a carbon substituent attached to position 3 of coumarin. For example, oxidation of 3-methylcoumarins using selenium dioxide affords 3-formylcoumarins with moderate yields (up to 60%) [10], [11]. Some functionalities do not tolerate the SeO₂ treatment. A two-step sequence including dibromination of 3-methylcoumarin with subsequent hydrolysis in AcONa/AcOH has been reported for preparation of 7-butoxy-3-formylcoumarin [12], [13]. 3-Methylcoumarins can be synthesized from salicylaldehydes via the Baylis-Hillman reaction [14]. Some 3-formylcoumarins have been prepared via dihydroxylation/diol cleavage in one pot starting from 3-(3-coumarinyl)acrylates using OsO₄ and NaIO₄ as reagents [15]. Starting acrylates can be prepared from salicylaldehydes and diethyl glutaconate. The major drawback of this procedure is toxicity of osmium. An alternative transformation of acrylate to 3-formylcoumarin by sequential treatment with ozone and dimethyl sulfide has been also reported [16]. Heating of trimethylsilylpropiolate esters of salicylaldehydes with DABCO in THF gives rise to up to 81% yields of 3-formylcoumarins [17]. Although this method may be considered as versatile, it requires starting material trimethylsilylpropiolic acid that is relatively expensive. An unusual rearrangement of 2-morpholino-3-cyanochromenes leading to 3-formylcoumarins upon acidic hydrolysis has been reported [18]. The Rosenmund reduction of some coumarin-3-carbonyl chlorides also gives corresponding aldehydes [19]. Starting coumarin carboxylic acid chlorides may be prepared in several stages from salicyl aldehydes. Thus, approaches to 3-formylcoumarins discussed here are relying on difficult to access starting compounds, expensive or toxic re-agents and they lack versatility for synthesis of coumarins with various substituted benzene moiety.

Derivatives of coumarin-3-carboxylic acids (esters or nitriles), which are easily accessible by the Knoevenagel reaction from a variety of commercially available salicylic aldehydes are attractive substrates for reduction to aldehydes (directly or using reduction-oxidation sequence via alcohol intermediate). Unfortunately, complex metal hydrides usually applied for such reductions (LiAlH₄, DIBAL-H or NaBH₄) are not compatible with coumarin due to ease of the reduction of the 3,4-double bond and lactone moiety. Raney nickel/formic acid reagent has been reported to convert aromatic nitriles to corresponding aldehydes, without affecting either the ester or conjugated double bond functionalities [20], [21], [22]. This reagent has also been successfully employed for preparation of some heterocyclic aldehydes. Pyridine [23], [24], [25], pyrimidine [26], [27], [28], pyrrole [29], [30] and chromone [31] derivatives should be mentioned as representative examples. With these considerations, we studied a novel approach to 3-formylcoumarins via corresponding nitriles. In this work, a new facile synthesis of 3-formylcoumarins by reduction of 3-cyanocoumarins with Raney nickel in formic acid is reported (Scheme 1). The starting materials, 3-cyanocoumarins, are easily accessible from commercial salicylaldehydes.

Scheme 1

A series of starting 3-cyanocoumarins 1a–d has been prepared per reported methods by condensation of salicylaldehydes with malononitrile [32]. Substrate 1e has been prepared from ethyl cyanoacetate [33]. Reduction of 3-cyanocoumarins proceeds smoothly upon stirring with Raney nickel in formic acid at 80–90°C for 1–2 h. Yields of 3-formylcoumarins vary from good to excellent. Purification does not require column chromatography and is achieved by simple crystallization. Analytically pure products 2b,c crystallize directly from the reaction mixture upon cooling. All prepared aldehydes 2 are known compounds; their ¹H NMR spectra and melting points are virtually identical with the reported literature data.

Experimental

Starting materials and reagents were purchased from Sigma-Aldrich, Acros Organics, ABCR, Merck and Alfa Aesar and used as received. Melting points were measured on a Stuart melting point apparatus SMP30 and are uncorrected. ¹H NMR (500 MHz) and ¹³C NMR (125 MHz) spectra were recorded on a Bruker 500 spectrometer.

General procedure for preparation of coumarin- 3-carbaldehydes 2

Commercial Raney nickel (suspension in water) was placed in a weighing bottle and water was decanted as much as possible. After weighing, the nickel was washed with ethanol and the suspension was decanted again. Raney nickel was suspended in formic acid immediately before use.

A solution of 3-cyanocoumarin (1a–e, 11.3 mmol, 1.94 g) in hot (80–90°C) formic acid (30 mL) was stirred and treated with Raney nickel (2 g, wet) as suspension in formic acid (5 mL) prepared as described above. The mixture was vigorously stirred at 80–90°C until completion of reaction (1.5–2 h) as monitored by TLC. Then the mixture was filtered through a Celite pad, which was washed with hot ethyl acetate (100 mL). The resulting clear yellow solution was concentrated in vacuo to give crude aldehyde 2 as yellow oil (2 g). A solution of this oil was dissolved in dichloromethane and filtered through a silica gel pad (3–4 cm), which was further washed with dichloromethane until the eluting solution contained no product. Analytically pure crystals of 2a–e precipitated after concentration. Product 2 may be purified (if required) by crystallization from ethanol.

2-Oxo-2H-chromene-3-carbaldehyde (2a) This compound was obtained from 1a; reaction time 1.5 h, yellow crystals; yield 86%; mp 132–134°C (Lit. [14]: mp 131–132°C); ¹H NMR (CDCl₃): δ 7.38–7.43 (m, 2H), 7.70–7.73 (m, 2H), 8.45 (s, 1H), 10.27 (s, 1H); ¹³C NMR (CDCl₃): δ 116.6, 117.7, 121.2, 124.8, 130.3, 134.5, 145.1, 155.0, 159.6, 187.2. NMR data for 2a have been reported in [14].

7-Hydroxy-2-oxo-2H-chromene-3-carbaldehyde (2b) This compound was prepared from 1b per general procedure using the following simplified isolation. After filtering through Celite the mixture was cooled and the precipitated crystals were filtered off to give analytically pure product. Reaction time 2 h; yellow crystals; yield 72%; mp>300°C (dec.) (Lit. [19]: mp>300°C); ¹H NMR (DMSO-d₆): δ 6.77 (d, 1H , J=1.83 Hz), 6.87 (dd, 1H, J=2.44 Hz, J=8.55 Hz), 7.81 (d, 1H, J=8.55 Hz), 8.57 (s, 1H), 9.96 (s, 1H); ¹³C NMR (DMSO-d₆): δ 102.2, 110.8, 114.5, 116.9, 133.3, 147.2, 157.5, 159.7, 165.0, 187.7. NMR data for 2b have been reported in [34].

7-Methoxy-2-oxo-2H-chromene-3-carbaldehyde (2c) This compound was prepared from 1c per general procedure using the following simplified isolation. After filtering through Celite the mixture was cooled and the precipitated crystals were filtered off to give analytically pure product. Reaction time 2 h; yellow crystals; yield 66%; mp 235.2–238.3°C (Lit. [18]: mp 238°C); ¹H NMR (DMSO-d₆): δ 3.89 (s, 3H), 6.90–6.93 (m, 1H), 7.73 (d, 1H, J=8.54 Hz), 8.49 (s, 1H), 10.02 (s, 1H); ¹³C NMR (DMSO-d₆): δ 55.9, 100.4, 111.6, 113.5, 117.8, 132.3, 146.5, 157.4, 159.5, 165.4, 187.1. NMR data for 2c have been reported in [18].

3-Oxo-3H-benzo[f]chromene-2-carbaldehyde (2d) This compound was obtained from 1d; reaction time 1.5 h; yellow crystals; yield 63%; mp 217–219°C (Lit. [18]: mp 220°C); ¹H NMR (CDCl₃): δ 7.51 (d, 1H, J=9.16 Hz), 7.64–7.67 (m, 1H), 7.77–7.81 (m, 1H), 7.96 (d, 1H, J=8.24 Hz), 8.16 (d, 1H, J=9.16 Hz), 8.36 (d, 1H, J=8.24 Hz), 9.18 (s, 1H), 10.33 (s, 1H); ¹³C NMR (CDCl₃): δ 112.4, 116.3, 119.5, 121.1, 126.4, 128.8, 129.0, 129.5, 129.8, 136.5, 140.6, 156.2, 159.8, 187.3. NMR data for 2d have been reported in [18].

7-(Diethylamino)-2-oxo-2H-chromene-3-carbaldehyde (2e) This compound was obtained from 1e; reaction time 2 h; orange crystals; yield 59%; mp 163.4–167.5°C (Lit. [9]: mp 160–161°C); ¹H NMR (CDCl₃): δ 1.27 (t, 6H, J=7.02 Hz), 3.49 (q, 4H, J=7.32 Hz), 6.50 (d, 1H, J=2.44 Hz), 6.65 (dd, 1H, J=2.59 Hz, J=9.00 Hz ), 7.42 (d, 1H, J=8.85 Hz), 8.25 (s, 1H), 10.13 (s, 1H); ¹³C NMR (CDCl₃): δ 11.9, 44.8, 96.7, 107.8, 109.7, 113.9, 132.0, 144.8, 152.9, 158.4, 161.3, 187.3. NMR data for 2e have been reported in [9].

Acknowledgment

The authors are grateful to the Russian Foundation for Basic Research (project No 14-03-31720) for financial support.

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Received: 2017-2-15

Accepted: 2017-2-24

Published Online: 2017-3-28

Published in Print: 2017-4-1

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https://doi.org/10.1515/hc-2017-0038

Keywords for this article

3-cyanocoumarins; 3-formylcoumarins; Raney nickel; reduction

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