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Communication

Synthesis of Vanillic Acid—Meldrum’s Acid Conjugate

by
Laima Bērziņa
and
Inese Mieriņa
*
Institute of Chemistry and Chemical Technology, Faculty of Natural Sciences and Technology, Riga Technical University, Str. P. Valdena 3, LV-1048 Riga, Latvia
*
Author to whom correspondence should be addressed.
Molbank 2025, 2025(2), M2005; https://doi.org/10.3390/M2005
Submission received: 31 March 2025 / Revised: 24 April 2025 / Accepted: 28 April 2025 / Published: 7 May 2025
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Abstract

:
A vanillic acid—Meldrum’s acid conjugate with a 1,2,3-triazole linker is synthesized. The reaction sequence foresees the Huisgen reaction and the Knoevenagel condensation as the key-steps.

Graphical Abstract

1. Introduction

Meldrum’s acid is an excellent platform for the synthesis of various cyclic and acyclic structures [1,2,3]. Some of the latest examples include the synthesis of spiro-tetrahydrofuranes through [3 + 2] cycloaddition with dicyanoepoxides [4], dihydroquinoline-2,5(1H,6H)-dione via one-pot method from acyl Meldrum’s acid and enaminone [5], multisubstituted pyrazolines [6], and Meldrum’s acid derivatives as the methylenation reagent for synthesis of twisted macrocyclic compounds [7]. Meldrum’s acid derivatives have also been utilized in the synthesis [8,9] and modification [10,11] of polymers. The photophysical properties of some derivatives have prompted investigations into their use as sensors for hypochlorite [12], cyanide [13], and sulfide [14] ions, as well as possible UV filters [15] or dyes [16].
Aside from the aforementioned applications, Meldrum’s acid derivatives demonstrate various biological activities: inhibition of chymotrypsin and urease [17], antibacterial activity against Staphylococcus aureus strains [18], and anticancer activity [19]. Our group has previously explored substituted Meldrum’s acids as a new type of synthetic antioxidant [20,21], belonging to the 1,3-dicarbonyl-type antioxidant class [22]. These compounds serve as antioxidants due to the acidic hydrogen atom between both carbonyl groups. Unlike phenol type antioxidants, the antiradical activity of these compounds does not strongly depend on the substituents in the aryl system. Though admittedly, the compounds with guaiacol- or syringol-like substituent positions do tend to demonstrate increased free radical scavenging activity. It can be speculated that, in these compounds, synergy between the dicarbonyl type and phenol type fragment occurs.
Inspired by these results, we have turned our efforts to the synthesis of Meldrum’s acid—natural phenol type antioxidant conjugates [23]. Vanillin [24] and vanillic acid [25] moieties are widely distributed in various types of biomass. Thus, their further modification is a valuable tool for increasing the value of such simple and rather cheap compounds. In this study, a 1,2,3-triazole linker was employed to combine the vanillic acid and arylmethyl Meldrum’s acid moiety in the same structure 1 (Scheme 1).

2. Results and Discussion

The retrosynthetic analysis (Scheme 1) of the target compound 1 has revealed two plausible routes. Route a is the convergent strategy which foresees construction of the 1,2,3-triazole linker as the last step. This strategy would be a beneficial route leading to a wide scope of products. Unfortunately, our experience has shown that neither aryl methyl nor arylidene Meldrum’s acids are compatible with the conditions of the Cu(I) catalyzed 1,3-dipolar cycloaddition reaction. Thus, the target compound 1 was synthesized via route b: firstly, the aldehyde 4 was synthesized and later it was transformed to the target compound through the Knoevenagel condensation.
To synthesize the strategic aldehyde 4, firstly the azide 6 was obtained in a high yield in two steps (Scheme 2). In our previous research on the alkylation of vanillin (7) with various dihalopropanes 8 [21,23], we observed considerable formation of side products 9d and 9e when 1,3-dibromo (8a) or 1-chloro-3-iodopropane (8b) was used. Switching to 1-bromo-3-chloropropane (8c) remarkably reduced the formation of these side products, giving the mixture of halogenides 9a and 9b with a 95% yield. Ion exchange with sodium azide quantitatively yielded the desired azide 6.
The next step was the synthesis of the vanillic acid propargyl ester. Our initial attempts to do a selective alkylation of the acid moiety of vanillic acid (10) with propargyl bromide (11) failed; instead, mainly the dialkylated product 12 was isolated (Scheme 3). Due to that, the hydroxy group of vanillic acid (10) was protected with an acetyl group and the alkylation of the acid 13 with propargyl bromide (11) gave the desired ester 14 in a 78% yield.
With both building blocks 6 and 14 in hand, the intermediate 15 was synthesized through a copper (I) catalyzed “click” reaction (Scheme 4). Deprotection of the acetyl group gave aldehyde 16. One of the final steps was the Knoevenagel condensation between the aldehyde 16 and Meldrum’s acid (5). The Knoevenagel condensation may occur through various mechanistic pathways. Commonly, amine-containing (including amino acids) reaction media is employed, which foresees the formation of an iminium intermediate. Previously, our group ran this condensation under l-proline catalysis, similarly as described in the literature [26,27]. Unfortunately, when we used l-proline to catalyze this reaction, the yield of the arylidene Meldrum’s acid 17 was quite low (28%). Additionally, multiple difficult-to-separate, unidentified side products were formed. After screening various conditions for this transformation on a similar substrate (see Supplementary Materials), (PhNH3)2CuCl4 emerged as the most suitable catalyst [28]. This catalyst led to the desired product 17 exclusively, and only the removal of excess Meldrum’s acid was necessary in terms of purification. The effectiveness of (PHNH3)CuCl4 may be explained by the synergy between two mild catalytic species—aniline and copper (II) [29,30,31]. Due to the excellent reactivity of Meldrum’s acid, the use of harsher conditions (e.g., higher temperature, strongly basic or acidic conditions, or the presence of highly nucleophilic amines) increases the risk of various side reactions, notably the opening of the Meldrum’s acid ring [32,33,34]. Finally, we used NaBH4 in the presence of acetic acid to turn the arylidene Meldrum’s acid derivative 17 into the arylmethyl Meldrum’s acid derivative 1. The reaction was initially sluggish; therefore, to reduce the duration of the reaction and to minimize the risk of the final product 1 beginning to degrade (for example, this molecule possesses antioxidant properties, and thus is prone to oxidation itself), a large excess of NaBH4 was eventually added.

3. Materials and Methods

3.1. General

NMR spectra were recorded on a Bruker Avance 300 (1H: 300 MHz) or Bruker Avance Neo 500 (1H: 500 MHz; 13C: 126 MHz) spectrometer (Fällanden, Switzerland). The spectra were calibrated to the residual solvent peak (CHCl3, 1H: δ = 7.26 ppm; 13C: δ = 77.16 ppm). NMR and HRMS spectra of new compounds are available in the Supplementary Materials. All commercially available reagents were used without additional purification. (PhNH3)2CuCl4 catalyst was prepared according to the literature procedure [35].

3.2. Synthesis

3.2.1. 4-(3-Azidopropoxy)-3-methoxybenzaldehyde (6)

Molbank 2025 m2005 i001
The halogenides 9 (1.585 g, 6.58 mmol, 1.0 eq.) were dissolved in DMF (6 mL), NaN3 (0.855 g, 13.26 mmol, 2.0 eq.) was added, and the mixture was stirred at 60 °C overnight. The reaction mixture was diluted with brine (10 mL) and extracted with DCM (3 × 10 mL). The organic layer was washed with brine (3 × 10 mL), dried over anhydrous Na2SO4, filtered, and the solvent was evaporated to afford the product as a pale-yellow oil (1.524 g, quant.). The product was used in the next step without further purification. 1H NMR (500 MHz, CDCl3) δ, ppm 9.85 (s, 1H, CHO), 7.44 (dd, J = 8.1 Hz, J = 1.6 Hz, 1H, H-2), 7.41 (d, J = 1.6 Hz, 1H, H-1), 6.98 (d, J = 8.1 Hz, 1H, H-3), 4.19 (t, J = 6.3 Hz, 2H, OCH2), 3.92 (s, 3H, OMe), 3.56 (t, J = 6.3 Hz, 2H, CH2N3), 2.14 (quint., J = 6.3 Hz, 2H, CH2CH2CH2). The 1H NMR spectrum of the compound is in accordance with the literature [36].

3.2.2. 4-(3-Halopropoxy)-3-methoxybenzaldehyde 9

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Vanillin 7 (1.000 g, 6.58 mmol, 1.0 eq.) and K2CO3 (1.362 g, 7.14 mmol, 1.1 eq.) were suspended in DMF (6 mL), 1-bromo-3-chloropropane 8 (3.10 g, 1.95 mL, 19.74 mmol, 3.0 eq.) was added dropwise, and the mixture was stirred at 80 °C for 1 h. After cooling in an ice bath, the reaction mixture was diluted with brine (50 mL) and extracted with DCM (3 × 10 mL). The organic layer was washed with brine (3 × 10 mL), dried over anhydrous Na2SO4, filtered, and the solvent was evaporated to afford the mixture of products 9a (X = Cl) and 9b (X = Br) (9a:9b = 2.7:1) as an off-white solid (1.585 g, 95%). The mixture was used in the next step without further purification. 4-(3-Chloropropoxy)-3-methoxybenzaldehyde (9a): 1H NMR (500 MHz, CDCl3) δ, ppm 9.85 (s, 1H, CHO), 7.44 (dd, J = 8.1 Hz, J = 1.3 Hz, 1H, H-2), 7.41 (d, J = 1.3 Hz, 1H, H-1), 7.00 (d, J = 8.1 Hz, 1H, H-3), 4.26 (t, J = 6.1 Hz, 2H, OCH2), 3.92 (s, 3H, OMe), 3.78 (t, J = 6.1 Hz, 2H, ClCH2), 2.41 (quint., J = 6.3 Hz, 2H, CH2CH2CH2). 4-(3-Bromopropoxy)-3-methoxybenzaldehyde (9b): 1H NMR (500 MHz, CDCl3) δ, ppm 9.85 (s, 1H, CHO), 7.44 (dd, J = 8.1 Hz, J = 1.3 Hz, 1H, H-2), 7.41 (d, J = 1.3 Hz, 1H, H-1), 7.00 (d, J = 8.1 Hz, 1H, H-3), 4.24 (t, J = 6.3 Hz, 2H, OCH2), 3.92 (s, 3H, OMe), 3.63 (t, J = 6.3 Hz, 2H, BrCH2), 2.41 (quint., J = 6.3 Hz, 2H, CH2CH2CH2). The 1H NMR spectra of compounds 9a [37] and 9b [38] are in accordance with the literature.

3.2.3. 4-Acetoxy-3-methoxybenzoic acid (13)

Molbank 2025 m2005 i003
Vanillic acid 10 (500 mg, 2.98 mmol, 1.0 eq.) was dissolved in acetic anhydride (10 mL) and refluxed for 1 h. When the solution was cooled to room temperature, the mixture was poured onto ice. After the ice melted, the solution was extracted with DCM (2 × 10 mL). The organic layer was washed with brine (3 × 10 mL), dried over anhydrous Na2SO4, filtered, and the solvent was evaporated to afford the product as a white solid (554 mg, 89%). The product was used in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ, ppm 7.76 (dd, J = 8.2 Hz, J = 1.3 Hz, 1H, H-2), 7.71 (d, J = 1.3 Hz, 1H, H-1), 7.15 (d, J = 8.2 Hz, 1H, H-3), 3.91 (s, 3H, OMe), 2.35 (s, 3H, OAc). 13C NMR (126 MHz, CDCl3) δ, ppm 171.5, 168.6, 151.3, 144.5, 128.0, 123.6, 123.1, 114.0, 56.2, 20.8. HRMS(ESI+): calcd. for C10H9O5− 209.0455 [M-H]−; found: 209.0457.

3.2.4. Prop-2-yn-1-yl 4-acetoxy-3-methoxybenzoate (14)

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4-Acetoxy-3-methoxybenzoic acid 13 (500 mg, 2.38 mmol, 1.0 eq.) was dissolved in DMF (5 mL), K2CO3 (986 mg, 7.14 mmol, 3 eq.) was added, and the mixture was cooled to 0 °C. Propargyl bromide 11 (80% solution in toluene, 0.34 mL, 3.10 mmol, 1.3 eq.) was added dropwise, and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with brine (20 mL), brought to an acidic pH with concentrated hydrochloric acid, and then extracted with DCM (3 × 10 mL). The organic layer was washed with brine (12 × 10 mL), dried over anhydrous Na2SO4, and filtered, and the solvent was evaporated to afford the product as a light brown solid (463 mg, 78%). The product was used in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ, ppm 7.71 (dd, J = 8.2 Hz, J = 1.6 Hz, 1H, H-2), 7.66 (d, J = 1.6 Hz, 1H, H-1), 7.11 (d, J = 8.2 Hz, 1H, H-3), 4.92 (d, J = 2.4 Hz, 2H, CH2), 3.89 (s, 3H, OMe), 2.52 (t, J = 2.4 Hz, 1H, C≡CH), 2.33 (s, 3H, OAc). 13C NMR (126 MHz, CDCl3) δ, ppm 168.6, 165.2, 151.3, 144.1, 128.2, 123.1, 123.0, 113.7, 77.7, 75.2, 56.2, 52.8, 20.8. HRMS(ESI+): calcd. for C13H13O5+ 249.0758 [M + H]+; found: 249.0758.

3.2.5. {1-[3-(4-Formyl-2-methoxyphenoxy)propyl]-1H-1,2,3-triazol-4-yl}methyl 4-acetoxy-3-methoxybenzoate (15)

Molbank 2025 m2005 i005
The azide 6 (179 mg, 0.76 mmol, 1.0 eq.) and alkyne 14 (208 mg, 0.84 mmol, 1.1 eq.) were dissolved in a t-BuOH/water mixture (1 mL, 1:1 v/v). CuSO4∙5H2O (19 mg, 0.08 mmol, 0.1 eq.) and sodium ascorbate (15 mg, 0.08 mmol, 0.1 eq.) were added, and the mixture was stirred at 60 °C overnight. After cooling to room temperature, the reaction mixture was diluted with brine (30 mL) and extracted with DCM (2 × 10 mL). The organic layer was washed with brine (1 × 10 mL), trilon B solution (2 × 10 mL), and brine (2 × 10 mL), dried over anhydrous Na2SO4, and filtered, and the solvent was evaporated. The residue was purified on silica (Hex:EtOAc = 1:1 v/v) to afford the product as a white solid (201 mg, 55%). 1H NMR (500 MHz, CDCl3) δ, ppm 9.83 (s, 1H, CHO), 7.73 (s, 1H, H-5), 7.64–7.59 (m, 2H, H-1, H-2), 7.41 (d, J = 1.2 Hz, 1H, H-6), 7.38 (dd, J = 8.1 Hz, J = 1.2 Hz, 1H, H-7), 7.06 (d, J = 8.1 Hz, 1H, H-3), 6.90 (d, J = 8.2 Hz, 1H, H-8), 5.45 (s, 2H, CH2-4), 4.63 (t, J = 6.2 Hz, 2H, NCH2), 4.07 (t, J = 6.2 Hz, 2H, OCH2), 3.93 (s, 3H, OMe), 3.86 (s, 3H, OMe), 2.49 (quint., J = 6.2 Hz, 2H, CH2CH2CH2), 2.32 (s, 3H, OAc). 13C NMR (126 MHz, CDCl3) δ, ppm 190.9, 168.5, 165.7, 153.3, 151.1, 149.9, 143.9, 142.9, 130.6, 128.4, 126.6, 124.7, 122.85, 122.81, 113.5, 111.9, 109.4, 65.2, 58.2, 56.1, 56.0, 47.0, 29.6, 20.6. HRMS(ESI+): calcd. for C24H26N3O8+ 484.1715 [M + H]+; found: 484.1713.

3.2.6. {1-[3-(4-Formyl-2-methoxyphenoxy)propyl]-1H-1,2,3-triazol-4-yl}methyl 4-hydroxy-3-methoxybenzoate (16)

Molbank 2025 m2005 i006
Compound 15 (81 mg, 0.17 mmol, 1.0 eq.) was dissolved in MeOH (12 mL), and a 1 M NaOH solution in water (0.5 mL) was added. The mixture was stirred at room temperature for 2 h and then acidified with hydrochloric acid (0.5 mL, 10% w/w), and the MeOH was evaporated. The residue was diluted with brine (6 mL) and extracted with DCM (3 × 8 mL). The organic layer was washed with brine (2 × 10 mL), dried over anhydrous Na2SO4, and filtered, and the solvent was evaporated to afford the product as a white solid (72 mg, 97%). The product was used in the next step without further purification. 1H NMR (500 MHz, CDCl3) δ, ppm 9.83 (s, 1H, CHO), 7.74 (s, 1H, H-5), 7.60 (dd, J = 8.1 Hz, J = 1.0 Hz, 1H, H-2), 7.50 (d, J = 1.0 Hz, 1H, H-1), 7.41 (d, J = 1.5 Hz, 1H, H-6), 7.38 (dd, J = 8.1 Hz, J = 1.5 Hz, 1H, H-7), 6.93−6.88 (m, 2H, H-3, H-8), 6.16 (brs, 1H, OH), 5.42 (s, 2H, CH2-4), 4.62 (t, J = 6.2 Hz, 2H, NCH2), 4.08 (t, J = 6.2 Hz, 2H, OCH2), 3.93 (s, 3H, OMe), 3.91 (s, 3H, OMe), 2.49 (quint., J = 6.2 Hz, 2H, CH2CH2CH2). 13C NMR (126 MHz, CDCl3) δ, ppm 191.0, 166.3, 153.4, 150.5, 150.1, 146.3, 143.3, 130.7, 126.7, 124.8, 124.6, 121.9, 114.3, 112.0, 111.9, 109.5, 65.3, 58.0, 56.3, 56.1, 47.1, 29.7. HRMS(ESI+): calcd. for C22H24N3O7+ 442.1609 [M + H]+; found: 442.1600.

3.2.7. Arylidene Meldrum’s Acid Derivative 17

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Aldehyde 16 (70 mg, 0.16 mmol, 1.0 eq.) and Meldrum’s acid 5 (27 mg, 0.19 mmol, 1.2 eq.) were dissolved in DCM (3 mL), and MeOH (12 mL) was added. (PhNH3)2CuCl4 (1.3 mg, 3 μmol, 0.02 eq.) was added, and the mixture was stirred at 45 °C overnight. Then, the solvents were evaporated, and the residue was dissolved in DCM (15 mL) and washed with a NH4Cl solution (8 mL) and water (8 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and the solvent was evaporated. To purify the product, the solid residue was ground in a mortar with EtOH (2 mL) and water (8 mL). The resulting suspension was transferred to vials with a mixture of EtOH (2 mL) and water (6 mL), sonified for 10 s, and centrifuged at 3700 rpm for 1 min. The water/EtOH was decanted, and the solid residue was dissolved in DCM, dried over anhydrous Na2SO4, and filtered, and the solvent was evaporated. The product was obtained as a yellow solid (79 mg, 88%). 1H NMR (500 MHz, CDCl3) δ, ppm 8.32 (s, 1H, H-9), 8.28 (d, J = 1.6 Hz, 1H, H-6), 7.73 (s, 1H, H-5), 7.61 (dd, J = 8.3 Hz, J = 1.3 Hz, 1H, H-2), 7.54 (dd, J = 8.6 Hz, J = 1.6 Hz, 1H, H-7), 7.51 (d, J = 1.3 Hz, 1H, H-1), 6.91 (d, J = 8.3 Hz, 1H, H-3), 6.85 (d, J = 8.6 Hz, 1H, H-8), 6.07 (brs, 1H, OH), 5.43 (s, 2H, CH2-4), 4.62 (t, J = 6.6 Hz, 2H, NCH2), 4.10 (t, J = 5.8 Hz, 2H, OCH2), 3.94 (s, 3H, OMe), 3.92 (s, 3H, OMe), 2.50 (quint., J = 6.2 Hz, 2H, CH2CH2CH2), 1.79 (s, 6H, 2×MeMA). 13C NMR (126 MHz, CDCl3) δ, ppm 166.3, 164.3, 160.7, 158.2, 153.6, 150.5, 149.1, 146.3, 143.4, 132.4, 125.7, 124.8, 124.6, 121.9, 116.2, 114.3, 111.9 (overlapping C-8 and C-1, from HSQC), 111.2, 104.4, 65.3, 58.0, 56.3, 56.1, 47.0, 29.6, 27.7. HRMS(ESI+): calcd. for C28H30N3O10+ 568.1926 [M + H]+; found: 568.1927.

3.2.8. Arylmethyl Meldrum’s Acid Derivative 1

Molbank 2025 m2005 i008
Arylidene Meldrum’s acid 17 (76 mg, 0.13 mmol, 1.0 eq.) was dissolved in DCM (20 mL), cooled in an ice bath, and acetic acid was added (0.03 mL, 0.53 mmol, 4.1 eq.). NaBH4 (10 mg, 0.27 mmol, 2.1 eq.) was added portion-wise. After 40 min, additional NaBH4 (486 mg, 12.78 mmol, 98.0 eq.) and MeOH (0.5 mL) were added. After 15 min, the reaction was quenched with water (10 mL), and the pH was adjusted to 5 with acetic acid (0.5 mL). The DCM layer was separated, and the aqueous layer was extracted with DCM (2 × 8 mL). The organic layer was washed with brine (3 × 8 mL), dried over anhydrous Na2SO4, and filtered, and the solvent was evaporated to afford the product as a white solid (72 mg, 95%). 1H NMR (500 MHz, CDCl3) δ, ppm 7.74 (s, 1H, H-5), 7.62 (dd, J = 8.4 Hz, J =1.6 Hz, 1H, H-2), 7.53 (d, J = 1.6 Hz, 1H, H-1), 6.92 (d, J = 8.4 Hz, 1H, H-3), 6.89 (d, J = 1.4 Hz, 1H, H-6), 6.81 (dd, J = 8.2 Hz, J =1.4 Hz, 1H, H-7), 6.74 (d, J = 8.2 Hz, 1H, H-8), 6.03 (brs, 1H, OH), 5.42 (s, 2H, CH2-4), 4.60 (t, J = 6.8 Hz, 2H, NCH2), 3.97 (t, J = 5.7 Hz, 2H, OCH2), 3.93 (s, 3H, OMe-9), 3.85 (s, 3H, OMe-10), 3.72 (t, J = 4.7 Hz, 1H, CHMA), 3.43 (d, J = 4.7 Hz, 2H, CH2Bn), 2.41 (quint., J = 6.3 Hz, 2H, CH2CH2CH2), 1.73 (s, 3H, MeMA), 1.51 (s, 3H, MeMA). 13C NMR (126 MHz, CDCl3) δ, ppm 166.3, 165.6, 150.4, 149.6, 147.1, 146.3, 143.1, 130.9, 124.7, 124.6, 122.2, 121.9, 114.3, 114.1, 113.9, 112.0, 105.4, 65.6, 58.0, 56.3, 56.0, 48.4, 47.3, 32.0, 30.0, 28.6, 27.5. HRMS(ESI+): calcd. for C28H30N3O10+ 570.2083 [M + H]+; found: 570.2071.

4. Conclusions

A new vanillic acid–Meldrum’s acid conjugate with a 1,2,3-triazole linker was synthesized through the following sequence: (1) synthesis of alkyl azide and propargyl ester; (2) 1,3-dipolar cycloaddition reaction; (3) the Knoevenagel condensation; (4) reduction of the arylidene Meldrum’s acid. The product has demonstrated good antiradical activity in the DPPH test system (IC50 = 39.6 ± 1.1 µM and Inh(100µM, 1:1 n/n) = 69.2 ± 0.2%) and could thus find applications as an antioxidant.

Supplementary Materials

Figures S1, S4, S7, S10, S13, and S18: 1H NMR spectra for compounds 13, 14, 15, 16, 17 and 1, respectively; Figures S2, S5, S8, S11, S14, and S19: 13C NMR spectra for compounds 13, 14, 15, 16, 17, and 1, respectively; Figures S3, S6a,b, S9, S12, S17, and S22: HRMS data for compounds 13, 14, 15, 16, 17, and 1, respectively; Figures S15 and S20: HSQC spectra for compounds 17 and 1, respectively; Figures S16 and S21: HMBC spectra for compounds 17 and 1, respectively; Scheme S23, Table S24 and Figure S25: conditions screening for the Knoevenagel condensation.

Author Contributions

Conceptualization, I.M. and L.B.; investigation, L.B.; writing—original draft preparation, L.B.; writing—review and editing, I.M. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

The data are contained within this article and the Supplementary Materials.

Conflicts of Interest

The authors declare no conflicts of interest.

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Molbank 2025 m2005 sch001
Scheme 1. Retrosynthetic analysis of the target compound 1.
Scheme 1. Retrosynthetic analysis of the target compound 1.
Molbank 2025 m2005 sch001
Molbank 2025 m2005 sch002
Scheme 2. Synthesis of the azide 6.
Scheme 2. Synthesis of the azide 6.
Molbank 2025 m2005 sch002
Molbank 2025 m2005 sch003
Scheme 3. Synthesis of the alkyne 14.
Scheme 3. Synthesis of the alkyne 14.
Molbank 2025 m2005 sch003
Molbank 2025 m2005 sch004
Scheme 4. Synthesis of the arylmethyl Meldrum’s acid derivative 1.
Scheme 4. Synthesis of the arylmethyl Meldrum’s acid derivative 1.
Molbank 2025 m2005 sch004
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Bērziņa, L.; Mieriņa, I. Synthesis of Vanillic Acid—Meldrum’s Acid Conjugate. Molbank 2025, 2025, M2005. https://doi.org/10.3390/M2005

AMA Style

Bērziņa L, Mieriņa I. Synthesis of Vanillic Acid—Meldrum’s Acid Conjugate. Molbank. 2025; 2025(2):M2005. https://doi.org/10.3390/M2005

Chicago/Turabian Style

Bērziņa, Laima, and Inese Mieriņa. 2025. "Synthesis of Vanillic Acid—Meldrum’s Acid Conjugate" Molbank 2025, no. 2: M2005. https://doi.org/10.3390/M2005

APA Style

Bērziņa, L., & Mieriņa, I. (2025). Synthesis of Vanillic Acid—Meldrum’s Acid Conjugate. Molbank, 2025(2), M2005. https://doi.org/10.3390/M2005

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