The synthesis of some dialkyl 4-(3-substituted amino)phenyl-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates

Dialkyl 4-(3-aminophenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates 1 were transformed into alkyl 4-(3-(((2-benzoylamino-2-methoxycarbonyl)ethenyl)amino)phenyl)-1,4-dihydro-2,6-dimethyl-pyridine-3,5-dicarboxylates 4 and with 2,2-disubstituted-1-dimethylaminoethenes 7 into dimethyl 4-(3-(((2,2-diacyl- or 2-acyl-2-alkoxycarbonyl)ethenyl)amino)phenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates 8 and their ethyl methyl analogues 9.     

1,4-二氢-4-芳基-3,5-吡啶二羧酸酯的合成及表征

基于二氢吡啶化合物的构效关系, 设计了一系列1,4-二氢-4-芳基-3,5-吡啶二羧酸酯新化合物. 含有易于水解基团的1,4-二氢-4-芳基-3,5-吡啶二羧酸酯类化合物在碱性条件下水解合成了重要中间体1,4-二氢-4-芳基-3,5-吡啶二羧酸单酯, 收率93%～99.8%. 该二羧酸单酯与α-溴代芳基乙酮在相转移剂催化下反应合成目标化合物, 收率74%～99%. 中间体和目标化合物经¹H NMR, ¹³C NMR, IR, MS和元素分析等确证.     

A ‘One-Pot’ Anellation Method for the Transformation of Heptalene-4,5-dicarboxylates into Benzo[a]heptalenes

It has been found that dimethyl heptalene-4,5-dicarboxylates, when treated with 4 mol-equiv. of lithiated N,N-dialkylamino methyl sulfones or methyl phenyl sulfone, followed by 4 mol-equiv. of BuLi in THF in the temperature range of ?78 to 20°, give rise to the formation of 3-[(N,N-dialkylamino)sulfonyl]- or 3-(phenylsul-fonyl)benzo[a]heptalene-2,4-diols of. (cf. Scheme 4, and Tables 2 and 3). Accompanying products are 2,4-bis{[(N,N-dialkylamino)sulfonyl]methyl}- or 2,4-bis[(phenylsulfonyl)methyl]-4,10a-dihydro-3H-heptaleno[1,10-bc]furan-3-carboxylates as mixtures of diastereoisomers of. cf. Scheme 4, and (Tables 2 and 3) which are the result of a Michael addition reaction of the lithiated methyl sulfones at C(3) of the heptalene-4,5-dicarboxylates, followed by (sulfonyl)methylation of the methoxycarbonyl group at C(5) and cyclization of. (cf. Scheme 5). It is assumed that the benzo[a]heptalene formation is due to (sulfonyl)methylation of both methoxycarbonyl groups of the heptalene-4,5-dicarboxylates of. (cf. Schemes 6 and 8). The resulting bis-enolates 35 are deprotonated further. The thus formed tris-anions 36 can then cyclize to corresponding tris-anions 37 of cyclopenta[d]heptalenes which, after loss of N,N-dialkylamido sulfite or phenyl sulfinate, undergo a ring-enlargement reaction by 1,2-C migration finally leading to the observed benzo[a]heptalenes of. (cf. Schemes 8 and 9). The structures of the new product types have been finally established by X-ray crystal-structure analyses (cf. Figs. 1 and 2 as well as Exper. Part).     

Formation of 3-Sulfonyl-Substituted Benzo[a]heptalene-2,4-diols from Heptalene-1,2-dicarboxylates and Lithiomethyl Phenyl Sulfones

On treatment with 6 mol-equiv. of lithiomethyl phenyl sulfone at −78° in THF, dimethyl 5,6,8,10-tetramethylheptalene-1,2-dicarboxylate ( 1′b ) gives, after raising the temperature to −10° and addition of 6 mol-equiv. of BuLi, followed by further warming to ambient temperature, the corresponding 3-(phenylsulfonyl)benzo[a]heptalene-2,4-diol 2b in yields up to 65% (cf. Scheme 6 and Table 2), in contrast to its double-bond-shifted (DBS) isomer 1b which gave 2b in a yield of only 6% [1]. The bisanion [ 9 ]²⁻ of the cyclopenta[a]heptalen-1(1H)-one 9 (cf. Fig. 1), carrying a (phenylsulfonyl)methyl substituent at C(11b), seems to be a key intermediate on the reaction path to 2b , because 9 is transformed in high yield into 2b in the presence of 6 mol-equiv. of BuLi in the temperature range of −10° to room temperature (cf. Scheme 7). Heptalene-dicarboxylate 1′b was also transformed into benzo[a]heptalene-2,4-diols 2c – g by a number of lithiated methyl X-phenyl sulfones and BuLi (cf. Scheme 9 and Table 3).     

Double-Bond Shifts in [4n]Annulenes as a New Principle for Molecular Switches: First Results with Dimethyl Heptalene-1,2- and -4,5-dicarboxylates

A new concept for molecular switches, based on thermal or photochemical double-bond shifts (DBS) in [4n]annulenes such as heptalenes or cyclooctatetraenes, is introduced (cf. Scheme 2). Several heptalene-1,2- and -4,5-dicarboxylates (cf. Scheme 4) with (E)-styryl and Ph groups at C(5) and C(1), or C(4) and C(2), respectively, have been investigated. Several X-ray crystal-structure analyses (cf. Figs. 1–5) showed that the (E)-styryl group occupies in the crystals an almost perfect s-trans-conformation with respect to the C?C bond of the (E)-styryl moiety and the adjacent C?C bond of the heptalene core. Supplementary ¹H-NOE measurements showed that the s-trans-conformations are also adopted in solution (cf. Schemes 6 and 9). Therefore, the DBS process in heptalenes (cf. Schemes 5 and 8) is always accompanied by a 180° torsion of the (E)-styryl group with respect to its adjacent C?C bond of the heptalene core. The UV/VIS spectra of the heptalene-1,2- and -4,5-dicarboxylates illustrated that it can indeed be differentiated between an ‘off-state’, which possesses no ‘through-conjugation’ of the π-donor substituent and the corresponding MeOCO group and an ‘on-state’ where this ‘through-conjugation’ is realized. The ‘through-conjugation’, i.e., conjugative interaction via the involved s-cis-butadiene substructure of the heptalene skeleton, is indicated by a strong enhancement of the intensities of the heptalene absorption bands I and II (cf. Tables 3–6). The most impressive examples are the heptalene-dicarboxylates 11a , representing the off-state, and 11b which stands for the on-state (cf. Fig.8).     

Reaction of dialkyl 2-aryl-4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylates with aliphatic amines

Benzylamine, phenethylamine, and homoveratrylamine reacted with dialkyl 2-aryl-4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylates at the endocyclic carbonyl group with conservation of the enolic hydroxy group to give dialkyl 4-alkylamino-2-aryl-6-hydroxy-6-methylcyclohex-3-ene-1,3-dicarboxylates. The reaction of dimethyl 4-hydroxy-4-methyl-6-oxo-2-phenylcyclohexane-1,3-dicarboxylate with tryptamine was accompanied by dehydration with formation of dimethyl 4-[2-(1H-indol-3-yl)ethylamino]-6-methyl-2-phenylcyclohexa-3,5-diene-1,3-dicarboxylate, presumably due to basic properties of the indole nitrogen atom.     

Cationic RhI Complexes of Azulenes and Their Catalytic Activity on the Formation of Heptalene-1,2-dicarboxylates from Dimethyl Acetylenedicarboxylate and Azulenes

[Rh¹(η⁵-azulene)(cod)]⁺BF complexes 3a–g (cod = (Z,Z)-cycloocta-1,5-diene) have been synthesized by reaction of [Rh¹(cod)]⁺BF in THF with the corresponding azulenes 1a–g (Table 1). The structure of [Rh¹(cod)(η⁵-guaiazulene)]⁺BF ( 3a ) has been determined by X-ray diffraction analysis (Fig. 1 and 2). The Rh-atom is oriented above the five-membered ring of the azulene with almost equal Rh? C distances to all five C-atoms of the ring. The (Z,Z)-cycloocta-1,5-diene ring occurs in two enantiomorphic distorted (C_2v → C₂) tub conformations in the crystals (Fig. 3). In CDCl₃ solution, the cod ligand in the complexes 3 shows a dynamic behavior on the ¹H-NMR time scale which is best explained by rotation of the cod ligand relative to the azulene ligands around an imaginary cod? Rh? azulene axis. The new complexes 3 catalyze the formation of heptalene-1,2-dicarboxylates 2 from dimethyl acetylenedicarboxylate (ADM) and the corresponding azulenes 1 just as effectively as [RuH₂(PPh₃)₄] and the analogous [RhH(PPh₃)₄] complex in MeCN solution (Table 3). On grounds of simplicity, 3 can be generated in situ, when [RhCl(cod)]₂ is applied as catalyst (Table 3).     

Synthesis,structural, and biochemical study of a series of methyl 2,6-diaryl-1-methyl-4-oxopiperidine-3,5-dicarboxylates and a series of methyl 2,4-diaryl-3,7-dimethyl-9-oxo-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarboxylates

A series of methyl-2,6-diaryl-1-methyl-4-oxopiperidine-3,5-dicarboxylates Ia-c and 2,4-diaryl-3,7-dimethyl-1,5-dimethoxycarbonyl-9-bispidinones IIa-c have been synthesized and studied by ir, ¹H and ¹³C nmr spectroscopy and the crystal structure of methyl 2,4-diphenyl-3,7-dimethyl-9-oxo-3,7-diazabicyclo[3,3.1]nonane-1,5-dicarboxylate (IIa) has been determined by X-ray diffraction. The enolic form of compound Ia (I'a) was also studied.     

A novel one-pot isocyanide-based four-component reaction: synthesis of highly functionalized 1H-pyrazolo[1,2-b]phthalazine-1,2-dicarboxylates and 1H-pyrazolo[1,2-a]pyridazine-1,2-dicarboxylates

A new protocol has been developed for the efficient synthesis of structurally diverse 1H-pyrazolo[1,2-b]phthalazine-1,2-dicarboxylates and 1H-pyrazolo[1,2-a]pyridazine-1,2-dicarboxylates via a four-component reaction of hydrazine hydrate, dialkyl acetylenedicarboxylates, isocyanides and various cyclic anhydrides such as succinic anhydride, maleic anhydride and phthalic anhydride in ethanol/acetone (1:1) at room temperature in good to moderate yields.     

First Optically Active Heptalenes and their Absolute Configuration

It is shown that dimethyl 7-isopropyl-5, 10-dimethylheptalene-1, 2-dicarboxylate ( 1 ) and dimethyl 5, 6, 8, 10-tetramethylheptalene-1, 2-dicarboxylate ( 2 ) can be resolved via the corresponding mono-acids and with the aid of optically active primary or secondary amines such as 1-phenylethylamine or ephedrine into the (?)-(P)- and (+)-(M)-enantiomeres, respectively. Characteristic for the (P)-chirality of the heptalene π-skeleton with C₂ or pseudo-C₂ symmetry are two (?)-CE's at the long wavelength region (450–300 nm) followed by at least one intense (+)-CE at wavelengths about or below 300 nm. The absolute configuration of the heptalenes was correlated with the well-established absolute configuration of (+)-(R)- and (?)-(S)-1-phenylethanol.     

Synthesis and calcium channel antagonist activities of new derivatives of dialkyl 1,4-dihydro-2,6-dimethyl-4-(5-phenylisoxazol-3-yl)pyridine-3,5-dicarboxylates

The new analogues of nifedipine, in which 2-nitrophenyl group at position 4 is replaced by phenylisoxazolyl substituent, were synthesized. The symmetrical dialkyl 1,4-dihydro-2,6-dimethyl-4-(5-phenylisoxazol-3-yl)pyridine-3,5-dicarboxylates were prepared by classical Hantzsch condensation, and the asymmetrical analogues were synthesized using a procedure reported by Dagnino that involved the condensation of alkyl acetoacetate with alkyl 3-aminocrotonate and 5-phenylisoxazole-3-carboxaldehyde. The structure of all compounds was confirmed by IR, ¹H NMR and Mass spectra. In vitro calcium channel antagonist activities were evaluated as calcium channel antagonists using the high K⁺ concentration of guinea-pig ileum longitudinal smooth muscle (GPILSM) assay. These compounds exhibited moderate calcium antagonist activity (IC₅₀ = 10^?7 to 10^{? 5} M range) relative to the reference drug nifedipine (IC₅₀ = 1.10 ± 0.40 × 10^?8 M).     

Synthesis of 3-(quinolin-2-yl)indolizines through iodine-mediated sp3C–H functionalization of azaarenes

An efficient approach toward C–H bond activation using iodine-mediated sp³C–H bond functionalization for the synthesis of dialkyl 3-(quinolin-2-yl)indolizine-1,2-dicarboxylates and dialkyl 3-(quinolin-2-yl)pyrrolo[2,1-a]isoquinoline-1,2-dicarboxylates through 1,3-dipolar cycloaddition reaction of nitrogen ylides with acetylenic esters is described.     

Thermal Reaction of Azulene and Some of Its Symmetrically Substituted Methyl Derivatives with Dimethyl Acetylenedicarboxylate

It is shown that azulene ( 1 ) and dimethyl acetylenedicarboxylate (ADM) in a fourfold molar excess react at 200° in decalin to yield, beside the known heptalene- ( 5 ) and azulene-1,2-dicarboxylates ( 6 ), in an amount of 1.6% tetramethyl (1RS,2RS,5SR,8RS)-tetracyclo[6.2.2.2^2,50^1,5]tetradeca-3,6,9,11,13-pentaene-3,4,9,10-tetracarboxylate(‘anti’-7) as a result of a SHOMO (azulene)/LUMO(ADM)-controlled addition of ADM to the seven-membered ring of 1 followed by a Diels-Alder reaction of the so formed tricyclic intermediate 16 (cf. Scheme 3) with a second molecule of ADM. The structure of ‘anti’-7 was confirmed by an X-ray diffraction analysis. Similarly, the thermal reaction of 5,7-dimehtylazulene ( 3 ) with excess ADM in decalin at 120° led to the formation of ca. 1% of ‘anti’- 12 , the 7,12-dimethyl derivative of‘anti’-7, beside of the corresponding heptalene- 10 and azulene-1,2-dicaboxylated (cf Scheme 2). The introduction of Me groups at C(1)and C(3)of azulene ( 1 ) and its 5,7-dimethyl derivative 3 strongly enhance the thermal formation of the corresponding tetracyclic compound. Thus, 1,3-dimethylazulene ( 2 ) in the presence of a sevenfold molar excess of ADM at 200° yielded 20% of ‘anti’- 9 beside an equal amount of dimethyl 3-mehtylazulene-1,2-dicarboxylate ( 8 ;cf. Scheme 1), and 1,3,5,7-tetramethylazulene ( 4 ) with a fourfold molar excess of ADM AT 200° gave a yield of 37% of‘anti’- 15 beside small amount of the corresponding heptalene- 13 and azulene-1,2-dicarboxylates 14 (cf.Scheme 2).     

Reactions of dimethyl and di-tert-butyl 2-aryl-4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylates with difunctional nucleophiles

The nature of the alkyl group in the ester moieties of dimethyl and di-tert-butyl 2-aryl-4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylates affects the direction of their reactions with difunctional nucleophiles. The dimethyl esters react with hydrazine hydrate to give the corresponding tetrahydroindazoles, while their tert-butyl analogs are converted under similar conditions into 6-hydrazones. Reactions of both dimethyl and di-tert-butyl 6-oxocyclohexane-1,3-dicarboxylates with hydroxylamine lead to formation of 6-hydroxyimino derivatives.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 10, 2004, pp. 1687–1691.Original Russian Text Copyright © 2004 by V. Gein, N. Gein, Potemkin, Krivenko.This revised version was published online in April 2005 with a corrected cover date.     

Thermal Reactions of Guaiazulene and Its 3-Methyl Derivative with Dimethyl Acetylenedicarboxylate

The thermal reaction of 7-isopropyl-1,3,4-trimethylazulene (3-methylguaiazulene; 2 ) with excess dimethyl acetylenedicarboxylate (ADM) in decalin at 200° leads to the formation of the corresponding heptalene- ( 5a/5b and 6a/6b ; cf. Scheme 3) and azulene-1,2-dicarboxylates ( 7 and 8 , respectively). Together with small amounts of a corresponding tetracyclic compound (‘anti’- 13 ) these compounds are obtained via rearrangement (→ 5a/5b and 6a/6b ), retro-Diels-Alder reaction (→ 7 and 8 ), and Diels-Alder reaction with ADM (→ ‘anti’- 13 ) from the two primary tricyclic intermediates ( 14 and 15 ; cf. Scheme 5) which are formed by site-selective addition of ADM to the five-membered ring of 2 . In a competing Diels-Alder reaction, ADM is also added to the seven-membered ring of 2 , leading to the formation of the tricyclic compounds 9 and 10 and of the Diels-Alder adducts ‘anti’- 11 and ‘anti’- 12 , respectively of 9 and of a third tricyclic intermediate 16 which is at 200° in thermal equilibrium with 9 and 10 (cf. Scheme 6). The heptalenedicarboxylates 5a and 5b as well as 6a and 6b are interconverting slowly already at ambient temperature (Scheme 4). The thermal reaction of guaiazulene ( 1 ) with excess ADM in decalin at 190° leads alongside with the known heptalene- ( 3a ) and azulene-1,2-dicarboxylates ( 4 ; cf. Schemes 2 and 7) to the formation of six tetracyclic compounds ‘anti’- 17 to ‘anti’- 21 as well as ‘syn’- 19 and small amounts of a 4:1 mixture of the tricyclic tetracarboxylates 22 and 23 . The structure of the tetracyclic compounds can be traced back by a retro-Diels-Alder reaction to the corresponding structures of tricyclic compounds ( 24--29 ; cf. Scheme 8) which are thermally interconverting by [1,5]-C shifts at 190°. The tricyclic tetracarboxylates 22 and 23 , which are slowly equilibrating already at ambient temperature, are formed by thermal addition of ADM to the seven-membered ring of dimethyl 5-isopropyl-3,8-dimethylazulene-1,2-dicarboxylate ( 7 ; cf. Scheme 10). Azulene 7 which is electronically deactivated by the two MeOCO groups at C(1) and C(2) shows no more thermal reactivity in the presence of ADM at the five-membered ring (cf. Scheme 11). The tricyclic tetracarboxylates 22 and 23 react with excess ADM at 200° in a slow Diels-Alder reaction to form the tetracyclic hexacarboxylates 32 , ‘anti’- 33 , and ‘anti’- 34 (cf. Schemes 10–12 as well as Scheme 13). A structural correlation of the tri- and tetracyclic compounds is only feasible if thermal equilibration via [1,5]-C shifts between all six possible tricyclic tetracarboxylates ( 22, 23 , and 35–38 ; cf. Scheme 13) is assumed. The tetracyclic hexacarboxylates 32 , ‘anti’- 33 , and ‘anti’- 34 seem to arise from the most strained tricyclic intermediates ( 36–38 ) by the Diels-Alder reaction with ADM.     

Synthesis of 4,6-Disubstituted Dimethyl Pyridazine-3,5-dicarboxylates

Dimethyl pyridazine-3,5-dicarboxylates were synthesized by reaction of substituted 2-cyclo-propenecarboxylates with methyl diazoacetate, followed by oxidation of the resulting 1,4-dihydropyridazine-4,6-dicarboxylates.     

K2CO3-assisted one-pot sequential synthesis of 2-trifluoromethyl-6-difluoromethylpyridine-3,5-dicarboxylates under solvent-free conditions

A novel synthesis of 2-trifluoromethyl-6-difluoromethylpyridine-3,5-dicarboxylates by three-component reaction of ethyl trifluoroacetoacetate, aldehydes, and ammonium acetate in the presence of K₂CO₃ under solvent-free conditions via sequential Hantzsch reaction/dehydration/dehydrofluorination in a one-pot process was described.     

Synthesis of substituted 1,2-dihydropyridines by reaction of ethyl <Emphasis Type="Italic">N</Emphasis>-arylmalonamates with ethyl 2-(ethoxymethylidene)-3-oxobutanoate

Michael addition of ethyl N-arylmalonamates to ethyl 2-(ethoxymethylidene)-3-oxobutanoate in ethanol in the presence of triethylamine at room temperature afforded the corresponding adducts which underwent cyclization to diethyl 1-aryl-6-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxylates in 17–65% yield. N-Alkylmalonamic acid esters failed to react with ethyl 2-(ethoxymethylidene)-3-oxobutanoate under analogous conditions.     

Thermal and Ru-catalyzed Reactions of Styryl-Substituted Azulenes with Dimethyl Acetylenedicarboxylate

The thermal reaction of 1-[(E)-styrl]azulenes with dimethyl acetylenedicarboxylate (ADM) in decalin at 190–200° does not lead to the formation fo the corresponding heptalene-1,2-dicarboxylates (Scheme 2). Main products are the corresponding azulene-1,2-dicarboxylates (see 4 and 9 ), accompanied by the benzanellated azulenes trans- 10a and trans- 11 , respectively. The latter compounds are formed by a Diels-Alder reaction of the starting azulenes and ADM, followed by an ene reaction with ADM (cf. Scheme 3). The [RuH₂(PPh₃)₄]-catalyzed reaction of 4,6,8-trimethyl-1-[(E)-4-R-styryl]azulenes (R=H, MeO, Cl; Scheme 4) with ADM in MeCN at 110° yields again the azulene-1,2-dicarboxylates as main products. However, in this case, the corresponding heptalene-1,2-dicarboxylates are also formed in small amounts (3–5%; Scheme 4). The benzanellated azulenes trans- 10a and trans- 10b are also found in small amounts (2–3%) in the reaction mixture. ADM Addition products at C(3) of the azulene ring as well as at C(2) of the styryl moiety are also observed in minor amounts (1–3%). Similar results are obtained in the [RuH₂(PPh₃)₄]-catalyzed reaction of 3-[(E)-styryl]guaiazulene ((E)- 8 ; Scheme 5) with ADM in MeCN. However, in this case, no heptalene formation is observed, and the amount of the ADM-addition products at C(2) of the styryl group is remarkably increased (29%). That the substitutent pattern at the seven-membered ring of (E)- 8 is not responsible for the failure of heptalene formation is demonstrated by the Ru-catalyzed reaction of 7-isopropyl-4-methyl-1-[(E)-styryl]azulene ((E)- 23 ; Scheme 11) with ADM in MeCN, yielding the corresponding heptalene-1,2-dicarboxylate (E)- 26 (10%). Again, the main product is the corresponding azulene-1,2-dicarboxylate 25 (20%). Reaction of 4,6,8-trimethyl-2-[(E)-styryl]azulene ((E)- 27 ; Scheme 12) and ADM yields the heptalene-dicarboxylates (E)- 30A / B , purely thermally in decalin (28%) as well as Ru-catalyzed in MeCN (40%). Whereas only small amounts of the azulene-1,2-dicarboxylate 8 (1 and 5%, respectively) are formed, the corresponding benzanellated azulene trans- 29 ist found to be the second main product (21 and 10%, respectively) under both reaction conditions. The thermal reaction yields also the benzanellated azulene 28 which is not found in the catalyzed variant of the reaction. Heptalene-1,2-dicarboxylates are also formed from 4-[(E)-styryl]azulenes (e.g. (E)- 33 and (E)- 34 ; Scheme 14) and ADM at 180–190° in decalin and at 110° in MeCN by [RuH₂(PPh₃)₄] catalysis. The yields (30%) are much better in the catalyzed reaction. The formation of by-products (e.g. 39–41 ; Scheme 14) in small amounts (0.5–5%) in the Ru-catalyzed reactions allows to understand better the reactivity of zwitterions (e.g. 42 ) and their triyclic follow-up products (e.g. 43 ) built from azulenes and ADM (cf. Scheme 15).     

Optimization of the selective monohydrolysis of diethyl 4-aryl-4H-pyran-3,5-dicarboxylates

A simple, efficient and eco-friendly procedure for the selective monohydrolysis of diethyl 2,6-dimethyl-4-aryl-4H-pyran-3,5-dicarboxylates under quaternary ammonium salt catalysis conditions is presented. The catalytic activities of various quaternary ammonium salts were investigated using different molar ratios of NaOH and water-organic solvent mixtures. The results indicate that the combination of 1.0 equivalent of tetraethyl-ammonium bromide (TEAB) with 1.2 equivalents of NaOH in a 10% water-ethanol media at 40 °C displays remarkable selectivity for the monohydrolysis of diethyl 2,6-dimethyl-4-aryl-4H-pyran-3,5-dicarboxylates. The utility of this process is demonstrated by the monohydrolysis of a series of 4-aryl-4H-pyran-3,5-dicarboxylate esters to afford the corresponding monoesters in 20-80% yields under the optimized conditions.