Syntheses and UV/Vis-spectroscopic properties of hydrophilic 2-, 3-, and 4-pyridyl-substituted solvatochromic and halochromic pyridinium N-phenolate betaine dyes as new empirical solvent polarity indicators

FULL PAPER

Syntheses and UV/Vis-Spectroscopic Properties of Hydrophilic 2-, 3-, and 4-

Pyridyl-Substituted Solvatochromic and Halochromic Pyridinium N-Phenolate

Betaine Dyes as New Empirical Solvent Polarity Indicators^[‡]

Christian Reichardt,*^[a]Daqing Che,^[a]Guido Heckenkemper,^[a]and Gerhard Schäfer^[a]

Keywords: Betaines / Dyes / E_T(30) values / Halochromism / Solvatochromism / Solvent effects

Syntheses and negative solvatochromism of nine new hydro- hydrophobic standard betaine dyes 1 and 2, which have been

philic 2-, 3-, and 4-pyridyl-substituted pyridinium N-

phenolate betaine dyes 3−11 are described. These were pro- the E_T(30) scale. Betaine dye 8, in which three of the peri-

duced in order to obtain zwitterionic dyes better soluble in pheral phenyl groups of 1 are replaced by two 3-pyridyl rings

water and other aqueous media (such as binary water/solv- and one 4-pyridyl ring, proved to be particularly suitable for

used to establish an empirical scale of solvent polarity, called

ent mixtures, aqueous ionophore solutions) than the rather

the determination of E_T(30) values in aqueous media.

Introduction

transition energies (in kcal/mol) of the standard betaine dye

1, measured in solvents of different polarity at room tem-

perature (25 °C) and normal pressure (1 bar), according to

Solutions of the pyridinium N-phenolate betaine dye 1

(Scheme 1) are solvatochromic, thermochromic, piezoch-

romic, and halochromic.^[4Ϫ6]This means that the longest-

wavelength intramolecular charge-transfer absorption band

˜

Equation (1), where ν_maxis the wavenumber and λ_maxthe

wavelength of the maximum of the long-wavelength solva-

tochromic absorption band of betaine dye 1.

of the UV/Vis spectrum of

1 depends on solvent

˜

E_T(30) [kcal/mol] ϭ h · c · ν_max· N_Aϭ

polarity,^[7Ϫ10]solution temperature,^[11Ϫ15]external pres-

sure,^[16,17]and on the nature and concentration of added

salts.^[18Ϫ28]By definition, negative (positive) solvatochro-

mism means that solvent-dependent UV/Vis absorption

bands of the solute are shifted hypsochromically (bathoch-

romically) with increasing solvent polarity.^[5,31]Solutions of

a chirally modified betaine dye 1 with four stereogenic cen-

ters even exhibit the phenomenon of chirosolvatochro-

mism.^[29]The extraordinarily large negative solvatochro-

mism of the standard betaine dye 1 has been used to estab-

lish UV/Vis-spectroscopically derived empirical parameters

of solvent polarity, known as E_T(30) values.^[5,7,30,31]These

E_T(30) values are simply defined as the molar electronic

(1)

(2.8591·10^Ϫ3) · ν˜_max[cm^Ϫ1] ϭ 28591/λ_max[nm]

High E_T(30) values correspond to high solvent polarity,

here defined as the overall solvation capability of a solvent

(for definitions of the term solvent polarity see refs.^[8Ϫ10,31]).

Since, in the first publication,^[7]the betaine dye 1 had hap-

pened to have the formula number 30, the number (30) was

later added in order to avoid confusion with E_T, used in

photochemistry as an abbreviation for triplet excitation en-

ergy. E_T(30) values for more than 360 solvents and numer-

ous binary solvent mixtures are known.^{[4Ϫ6,30,31,34]}These

and other empirical parameters of solvent polarity have

successfully been used in the correlation analysis of solvent

effects on chemical equilibria, reaction rates, and spectral

absorptions.^[31Ϫ35]

The E_T(30) solvent polarity scale ranges from 63.1 kcal/

mol for water, as the most polar solvent, to 30.7 kcal/mol

for tetramethylsilane (TMS) as the least polar solvent. In

1983, in order to avoid use of the non-SI unit kcal/mol, the

dimensionless, normalized E^N_Tscale was introduced, using

water (E^N_Tϭ 1.000) and TMS (E^N_Tϭ 0.000) as extreme po-

lar and nonpolar reference solvents, respectively, by which

to fix this scale.^[30]

The primary indicator dye 1 is sufficiently soluble in most

solvents, although insoluble or only sparingly soluble in

nonpolar solvents such as aliphatic hydrocarbons, per-

fluorohydrocarbons, and TMS, as well as in water. In order

to obtain betaine dyes that were soluble in nonpolar solv-

ents, the lipophilic penta-tert-butyl-substituted betaine dye

2 was introduced as a secondary probe.^[30]Even hepta-tert-

butyl-substituted and tri-tert-butyl-bis(adamantan-1-yl)-

Scheme 1

[‡]

Pyridinium N-Phenoxide Betaines and Their Application to the

Determination of Solvent Polarities, XXV. Ϫ Part XXIV: Ref.^[1]

[a]

Department of Chemistry and Scientific Center of Material

Sciences, Philipps University,

Hans-Meerwein-Strasse, 35032 Marburg, Germany

Fax: (internat.) ϩ 49-(0)6421/282-8917

Eur. J. Org. Chem. 2001, 2343Ϫ2361

WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001

1434Ϫ193X/01/0612Ϫ2343 $ 17.50ϩ.50/0

2343

C. Reichardt, D. Che, G. Heckenkemper, G. Schäfer

FULL PAPER

substituted pyridinium N-phenolate betaine dyes were syn-

On the basis of the simple observation that benzene is

thesized in order to increase solubility in nonpolar solv- practically insoluble in water, whereas pyridine is com-

ents.^[1]The excellent linear correlation between the E_Tpletely miscible with water, the replacement of some of the

values of 1 and 2 for those solvents in which both dyes five peripheral phenyl rings in 1 with pyridyl rings should

are soluble allows E_T(30) values to be calculated for such result in betaine dyes with better water solubilities. Without

nonpolar solvents in which the primary probe dye 1 is not changing the basic zwitterionic chromophore of these solva-

soluble enough for UV/Vis-spectroscopic measure- tochromic betaine dyes, the additional peripheral nitrogen

ments.^[5,30,37]The quantitative link between the E_Tvalues of atoms should be prone to forming intermolecular hydrogen

the primary indicator dye 1 [i.e., E_T(30)] and the secondary bonds with surrounding water molecules, thus pulling the

indicator dye 2 [i.e., E_T(2)] is given by Equation (2), with whole dye into the aqueous solution. Here, we report on

n ϭ 57, r ϭ 0.999, and s ϭ 0.17 kcal/mol.^[37]

the synthesis, solvatochromism, and halochromism of such

2-, 3-, and 4-pyridyl-substituted betaine dyes (3Ϫ11; see

Scheme 1), which did indeed prove to be much more water-

soluble than 1, thus allowing the empirical study of the

polarities^[8Ϫ10]of aqueous ionophore^[39]solutions.^[42]

E_T(2) [kcal/mol] ϭ 0.9424 · E_T(30) [kcal/mol] ϩ 1.808

(2)

In this way, it was easily possible to extend the E_T(30)

scale to nonpolar solvents such as aliphatic hydrocarbons

and the supercritical fluid carbon dioxide.^[36]Unfortunately,

it was not possible previously to find a solvatochromic be-

taine dye that is soluble in perfluorohydrocarbons.^[1]

The primary indicator dye 1 is only sparingly soluble in

water (its solubility in water is only about 2·10^Ϫ6mol/L),

just enough to determine its E_T(30) value directly.^[38]This

low solubility of 1 in water is clearly due to the core of five

Results and Discussion

1. Syntheses

The key step in the synthesis of pyridinium N-phenolate

hydrophobic phenyl groups around the betaine chromo- betaine dyes is the condensation reaction between 2,4,6-tri-

phore. The low water solubility of 1 does not allow direct aryl-substituted pyrylium salts and 2,6-disubstituted 4-ami-

UV/Vis-spectroscopic determination of the polarity of nophenols, producing N-(4-hydroxyphenyl)pyridinium salts,

highly aqueous binary solvent mixtures and of aqueous which are eventually deprotonated to give the correspond-

ionophore solutions.^[39]In order to obtain solvatochromic ing betaine dyes.^{[7,30,43Ϫ48]}In order to obtain the desired

betaine dyes with better water solubilities, we synthesized pyridyl-substituted betaine dyes 3Ϫ11, it was first necessary

pyridinium N-phenolates with one or more hydrophilic sub- to synthesize pyridyl-substituted pyrylium salts and 2,6-di-

stituents, such as the carboxylate (ϪCO₂^ϪNa^ϩ)^[40]and pyridyl-substituted 4-aminophenols. None of these com-

methanesulfonyl (ϪSO₂CH₃)^[41]groups, in the peripheral pounds were known previously, with the exception of an

phenyl rings, but with limited success.^[40,41]

inseparable mixture of 4-phenyl-2,6-bis(pyridin-2-yl)pyryl-

Scheme 2. Synthesis of betaine dye 3 with two 2-pyridyl rings in the phenolate part

2344

Eur. J. Org. Chem. 2001, 2343Ϫ2361

Pyridinium N-Phenolate Betaine Dyes as Empirical Solvent Polarity Indicators

FULL PAPER

ium tetrafluoroborate and 4,6-diphenyl-2-(pyridin-2-yl)pyr- deprotonated to the betaine dye 4, obtained as dark green

ylium tetrafluoroborate, obtained by Katritzky et al.^[49]crystals.

from 3-phenyl-1-(pyridin-2-yl)prop-2-en-1-one,^[50]aceto-

phenone, and tetrafluoroboric acid. Our attempts to obtain

Betaine dye 5, with four pyridyl rings, was prepared cor-

respondingly, through the pyridinium salt 20, from 4-

phenyl-2,6-bis(pyridin-4-yl)pyrylium salt 19 and the 4-ami-

nophenol 14, as black-violet crystals (Scheme 4). The pyryl-

ium salt 19 was synthesized directly from 4-acetylpyridine,

benzaldehyde, and tetrafluoroboric acid (54%) in diethyl

the former pyrylium salt in pure form by various classical

methods for the synthesis of substituted pyrylium salts^[51,52]

were unsuccessful.^[3]

The synthesis of betaine dye 3, with two 2-pyridyl rings

in the phenolate part, is outlined in Scheme 2. Lithiation of

ether in moderate yield, analogously to the procedure in

2-methylpyridine with n-butyllithium in THF, according to

ref.^[57,59]but with a slight modification.^[2]

Beumel et al.,^[53]and subsequent addition to (pyridin-2-yl)-

For the synthesis of betaine dye 6 (Scheme 5), with two

3-pyridyl rings in the phenolate part, it was first necessary

to prepare the intermediate 1,3-bis(pyridin-3-yl)acetone

acetonitrile resulted, after hydrolysis, in a sufficient yield of

1,3-bis(pyridin-2-yl)acetone (12a),^[54,55]which is partly enol-

ized to 12b in solution (ca. 60% enol form in CDCl₃). Base-

(24). WillgerodtϪKindler redox amidation of 3-acetylpyrid-

catalyzed double aldol condensation of 12 with sodium

ine with sulfur and morpholine gave the thiomorpholide 21,

which was hydrolyzed to (pyridin-3-yl)acetic acid hydro-

nitromalonaldehyde monohydrate^[56]gave the 4-nitrophenol

13 in good yield, and this was subsequently reduced to the

chloride (22).^[60]Acid-catalyzed esterification of 22 with

4-aminophenol 14 with dihydrogen and palladium as cata-

ethanol produced the ester 23,^[61]which on treatment with

lyst. Condensation of 14 with 2,4,6-triphenylpyrylium tetra-

sodium ethoxide in ethanol yielded the desired ketone 24,

fluoroborate^[7,57]yielded the N-(4-hydroxyphenyl)pyridin-

though in rather low yield. Ketone 24 had previously been

ium salt 15, which, on deprotonation with sodium methox-

obtained by Novelli et al. as an undesired side product, in

ide in methanol, gave the desired betaine dye 3 as red-violet

crystals, containing some water of crystallization (dihy-

6% yield.^[62]Condensation of ketone 24 with sodium nitro-

malonaldehyde monohydrate^[56]yielded the 4-nitrophenol

drate).

25, which was easily reduced to the 4-aminophenol 26. Con-

The synthesis of betaine dye 4 with three pyridyl rings

densation of 26 with 2,4,6-triphenylpyrylium tetrafluoro-

(Scheme 3) began with the preparation of 2,6-diphenyl-4-

borate^[7,57]eventually gave (via 27) the desired betaine dye

(pyridin-4-yl)pyrylium salt 17. Using a method of Katritzky

6 as a violet, amorphous powder.

et al.,^[58]base-catalyzed condensation of pyridin-4-carbal-

dehyde with acetophenone first gave the 1,5-diketone 16,

Betaine dye 7 (Scheme 6), with four 3-pyridyl rings alto-

which on treatment with boron trifluorideϪdiethyl ether in gether, was prepared analogously, from 4-aminophenol 26

acetic acid, in the presence of benzalacetophenone as hy- and 4-phenyl-2,6-bis(pyridin-3-yl)pyrylium salt 28, via 29,

dride acceptor, underwent ring closure to give the pyrylium as violet powder. The pyrylium salt 28 was obtained by

salt 17.^[58]Subsequent condensation of 17 with the 4-amino- treatment of 3-acetylpyridine, benzaldehyde, and tetra-

phenol 14 yielded the pyridinium salt 18, which was then fluoroboric acid (54%), dissolved in diethyl ether, in

Scheme 3. Synthesis of betaine dye 4 with two 2-pyridyl rings in the phenolate part and one 4-pyridyl ring in the pyridinium part

Eur. J. Org. Chem. 2001, 2343Ϫ2361

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C. Reichardt, D. Che, G. Heckenkemper, G. Schäfer

FULL PAPER

Scheme 4. Synthesis of betaine dye 5 with two 2-pyridyl rings in the phenolate part and two 4-pyridyl rings in the pyridinium part

Scheme 5. Synthesis of betaine dye 6 with two 3-pyridyl rings in the phenolate part

analogy to the preparation of pyrylium salt 19

The synthesis of betaine dye 9, with two 4-pyridyl rings

in the phenolate part, was more difficult (Scheme 8). The

(Scheme 4).^[2,57,59]

Betaine dye 8 (Scheme 7) was similarly obtained as a vi- necessary intermediate, 1,3-bis(pyridin-4-yl)acetone (30),

olet powder by treatment of pyrylium salt 17 (see Scheme 3) was unknown. It was first attempted to produce 30 by ox-

with the 4-aminophenol 26 (see Scheme 5), but without idation of 1,3-bis(pyridin-4-yl)-2-propanol with various ox-

isolation of the corresponding intermediary N-(4-hydroxy- idizing agents (such as KMnO₄, DMSO/Ac₂O, DCC,

phenyl)pyridinium salt. It was not possible to isolate this DessϪMartin periodinane), but without success.^[3]1,3-Bis-

pyridinium salt in pure form.^[3]

(pyridin-4-yl)-2-propanol was prepared from 4-(sodiome-

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Pyridinium N-Phenolate Betaine Dyes as Empirical Solvent Polarity Indicators

FULL PAPER

Scheme 6. Synthesis of betaine dye 7 with four 3-pyridyl rings

32 (see Scheme 8), again without isolation of the interme-

diate N-(4-hydroxyphenyl)pyridinium salt. Betaine 10 exists

as an amorphous violet powder containing ca. 3.5 mol of

water of recrystallization.

The last betaine dye in this series, compound 11 with

three 4-phenyl rings (Scheme 10), was synthesized analog-

ously from the pyrylium salt 17 (see Scheme 3) and the 4-

aminophenol 32 (see Scheme 8) and isolated as violet crys-

tals with 3 mol of water of recrystallization.

The molecular structures of all the new compounds were

confirmed by elemental analysis, UV/Vis, IR, mass spectro-

1

metry, H NMR, and ¹³C NMR (see Exp. Sect.).

Scheme 7. Synthesis of betaine dye 8 with two 3-pyridyl rings in

the phenolate part and one 4-pyridyl ring in the pyridinium part

2. UV/Vis Spectra and Solvatochromism of Betaine Dyes

3؊11

thyl)pyridine (obtained from 4-methylpyridine with sodium

All pyridyl-substituted betaine dyes 3Ϫ11 are suitably

amide in liquid ammonia) and ethyl formate, analogously soluble in water and sufficiently soluble in most organic

to a procedure given by Bekun and Levine for the synthesis solvents, including benzene as a nonpolar solvent (except

of 1,3-bis(pyrazin-2-yl)-2-propanol.^[63]The preparation of 10 and 11), but insoluble in tetrachloromethane and cyclo-

1,3-bis(pyridin-4-yl)-2-propanol as described in a patent^[64]hexane. Obviously, together with the phenolate oxygen

could not be reproduced in our hands.^[3]Therefore, a differ- atom, the peripheral pyridyl nitrogen atoms are capable of

ent procedure for the preparation of 30 had to be found. In forming further intermolecular hydrogen bonds to the sur-

analogy to the synthesis of ketone 24 (Scheme 5),^[62]ethyl rounding water molecules, pulling the whole dye molecule

(pyridin-4-yl)acetate was treated with sodium ethoxide in into aqueous solution. The betaine dyes 3Ϫ11 exhibit ex-

ethanol to give the desired, not very stable, ketone 30, but treme negative solvatochromism, comparable to that of the

only in a very low yield (ca. 2%). In order to obtain suffi- standard betaine dye 1 used to establish the E_T(30) scale:

cient quantities of 30, this reaction step was repeated sev- On going from benzene to water as solvent, the long-wave-

eral times. Finally, double aldol condensation of 30 with length Vis absorption band of 3Ϫ11 is hypsochromically

sodium nitromalonaldehyde monohydrate^[56]to give the 4- shifted by ∆λ ഠ 340 nm (!), corresponding to a solvent-

nitrophenol 31, reduction of this to the 4-aminophenol 32, induced increase in the molar excitation energy of ∆E_T

ഠ

and condensation with 2,4,6-triphenylpyrylium tetrafluoro- 26 kcal/mol. Hence, the new dyes meet the requirements for

borate^[7,57]yielded the desired betaine dye 9 as a red-violet new solvatochromic probe molecules,^[5]particularly for the

powder, without isolation of the intermediate N-(4-hydroxy- determination of polarity in all kinds of aqueous media.

phenyl)pyridinium salt.

The solvent-dependent long-wavelength absorption maxima

The symmetrical betaine dye 10 (Scheme 9) with four 4- of 3Ϫ11, measured in 27 solvents of different polarity, are

pyridyl rings altogether, two in the phenolate and two in collected in Table 1.

the pyridinium moiety, was prepared directly by condensa-

Why did we synthesize such a variety of nine pyridyl-

tion of pyrylium salt 19 (see Scheme 4) with 4-aminophenol substituted betaine dyes, and which of them is the most

Eur. J. Org. Chem. 2001, 2343Ϫ2361

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C. Reichardt, D. Che, G. Heckenkemper, G. Schäfer

FULL PAPER

Scheme 8. Synthesis of betaine dye 9 with two 4-pyridyl rings in the phenolate part

Table 1. Long-wavelength, solvent-dependent CT absorption max-

ima, λ_maxin nm, of betaine dyes 3؊11, measured in 27 solvents of

decreasing polarity at 25 °C and at normal pressure (1 bar)

Solvents

Water

3

4

5

6

7

8

9

10 11

Ϫ^[a]464 461 447 460 473 Ϫ^[a]451 462

2,2,2-Trifluoroethanol Ϫ^[a]Ϫ^[a]Ϫ^[a]451 475 491 440 476 478

Formamide

Methanol

489 522 516 497 511 529 488 511 519

474 507 499 482 495 514 473 493 503

N-Methylformamide 500 532 522 506 516 536 496 513 525

Ethanol

1-Propanol

1-Butanol

1-Pentanol

1-Hexanol

1-Heptanol

2-Propanol

1-Octanol

497 529 521 505 516 538 494 514 525

503 539 530 516 530 550 504 529 536

507 543 535 523 538 557 511 536 544

514 548 541 526 541 562 516 543 550

511 546 541 532 546 568 523 550 556

515 550 545 535 548 570 528 554 561

524 562 551 534 551 569 523 550 558

519 552 549 538 551 570 531 556 564

Scheme 9. Synthesis of betaine dye 10 with four 4-pyridyl rings

1-Nonanol

1-Decanol

520 553 550

Ϫ

519 551 552 539 552 578 538 562 571

575 612 607 590 605 629 571 597 603

583 619 605 594 603 632 573 588 605

599 637 624 614 624 653 589 605 623

618 658 647 634 646 675 608 638 643

631 682 685 650 684 703 627 678 676

637 691 692 657 691 709 637 685 686

637 685 675 657 676 703 631 662 672

652 713 717 671 711 731 655 709 711

673 723 707 695 709 738 666 Ϫ^[b]703

684 731 719 705 723 750 675 703 715

697 757 757 735 761 787 710 Ϫ^[c]Ϫ^[c]

Acetonitrile

Dimethyl sulfoxide

Dimethylformamide

Acetone

1,2-Dichloroethane

Dichloromethane

Pyridine

Trichloromethane

Ethyl acetate

Tetrahydrofuran

1,4-Dioxane

tert-Butyl methyl ether 742 Ϫ^[c]787 762 Ϫ^[c]Ϫ^[c]731 Ϫ^[c]Ϫ^[c]

Scheme 10. Synthesis of betaine dye 11 with three 4-pyridyl rings

Benzene

736 809 804 769 795 824 748 Ϫ^[c]Ϫ^[c]

suitable for our purpose? In acetonitrile, a solvent of inter-

mediate polarity, the UV/Vis spectra of 3Ϫ11 exhibit four

[a]

Not measurable because of overlap with the intensive UV/Vis

absorption band at shorter wavelength, leading to a shoulder only.

[b]

[c]

Ϫ

Decomposition. Ϫ Not soluble in this solvent.

main absorption bands of different intensities: at λ_max

570Ϫ630 nm (ε 2600Ϫ5300), 415Ϫ440 nm (ε

8000Ϫ14000), 300Ϫ390 nm (ε

ϭ

9000Ϫ42000), and the pyridinium moiety (for various quantum chemical cal-

230Ϫ250 nm (ε ϭ 25000Ϫ42000 L/mol·cm). Only the posi- culations of the UV/Vis spectrum of betaine dye 1, see

tion of the long-wavelength absorption band is strongly refs.^[65Ϫ73]). Therefore, the position of the CT band should

solvent-dependent; the others are not. This absorption depend on the ionization energy of the electron donor (i.e.,

band is the product of an intramolecular charge transfer the phenolate part) and on the electron affinity of the elec-

(CT) from the HOMO of the phenolate to the LUMO of tron acceptor (i.e., the pyridinium part). On protonation of

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Pyridinium N-Phenolate Betaine Dyes as Empirical Solvent Polarity Indicators

FULL PAPER

the phenolate parts of 3Ϫ11, the solvent-dependent CT phenolate moiety should be strongly twisted, but also the

bands disappear and the corresponding N-(4-hydroxyphen- peripheral phenyl and pyridyl rings. This assumption is

yl)pyridinium salts formed (i.e., 15, 18, 20, 27, and 29) ab- made by analogy with a peripheral 4-bromo-substituted de-

sorb at λ_maxϭ 300Ϫ310 nm, corresponding to a πϪπ* ab- rivative of betaine dye 1, for which an X-ray molecular

sorption in the 2,4,6-triarylpyridinium chromophore. For structure analysis is known.^[76]The extent of the electron-

this reason, betaine dyes 3Ϫ11, as well as 1 and 2, cannot withdrawing effect of the pyridyl rings also depends on the

be used as polarity indicators in acidic solvents.

Replacement of the two 2,6-phenyl groups in the quantitatively.

phenolate part of the standard betaine dye 1 (λ_maxA solvent-induced and/or substituent-induced hypsoch-

twist angle, and is therefore difficult to estimate any more

ϭ

627 nm in acetonitrile) by two pyridyl rings results in all romic shift of the solvent-dependent long-wavelength CT

three cases (3, 6, and 9) in a hypsochromic shift of the long- band means that this band comes closer to the more intens-

wavelength CT band, amounting to ∆λ ϭ 575Ϫ627 ϭ ive solvent-independent absorption band at shorter wave-

Ϫ52 nm for 3 (with two 2-pyridyl rings), ∆λ ϭ Ϫ37 nm for lengths. In water as solvent, this can lead to some overlap,

6 (with two 3-pyridyl rings), and ∆λ ϭ Ϫ56 nm for 9 (with and the solvatochromic CT band degenerates to a shoulder.

two 4-pyridyl rings). Introduction of electron-withdrawing This is the case for betaine dyes 3 and 9 (see Table 1). For

pyridyl substituents in the phenolate part of the zwitterionic betaine dyes 10 and 11, when they are dissolved in water,

chromophore increases the ionization energy of the the CT band is also only poorly separated from the strong

phenolate moiety, with the experimentally observed hyp- bands at shorter wavelengths. Therefore, these dyes are less

sochromic CT band shift as a consequence. According to well suited for the study of the polarity of aqueous media.

the ∆λ values of 3, 6, and 9, the electron-withdrawing effect From the remaining betaine dyes, 4Ϫ8, dye 8 is obviously

of the pyridyl rings increases in the order 3-pyridyl (σ_aϭ the most suitable for this purpose, because its CT band,

ϩ0.72) Ͻ 2-pyridyl (σ_aϭ ϩ0.81) Ͻ 4-pyridyl (σ_aϭ ϩ0.95); with λ_maxϭ 473 nm, is located at the longest wavelength

that is, in the same sequence as given by the Hammett sub- position, which leaves a margin for further hypsochromic

stituent constants σ_aof the 2-, 3-, and 4-pyridyl groups band shifts without overlap, which might be induced by me-

(given in parentheses).^[74,75]These σ_avalues (taken from dia more polar than water. For this reason, and because of

ref.^[75]) are interpreted as due to the substitution of pyridyl its relatively easy availability (see Scheme 7), we have chosen

for phenyl (σ_aϭ 0).^[74]

Replacement of the three 2-, 4-, and 6-phenyl groups in

Table 2. E_T(8) values of the new tertiary standard betaine dye 8

the pyridinium part of betaine dye 1 by pyridyl rings should

increase the electron affinity of the pyridinium moiety, with

a bathochromic CT band shift as the result. This is indeed

the case: Replacement of the 4-phenyl or the 2-phenyl ring

of 1 by one 4-pyridyl group results in bathochromic CT

band shifts of ∆λ ϭ ϩ43 and ϩ41 nm, respectively.^[2]How-

ever, the corresponding new betaine dyes with only one

peripheral pyridyl substituent are not included in this paper

and in Scheme 1, because they are insufficiently water-sol-

uble.^[2]

For the other betaine dyes (4, 5, 7, 8, and 10) in

Scheme 1, with pyridyl rings in both parts of the zwitter-

ionic chromophore, a hypsochromic CT band shift is always

Ϫ with one exception (8) Ϫ obtained as result of a phenyl

Ǟ pyridyl replacement in 1: ∆λ (measured in acetonitrile) ϭ

Ϫ15 nm (for 4), Ϫ20 nm (for 5), Ϫ22 nm (for 7), and

Ϫ30 nm (for 10), demonstrating the dominating electron-

withdrawing influence of the pyridyl groups in the

phenolate part of the betaine chromophore.

and the E_T(30) values of the primary standard betaine dye 1 for 26

solvents, in kcal/mol

No.

Solvents

E_T(30)^[a]

E_T(8)^[b]

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

Water

2,2,2-Trifluoroethanol

Formamide

Methanol

N-Methylformamide

Ethanol

63.1

59.8

55.8

55.4

54.1

51.9

50.7

49.7

49.1

48.8

48.5

48.4

48.2

47.7

45.6

45.1

43.2

42.2

41.3

40.7

40.5

39.1

38.1

37.4

36.0

34.3

28.8^[c]

60.4

58.2

54.0

55.6

53.3

53.1

52.0

51.3

50.9

50.3

50.2

49.5

45.5

45.2

43.8

42.4

40.7

40.3

40.7

39.1

38.7

38.1

36.3

34.7

25.7^[c]

1-Propanol

1-Butanol

1-Pentanol

1-Hexanol

1-Heptanol

2-Propanol

1-Octanol

1-Decanol

Acetonitrile

Dimethyl sulfoxide

Dimethylformamide

Acetone

1,2-Dichloroethane

Dichloromethane

Pyridine

Trichloromethane

Ethyl acetate

Tetrahydrofuran

1,4-Dioxane

Benzene

Only betaine dye 8, with ∆λ ϭ 629 Ϫ 627 ϭ ϩ2 nm (in

acetonitrile), shows a small bathochromic CT band shift, 20

due to dominance of the electron-withdrawing effect of the

4-(4-pyridyl) ring in the pyridinium part over that of the

21

22

23

24

25

26

two 2,6-bis(3-pyridyl) rings in the phenolate part of 8. Cle-

arly, the positions of the long-wavelength CT absorption

band of dyes 3Ϫ11 depend on subtle mutual interplay be-

tween the pyridyl substituents in the electron donor and

electron acceptor parts of the zwitterionic chromophore. In

addition, it should be mentioned that the molecules of dyes

∆E_T[kcal/mol] ϭ

[a]

[b]

Taken from ref.^[5]

Ϫ

Calculated according to Equation (1)

from the Vis absorption maxima of 8 given in Table 1. Ϫ ^[c]∆E_Tϭ

3Ϫ11 are certainly not planar: Not only the pyridinium and E_T(H₂O) Ϫ E_T(C₆H₆).

Eur. J. Org. Chem. 2001, 2343Ϫ2361

2349

C. Reichardt, D. Che, G. Heckenkemper, G. Schäfer

FULL PAPER

betaine dye 8 (in addition to dyes 1 and 2) as a new ternary,

suitably water-soluble standard betaine dye for the study of

aqueous media.

Table 3. Regression parameters for the linear correlations between

the E_T(X) values of betaine dyes X ϭ 3؊11 and the E_T(30) values

of the standard betaine dye 1,^[5]according to the correlation equa-

tion: E_T(X) [kcal/mol] ϭ a · E_T(30) [kcal/mol] ϩ b

Table 2 shows the molar transition energies E_T(8) of be-

taine dye 8 in 26 hydrogen-bond donor (HBD) and non-

HBD solvents, together with the corresponding E_T(30)

values of the primary indicator dye 1. As regression Equa-

tion (3) and Figure 1 show, there is a good linear correlation

between the E_Tvalues of the two solvatochromic dyes, with

a correlation coefficient of r ϭ 0.987 and a standard devi-

ation of σ[E_T(8)] ϭ 1.172 kcal/mol for n ϭ 26 solvents.

X

a

b

n^[a]

r^[b]

σ[E_T(X)]^[c]

3

1.058

0.970

0.996

1.010

0.981

0.948

1.031

0.940

0.909

2.535

3.086

2.424

3.078

3.049

2.799

3.555

5.388

6.148

26

27

26

23

24

0.981

0.977

0.980

0.989

0.984

0.987

0.993

0.982

0.987

1.348

1.473

1.475

1.189

1.342

1.172

0.882

1.210

1.021

4

5

6

7

8

9

10

11

^[a]Number of solvents. Ϫ ^[b]Correlation coefficient. Ϫ ^[c]Standard

deviation of the estimate in kcal/mol.

A closer look at the correlation given by Equation (3)

and illustrated in Figure 1 reveals some family-dependent

behavior; the HBD solvents (i.e., alcohols and water) follow

a regression line with a slope somewhat smaller than that

of the regression line for the non-HBD solvents. This line

dispersion is illustrated in Figure 2 and can be quantitat-

ively described by Equation (4) (HBD solvents) and Equa-

tion (5) (non-HBD solvents).

Figure 1. Linear correlation between the E_T(30) values of standard

betaine dye 1 and the E_T(8) values of the tripyridyl-substituted be-

taine dye 8, measured in 26 solvents (numbering as in Table 2),

according to Equation (3)

E_T(8) [kcal/mol] ϭ 0.948 · E_T(30) [kcal/mol] ϩ 2.799

(3)

Equation (3) allows the calculation of E_T(30) values for

aqueous media in which the hydrophobic standard dye 1 is

insufficiently soluble, in the same way that the secondary

lipophilic probe dye 2 has permitted the indirect determina-

tion of E_T(30) values for nonpolar solvents by means of

Equation (2).^[30]The slope of the regression line, at 0.948,

is slightly less than unity, indicating that betaine dye 8 is

somewhat less sensitive to changes in solvent polarity than

dye 1 is. The corresponding regression coefficients for the

linear correlations between the E_Tvalues of all new hydro-

philic betaine dyes 3Ϫ11 and the E_T(30) values of 1 are

collected in Table 3. It can be seen that the E_Tvalues of all

new betaine dyes 3Ϫ11 exhibit good linear correlations with

E_T(30), with correlation coefficients of r ϭ 0.98Ϫ0.99. The

slopes of the regression lines vary between a ഠ 0.91 (for 11)

Figure 2. Linear correlations between the E_T(30) values of standard

betaine dye 1 and the E_T(8) values of betaine dye 8 with separate

lines for 12 HBD (open circles) and 14 non-HBD solvents (full

circles) (numbering as in Table 2), according to Equations (4) and

(5), respectively

E_T(8) (HBD) ϭ 0.704 · E_T(30) ϩ 16.236

(4)

(n ϭ 12; r ϭ 0.998; σ ϭ 0.238)

E_T(8) (non-HBD) ϭ 0.914 · E_T(30) ϩ 3.610

(n ϭ 14; r ϭ 0.997; σ ϭ 0.428)

(5)

According to r and σ, the linear correlations are now

and 1.06 (for 3), indicating that dyes 3Ϫ11 exhibit suscept- excellent. Analogous HBD/non-HBD dispersions of the lin-

ibilities to changes in solvent polarity similar to that of the ear correlations compiled in Table 3 are also found for the

standard dye 1.

other pyridyl-substituted betaine dyes. Obviously, the spe-

2350

Eur. J. Org. Chem. 2001, 2343Ϫ2361

Pyridinium N-Phenolate Betaine Dyes as Empirical Solvent Polarity Indicators

FULL PAPER

cific solvation of dye 8 with four hydrogen-bond-accepting

sites by HBD solvents according to Scheme 11 results in an

enhanced stabilization of the electronic ground state and

somewhat reduces its susceptibility to changes in the sur-

rounding HBD solvent (i.e., changes of R in ROH). Never-

theless, Equation (3) can be used for the calculation of

E_T(30) values for aqueous media, with the aid of E_T(8)

values of the hydrophilic betaine dye 8, without making a

larger mistake.

Table 4. Long-wavelength CT absorption maxima, λ_maxin nm, of

betaine dye 8, measured in binary water/1,4-dioxane mixtures at

25 °C, and the corresponding E_T(8) values in kcal/mol, calculated

according to Equation (1)

x(1,4-dioxane)^[a]

λ_max

E_T(8)

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

473

520

541

559

573

589

605

627

657

707

787

60.4

55.0

52.8

51.1

49.9

48.5

47.3

45.6

43.5

40.4

36.3

[a]

Mol fraction of 1,4-dioxane. ∆λ ϭ Ϫ314 nm; ∆E_Tϭ 24.1 kcal/

mol.

Scheme 11. Specific solvation of betaine dye 8 by HBD solvents

ROH (with R ϭ H, alkyl)

3. Solvatochromism of Betaine Dye 8 in a Binary Solvent

Mixture

Investigation, with standard dye 1, of polarities^[8Ϫ10]of

binary solvent mixtures containing water as one of the two

components often suffers from the low solubility of 1 in the

highly aqueous region. Addition of water to an organic

stock solution of 1 can result in the precipitation of 1, for-

ming a cloudy solution not suitable for UV/Vis measure-

Figure 3. Nonlinear correlation between the E_T(8) values of betaine

dye 8 and the mol fraction x of 1,4-dioxane for binary water/1,4-

dioxane mixtures

ments. In order to demonstrate the usefulness of the new ous non-ideal behavior of standard dye 1 observed in the

hydrophilic betaine dye 8 for the study of aqueous binaries, same binary solvent mixture.^[86Ϫ92]The deviations found on

the E_T(8) values of a water/1,4-dioxane mixture were deter- addition of polar water to a solution of dye 8 (or 1) in less

mined and are collected in Table 4.

polar 1,4-dioxane can easily be explained by preferential

The graphical illustration in Figure 3 shows that the addi- solvation of the dye molecule by water molecules, producing

tion of small amounts of water to a solution of 8 in 1,4- the observed disproportional hypsochromic CT band shift.

dioxane, and also the addition of a little 1,4-dioxane to an The deviations from linearity found for solutions of dye 8

aqueous solution of 8, produces a disproportionately large in water on addition of 1,4-dioxane are the result of specific

hypsochromic/bathochromic CT band shift.

solute/solvent and solvent/solvent interactions. Presumably,

This S-shape deviation from linearity is typical of prefer- the addition of 1,4-dioxane as a double hydrogen-bond ac-

ential solvation of the solute by one of the two solvent com- ceptor changes the structure of the water through its HBD

ponents and has been widely studied with various solva- and HBA abilities, resulting in a new kind of solvent with

tochromic probes, particularly with betaine dye 1 (for some a different solvation capability for solutes.^[82,91]Using a

leading work on preferential solvation of solvatochromic two-step solvent exchange model, an excellent quantitative

probes in binary solvent mixtures, see refs.^[77Ϫ85]). The description of the E_T(30) behavior of such binary solvent

dashed line in Figure 3 represents the expected behavior for mixtures has been found.^[79,91]With the new hydrophilic be-

an ideal binary solvent mixture without preferential solva- taine dye 8, the study of such aqueous binaries should now

tion. The non-ideal behavior of solutions of dye 8 in water/ be much easier to perform, particularly in water-rich re-

1,4-dioxane mixtures corresponds precisely to the analog- gions.

Eur. J. Org. Chem. 2001, 2343Ϫ2361

2351

C. Reichardt, D. Che, G. Heckenkemper, G. Schäfer

FULL PAPER

4. Halochromism of Betaine Dye 8 in Aqueous Ionophore

Solutions

smaller its charge density and the band shift ∆λ. These hyp-

sochromic band shifts correspond to an increase in the

molar transition energies of 8 by ∆E_Tϭ 0.4 to 1.1 kcal/mol

for 3  salt solutions. Entries 6Ϫ8 in Table 5 show that the

observed genuine halochromism of 8 depends not only on

the charge density of the cation, but also on that of the

anion: Addition of various sodium halides also results in a

hypsochromic band shift of ∆λ ϭ Ϫ4 to Ϫ7 nm, corres-

ponding to ∆E_Tvalues of 0.6 to 1.0 kcal/mol, depending

on the charge density of the anion. Because of the low solu-

bility of sodium fluoride in water [c(NaF) only ca. 0.95 mol/

L for a saturated solution], this salt was excluded from

these measurements.

Are aqueous solutions of ionophores^[39](electrolytes,

salts) more polar than pure water? Is it possible to measure

their polarity empirically by means of solvatochromic probe

dyes? It is well known that not only solvent change, but also

addition of chemically inert ionophores to reaction media,

can influence the course (e.g., rate, yield, stereochemistry,

regioselectivity) and equilibrium position of chemical reac-

tions; this is normally called a salt effect.^[93Ϫ95]The change

in E_T(30) values after addition of ionophores to solutions

of probe dye

1

in organic solvents has been

investigated,^[4,5,18Ϫ28]and termed genuine halochromism.^[40]

The term negative (positive) halochromism was suggested

for a hypsochromic (bathochromic) shift of the UV/Vis ab-

sorption band of a dissolved light-absorbing probe dye on

increasing ionophore concentration, provided that this

band shift is not caused by a drastic change in the molecu-

lar structure of the chromophore.^[40]This definition is in

contrast to the trivial halochromism first described by Ba-

eyer et al.,^[96]when studying salt formation during the reac-

tion between colorless triphenylcarbinol and sulfuric acid,

which produced a yellow solution of a triphenylcarbenium

salt. During this treatment, the molecular structure of the

chromophore is completely changed, whereas the chromo-

phore of a genuine halochromic compound maintains its

molecular structure on addition of ionophores. Further-

more, the genuine halochromism of a solvatochromic probe

dye can be preferentially anion- or cation-dependent.^[97]

In some exploratory measurements, we have studied the

Vis-spectral behavior of aqueous solutions of the new hy-

drophilic betaine dye 8 on addition of alkali metal halides,

urea, and tetramethylammonium chloride (see Table 5). Ac-

cording to Entries 1Ϫ5 in Table 5, addition of alkali metal

chlorides to aqueous solutions of dye 8 always results, with

increasing salt concentration, in small hypsochromic band

shifts. These can be up to ∆λ ϭ Ϫ2 to Ϫ8 nm for a 3 

salt solution, depending on the charge density (ϭ charge/

These results demonstrate that aqueous ionophore solu-

tions behave as media slightly more polar than pure water

towards the solvatochromic probe dye 8. This polarity in-

crease is graphically illustrated by the block diagram given

Figure 4. Graphical representation of the increase in E_T(8) values

on addition of alkali metal chlorides to aqueous solutions of dye

8, depending on the concentration and the charge density of the

alkali cation, with a base plane corresponding to the E_T(8) value

volume) of the alkali cation: The larger the cation, the of pure water (60.4 kcal/mol; cf. Table 5)

Table 5. Long-wavelength CT absorption maxima, λ_maxin nm, of betaine dye 8, measured in nine ionophore/water solutions at 25

°C with four salt concentrations, together with the corresponding E_T(8) values in kcal/mol (in parentheses), calculated according to

Equation (1)

λ_max[E_T(8)]

3 mol

Entry

Ionophore 1 mol

2 mol

Sat. sol.^[a]

∆λ (∆E_T)^[b]

1

2

3

4

5

6

7

8

9

LiCl 470 (60.8)

NaCl 471 (60.7)

467 (61.2)

468 (61.1)

470 (60.8)

471 (60.7)

468 (61.1)

469 (61.0)

479 (59.7)

481 (59.4)

465 (61.5)

466 (61.4)

469 (61.0)

471 (60.7)

466 (61.4)

467 (61.2)

469 (61.0)

481 (59.4)

486 (58.8)

Ϫ^[c]

Ϫ8 (ϩ1.1)

Ϫ7 (ϩ1.0)

Ϫ4 (ϩ0.6)

Ϫ2 (ϩ0.4)

Ϫ7 (ϩ1.0)

Ϫ6 (ϩ0.8)

Ϫ4 (ϩ0.6)

ϩ8 (Ϫ1.0)

ϩ13 (Ϫ1.6)

463 (61.8)

465 (61.5)

468 (61.1)

Ϫ^[c]

KCl

472 (60.6)

RbCl 471 (60.7)

CsCl 472 (60.6)

NaCl 471 (60.7)

NaBr 470 (60.8)

463 (61.8)

Ϫ^[c]

NaI

470 (60.8)

Ϫ^[d]

Urea 477 (59.9)

491 (58.3)

505 (56.6)

10

Me₄N^ϩCl^Ϫ476 (60.1)

[a]

Saturated aqueous solutions: c(LiCl) ഠ 19.3; c(NaCl) ഠ 6.2; c(KCl) ഠ 4.6; c(RbCl) ഠ 7.5; c(CsCl) ഠ 10.7; c(NaBr) ഠ 7.7; c(NaI) ഠ

11.9; c(urea) ഠ 18.2; and c(Me₄N^ϩCl^Ϫ) ഠ 6.0 mol/L. Ϫ

salt) Ϫ E_T(H₂O) ϭ E_T(3  salt) Ϫ 60.4. Ϫ Dye not soluble. Ϫ Not measurable.

∆λ ϭ λ_max(3  salt) Ϫ λ_max(H₂O) ϭ λ_max(3  salt) Ϫ 473; ∆E_Tϭ E_T(3 

[b]

[c]

[d]

2352

Eur. J. Org. Chem. 2001, 2343Ϫ2361

Pyridinium N-Phenolate Betaine Dyes as Empirical Solvent Polarity Indicators

FULL PAPER

in Figure 4, the basal plane of which corresponds to the density) corresponds to the decreasing capability of the ad-

E_T(8) value of 60.4 kcal/mol for plain water. The increase ded salts to act as structure-breakers, which in turn corre-

in E_T(8) with increasing salt concentration and increasing sponds to an increasing activity as structure-makers.^[99]The

charge density of the alkali cation can be seen nicely in better the structure-breaking ability of the ionophore ad-

Figure 4, despite some small irregularities (e.g. RbCl).

ded, the more disoriented mobile water molecules are avail-

In contrast to Entries 1Ϫ8, Entries 9,10 in Table 5 display able for the hydration of betaine dye 8, with an increase in

a small bathochromic band shift of ∆λ ϭ 8Ϫ13 nm, corres- its E_T(8) values and thus of the polarity of the aqueous

ponding to a decrease of ∆E_Tϭ Ϫ1.0 to Ϫ1.6 kcal/mol in ionophore solution as the result.

the molar transition energy, on addition of urea or tetra-

The adverse influence of tetramethylammonium chloride

methylammonium chloride to aqueous solutions of dye 8.

and urea on ∆λ (Entries 9,10 in Table 5) is more difficult to

Such aqueous solutions, as determined by the probe dye 8,

explain. Tetraalkylammonium salts are usually regarded as

possessing structure-making properties; however, for a

seem to be less polar than water. Analogous results have

been obtained by Spange et al. for aqueous urea solutions,

somewhat different reason.^{[99Ϫ102,107,108]}Large tetraal-

with the standard betaine 1:^[98]Addition of urea or N,NЈ-

kylammonium ions with hydrophobic alkyl groups and low

charge densities enhance the tetrahedral structure of water

with its three-dimensional hydrogen-bonded network in the

same way that other hydrophobic solutes do. The increasing

dimethylurea to aqueous solutions of 1 not only resulted in

a similar bathochromic band shift, but also substantially

increased the solubility of dye 1 in water! Addition of urea

(up to 75 cg/g) to an aqueous solution of dye 1 reduced the

degree of waterϪwater hydrogen bonding in the cybotactic

polarity of water [E_T(30) ϭ 63.1 kcal/mol] to E_T(30) ϭ 60.6

region around the nonpolar solute has been termed hydro-

kcal/mol.^[98]

phobic hydration.^[109]This hydrophobic hydration can be

somewhat reduced by the corresponding anions, depending

What is the reason for this genuine halochromism, with no

substantial change of the molecular structure of the betaine

on its size and charge density.^[110]A strengthening of the

chromophore on ionophore addition in water? Because of

three-dimensional water structure by hydrophobic solutes

the high relative permittivity of water (ε_rϭ 78.3), a loose

diminishes the quantity of disordered, more mobile water

molecules necessary for the hydration of dye 8, with the

association or a stronger complex formation between the

betaine dye and the cations (at the phenolate part) or an-

observed small bathochromic band shift as its consequence

ions (at the pyridinium part) of the added salt, as has been

(Entry 10 in Table 5).

found for some organic solvents,^[18Ϫ27]cannot be the reason

Urea changes the water structure so that it suppresses

for the ionophore-induced band shifts in the Vis spectrum

hydrophobic interactions, which results in an increase of the

of dye 8. All these results can be better explained at least

qualitatively by the assumption that some of the added spe-

cies are structure breakers or structure makers with respect

water solubility of hydrocarbons such as benzene; in other

words, urea ‘‘salts in’’ nonpolar compounds.^[107,108]Even

the solubility of standard betaine dye 1 increases substan-

to the intermolecular long-range order characteristic of

tially on addition of urea to its aqueous solution.^[98]This

pure bulk water.^[99Ϫ102]

urea-induced solubility increase may be due to a change in

According to Frank and Wen,^[103,104]the solvation of ions

the water structure,^[107,108]but may also be due to a specific

(cations and anions) in highly ordered solvents such as

hydrogen-bond formation between urea as hydrogen-bond

water gives rise to three different regions in the solvent sur-

rounding the solute ion: a primary hydration shell A, with

profoundly immobilized water molecules, interacting dir-

ectly with the ions through ionϪdipole forces and, at a suf-

donor/acceptor and the solute.^[111]According to Franks et

al.,^[107,108]urea displaces the water equilibrium by des-

troying the long-range order of bulk water towards a liquid

with a short-range order, by resembling water in its ability

ficient distance from the ion, a region C with the normal,

to form hydrogen bonds, but by having the wrong geometry

tetrahedrally ordered structure of undisturbed bulk water;

to take part in the three-dimensional hydrogen-bonded net-

work of water. More recent results show, however, that urea

seems to fit very comfortably into the normal tetrahedral

because of the incompatibility of regions A and C, an inter-

mediate region B, with disoriented, more mobile water mo-

lecules, must exist. The difference in the development of

regions A and B determines whether an ion is structure-

structure of water, not being the strong water structure-

breaker that is usually supposed.^[112]According to Dempsey

making or structure-breaking. Small ions with high charge

et al.,^[111]the increase in the water solubility of suitable sol-

density, such as Li^ϩor F^Ϫ, cause enhanced development of

utes (e.g., 4-hydroxybenzoic acid and its alkyl esters) arising

A at the expense of B and are considered as structure-mak-

from addition of urea as cosolute can alternatively be ex-

ing ions. Large ions with small charge density, such as Cs^ϩ

plained by a 1:1 association between solute and urea, due

or I^Ϫ, are considered as structure-breaking, because in this

mainly to mutual hydrogen bonding with urea as hydrogen-

case the first hydration shell is less well developed.^[99Ϫ102]

bond donor and acceptor.

At high salt concentrations (c Ͼ 5 mol/L), region C can be

abolished and only regions A and B survive, resulting in an

In any case, addition of urea to aqueous solutions of dye

8 seems to reduce the amount of disordered, more mobile

aqueous solvent called ‘‘dihydrogen ether’’.^[105,106]

The decrease in ∆λ on going from Entry 1 to Entry 5 in water molecules necessary for the specific hydration of the

Table 5 (with decreasing cation charge density) and on go- dye molecule, with the observed small bathochromic band

ing from Entry 6 to Entry 8 (with decreasing anion charge shift as its result (Entry 9 in Table 5).

Eur. J. Org. Chem. 2001, 2343Ϫ2361

2353

C. Reichardt, D. Che, G. Heckenkemper, G. Schäfer

Preparation of Betaine Dye 3: See Scheme 2.

FULL PAPER

This qualitative discussion of the genuine halochromism

of betaine dyes such as 8 is certainly oversimplified. For a

sounder, more quantitative discussion, additional system-

atic UV/Vis-spectroscopic measurements are necessary, to

augment the more exploratory data in Table 5. Water-sol-

uble pyridyl-substituted pyridinium N-phenolate betaine

1,3-Bis(pyridin-2-yl)propan-2-one (12): nBuLi (250 mL of a 1.5 

solution in n-hexane, 0.38 mol) was added at Ϫ30 °C under nitro-

gen to a stirred solution of 2-methylpyridine (37.3 g, 40 mL, 0.40

mol) in dry THF (200 mL), over a period of 30 min. The dark red

solution was allowed to warm up to room temp. and stirring was

dyes such as 3Ϫ11 should be ideal candidates for such stud- continued for 1 h. It was cooled to 0 °C, and a solution of (pyridin-

2-yl)acetonitrile (23.6 g, 22 mL, 0.20 mol) in dry THF (50 mL) was

added, with stirring, over 30 min. The reaction mixture was then

heated under reflux for 1.5 h. It was then cooled to 0 °C, and aque-

ous HCl (300 mL of 2  HCl) was added dropwise. The two phases

thus formed were separated. The aqueous phase was neutralized

by addition of aqueous ammonia (15%) and then extracted three

times, each time with 200 mL of dichloromethane. The four organic

phases were combined and the solvent was distilled off in a rotary

evaporator. The remaining liquid was purified by fractional distilla-

tion in vacuo (b.p. 149 °C/0.1 Torr) to afford 15.4 g (35%; ref.^[54,55]

38%) of 12 as a yellow liquid, which crystallized after cooling to 4

ies of the polarity of aqueous solutions of ionophores, iono-

gens, and nonelectrolytes, because their chemical structures

combine features of (zwitter)ionic and nonelectrolyte spe-

cies.

Conclusion

Replacement of some of the peripheral hydrophobic

phenyl groups in the standard betaine dye 1, used as a prim-

ary probe dye for the E_T(30) solvent polarity scale, by more

hydrophilic pyridyl rings results in betaine dyes 3Ϫ11, with

better water solubilities. Thanks to the good linear correla-

tion between the E_T(30) values of 1 and the corresponding

E_Tvalues of dyes 3Ϫ11, particularly with E_T(8) [see Equa-

tion (3)], the new water-soluble probe dyes can be used to

extend the E_T(30) scale to all kinds of aqueous media; for

example, to binary water/solvent mixtures and to aqueous

ionophore solutions as preliminarily shown in this paper,

but also, presumably, to microheterogeneous media such as

aqueous solutions of surfactants, micelles, vesicles, and bi-

layers.

1

°C to give yellow crystals with m.p. 80 °C (ref.^[54,55]81 °C). Ϫ H

NMR (CDCl₃): δ ϭ 3.55 (s, 2 H, CH₂of enol form), 3.93 (s, 4 H,

CH₂of keto form), 5.30 (s, 1 H, CHϭ of enol form), 6.7Ϫ8.5 (m,

pyridyl-H), 15.04 (s, 1 H, OH of enol form). Ϫ ¹³C NMR (CDCl₃):

δ ϭ 45.7 (CH₂of keto form), 51.9 (CH₂of enol form), 95.9 (CHϭ

of enol form), 117.8, 120.6, 121.4, 121.8, 123.5, 124.2, 136.3, 136.4,

136.9, 143.2, 149.2, 149.4, 154.5, 157.9, and 158.0 (pyridyl-C),

168.5 (ϭCOH of enol form), 203.7 (CϭO of keto form).

4-Nitro-2,6-bis(pyridin-2-yl)phenol (13):

A solution of NaOH

(1.60 g, 40.0 mmol) in water (40 mL) was added to a solution of 12

(4.40 g, 20.7 mmol) and sodium nitromalonaldehyde monohydrate

(3.40 g, 21.7 mmol)^[56]in ethanol (30 mL), and the mixture was

stirred at room temp. over a period of 3 d. The red solution was

transferred in a rotary evaporator and about half of the solvent

was distilled off. The remaining solution was neutralized with aque-

ous acetic acid (30%, w/w), and the precipitate formed was filtered

off, washed several times with water, and recrystallized from eth-

anol (300 mL) to afford 5.10 g (81%) of 13 as yellow needles with

m.p. 205 °C. Ϫ ¹H NMR (CD₃SOCD₃): δ ϭ 7.49 (m, 2 H, pyridyl-

Experimental Section

General

Methods:

Melting

points

(not

corrected):

KoflerϪMikroheiztisch (Reichert). ϪElemental analyses: per-

formed with a CHN-Automat Vario EL (Heraeus) at the Analytik-

Servicelabor of the Department of Chemistry, Marburg. Ϫ UV/

Vis spectra: Double-beam UV/Vis/NIR U-3410 spectrophotometer

(Hitachi) with thermostatted 1.00-cm quartz cells SUPRASIL

(Hellma). Ϫ IR spectra: IFS 88 spectrophotometer (Bruker) with

KBr discs. Ϫ ¹H and ¹³C NMR spectra: ARX 200 and AM 300

spectrometers (Bruker), in CDCl₃or CD₃SOCD₃with tetramethyl-

silane as internal standard. Because of low solubility and signal

overlap, not all expected signals can be seen in some ¹³C NMR

spectra. Ϫ Mass spectra: MAT CH-7A spectrometer (Varian) with

electron impact (EI, 70 eV), MAT 711 (Varian) with field desorp-

tion (FD), and HP 5989-B (HewlettϪPackard) with atmospheric

pressure chemical ionization (APCI) technique. Ϫ Analytical TLC:

60F-245 plates with silica gel and fluorescence indicator on alumi-

nium foil (Merck). Ϫ Flash chromatography: Silica gel 60 (Merck),

particle size 0.040Ϫ0.063 mm; carried out according to Still et

al.^[113]Ϫ Solvents: Solvents for the solvatochromic measurements

were used as commercially available in the highest available quality

(analytical or spectroscopic grade) and were additionally dried and

3

5/5Ј-H), 8.02 (m, 2 H, pyridyl-3/3Ј-H), 8.42 (d, J ϭ 8.1 Hz, 2 H,

3

4

pyridyl-4/4Ј-H), 8.71 (dd, 2 H, J ϭ 4.1 and J ϭ 1.8 Hz, pyridyl-

6/6Ј-H), 8.88 (s, 2 H, aromatic phenol-H), 14.31 (s, 1 H, OH). Ϫ ¹³C

NMR (CD₃SOCD₃): 122.9, 123.4, 125.2, 138.1, 147.3, and 154.0

(phenol and pyridyl-C). Ϫ IR (KBr): ν ϭ 3438 (OH) cm^Ϫ1, 1339

˜

(NO₂). Ϫ MS (EI): m/z (%) ϭ 293 (100) [M^ϩ]. Ϫ C₁₆H₁₁N₃O₃· 0.5

C₂H₅OH (293.3 ϩ 23.0 ϭ 316.2): calcd. C 64.55, H 4.46, N 13.26;

found C 64.13, H 4.16, N 13.69.

4-Amino-2,6-bis(pyridin-2-yl)phenol (14): A suspension of a palla-

dium catalyst (10% Pd on charcoal; ca. 200 mg) in a solution of 13

(1.47 g, 5.00 mmol) in methanol (150 mL) was reduced with dihy-

drogen (ca. 380 mL of H₂) at room temp. and normal pressure over

a period of 2 d. The catalyst was filtered off under nitrogen, and

the solvent was distilled off in vacuo to give 14 (1.34 g, ca. 100%)

as a pale brown solid, which turned dark on contact with air. Be-

cause of its sensitivity to oxygen, 14 was immediately transformed

into the pyridinium salt 15 without further characterization.

purified by means of molecular sieves and, if necessary, by filtration 1-[4-Hydroxy-3,5-bis(pyridin-2-yl)phenyl]-2,4,6-triphenylpyridinium

through a column of basic alumina, activity grade I, in order to

remove traces of acids. For these measurements the solvents must

be acid-free. Otherwise, the betaine dyes are (reversibly) protonated

at the phenolate oxygen atom and the long-wavelength CT absorp-

tion band disappears. Solvents for synthetic work were purified ac-

cording to the usual standard methods.^{[31,114Ϫ116]}

Tetrafluoroborate (15): Anhydrous sodium acetate (1.65 g,

20.0 mmol) and 2,4,6-triphenylpyrylium tetrafluoroborate (1.98 g,

5.00 mmol)^[57]were added to a stirred solution of freshly prepared

14 (1.34 g, 5.00 mmol) in dry methanol (40 mL) and the mixture

was heated at reflux with a water bath for 3 h. Water (30 mL) was

added to the hot, dark red solution, resulting in a yellow precipit-

2354

Eur. J. Org. Chem. 2001, 2343Ϫ2361

Pyridinium N-Phenolate Betaine Dyes as Empirical Solvent Polarity Indicators

FULL PAPER

ate. After the reaction mixture had been stirred for ca. 12 h at room formed was filtered off and recrystallized from acetic acid to give

temp., the yellow precipitate formed was filtered off and dried in 17 (4.30 g, 69%) as orange crystals with m.p. 275Ϫ277 °C (ref.^[58]

vacuo to give 15 (2.89 g, 90%) as light yellow, fine crystals with 275Ϫ277 °C).

1

m.p. 171 °C. Ϫ H NMR (CD₃SOCD₃): δ ϭ 7.30Ϫ7.46 (m, 8 H,

6 phenyl-H and 2 pyridyl-5/5Ј-H), 7.54Ϫ7.60 (m, 4 H, phenyl-H),

7.64Ϫ7.74 (m, 3 H, phenyl-H), 7.88Ϫ7.99 (m, 4 H, 2 phenyl-H and

1-[4-Hydroxy-3,5-bis(pyridin-2-yl)phenyl]-2,6-diphenyl-4-(pyridin-4-

yl)pyridinium Tetrafluoroborate (18): According to the procedure

described for 15, freshly prepared 4-aminophenol 14 (1.34 g,

5.00 mmol), the pyrylium salt 17 (2.05 g, 5.00 mmol), and sodium

acetate (1.65 g, 20.00 mmol) in methanol (40 mL) were transformed

into 18, which was recrystallized from water/methanol (1:3) and

dried with P₄O₁₀in vacuo to afford 18 (2.78 g, 82%) as yellow crys-

tals, containing ca. 2 mol of water of crystallization, with m.p. 191

2 phenol-3/3Ј-H), 8.19 (s, 2 H, pyridyl-3/3Ј-H), 8.37 (d, ³J ϭ 8.2 Hz,

2 H, pyridyl-4/4Ј-H), 8.60 (d, ³J ϭ 4.1 Hz, 2 H, pyridyl-6/6Ј-H),

8.71 (s, 2 H pyridinium-3/3Ј-H), 15.89 (s, 1 H, OH). Ϫ ¹³C NMR

(CD₃SOCD₃): δ ϭ 122.3, 123.2, 125.3, 128.4, 129.0, 130.0, 130.2,

130.4, 132.8, 133.5, 133.7, 138.1, 147.7, 154.4, 155.8, 157.0, and

158.2 (aromatic and heteroaromatic C); because of poor resolution,

only 17 signals were observed instead of the expected 20. Ϫ IR

1

°C. Ϫ H NMR (CD₃SOCD₃): δ ϭ 7.38Ϫ7.52 (m, 8 H, 6 phenyl-

H and 2 2-pyridyl-5/5Ј-H), 7.62 (m, 4 H, 2 phenyl-H and 2 2-pyri-

dyl-3/3Ј-H), 7.92Ϫ8.06 (m, 4 H, 2 phenyl-H and 2 2-pyridyl-4/4Ј-

H), 8.23 (s, 2 H, phenol-3/3Ј-H), 8.38 (d, ³J ϭ 4.5 Hz, 2 H, 4-

(KBr): ν ϭ 3446 (OH) cm^Ϫ1, 1083 (BF₄). Ϫ UV (CH₃CN): λ_max

˜

(lg ε) ϭ 303 nm (4.62), 233 (4.57). Ϫ MS (FD): m/z (%) ϭ 554

(100) [M^ϩϪ BF₄]. Ϫ C₃₉H₂₈BF₄N₃O·2H₂O (641.5 ϩ 36.0 ϭ

677.5): calcd. C 69.14, H 4.76, N 6.20; found C 69.29, H 4.52,

N 6.14.

3

pyridyl-3/3Ј-H), 8.64 (d, J ϭ 4.5 Hz, 2 H, 2-pyridyl-6/6Ј-H), 8.89

(s, 2 H, pyridinium-3/3Ј-H), 8.97 (d, 3J ϭ 4.5 Hz, 2 H, 4-pyridyl-

2/2Ј-H), 16.80 (s, 1 H, OH). Ϫ ¹³C NMR (CD₃SOCD₃): δ ϭ 122.0,

122.3, 122.9, 123.0, 126.0, 128.1, 129.6, 129.7, 130.0, 130.1, 133.0,

2,6-Bis(pyridin-2-yl)-4-(2,4,6-triphenylpyridinium-1-yl)phenolate (3):

Sodium methoxide (0.22 g, 4.00 mmol) was added at room temp. 137.8, 140.7, 147.4, 151.0, 153.1, 154.1, 157.3, and 158.1 (aromatic

to a solution of 15 (0.68 g, 1.00 mmol) in dry methanol (30 mL),

and heteroaromatic C). Ϫ IR (KBr): ν˜ ϭ 3429 (OH) cm^Ϫ1, 1093

during which the color of the solution changed from yellow to (BF₄). Ϫ UV (CH₃CN): λ_max(lg ε) ϭ 267 nm (4.62), 240 (4.60). Ϫ

dark. After having been heated under reflux for 5 min, the hot MS (FD): m/z (%) BF₄].

555 (100) [M^ϩ

solution was poured into aqueous NaOH (10% w/w, 100 mL). C₃₈H₂₇BF₄N₄O·2H₂O (642.5 ϩ 36.0 ϭ 678.5): calcd. C 67.27, H

ϭ

Ϫ

After standing for ca. 24 h at room temp., the violet precipitate

formed was filtered off and washed several times with water and

three times with diethyl ether (3 ϫ 50 mL). Purification by twofold

hot extraction, first with 80 mL of boiling water/methanol (1:1) and

then with 80 mL of boiling water/methanol (1:2) gave, after drying

with P₄O₁₀in vacuo, betaine dye 3 (0.51 g, 86%) as red-violet crys-

tals with m.p. 260 °C, still containing ca. 2 mol of water of crystal-

lization. Ϫ ¹H NMR (CD₃SOCD₃): δ ϭ 7.08 (m, 2 H, pyridyl-5/

5Ј-H), 7.36Ϫ7.78 (m,15 H, phenyl-H), 7.90 (s, 2 H, phenolate-3/3Ј-

H), 8.10 (m, 2 H, pyridyl-3/3Ј-H), 8.48 (m, 2 H, pyridyl-4/4Ј-H),

8.57 (s, 2 H, pyridinium-3/3Ј-H), 9.06 (m, 2 H, pyridyl-6/6Ј-H). Ϫ

¹³C NMR (CD₃SOCD₃): δ ϭ 128.2, 128.9, 130.1, and 148.1 (aro-

matic and heteroaromatic C); because of low solubility, only 4 sig-

4.61, N 8.26; found C 67.59, H 4.43, N 8.20.

4-[2,6-Diphenyl-4-(pyridin-4-yl)pyridinium-1-yl]-2,6-bis(pyridin-2-

yl)phenolate (4): According to the procedure described for betaine

dye 3, the pyridinium salt 18 (0.68 g, 1.00 mmol), dissolved in

methanol (30 mL), was transformed into 4 using sodium methoxide

(0.22 g, 4.00 mmol). The product was purified analogously, by two-

fold hot extraction, filtered off, and dried with P₄O₁₀in vacuo to

afford 4 (0.50 g, 86%) as dark green crystals, containing ca. 1.5 mol

of water of crystallization, with m.p. 292 °C. Ϫ ¹H NMR

(CD₃SOCD₃): δ ϭ 7.00 (m, 2 H, 2-pyridyl-5/5Ј-H), 7.32 Ϫ7.58 (m,

12 H, 10 phenyl-H and 2 2-pyridyl-3/3Ј-H), 7.83 (s, 2 H, phenolate-

3

3/3Ј-H), 8.27 (d, J ϭ 4.8 Hz, 2 H, 2-pyridyl-4/4Ј-H), 8.39 (d, J ϭ

4.5 Hz, 2 H, 4-pyridyl-3/3Ј-H), 8.62 (s, 2 H, pyridinium-3/3Ј-H),

˜

nals were observed instead of the expected 20. Ϫ IR (KBr): ν ϭ

3

8.86 (d, J ϭ 4.5 Hz, 2 H, 4-pyridyl-2/2Ј-H), 9.00 (d, J ϭ 8.1 Hz,

2 H, 2-pyridyl-6/6Ј-H). Ϫ ¹³C NMR (CDCl₃): δ ϭ 121.7, 123.9,

127.9, 128.2, 129.0, 129.2, 131.2, 136.8, 137.4, 149.1, and 151.5

(aromatic and heteroaromatic C); because of poor resolution, only

11 signals were observed instead of the expected 19. Ϫ IR (KBr):

3371 (OH) cm^Ϫ1. Ϫ UV/Vis (CH₃CN): λ_max(lg ε) ϭ 574.5 nm

(3.41), 437.5 (4.10), 301 (4.54), 242 (4.52). Ϫ MS (FD): m/z (%) ϭ

554 (100) [M^ϩϩ 1], 553 (94) [M^ϩ]. Ϫ C₃₉H₂₇N₃O·2H₂O (553.7 ϩ

36.0 ϭ 589.7): calcd. C 79.44, H 5.30, N 7.13; found C 79.38, H

5.18, N 7.11.

ν ϭ 3368 (OH) cm^Ϫ1. Ϫ UV/Vis (CH₃CN): λ_max(lg ε) ϭ 612 nm

˜

Preparation of Betaine Dye 4: See Scheme 3.

(3.47), 438 (4.12), 249 (4.63). Ϫ MS (FD): m/z (%) ϭ 555 (100)

[M^ϩϩ 1], 554 (73) [M^ϩ]. Ϫ C₃₈H₂₆N₄O · 1.5 H₂O (554.6 ϩ 27.0 ϭ

581.6): calcd. C 78.47, H 5.03, N 9.63; found C 78.30, H 4.94,

N 9.51.

1,5-Diphenyl-3-(pyridin-4-yl)pentane-1,5-dione (16): Acetophenone

(5.00 g, 41.6 mmol) was added at 0 °C to a well-stirred solution

of sodium hydride (0.15 g, 6.25 mmol) in dry methanol (15 mL),

followed, slowly at 0 to 10 °C, by pyridin-4-carbaldehyde (2.00 g,

21.0 mmol). Water was then added dropwise until a milky suspen-

sion was formed. After further stirring for 4 h at room temp., a

brown viscous oil was beginning to separate from the reaction mix-

ture. After standing for ca. 24 h at 0 °C, the oil had crystallized.

The solid was filtered off and recrystallized from ethanol/water

(9:1) to afford 16 (3.02 g, 44%) as fine, colorless needles with m.p.

124Ϫ126 °C (ref.^[58]125Ϫ126 °C).

Preparation of Betaine Dye 5: See Scheme 4.

4-Phenyl-2,6-bis[(1H)-pyridinium-4-yl]pyrylium Tris(tetrafluorobor-

ate) (19):

A one-necked, round-bottomed 50-mL flask was

equipped with dropping funnel (with pressure equalizer), reflux

condenser (on top of the dropping funnel), and magnetic stirrer. 4-

Acetylpyridine (7.50 g, 62.0 mmol) and freshly distilled benzal-

dehyde (3.30 g, 31.1 mmol) were placed inside, and tetrafluoroboric

acid in diethyl ether (54% w/w, 20 mL, 146 mmol) was added drop-

wise at room temp. to the stirred mixture. The yellow precipitate

2,6-Diphenyl-4-[(1H)-pyridinium-4-yl]pyrylium Bis(tetrafluorobor-

ate) (17): Boron trifluorideϪdiethyl ether (20 mL) was added drop- formed was dissolved by heating the reaction mixture, during which

wise to a stirred solution of 16 (5.00 g, 15.2 mmol) and benzalace-

the diethyl ether was distilled off and collected in the dropping

tophenone (3.30 g, 15.8 mmol) in hot, anhydrous acetic acid (8 mL)

funnel. The remaining stirred mixture was heated to ca. 150 °C for

and the red solution was heated at reflux for 6 h. After cooling to 10 min. After cooling to room temp., the mixture was thoroughly

room temp. and addition of diethyl ether (50 mL), the precipitate digested with diethyl ether. Acetone (15 mL) was then added to the

Eur. J. Org. Chem. 2001, 2343Ϫ2361

2355

C. Reichardt, D. Che, G. Heckenkemper, G. Schäfer

Preparation of Betaine Dye 6: See Scheme 5.

FULL PAPER

remaining solid, and the suspension was stirred for 2 h at room

temp. The solid was filtered off and washed several times with acet-

one. For further purification, a suspension of this solid in hot acet-

one (15 mL) was stirred for 15 min. After cooling to room temp.,

the solid was filtered off and this procedure was repeated to afford,

after drying with P₄O₁₀in vacuo, the pyrylium salt 19 (6.40 g, 36%)

(Pyridin-3-yl)thioacetmorpholide (21):^[60]A mixture of 3-acetylpyr-

idine (228 g, 1.88 mol), morpholine (164 g, 1.88 mol), and sulfur

powder (60 g, 1.88 mol) was heated under reflux for 12 h in a

round-bottomed 1-L flask equipped with reflux condenser. The

warm solution was then poured onto an ice/water slush (ca.

500 mL). The yellow precipitate formed was filtered off and dried

with P₄O₁₀in vacuo to afford 21 (318 g, 76%) as a yellow solid

of m.p. 78 °C (ref.^[60]78Ϫ80 °C), which was used without further

purification in the next reaction step.

1

as yellow, fluorescent crystals with m.p. 236Ϫ247 °C (dec.). Ϫ H

NMR (CF₃CO₂D): δ ϭ 8.17Ϫ8.85 (m, 5 H, phenyl-H), 9.48 (d,

³J ϭ 5.5 Hz, 4 H, 2 pairs of 4-pyridyl-3/3Ј-H), 9.67 (d, ³J ϭ 5.5 Hz,

4 H, 2 pairs of 4-pyridyl-2/2Ј-H), 9.80 (s, 2 H, pyrylium-3/3Ј-H). Ϫ

¹³C NMR (CF₃CO₂D): δ ϭ 111.3 (pyrylium-C-3/3Ј), 115.1 (4-pyri-

dyl-C-3/3Ј), 118.8 (4-phenyl-C-2/2Ј), 122.6 (4-phenyl-C-3/3Ј), 129.1

(4-pyridyl-C-4/4Ј), 143.1 (4-phenyl-C-4), 146.2 (4-pyridyl-C-2/2Ј),

(Pyridin-3-yl)acetic Acid Hydrochloride (22):^[60]A solution of 21

(44.5 g, 200 mmol) and KOH (12.0 g, 214 mmol) in ethanol (95%,

200 mL) was heated at reflux for 72 h in a round-bottomed 500-

mL flask equipped with reflux condenser. The mixture was then

poured into water (400 mL). The volume of the solution was re-

duced to ca. 200 mL by distilling off the solvents in a rotary evapor-

147.8 (4-phenyl-C-1), 168.5 (pyrylium-C-4), 174.8 (pyrylium-C-2/

Ϫ1

˜

2Ј). Ϫ IR (KBr): ν ϭ 1053 cm (BF₄). Ϫ MS (FD): m/z (%) ϭ

312 (100) [M^ϩϪ 3 BF₄Ϫ 2 H^ϩ]. Ϫ C₂₁H₁₇B₃F₁₂N₂O (573.8):

Ϫ

calcd. C 43.96, H 2.99, N 4.88; found C 43.59, H 3.11, N 4.84.

1-[4-Hydroxy-3,5-bis(pyridin-2-yl)phenyl]-4-phenyl-2,6-bis(pyridin- ator (hood!). After further addition of water (200 mL), the solvents

4-yl)pyridinium Tetrafluoroborate (20): Anhydrous sodium acetate were distilled off nearly to dryness in a rotary evaporator. Aqueous

(1.65 g, 20.0 mmol) and the pyrylium salt 19 (2.87 g, 5.00 mmol) HCl (6 , 200 mL) was then added, and the solvents were com-

were added to a stirred solution of freshly prepared 4-aminophenol pletely distilled off in the rotary evaporator. The remaining solid

14 (1.34 g, 5.00 mmol) in dry methanol (40 mL). The mixture was was thoroughly digested three times with ethanol (3 ϫ 200 mL),

heated with a water bath at reflux for 3 h, and a yellow precipitate the ethanolic solution was transferred into a rotary evaporator, and

formed. After the mixture had stood for ca. 12 h at room temp.,

water (40 mL) was added. The precipitate formed was filtered off

the solvent was distilled off to yield the hydrochloride 22 (26.70 g,

77%) as yellow crystals. It was used without further purification in

and thoroughly washed with water and three times with diethyl the next reaction step.

ether (3 ϫ 80 mL), and dried with P₄O₁₀in vacuo to afford 20

Ethyl (Pyridin-3-yl)acetate (23):^[60,61]A solution of hydrochloride

(2.58 g, 78%) as yellow crystals with m.p. 218 °C, containing ca. 1

22 (26.0 g, 150 mmol) in a mixture of concd. sulfuric acid (30 mL)

and anhydrous ethanol (70 mL) was heated at reflux for 4 h in a

round-bottomed 250-mL flask equipped with a reflux condenser.

After cooling to room temp., the reaction mixture was poured onto

ice (ca. 300 g). Concd. aqueous ammonia was then added, until a

pH value of Ͼ 7 was reached. The aqueous solution was extracted

four times with diethyl ether (4 ϫ 300 mL), the collected ethereal

phases were dried with MgSO₄, and the solvent was distilled off in

a rotary evaporator. The remaining liquid was fractionally distilled

to afford 23 (14.9 g, 60%) as a colorless liquid with b.p. 120Ϫ122

°C/10 Torr (ref.^[60]121Ϫ122 °C/10 Torr). The compound partially

mol of water of crystallization. Ϫ ¹H NMR (CD₃SOCD₃): δ ϭ

3

7.36 (m, 2 H, 2-pyridyl-5/5Ј-H), 7.49 (d, J ϭ 4.5 Hz, 4 H, 2 pairs

of 4-pyridyl-3/3Ј-H), 7.58Ϫ7.94 (m, 7 H, phenyl-H and 2 2-pyridyl-

3

3/3Ј-H), 8.17 (s, 2 H, phenol-3/3Ј-H), 8.32 (d, J ϭ 8.2 Hz, 2 H, 2-

pyridyl-4/4Ј-H), 8.53Ϫ8.57 (m, 6 H, 2 2-pyridyl-6/6Ј-H and 2 pairs

of 4-pyridyl-2/2Ј-H), 8.80 (s, 2 H, pyridinium-3/3Ј-H), 15.83 (s, 1

H, OH). Ϫ ¹³C NMR (CD₃SOCD₃): δ ϭ 122.0, 123.2, 123.8, 123.9,

125.4, 128.8, 129.1, 129.4, 129.7, 132.8, 133.0, 137.8, 140.4, 147.4,

149.5, 153.8, 154.2, 156.2, and 158.5 (aromatic and heteroaromatic

C). Ϫ IR (KBr): ν ϭ 3410 (OH) cm^Ϫ1, 1070 (BF₄). Ϫ UV

˜

(CH₃CN): λ_max(lg ε) ϭ 303 nm (4.68), 234 (4.70). Ϫ MS (FD):

m/z (%) ϭ 556 (100) [M^ϩϪ BF₄]. Ϫ C₃₇H₂₆BF₄N₅O · H₂O (643.4

ϩ 18.0 ϭ 661.4): calcd. C 67.19, H 4.27, N 10.59; found C 67.17,

H 4.68, N 10.36.

1

crystallized on standing at ϩ4 °C. Ϫ H NMR (CDCl₃): δ ϭ 1.14

(t, ³J ϭ 7.1 Hz, 3 H, CH₃), 3.50 (s, 2 H, CH₂CO), 4.05 (q, ³J ϭ

7.1 Hz, 2 H, OCH₂), 7.14 (dd, 1 H, pyridyl-5-H), 7.53 (m, 1 H,

pyridyl-4-H), 8.40 (m, 2 H, pyridyl-2-H and 6-H). Ϫ ¹³C NMR

(CDCl₃): δ ϭ 13.8 (CH₃), 38.2 (OϪCH₂), 60.9 (CH₂ϪCO), 123.1,

129.7, 136.5, 148.3, and 150.2 (pyridyl-C), 170.4 (CϭO).

4-[4-Phenyl-2,6-bis(pyridin-4-yl)pyridinium-1-yl]-2,6-bis(pyridin-2-

yl)phenolate (5): In analogy with the procedure described for be-

taine dye 3, the pyridinium salt 20 (0.66 g, 1.00 mmol), dissolved in

methanol (30 mL), was transformed into 5 using sodium methoxide 1,3-Bis(pyridin-3-yl)propan-2-one (24):^[62]The ester 23 (16.5 g,

(0.22 g, 4.00 mmol). The product was purified by hot extraction 100 mmol) was added dropwise at room temp., over a period of

with water/methanol (4:1, 50 mL), filtered off, and dried with P₄O₁₀30 min, to a stirred solution of sodium ethoxide in ethanol, pre-

in vacuo to give 5 (0.33 g, 56%) as black-violet crystals, containing

pared from sodium (2.3 g, 100 mmol) and anhydrous ethanol

(100 mL). The mixture was then stirred for 12 h at 60Ϫ70 °C. After

ca. 2 mol of water of crystallization, with m.p. 237 °C. Ϫ ¹H NMR

(CD₃SOCD₃): δ ϭ 7.00 (m, 2 H, 2-pyridyl-5/5Ј-H), 7.51Ϫ7.72 (m, it had cooled to room temp., concd. aqueous HCl (80 mL) was

9 H, phenyl-H and 2 pairs of 4-pyridyl-3/3Ј-H), 7.85 (s, 2 H, added and the solution was heated under reflux for 3 h. After it

phenolate-3/3Ј-H), 8.31 (m, 2 H, 2-pyridyl-3/3Ј-H), 8.39 (m, 2 H, had cooled to room temp., water (100 mL) was added and the solu-

2-pyridyl-4/4Ј-H), 8.57 (m, 4 H, 2 pairs of 4-pyridyl-2/2Ј-H), 8.65 tion was extracted twice with trichloromethane (2 ϫ 100 mL).

3

(s, 2 H, pyridinium-3/3Ј-H), 8.98 (d, J ϭ 8.1 Hz, 2 H, 2-pyridyl-6/

Aqueous NaOH (10% w/w) was added to the aqueous phase until

6Ј-H). Ϫ ¹³C NMR (CD₃SOCD₃): δ ϭ 118.8, 119.7, 123.0, 123.8, the pH value had reached a value of Ͼ 7 and this solution was

125.8, 126.8, 128.5, 129.2, 129.5, 132.2, 133.4, 134.7, 141.3, 147.8, extracted three times with trichloromethane (3 ϫ 100 mL). The or-

149.2, 154.1, 154.2, 157.2, and 171.6 (aromatic and heteroaromatic

ganic phases were collected and dried with MgSO₄, and the solvent

C). Ϫ IR (KBr): ν˜ ϭ 3377 (OH) cm^Ϫ1. Ϫ UV/Vis (CH₃CN): λ_maxwas distilled off in a rotary evaporator to afford ketone 24 (2.5 g,

(lg ε) ϭ 607 nm (3.73), 438.5 (4.14), 302 (4.62), 240 (4.65). Ϫ MS

23%) as colorless crystals with m.p. 104 °C (ref.^[62]103Ϫ104 °C).

(FD): m/z (%) ϭ 556 (80) [M^ϩϩ 1], 555 (100) [M^ϩ]. Ϫ C₃₇H₂₅N₅O Ϫ H NMR (CDCl₃): δ ϭ 3.82 (s, 4 H, CH₂), 7.25Ϫ7.32 (m, 2 H,

1

· 2H₂O (555.6 ϩ 36.0 ϭ 591.6): calcd. C 75.11, H 4.94, N 11.84;

found C 74.99, H 5.18, N 11.43.

pyridyl-5/5Ј-H), 7.50Ϫ7.55 (m, 2 H, pyridyl-4/4Ј-H), 8.45 (s, 2 H,

pyridyl-2/2Ј-H), 8.55 (d, 3J ϭ 3.8 Hz, 2 H, pyridyl-6/6Ј-H). Ϫ ¹³C

2356

Eur. J. Org. Chem. 2001, 2343Ϫ2361

Pyridinium N-Phenolate Betaine Dyes as Empirical Solvent Polarity Indicators

NMR (CDCl₃): δ ϭ 46.2 (CH₂), 123.5, 129.1, 137.0, 148.7, and to a solution of pyridinium salt 27 (0.66 g, 1.00 mmol) in dry meth-

FULL PAPER

150.4 (pyridyl-C), 203.1 (CϭO).

anol (30 mL). After heating at reflux for 5 min, the hot solution

was poured into aqueous NaOH (10% w/w, 100 mL). The violet

solution was then extracted three times with trichloromethane (3

ϫ 100 mL). The collected organic phases were washed with water

(100 mL) and dried with MgSO₄, and the solvent was distilled off

in a rotary evaporator, to yield, after drying with P₄O₁₀in vacuo,

betaine dye 6 (0.39 g, 71%) as a violet amorphous powder, still

containing some water and trichloromethane, with m.p. 197Ϫ198

°C. Ϫ ¹H NMR (CD₃SOCD₃): δ ϭ 6.93 (s, 2 H, phenolate-3/3Ј-

H), 7.17 (dd, 2 H, 3-pyridyl-5/5Ј-H), 7.39Ϫ7.65 (m, 15 H, phenyl-

4-Nitro-2,6-bis(pyridin-3-yl)phenol (25):

A solution of NaOH

(1.60 g, 40.0 mmol) in water (40 mL) was added to a stirred solu-

tion of ketone 24 (4.40 g, 20.7 mmol) and sodium nitromalonal-

dehyde monohydrate (3.40 g, 21.7 mmol)^[56]in ethanol (30 mL),

and the mixture was stirred at room temp. over a period of 3 d.

The red solution was transferred into a rotary evaporator, the eth-

anol was distilled off, and the remaining solution was neutralized

by addition of aqueous acetic acid (30%, w/w). The yellow precipit-

ate formed was filtered off, washed several times with water, and

purified by hot extraction with ethanol (70 mL), to afford the nitro-

phenol 25 (5.18 g, 85%) as yellow needles with m.p. 238Ϫ239 °C.

3

H), 7.88 (m, 2 H, 3-pyridyl-4/4Ј-H), 8.23 (dd, 2 H, J ϭ 4.7 H and

⁴J ϭ 1.5 Hz, 3-pyridyl-6/6Ј-H), 8.37 (d, ⁴J ϭ 1.9 Hz, 2 H, 3-pyridyl-

2/2Ј-H), 8.55 (s,

2 H, pyridinium-3/3Ј-H). Ϫ

¹³C NMR

1

Ϫ H NMR (CD₃SOCD₃): δ ϭ 7.51Ϫ7.57 (dd, 2 H, pyridyl-5/5Ј-

(CD₃SOCD₃): δ ϭ 122.3, 124.7, 125.3, 128.3, 128.7, 128.9, 129.6,

129.8, 134.6, 135.2, 136.8, 145.7, 149.0, 153.8, 156.9, and 177.9

(aromatic and heteroaromatic C); because of low solubility and in-

sufficient resolution, only 16 signals were observed instead of the

expected 20. Ϫ IR (KBr): ν˜ ϭ 3440 (OH) cm^Ϫ1. Ϫ UV/Vis

(CH₃CN): λ_max(lg ε) ϭ 590 nm (3.56), 416 (3.89), 302 (4.53), 232

(4.52). Ϫ MS (APCI, positive): m/z ϭ 554 [M^ϩϩ 1]. Ϫ C₃₉H₂₇N₃O

· 0.5 H₂O · 0.5 CHCl₃(553.7 ϩ 45.0 ϩ 59.7 ϭ 658.4): calcd. C

72.06, H 4.98, N 6.38; found C 71.92, H 4.71, N 6.18.

H), 8.04 (m, 2 H, pyridyl-4/4Ј-H), 8.18 (s, 2 H, phenol-3/3Ј-H), 8.61

(dd, 2 H, ³J ϭ 4.8 Hz and ⁴J ϭ 1.5 Hz, pyridyl-6/6Ј-H), 8.82 (d,

⁴J ϭ 2.2 Hz, 2 H, pyridyl-2/2Ј-H); the broad OH signal was not

detectable. Ϫ ¹³C NMR (CD₃SOCD₃): δ ϭ 122.8, 125.2, and 136.4

(phenol and pyridyl-C); because of the low solubility, only 3 signals

˜

were observed instead of the expected 9. Ϫ IR (KBr): ν ϭ 3450

(OH) cm^Ϫ1, 1327 (NO₂). Ϫ MS (FD): m/z (%) ϭ 293 (100) [M^ϩ].

Ϫ C₁₆H₁₁N₃O₃(293.3): calcd. C 65.53, H 3. 78, N 14.33; found C

65.24, H 3.70, N 14.35.

Preparation of Betaine Dye 7: See Scheme 6.

4-Amino-2,6-bis(pyridin-3-yl)phenol (26): A suspension of a palla-

dium catalyst (10% Pd on charcoal, ca. 200 mg) in a solution of

25 (1.47 g, 5.00 mmol) in ethanol (75 mL) and trichloromethane

(75 mL) was reduced with dihydrogen (ca. 380 mL H₂) at room

temp. and normal pressure over a period of 2 d. The catalyst was

filtered off under nitrogen, and the solvents were distilled off in

vacuo to give, after drying in vacuo, the aminophenol 26 (1.34 g,

ca. 100%) as a pale brown solid, which turned dark on exposure

to air. Because of its sensitivity to oxygen, 26 was immediately con-

verted into the pyridinium salt 27 without further characterization.

4-Phenyl-2,6-bis[1H-pyridinium-3-yl]pyrylium Tris(tetrafluorobor-

ate) (28):

A one-necked, round-bottomed 50-mL flask was

equipped with dropping funnel (with pressure equalizer), reflux

condenser (on top of the dropping funnel), and magnetic stirrer.

Freshly distilled 3-acetylpyridine (7.50 g, 62.0 mmol) and freshly

distilled benzaldehyde (3.30 g, 31.1 mmol) were placed inside, and

tetrafluoroboric acid in diethyl ether (54% w/w, 20 mL, 146 mmol)

was added dropwise at room temp. to the stirred mixture, giving

rise to a yellow precipitate. The reaction mixture was heated until

the whole of the diethyl ether had distilled off and condensed in the

dropping funnel. The remaining stirred mixture was then heated to

ca. 150 °C for 10 min. After cooling to room temp., the brown

mixture was thoroughly digested several times with diethyl ether.

Acetone (20 mL) was added to the remaining, rubber-like solid and

the suspension was stirred at room temp. for 2 d. The solid was

filtered off and washed several times with acetone. For further puri-

fication, a suspension of this solid in hot acetone (15 mL) was

stirred for 15 min. After cooling to room temp., the solid was fil-

tered off and the procedure with hot acetone was repeated, to af-

ford, after drying with P₄O₁₀in vacuo, pyrylium salt 28 (7.29 g,

41%) as yellow fluorescent crystals, still containing some water,

1-[4-Hydroxy-3,5-bis(pyridin-3-yl)phenyl]-2,4,6-triphenylpyridinium

Tetrafluoroborate (27): Anhydrous sodium acetate (1.65 g,

20.0 mmol) and 2,4,6-triphenylpyrylium tetrafluoroborate (1.98 g,

5.00 mmol)^[57]were added to a stirred solution of freshly prepared

4-aminophenol 26 (1.34 g, 5.00 mmol) in dry methanol (40 mL),

and the mixture was heated with a water bath under reflux for 3 h.

Water (30 mL) was added to the hot, dark red solution, resulting

in a light green precipitate. After the mixture had been stirred for

ca. 12 h at room temp., the precipitate formed was filtered off,

washed once with water and several times with diethyl ether, and

dried with P₄O₁₀in vacuo, to afford 27 monohydrate (2.89 g, 90%)

as light green crystals with m.p. 237Ϫ239 °C. Ϫ ¹H NMR

(CD₃SOCD₃): δ ϭ 7.42Ϫ7.68 (m, 19 H, 15 phenyl-H, 2 phenol-3/

3Ј-H, and 2 3-pyridyl-5/5Ј-H), 8.27 (d, ⁴J ϭ 2.1 Hz, 2 H, 3-pyridyl-

2/2Ј-H), 8.37 (m, 2 H, 3-pyridyl-4/4Ј-H), 8.52 (dd, 2 H, ³J ϭ 4.8 Hz

1

with m.p. 167 °C. Ϫ H NMR (CF₃CO₂D): δ ϭ 7.97 (m, 2 H, 4-

phenyl-m-H), 8.17 (m, 1 H, 4-phenyl-p-H), 8.58 (m, 2 H, 3-pyridyl-

5/5Ј-H), 8.67 (m, 2 H, 4-phenyl-o-H), 9.35 (m, 2 H, 3-pyridyl-6/6Ј-

H, 9.43 (m, 2 H, 3-pyridyl-2/2Ј-H), 9.80 (m, 2 H, 3-pyridyl-4/4Ј-H),

10.15 (s, 2 H, pyrylium-3/3Ј-H). Ϫ ¹³C NMR (CD₃CO₂D): δ ϭ

120.5, 130.3, 132.3, 132.4, 143.7, 146.6, 148.1, and 167.1 (phenyl

and pyridyl-C), 188.4 (pyrylium-C-2); because of low solubility and

insufficient resolution, only 9 signals were observed instead of the

4

and J ϭ 1.6 Hz, 3-pyridyl-6/6Ј-H), 8.73 (s, 2 H, pyridinium-3/3Ј-

H); the broad OH signal was not detectable. Ϫ ¹³C NMR

(CD₃SOCD₃): δ ϭ 123.5, 125.1, 127.5, 128.4, 129.0, 129.9, 130.0,

130.2, 130.7, 132.7, 133.5, 136.6, 148.7, 149.4, 156.8, and 177.9

(aromatic and heteroaromatic C); because of low solubility and in-

sufficient resolution, only 16 signals were observed instead of the

expected 20. Ϫ IR (KBr): ν˜ ϭ 3430 (OH) cm^Ϫ1, 1090 (BF₄). Ϫ UV

(CH₃CN): λ_max(lg ε) ϭ 307 nm (4.58), 226 (4.63). Ϫ MS (APCI,

positive): m/z ϭ 554 [M^ϩ]. Ϫ C₃₉H₂₈BF₄N₃O · H₂O (641.5 ϩ

18.0 ϭ 659.5): calcd. C 71.03, H 4.58, N 6.37; found C 71.23, H

4.79, N 6.40.

expected 12. Ϫ IR (KBr): ν ϭ 3396 (OH) cm^Ϫ1, 1059 (BF₄). Ϫ MS

˜

(FD): m/z (%) BF₄Ϫ 2 HBF₄]. Ϫ

ϭ

311 (100) [M^ϩ

Ϫ

C₂₁H₁₇B₃F₁₂N₂O · 1.5 H₂O (573.8 ϩ 27.0 ϭ 600.8): calcd. C 42.25,

H 3.75, N 4.33; found C 41.98, H 3.36, N 4.66.

1-[4-Hydroxy-3,5-bis(pyridin-3-yl)phenyl]-4-phenyl-2,6-bis(pyridin-

3-yl)pyridinium Tetrafluoroborate (29): Anhydrous sodium acetate

(1.65 g, 20.0 mmol) and the pyrylium salt 28 (3.00 g, 5.00 mmol)

were added to a stirred solution of freshly prepared 4-aminophenol

2,6-Bis(pyridin-3-yl)-4-(2,4,6-triphenylpyridinium-1-yl)phenolate (6):

Sodium methoxide (0.22 g, 4.00 mmol) was added at room temp. 26 (1.34 g, 5.00 mmol) in dry methanol (40 mL). The mixture was

Eur. J. Org. Chem. 2001, 2343Ϫ2361 2357

C. Reichardt, D. Che, G. Heckenkemper, G. Schäfer

FULL PAPER

heated with a water bath under reflux for 3 h. Water (30 mL) was

added to the hot solution, producing a precipitate. After the mix-

(100 mL) and dried with MgSO₄, and the solvent was distilled off

in a rotary evaporator, to afford, after drying the remaining solid

ture had been stirred for ca. 12 h at room temp., the precipitate with P₄O₁₀in vacuo, betaine dye 8 (0.74 g, 67%) as violet amorph-

formed was filtered off, washed once with water and several times ous powder, containing ca. 2 mol of water, with m.p. 213Ϫ215°. Ϫ

with diethyl ether, and dried with P₄O₁₀in vacuo, to afford 29

¹H NMR (CDCl₃): δ ϭ 6.50 (s, 2 H, phenolate 3/3Ј-H), 7.06 (dd,

2 H, 3-pyridyl-5/5Ј-H), 7.30Ϫ7.46 (m, 1O H, phenyl-H), 7.72 (dd,

(2.76 g, 86%) as colorless crystals, still containing some water, with

1

m.p. 192Ϫ194 °C. Ϫ H NMR (CD₃SOCD₃): δ ϭ 7.43Ϫ7.74 (m, 2 H, ³J ϭ 4.5 and ⁴J ϭ 1.6 Hz, 4-pyridyl-3/3Ј-H), 7.89 (d, ⁴J ϭ

11 H, 5 4-phenyl-H, 2 phenol-3/3Ј-H, and 2 pairs of 3-pyridyl-5/5Ј-

1.9 Hz, 2 H, 3-pyridyl-2/2Ј-H), 8.04Ϫ8.16 (m, 4 H, pyridinium-3/

4

H), 7.95 (m, 2 H, 3-pyridyl-4/4Ј-H), 8.32 (d, J ϭ 1.9 Hz, 2 H, 3-

3Ј-H and 3-pyridyl-4/4Ј-H), 8.24 (dd, 2H, ³J ϭ 4.8 and ⁴J ϭ 1.7 Hz,

pyridyl-2/2Ј-H), 8.40 (m, 2 H, 3-pyridyl-4/4Ј-H), 8.55 (dd, 2 H, ³J ϭ 3-pyridyl-6/6Ј-H), 8.86 (dd, 2 H, J ϭ 4.5 and J ϭ 1.6 Hz, 4-pyri-

3

4

4.8 and ⁴J ϭ 1.5 Hz, 3-pyridyl-6/6Ј-H), 8.66 (dd, 2 H, ³J ϭ 4.8 and dyl-2/2Ј-H). Ϫ ¹³C NMR (CDCl₃): δ ϭ 118.5, 121.2, 122.1, 126.3,

⁴J ϭ 1.5 Hz, 3-pyridyl-6/6Ј-H), 8.78 (d, ⁴J ϭ 2.0 Hz, 2 H, 3-pyridyl-

127.3, 127.8, 128.9, 129.3, 130.7, 133.3, 136.1, 136.7, 141.2, 146.3,

2/2Ј-H), 8.91 (s, 2 H, pyridinium-3/3Ј-H); the broad OH signal was 148.8, 151.5, 151.6, 157.4, and 170.2 (aromatic and heteroaromatic

not detectable. Ϫ ¹³C NMR (CD₃SOCD₃): δ ϭ 123.3, 123.6, 126.0, C). Ϫ IR (KBr): ν ϭ 3414 (OH) cm^Ϫ1. Ϫ UV/Vis (CH₃CN): λ_max

˜

128.1, 129.1, 129.6, 132.4, 136.6, 137.5, 148.9, 149.3, 149.7, 151.1,

154.3, and 177.9 (aromatic and heteroaromatic C); because of low

(lg ε) ϭ 629 nm (3.67), 415 (3.93), 386 (3.95), 251 (4.61). Ϫ MS

(APCI, positive): m/z ϭ 555 [M^ϩϩ 1]. Ϫ C₃₈H₂₆N₄O·2H₂O (554.7

solubility and insufficient resolution, only 15 of the expected 21 ϩ 36.0 ϭ 590.7): calcd. C 77.27, H 5.12, N 9.49; found C 77.65, H

signals were observed. Ϫ IR (KBr): ν ϭ 3430 (OH) cm^Ϫ1, 1059 4.71, N 9.54.

˜

(BF₄). Ϫ UV (CH₃CN): λ_max(lg ε) ϭ 309 nm (4.56), 228 (4.60). Ϫ

Preparation of Betaine 9: See Scheme 8.

MS (APCI, positive): m/z ϭ 556 [M^ϩ]. Ϫ C₃₇H₂₆BF₄N₅O₂· H₂O

(643.4 ϩ 18.0 ϭ 661.5): calcd. C 67.19, H 4.27, N 10.59; found C

66.88, H 4.70, N 10.31.

1,3-Bis(pyridin-4-yl)propan-2-one (30): Ethyl (pyridin-4-yl)acetate

(16.5 g, 100 mmol) was added dropwise at room temp. over a

period of 30 min to a stirred sodium ethoxide solution, freshly pre-

pared from sodium (2.3 g, 100 mmol) and anhydrous ethanol

(100 mL). The mixture was stirred for 12 h at 60Ϫ70 °C. After the

mixture had cooled to room temp., concd. aqueous HCl (80 mL)

was added and the mixture was heated under reflux for 3 h. After

the mixture had cooled to room temp., water (100 mL) was added

and the solution was washed twice with trichloromethane (2 ϫ

100 mL). Aqueous NaOH (10% w/w) was then added to the aque-

ous phase until a pH of Ͼ 7 was reached. This solution was now

extracted three times with trichloromethane (3 ϫ 100 mL). The col-

lected organic phases were dried with MgSO₄and the solvent was

distilled off in a rotary evaporator. The remaining brown oil was

purified by flash chromatography ^[113](solvent: ethanol; R_fϭ 0.33),

to afford the ketone 30 (0.2 g, 2%) as brown, waxy solid, still con-

taining some water, with m.p. 65Ϫ67 °C. Ketone 30 was not very

stable; after two weeks of storage under argon at Ϫ18 °C, decom-

position had taken place and the color had changed to red. In

order to obtain sufficient amounts of 30 for the next reaction step,

this preparation procedure was repeated several times. Ϫ ¹H NMR

(CDCl₃): δ ϭ 3.73 (s, 4 H, CH₂), 7.04 (d, ³J ϭ 4.6 Hz, 4 H, 2 pairs

of 4-pyridyl-3/3Ј-H), 8.49 (d, ³J ϭ 4.6 Hz, 4 H, 2 pairs of 4-pyridyl-

2/2Ј-H). Ϫ ¹³C NMR (CDCl₃): δ ϭ 48.4 (CH₂), 124.7, 142.0, and

150.1 (pyridyl-C), 201.7 (CϭO). Ϫ IR (KBr): v ϭ 1712 (CϭO)

cm^Ϫ1. Ϫ MS (EI): m/z (%) ϭ 212 (2) [M^ϩ], 120 (28) [C₅H₄N Ϫ

CH₂Ϫ CO], 93 (100) [C₅H₄N Ϫ CH₃], 92 (52) [C₅H₄N Ϫ CH₂].

Ϫ C₁₃H₁₂N₂O · 0.25 H₂O (212.3 ϩ 4.5 ϭ 216.8): calcd. C 72.04,

H 5.81, N 12.92; found C 72.30, H 5.70, N 12.92.

4-[4-Phenyl-2,6-bis(pyridin-3-yl)pyridinium-1-yl]-2,6-bis(pyridin-3-

yl)phenolate (7): Sodium methoxide (0.22 g, 4.00 mmol) was added

at room temp. to a solution of pyridinium salt 29 (0.66 g,

1.00 mmol) in dry methanol (30 mL). After heating under reflux

for 5 min, the hot solution was poured into aqueous NaOH (10%

w/w, 100 mL). The violet solution was then extracted three times

with trichloromethane (3 ϫ 100 mL). The collected organic phases

were washed with water (100 mL), dried with MgSO₄, and the solv-

ent was distilled off in a rotary evaporator, to afford, after drying

the remaining solid with P₄O₁₀in vacuo, betaine dye 7 (0.38 g, 68%)

as a violet amorphous powder, still containing some water, with

m.p. 198Ϫ200 °C. Ϫ ¹H NMR (CDCl₃): δ ϭ 6.62 (s, 2 H,

phenolate-3/3Ј-H), 7.11 (dd, 2 H, 3-pyridyl-5/5Ј-H), 7.32 (dd, 2 H,

3-pyridyl-5/5Ј-H), 7.60Ϫ7.70 (m, 5 H, phenyl-H), 7.90 (dd, 2 H, 3-

pyridyl-4/4Ј-H), 8.06Ϫ8.10 (m, 4 H, 3-pyridyl-2/2Ј-H or 4/4Ј-H),

3

4

8.20 (s, 2 H, pyridinium-3/3Ј-H), 8.27 (dd, 2 H, J ϭ 4.6 and J ϭ

1.2 Hz, 3-pyridyl-6/6Ј-H), 8.66 (dd, 2 H, ³J ϭ 4.9 and ⁴J ϭ 1.6 Hz,

4

3-pyridyl-6/6Ј-H), 8.78 (d, J ϭ 2.2 Hz, 2 H, 3-pyridyl-2/2Ј-H); as-

signment of the 12 3-pyridyl-H signals to the 2 3-pyridyl rings

either at the pyridinium or at the phenolate ring was not possible.

Ϫ

¹³C NMR (CDCl₃): δ ϭ 122.4, 123.5, 126.2, 127.7, 127.9, 128.0,

129.8, 130.3, 133.1, 135.7, 136.2, 136.8, 146.7, 148.7, 148.9, and

151.7 (aromatic and heteroaromatic C); because of low solubility

and insufficient resolution, only 16 signals were observed instead

of the expected 21. Ϫ IR (KBr): ν ϭ 3430 (OH) cm^Ϫ1. Ϫ UV/Vis

˜

(CH₃CN): λ_max(lg ε) ϭ 605 nm (3.66), 419 (3.89), 381 (3.93), 305

(4.60), 229 (4.59). Ϫ MS (APCI, positive): m/z ϭ 556 [M^ϩϩ 1]. Ϫ

C₃₇H₂₅N₅O · 2.5 H₂O (555.6 ϩ 45.0 ϭ 600.7): calcd. C 73.98, H

5.03, N 11.66; found C 73.87, H 5.51, N 11.24.

4-Nitro-2,6-bis(pyridin-4-yl)phenol (31):

A solution of NaOH

(1.60 g, 40.0 mmol) in water (40 mL) was added to a stirred solu-

tion of ketone 30 (4.40 g, 20.8 mmol) and sodium nitromalonal-

dehyde monohydrate (3.40 g, 21.7 mmol)^[56]in ethanol (30 mL),

Preparation of Betaine Dye 8: See Scheme 7.

4-[2,6-Diphenyl-4-(pyridin-4-yl)pyridinium-1-yl]-2,6-bis(pyridin-3- and the mixture was stirred at room temp. over a period of 3 d,

yl)phenolate (8): Anhydrous sodium acetate (0.66 g, 8.00 mmol) during which time an orange precipitate formed. The ethanol was

and the pyrylium salt 17 (0.97 g, 2.00 mmol) were added to a stirred then distilled off in a rotary evaporator, and the remaining solution

solution of freshly prepared 4-aminophenol 26 (0.54 g, 2.00 mmol) was neutralized by addition of aqueous acetic acid (30%, w/w). The

in dry methanol (15 mL). The mixture was heated with a water orange precipitate was filtered off, washed several times with water,

bath under reflux for 3 h. Sodium methoxide (0.44 g, 8.00 mmol)

was then added, and the dark solution was heated under reflux for

and purified by hot extraction with ethanol (70 mL) to afford the

nitrophenol 31 (5.10 g, 81%) as orange needles, containing ca. 2

5 min and poured into aqueous NaOH (10% w/w, 100 mL). The mol of water, with m.p. 310 °C. Ϫ ¹H NMR (CD₃SOCD₃): δ ϭ

3

violet solution was extracted three times with trichloromethane (3

ϫ 100 mL). The collected organic phases were washed with water

3.44 (s, 1 H, OH), 7.86 (d, J ϭ 6.3 Hz, 4 H, 2 pairs of 4-pyridyl-

3

3/3Ј-H), 8.19 (s, 2 H, phenol-3/3Ј-H), 8.76 (d, J ϭ 6.3 Hz, 4 H, 2

2358

Eur. J. Org. Chem. 2001, 2343Ϫ2361

Pyridinium N-Phenolate Betaine Dyes as Empirical Solvent Polarity Indicators

FULL PAPER

13

pairs of 4-pyridyl-2/2Ј-H). Ϫ C NMR (CD₃SOCD₃): δ ϭ 123.7, 8.74 (s, 2 H, pyridinium-3/3Ј-H); assignment of the 16 4-pyridyl-H

127.1, 147.8, and 148.1 (aromatic and heteroaromatic C); because signals to the 2 pyridyl rings either at the pyridinium or the

of low solubility and insufficient resolution, only 4 of the expected

7 signals were observed. Ϫ IR (KBr): ν˜ ϭ 3386 (OH) cm^Ϫ1, 1332 122.4, 124.0, 148.7, and 149.8 (aromatic and heteroaromatic C);

(NO₂). MS (FD): m/z (%) because of low solubility and insufficient resolution, only 4 of the

293 (100) [M^ϩ].

phenolate ring was not possible. Ϫ ¹³C NMR (CD₃SOCD₃): δ ϭ

Ϫ

ϭ

Ϫ

˜

C₁₆H₁₁N₃O₃·2H₂O (293.3 ϩ 36.0 ϭ 329.3): calcd. C 58.36, N 4.59,

N 12.76; found C 58.79, H 4.66, N 12.64.

expected 17 signals were observed. Ϫ IR (KBr): ν ϭ 3415 (OH)

cm^Ϫ1. Ϫ UV/Vis (CH₃CN): λ_max(lg ε) ϭ 597 nm (3.57), 435 (3.89),

305 (4.35), 234 (4.40). Ϫ MS (APCI, positive): m/z ϭ 555 [M^ϩ],

556 [M^ϩϩ 1]. Ϫ C₃₇H₂₅N₅O · 3.5 H₂O (555.6 ϩ 63.1 ϭ 618.7):

calcd. C 71.83, H 5.21, N 11.32; found C 71.53, H 4.91, N 10.94.

4-Amino-2,6-bis(pyridin-4-yl)phenol (32): A suspension of a palla-

dium catalyst (10% Pd on charcoal, ca. 200 mg) in a solution of

nitrophenol 31 (0.33 g, 1.00 mmol) in methanol (150 mL) was re-

duced with dihydrogen (ca. 80 mL) at room temp. and normal pres-

sure over a period of 2 d. The catalyst was filtered off under nitro-

gen, and the solvent was distilled off in vacuo, to afford, after dry-

ing the remaining solid with P₄O₁₀in vacuo, aminophenol 32

(0.27 g, ca. 100%) as a pale brown solid. Because of its sensitivity

to oxygen, 32 was immediately transformed into 9 without fur-

ther characterization.

Preparation of Betaine Dye 11: See Scheme 10.

4-[2,6-Diphenyl-4-(pyridin-4-yl)pyridinium-1-yl]-2,6-bis(pyridin-4-

yl)phenolate (11): Anhydrous sodium acetate (0.33 g, 4.00 mmol)

and the pyrylium salt 17 (0.48 g, 1.00 mmol) were added to a stirred

solution of freshly prepared 4-aminophenol 32 (0.27 g, 1.00 mmol)

in dry methanol (40 mL), and the mixture was heated under reflux

with a water bath for 3 h. Sodium methoxide (0.22 g, 4.00 mmol)

was then added, the dark solution was heated under reflux for 5

min, and the hot solution was poured into aqueous NaOH (10%,

w/w, 100 mL). After the mixture had been left standing for ca. 24 h,

the precipitate was filtered off, and washed once with water and

three times with diethyl ether (3 ϫ 50 mL). Purification by hot

extraction with water/methanol (3:1, 50 mL) and drying with P₄O₁₀

in vacuo afforded 11 (0.43 g, 78%) as violet crystals, still containing

water of crystallization, with m.p. 350Ϫ352 °C. Ϫ ¹H NMR

(CD₃SOCD₃): δ ϭ 7.05 (s, 2 H, phenolate-3/3Ј-H), 7.40Ϫ7.58 (m,

14 H, 10 phenyl-H and 2 pairs of 4-pyridyl-3/3Ј-H, located at the

phenolate ring), 8.30 (m, 6 H, 2 pairs of 4-pyridyl-2/2Ј-H, located

at the phenolate ring, and 1 pair of 4-pyridyl-3/3Ј-H, located at the

pyridinium ring), 8.70 (s, 2 H, pyridinium-3/3Ј-H), 8.86 (s, 2H, ³J ϭ

6.2 Hz, 1 pair of 4-pyridyl-2/2Ј-H, located at the pyridinium ring).

2,6-Bis(pyridin-4-yl)-4-(2,4,6-triphenylpyridinium-1-yl)phenolate (9):

Anhydrous sodium acetate (0.33 g, 4.00 mmol) and 2,4,6-triphenyl-

pyrylium tetrafluoroborate (0.40 g, 1.00 mmol)^[57]were added to

a stirred solution of freshly prepared 4-aminophenol 32 (0.27 g,

1.00 mmol) in dry methanol (40 mL) and the mixture was heated

under reflux with a water bath for 3 h. Sodium methoxide (0.22 g,

4.00 mmol) was then added, the dark solution was heated under

reflux for 5 min, and the hot solution was poured into aqueous

NaOH (10%, w/w, 100 mL). After standing for ca. 24 h, the dark

red precipitate was filtered off, and washed once with water and

three times with diethyl ether (3 ϫ 50 mL). Purification by hot

extraction with water/methanol (3:1, 50 mL) and drying with P₄O₁₀

in vacuo afforded betaine dye 9 (0.47 g, 85%) as red crystals, con-

taining ca. 3 mol of water of crystallization, with m.p. 220 °C. Ϫ

¹H NMR (CDCl₃): δ ϭ 6.42 (s, 2 H, phenolate-3/3Ј-H), 7.25Ϫ7.67

(m, 15 H, phenyl-H), 7.91 (d, ³J ϭ 5.8 Hz, 4 H, 2 pairs of 4-pyridyl-

3/3Ј-H), 8.13 (s, 2 H, pyridinium-3/3Ј-H), 8.32 (d, ³J ϭ 5.8 Hz, 4

H, 2 pairs of 4-pyridyl-2/2Ј-H). Ϫ ¹³C NMR (CDCl₃): δ ϭ 123.1,

123.2, 128.7, 129.0, 129.2, 148.7, and 148.8 (aromatic and heteroar-

omatic C); because of low solubility and poor resolution, only 7 of

the expected 18 signals were observed. Ϫ IR (KBr): ν˜ ϭ 3430 (OH)

cm^Ϫ1. Ϫ UV/Vis (CH₃CN): λ_max(lg ε) ϭ 571 nm (3.67), 432 (4.16),

Ϫ

¹³C NMR (CD₃SOCD₃): δ ϭ 122.5, 128.4, 129.8, 134.4, 148.3,

148.6, and 151.1 (aromatic and heteroaromatic C); because of low

solubility and insufficient resolution, only 7 of the expected 17 sig-

nals were observed. Ϫ IR (KBr): ν ϭ 3432 (OH) cm^Ϫ1. Ϫ UV/Vis

˜

(CH₃CN): λ_max(lg ε): 603 nm (3.60), 433 (4.07), 250 (4.57). Ϫ MS

(APCI, positive): m/z ϭ 555 [M^ϩϩ 1]. Ϫ C₃₈H₂₆N₄O·3H₂O (554.7

ϩ 54.0 ϭ 608.7): calcd. C 74.98, H 5.30, N 9.20; found C 74.59, H

5.12, N 9.01.

301 (4.62), 239 (4.60). Ϫ MS (APCI, positive): m/z ϭ 554 [M^ϩ

ϩ

1]. Ϫ C₃₉H₂₇N₃O·3H₂O (553.7 ϩ 54.0 ϭ 607.7): calcd. C 75.96, H

5.56, N 6.81; found C 75.66, H 5.06, N 6.79.

Acknowledgments

Financial support of this work by the Deutsche Forschungsgemein-

schaft, Bonn, and the Fonds der Chemischen Industrie, Frankfurt

(Main) is gratefully acknowledged.

Preparation of Betaine Dye 10: See Scheme 9.

4-[4-Phenyl-2,6-bis(pyridin-4-yl)pyridinium-1-yl]-2,6-bis(pyridin-4-

yl)phenolate (10): Anhydrous sodium acetate (0.33 g, 4.00 mmol)

and the pyrylium salt 19 (0.57 g, 1.00 mmol) were added to a stirred

solution of freshly prepared 4-aminophenol 32 (0.27 g, 1.00 mmol)

in dry methanol (40 mL) and the mixture was heated under reflux

with a water bath for 3 h. Sodium methoxide (0.22 g, 4.00 mmol)

was then added, the dark solution was heated under reflux for 5

min, and the hot solution was poured into aqueous NaOH (10%

w/w, 100 mL). After the mixture had been stirred for ca. 24 h at

room temp., the precipitate formed was filtered off, and washed

once with water and three times with diethyl ether (3 ϫ 50 mL).

Purification by hot extraction with water/methanol (3:1, 50 mL)

and drying with P₄O₁₀in vacuo afforded betaine dye 10 (0.46 g,

83%) as violet crystals still containing water of crystallization with

m.p. 344 °C. Ϫ ¹H NMR (CD₃SOCD₃): δ ϭ 7.15 (s, 2 H,

phenolate-3/3Ј-H), 7.52Ϫ7.69 (m, 13 H, 5e phenyl-H and 4 pairs

of 4-pyridyl-3/3Ј-H), 8.16 (d, ³J ϭ 5.8 Hz, 4 H, 2 pairs of 4-pyridyl-

2/2Ј-H), 8.68 (d, ³J ϭ 5.8 Hz, 4 H, 2 pairs of 4-pyridyl-2/2Ј-H),

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Article Doi

Syntheses and UV/Vis-spectroscopic properties of hydrophilic 2-, 3-, and 4-pyridyl-substituted solvatochromic and halochromic pyridinium N-phenolate betaine dyes as new empirical solvent polarity indicators

DOI: 10.1002/1099-0690(200106)2001:12<2343::AID-EJOC2343>3.0.CO;2-I

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