Photoinduced Intramolecular Bifurcate Hydrogen Bond: Unusual

Article pubs.acs.org/joc

Photoinduced Intramolecular Bifurcate Hydrogen Bond: Unusual Mutual Influence of the Components Mark V. Sigalov,*,† Bagrat A. Shainyan,‡ and Irina V. Sterkhova‡ †

Department of Chemistry, Ben-Gurion University of the Negev, 84105 Beer-Sheva, Israel A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Division of Russian Academy of Sciences, 664033 Irkutsk, Russia

‡

S Supporting Information *

ABSTRACT: A series of 7-hydroxy-2-methylidene-2,3-dihydro-1H-inden-1ones with 2-pyrrolyl (3), 4-dimethylaminophenyl (4), 4-nitrophenyl (5), and carboxyl group (6) as substituents at the exocyclic double bond was synthesized in the form of the E-isomers (4−6) or predominantly as the Zisomer (3) which in solution is converted to the E-isomer. The synthesized compounds and their model analogues were studied by NMR spectroscopy, X-ray analysis, and MP2 theoretical calculations. The E-isomers having intramolecular O−H···OC hydrogen bond are converted by UV irradiation to the Z-isomers having bifurcated O−H···O···H−X hydrogen bond. Unexpected shortening (and, thus, strengthening) of the O−H···OC component of the bifurcated hydrogen bond upon the formation of the CO···H−X hydrogen bond was found experimentally, proved theoretically (MP2), and explained by a roundabout interaction of the H-donor (HX) and H-acceptor (CO) via the system of conjugated bonds.

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calculations14 the authors concluded that the addition of strong hydrogen bond acceptor DMSO to ortho-substituted phenols, including, among others, 7-hydroxy-1-indanone, does not break the intramolecular hydrogen bond but results in the formation of bifurcated hydrogen bond. According to X-ray data, 7-hydroxy-1-indanone 1 possesses hydrogen bond O−H···O of moderate strength (the distance H···OC is 2.18 Å15). The 1H NMR spectroscopy data show that the strength of the O−H···O hydrogen bond diminishes in the series 2-hydroxyacetophenone > 2-hydroxybenzaldehyde > 7-hydroxy-1-indanone.16

INTRODUCTION Bifurcated hydrogen bonding has been known for more than 50 years, from its disclosing by X-ray diffraction analysis in 1957,1−3 but the idea of its existence was first formulated much earlier, in 1939.4 The bifurcated hydrogen bond, also known as the three-center hydrogen bond,5 is responsible for biological activity of peptides, proteins, DNA, and other bioactive molecules.6−10 While the existence of bifurcated hydrogen bonds in crystals was unambiguously proved experimentally by different methods, and was studied in detail theoretically in the gas phase, the existence of bifurcated H-bond in liquids was disputable for a long time.11,12 Both IR and NMR spectroscopy methods used for investigation of bifurcated H-bonds in solution suffer from inherent limitations. The advantage of IR spectroscopy is its short characteristic time allowing observation of separate species in fast equilibrium with others, but its flaw is that the conclusions on the H-bonds are usually based on the changes observed for covalent X−H bonds (special measurements in far-IR region are very scarce, see, e.g., ref 13). NMR spectroscopy allows direct observation of the signals of H-bonded protons but, due to much longer characteristic time, without special measurements at low or very low temperatures, gives an averaged spectrum of all species in fast equilibrium. Therefore, the problem of bifurcated hydrogen bonds in solution is still far from being trivial and requires both new objects in which the H-bond donor and acceptor groups are properly oriented and the use of combined experimental and theoretical approach to the analysis of the structure and properties of the components of bifurcated hydrogen bonds. In a recent study based on IR spectroscopy and theoretical © 2017 American Chemical Society

Recently, we have shown that 2-pyrrolylidene derivatives of cycloalkanones including 1-indanone 217 undergo photochemical Z,E-isomerization with the formation of intramolecular hydrogen bond NH···O. It is worth considering the idea of combining the two-centered hydrogen-bonded moieties present in 1 and 2 in one molecule in order to design the system with possible bifurcation on oxygen and to study the mutual influence of the bifurcate bond components.18 Besides, replacement of the pyrrole cycle by other groups capable of forming O···H−X hydrogen bonds extends the series of Received: June 27, 2017 Published: August 10, 2017 9075

DOI: 10.1021/acs.joc.7b01589 J. Org. Chem. 2017, 82, 9075−9086

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The Journal of Organic Chemistry

BBr3.20 Compounds 4−6 were synthesized by acid-catalyzed aldol condensation of 1 with 4-dimethylaminophenylbenzaldehyde, 4-nitrophenylbenzaldehyde, or glyoxylic acid, respectively. It should be noted that all compounds except 3 isolated from reaction mixtures have E-configuration of the exocyclic double bond. Under UV irradiation they undergo photoisomerization to give the corresponding Z-isomers.

investigated compounds and allows to examine the effect of heteroatom X on the propensity to the E,Z-isomerization and on the strength of the intramolecular hydrogen bonds in the Zisomers. This article reports on the study of the series of 7hydroxyindanone derivatives 3−6 (Scheme 1) containing single

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Scheme 1. Studied Compounds

X-RAY ANALYSIS Compounds 6 and 7 form single crystals suitable for X-ray analysis during slow evaporation of CDCl3 from NMR tube. The data obtained confirm the E-configuration of the exocyclic double bond in molecules 6-E and 7-E (Figure 1). Both molecules form dimers by two strong O−H···OC intermolecular hydrogen bonds between the carbonyl groups in 6-E or by N−H···OC hydrogen bonds in 7-E. The intramolecular hydrogen bond O−H···O in molecule 6 (2.137 Å) is notably shorter than in the parent 7-hydroxy-1-indanone (2.18 Å15). Besides, the CO and OH groups in molecule 6 are involved in intermolecular interaction with aromatic protons by reduced contacts of 2.499 and 2.544 Å (Figure S3) forming a parquet structure of compound 6 in the crystal (Figure S4). Note also π-stacking interactions between the methylene protons of one molecule and the benzene ring of another molecule (Figure S5). In the crystal of compound 7, the molecules form a layer structure due to short contacts between the protons of the methoxy group and oxygen atoms of another molecule as well as with the carbon atoms of the third molecule (Figures S7 and S8).

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NMR SPECTROSCOPY Z/E-Isomerism and Photochromic Properties. 1H NMR spectrum of freshly prepared pyrrolyl derivative 3 given in Figure 2a shows two sets of signals corresponding to two isomers in the 5:1 ratio. Most informative are four signals in the low-field region. Two of them, at 8.68 and 13.10 ppm, belong respectively to nonbonded (E-isomer) and hydrogen-bonded (Z-isomer) pyrrolic NH. The downfield shift of NH by 4.62 ppm in the Z-isomer corresponds to a strong intramolecular hydrogen bond. Another pair of signals, at 9.40 and 9.67 ppm, was assigned to the hydrogen-bonded OH in the E- and Zisomers, respectively. The 0.27 ppm downfield shift of the second signal with respect to the first one indicates that the O− H···O hydrogen bond in the Z-isomer is stronger than that in the E-isomer. It should be emphasized that only compound 3 was isolated from reaction mixture with strong predominance of the Z-isomer, whereas others were synthesized as E-isomers converting to Z-isomers only by UV radiation. This difference in isomeric composition was assigned by us to different stability of the corresponding reactive complexes with BBr3 in the stage of demethylation (vide inf ra). Interestingly, the concentration of the Z-isomer of compound 3 rapidly decreases in favor of the E-isomer on standing the solution: after 2 days the initial ratio of 5:1 becomes 1:1.5 (Figure 2a). Similar behavior of the chemical shift of the intramolecularly hydrogen bonded OH is observed for the isomeric pairs 4-Z/4E and 5-Z/5-E. As mentioned above, these compounds were isolated exclusively in the E-configuration. It follows from the values of chemical shifts of olefinic protons (7.55 ppm for 4-E, Figure 3a, and 7.69 ppm for 5-E, Figure 4a).21 Singlets at 9.49 ppm (4-E) and 9.16 ppm (5-E) are assigned to the intramolecularly hydrogen bonded OH protons. The protons

O−H···O hydrogen bonds (E-isomers) and O−H···O···H−X bifurcate hydrogen bonds (Z-isomers). Comparison between the E- and Z-isomers allows evaluating the influence of the second component of the bifurcated bond on the strength of the first one (O−H···O). We believe this comparison to be correct and justified due to equal electronic effects of the substituent at C-2 in the E- and Z-isomers. Besides, we studied the model O-methylated compound 7 (Scheme 1), for the sake of comparison with Z-isomer of 3, which allows to estimate the similar influence of O−H···O bond on the second component of bifurcate bond (O···H−N). The study was carried out using NMR spectroscopy supported by quantum mechanical calculations.

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SYNTHESIS An attempt to synthesize compound 3 from 7-hydroxy-1indanone 1 under the conditions of basic catalysis similar to those used by us earlier16 failed. In the presence of KOH, compound 1 did not enter the reaction of condensation with 1H-pyrrole-2-carbaldehyde but, instead, gives the salt, potassium 3-oxo-2,3-dihydro-1H-inden-4-olate.19 Therefore, target compound 3 was obtained from 7-methoxy-1-indanone by condensation with 1H-pyrrole-2-carbaldehyde under basic conditions giving the model compound 7 with subsequent removal of the protecting methyl group by the reaction with 9076


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Figure 1. Molecular structure of compounds 6 and 7.

chemical shifts of the olefinic proton (6.82 and 6.58 ppm, respectively) and by the values of the allylic s-trans and s-cis spin−spin coupling constants 4J between CH and CH2 protons (2.3 and 1.8 Hz, respectively for the E- and Zisomers22). However, unlike to previous cases, isomeric pair 6Z/6-E shows quite different behavior of O−H···O hydrogen bond: the OH signal in Z-isomer is shifted by 0.21 ppm to high field relative to its E-counterpart. At first glance, it indicates the presence of a weaker hydrogen bond. The signals of carboxyl protons of 6-Z and 6-E are not visible in 1H NMR spectra, neither at room temperature nor by cooling the sample. It is known that observation of even strong hydrogen bonds with participation of COOH group like carboxylic acid−carboxylate anion requires careful elimination of residual water from the solvent.23 Otherwise, due to fast exchange, the signal of the carboxyl proton is not observable. As the consequence of such an exchange, one can expect weakening of the intramolecular hydrogen bond CO··· HOOC and distortion of its equilibrium geometry. We assume that it is this distortion that is responsible for the observed high-field displacement of the OH signal in the 6-Z isomer. Similar to compounds 3−6, compound 7 also reveals photochromic properties. As mentioned above, it was used as the starting compound for the synthesis of 3 and exists in the Econfiguration (Figure 6a). Under UV irradiation within 1 h it transforms to the Z-isomer (Figure 6b). Comparison of the chemical shift of the intramolecularly bonded NH in 7-Z (13.23 ppm) with that in 3-Z (13.10 ppm) allows to conclude that the presence of the O−H···OC component of the bifurcated hydrogen bond weakens the second component, N−H···OC. It is worth noting an upfield

of the 4-dimethylaminophenyl ring of 4-E form two multiplets of the AA’BB’ spin system at 7.63 (H-2′,6′) and 6.80 (H-3′,5′) ppm, (Figure 3a). The protons of the 4-nitrophenyl ring form a similar spin system at 7.89 (H-2′,6′) and 8.34 (H-3′,5′) ppm. UV irradiation of their CD2Cl2 solutions results in appearance of new subspectra corresponding to the Z-isomers (Figures 3b and 4b). In both cases, in accordance with the Z-isomeric structure, the olefinic signal appears in a higher field (6.98 and 7.15 ppm, respectively). New multiplets of H-2′,6′ appear at 8.23 and 8.15 ppm for 4-Z and 5-Z, respectively, and new OH singlets are at 9.96 and 9.43 ppm, respectively. It should be noted that during 2-h irradiation only 10% of 4-E was converted to the Z-isomer, whereas the conversion of 5-E was much faster and concentration of 5-Z reached 40% after 1 h irradiation. Low-field shift of H-2′,6′ in the Z-isomers relatively those in the E-isomers is due to their location near carbonyl oxygen and can be indicative of a weak C−H···O hydrogen bond. The atoms-in-molecules (AIM) calculations (vide inf ra) prove this assumption. Interestingly, the changes of chemical shift of H-2′,6′ after E- to Z-isomerization are quite different for 4 and 5 and amount to 0.60 and 0.26 ppm, respectively. As follows from the results of geometry optimization (see next section), it is a consequence of different dihedral angles between the planes of the aromatic and the indanone rings. Similar to the previous case, the low-filed shift of OH proton by 0.27 ppm indicates strengthening of the intramolecular hydrogen bond O−H···O in the Z-isomer. Compound 6 derived from glyoxylic acid, similar to aryl derivatives 4 and 5, was isolated exclusively in the Econfiguration (Figure 5a) which transforms to the Z-isomer under UV irradiation (Figure 5b). This is proved by relative 9077


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Figure 2. 1H NMR spectra of 3 in CDCl3: (a) fresh prepared solution; (b) after standing over 2 days.

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THEORETICAL CALCULATIONS Full geometry optimization for molecules 3−7 was performed by DFT (B3LYP, M062X) and MP2 methods. The analysis of the calculated geometry in conjunction with experimental NMR data (see below) allows to conclude that the best agreement was found with MP2/6-311G+(d,p),24 so, only the data obtained at this level will be used for consideration. However, it should be noted than even this method tends to overestimate the strength of the intramolecular hydrogen bond O−H···OC. In addition to structures 3−7 in Scheme 1, we have calculated 1-hydroxy-8-(1H-pyrrol-2-yl)-9H-fluoren-9-one 8, 1(4-dimethylaminophenyl)- and 1-(4-nitrophenyl)-8-hydroxy9H-fluoren-9-ones 9, 10 and 8-hydroxy-9-oxo-9H-fluorene-1carboxylic acid 11 as model structures simulating fixed Zconfiguration of the H-bond donor and acceptor components (Scheme 2). The results of calculations for compounds 3−6 are summarized in Tables 2 and 3. Among all studied compounds only for pyrrolylidene derivatives 3 and 7 the calculated total energies of the Z-isomers are lower than those of their Ecounterparts, whereas for the rest of compounds the E-form is energetically favorable (Table 2). In the case of compound 7, a lower energy of the E-isomer clearly indicates that a higher stability of the Z-isomers of compounds 4−6 is due to intramolecular O···H−X hydrogen bond as a component of bifurcated O−H···O···H−X hydrogen bond (X = O, C). The predominance of the Z-isomer of compound 3, apparently,

shift of the NH proton of 7-E by 0.23 ppm in the irradiated sample. According to X-ray data (see above) this compound forms hydrogen-bonded dimers in solid state. In line with the suggestion made by us earlier,17 these dimers can be assumed to retain their structure in solution, resulting in a low-field shift of the NH proton with respect to that of the monomer due to the influence of the carbonyl oxygen of the second molecule. The formation of the Z-isomer under irradiation decreases the concentration of the E-isomer and, hence, of its dimer that, in turn, leads to a high-field shift of the NH-proton. Solvent Effect on Bifurcated Hydrogen Bonding. In polar aprotic solvents like DMSO, compounds with an intramolecular hydrogen bond may form solvates in which the intramolecular hydrogen bond is weakened by intermolecular hydrogen bonding. The extent of the weakening is inversely proportional to the initial strength of this bond. With this in mind, we measured 1H NMR spectra of 3−6 in DMSOd6 with and without UV irradiation; chemical shifts of OH and XH protons in the E- and Z-isomers are given in Table 1. The variation of 1H NMR chemical shifts is different within the series, but there is obvious tendency that the values of ΔδOH for the E-isomers are larger than those for their Zcounterparts. This is in agreement with the calculated strength of the O−H···O hydrogen bonds (vide inf ra, Table 3) as well as with the above conclusion that the formation of the X−H···O component of the bifurcated bond may lead to strengthening of its O−H···O component. 9078


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Figure 3. 1H NMR spectra of 4 in CD2Cl2: (a) without irradiation; (b) after 2 h irradiation.


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are closely related to the phenomenon. When steric hindrances are outweighed by strong intramolecular hydrogen bonding, like in the Z-isomers of compounds 3 and 7, the latter isomers predominate. As to the glyoxylic acid derivative 6, in spite of existence of a strong intramolecular hydrogen bond OH···O C in the Z-isomer, the E-configuration is stabilized in the crystal by two intermolecular hydrogen bonds OH···OC, which remain sufficiently strong in solution. The E-isomers of molecules 3−6 are less strained than the Z-isomers and, therefore, should be more stable unless it is outweighed by stabilization of the latter by intramolecular hydrogen bonding as apparently is the case for compound 3 having strong NH··· OC hydrogen bond in the Z-isomer. It is worth noting that the above considerations refer only to isolated molecules whereas in solution the ratio of the isomers may change due to solvent effects. In the case of compound 3 this was proved experimentally by rapid conversion of 3-Z to 3-E in solution (vide supra). In the Z-isomer of 6, the intramolecular OC− OH···O hydrogen bond is also rather strong, but the dimeric structure formed by two intermolecular H-bonds connecting the carboxyl groups of the E-isomer is energetically more favorable. Note that the formation of a similar dimer for the Zisomer is impossible. Besides, the additional slight stabilization of 6-E comes from interactions of the carboxyl oxygen with two methylene protons of the ring. The analysis of the data in Tables 1 and 2 reveals a remarkable shortening of the O−H···OC hydrogen bond in going from the E to Z-isomers, that is, strengthening of one component of a bifurcated hydrogen bond upon the formation of its second component. The literature contains plenty of examples so-called “cooperativity” in regular and bifurcated hydrogen bonds. However, cooperative effect increases the

derives from the method of its synthesis. Unlike other products, compound 3 could not be obtained by direct aldol condensation and was prepared by demethylation with BBr3 (vide supra) via complex with BBr2, which is the product of elimination of methyl bromide and the precursor of compound 3. Calculation for such complexes for the Z- and E-isomers (3Z-BBr2 and 3-E-BBr2, Table 2) shows that the preferability of 3-Z-BBr2 over 3-E-BBr2 increases with respect to that of 3-Z over 3-E from 4.5 to 5.9 kcal/mol. Moreover, the extent of the roundabout conjugation in 3Z-BBr2 is higher as follows from the values of Δ(1−2) in Table 2. We believe that both factors are responsible for the predominance of 3-Z-BBr2 which is retained on the stage of hydrolytic decomposition of the complex.

Note that the product of aldol condensation of 2pyrrolylaldehyde with 1-indanone, which is a close analogue of compound 3, was isolated exclusively as the E-isomer in spite of its calculated lower stability.17 This was explained by the formation of dimers consisting of molecules in the Econfiguration connected by two intermolecular hydrogen bonds. Compound 7 forms similar dimers (Figure 1). This is in agreement with earlier observations21 that steric hindrances between the carbonyl oxygen and the aryl ring hydrogens prevent the formation of the Z-isomers of arylidene chalcones including indanone derivatives. In our case, compounds 4 and 5 9080


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Obviously, this is not the case in compounds considered here. The observed effect of such a “positive cooperativity” is in apparent contradiction with the classically accepted antibate dependence of the length and strength of the forming and breaking bonds in chemical reactions and is indicative of existence of an additional channel of interaction between the hydrogen bond donor and acceptor groups in the molecule leading finally to the resonance structure illustrated in Figure 7 in brackets. Formation of H-bond with pyrrolic NH in the Z-isomer results in lengthening of the N−H bond by 0.018 Å and should increase the electron density on nitrogen. However, the charge on the nitrogen atom remains practically the same and the total charge on the NH group even decreases by 0.027e. A notable increase of conjugation of the pyrrole ring with the indanone moiety in the Z-isomer is witnessed by analysis of bond lengths in the (N)C−CC−C(O) motif (Table 1), which points to

Table 1. Solvent Effect on Chemical Shifts of HydrogenBonded Protons in Molecules 3−6 δOH

a

ΔδOH

entry

CDCl3

DMSO

3-E 3-Z 4-E 4-Z 5-E 5-Z 6-E 6-Za

9.34 9.68 9.53 9.96 9.16 9.43 8.94

9.93 10.07 9.94 10.01 10.37 10.15 10.53

0.59 0.39 0.39 0.05 1.21 0.72 1.59

δXH

ΔδXH

CDCl3

DMSO

8.69 13.10 7.64 8.22 7.88 8.15

11.54 12.99 7.62 8.24 8.06 8.20

2.85 −0.11 −0.02 0.02 0.18 0.05

Not measured due to very broad OH-signals.

donor strength of a hydrogen bond donor if the latter is simultaneously the acceptor for a second hydrogen bond.26

Scheme 2. 1-Hydroxy-8-(1H-pyrrol-2-yl)-9H-fluoren-9-one 8, 1-(4-Dimethylaminophenyl)-8-hydroxy-9H-fluoren-9-ones 9, 1(4-Nitrophenyl)-8-hydroxy-9H-fluoren-9-ones 10, and 8-Hydroxy-9-oxo-9H-fluorene-1-carboxylic Acid 11

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Table 2. Selected Bond Lengths (Å), Total (a.u.), Dihedral Angle θ between the Aromatic and the Indanone or Fluorenone Ring (deg), and Relative (kcal/mol) Energies of Compounds 3−11

entry

O−H···O 1.959 2.009

3-Z 3-E 3-Z-BBr2 3-E-BBr2

1.812 O−H···O 1.938 2.003 O−H···O 1.976 2.029 O−H···O 2.020 2.041 O−H···O

4-Z 4-E 5-Z 5-E 6-Z 6-E 7-Z 7-E 8

O−H···O 2.029

9 10

2.050 2.073

11

2.089

1

2

3

Δ(1−2)

θ

E (total)

ΔE

1.468 1.484 1.427 1.441

1.373 1.359 1.382 1.368

1.426 1.435 1.414 1.422

0.095 0.125 0.045 0.073

2.0 0 2.0 1.0

−743.4080 −743.4008 −5912.7142 −5912.7048

0 4.5 0 5.9

1.487 1.490

1.365 1.357

1.456 1.455

0.122 0.133

21.6 21.0

−898.9752 −898.9811

3.7 0

1.499 1.498

1.357 1.356

1.469 1.459

0.142 0.142

42.9 27.0

−969.4785 −969.4830

2.8 0

1.494 1.505

1.356 1.349

1.504 1.478

0.138 0.156

4.4 1.0

−723.1469 −723.1530

3.8 0

1.479 1.495

1.372 1.357

1.428 1.437

0.107 0.138

0 6.3

−728.5725 −728.5655

0 4.4

1.495

1.418

1.454

0.077

∼0

−857.4438

1.502 1.502

1.403 1.401

1.475 1.479

0.099 0.101

53.1 56.1

−1013.0208 −1083.5255

1.497

1.409

1.522

0.088

0

−834.5029

N−H···O 1.761

C2−H···O 2.146 C2−H···O 2.463 (OC)O−H···O 1.656 N−H···O 1.744 N−H···O 1.758 C2−H···O 2.793 2.819 O−H···O 1.664

C3 double bond of the pyrrole ring are s-trans to each other, while in the E-isomer they are s-cis (Figure 7). The s-trans conjugation is known to be more efficient than s-cis. Similarly, in isomer 4-Z, the formation of the CAr−H···OC hydrogen bond increases the electron density on the Me2NC6H4 moiety and enhances direct polar conjugation with the carbonyl group. In isomer 5-Z, additional electronic density appearing on the aromatic ring due to the CAr−H···OC hydrogen bond formation, reduces the electron-withdrawing effect of the nitro group and makes the carbonyl group more polar, thus strengthening the O−H···OC hydrogen bond (Figure 8).

Table 3. 1H NMR Chemical Shifts of 7-OH and AIM Parameters of O−H···OC Hydrogen Bond entry

δ (OHexp)

3-Z 3-E 4-Z 4-E 5-Z 5-E 6-Z 6-E

9.67 9.40 9.96 9.49 9.43 9.16 8.71 8.92

Δδ 0.27 0.44 0.27 −0.21

ρ(rc)BCP × 102

∇2ρ(rc) × 102

EHBa

2.623 2.345 2.759 2.375 2.532 2.242 2.272 2.184

−2.188 −1.945 −2.266 −1.971 −2.105 −1.875 −1.946 −1.832

3.7 3.1 3.9 3.2 3.5 3.0 3.1 2.9

a

The energy of intramolecular hydrogen bonds was estimated using modified Espinoza equation.25

Figure 8. Oppositely directed conjugation in the Z-isomers of 7hydroxy-2-[(4-dimethylaminophenyl)methylidene]-2,3-dihydro-1Hinden-1-one 4 and 7-hydroxy-2-[(4-nitrophenyl)methylidene]-2,3dihydro-1H-inden-1-one 5.

Figure 7. Conjugation in the E- and Z-isomers of 7-hydroxy-2-(1Hpyrrol-2-ylmethylidene)-2,3-dihydro-1H-inden-1-one 3 [tautomeric 2(2H-pyrrol-2-ylidenemethyl)-1H-indene-3,4-diol in brackets].

These effects are responsible for larger downfield shift of the hydroxyl signal in 4-Z relative to that in 5-Z. In (7-hydroxy-1oxo-1,3-dihydro-2H-inden-2-ylidene)ethanoic acid 6, additional electronic density goes mainly to the second oxygen atom of the carboxyl group and only slightly affects the basicity of the carbonyl oxygen.

elongation of the double bond and shortening of ordinary bonds. More strong conjugation favors the electron density transfer from the pyrrole ring to the carbonyl oxygen thus strengthening the O−H···OC hydrogen bond. Additionally, in the Z-isomer, the exocyclic CC double bond and the C2 9082


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broken. In distinction, in molecules 8 and 11 the N−H···O or O−H···O hydrogen bond are stronger than in 9, 10 and very close to those in their analogues 3-Z and 6-Z, although the O− H···O hydrogen bond with the phenolic hydroxyl are by 0.07 Å longer and, hence, weaker than in 9, 10. As a result, molecules 8 and 11 are planar. In order to understand the behavior of the studied compounds in DMSO solution, we calculated the 1:1 complexes of DMSO with the E- and Z-isomers of compounds 3 and 6 (PCM-SM model, DMSO as the solvent). For compound 3, the combined effect of specific and nonspecific solvation decreases the energy difference almost twice, from 4.5 kcal/mol in 3 to 2.3 kcal/mol in 3·DMSO, also in favor of 3-Z. Complex 3-Z·DMSO is slightly distorted from planarity except O−H bond which forms the angle of ca. 40° with the aromatic ring. The intramolecular O−H···OC component of the bifurcated hydrogen bond is elongated from 1.959 Å in free molecule to 2.609 Å in the complex, that is, broken by the solvent, which forms very strong intermolecular H-bond O− H···OS (1.681 Å) and two weak hydrogen bonds between the methyl hydrogens and the CO group of molecule 3 (Figure 10a). The N−H···O hydrogen bond is only slightly elongated upon solvation, from 1.761 to1.782 Å. In complex 3-E·DMSO, the O−H bond is out-of-plane by ∼40° and, as in 3-Z·DMSO, the O−H···OC intramolecular component of the bifurcated hydrogen bond is strongly weakened by solvation, from 2.009 Å in free molecule to 2.634 Å in the complex. Solvate complex 3-E·DMSO is somewhat stronger than 3-Z·DMSO, as follows from comparison of the intermolecular hydrogen bonds between DMSO and the corresponding isomers of the solute (Figure 10). Although both in 3-Z·DMSO and 3-E·DMSO the intramolecular hydrogen bonds O−H···OC are very weak, the formation of intramolecular N−H···O bond in 3-Z·DMSO, as in the isolated molecule, shortens and, thus, strengthens the second component of the bifurcate hydrogen bond (2.609 Å vs 2.634 Å, Figure 10). In complexes 6·DMSO, as in 3·DMSO, the O−H bond forms the angle of ∼40° with the aromatic ring. Complex 6-Z· DMSO lies 2.7 kcal/mol lower in energy than 6-E·DMSO. Comparison of the structure of the 3-E·DMSO and 6-E·DMSO complexes in Figures 10 and 11 shows that the latter is more strongly bound with DMSO and, as a result, has a weaker

The efficacy of conjugation in 3-Z isomer as shown in Figure 7 was proven by turning off the conjugation between the pyrrole ring and the carbonyl group using saturated analogues of 3, the H-bonded and nonbonded conformers of compound 12. While in 3-Z the formation of the N−H···OC hydrogen bond leads to shortening of the O−H···OC hydrogen bond by 0.050 Å, the same transition from the H-nonbonded (or having a very weak H-bond with the C−H hydrogen atom) to the H-bonded conformer of 12 leads to its elongation by 0.009 Å (Figure 9).

Figure 9. H-Bonded and H-nonbonded conformers of 7-hydroxy-2(1H-pyrrol-2-ylmethyl)-2,3-dihydro-1H-inden-1-one 12.

The above analysis draws to the conclusion that the strength of the O−H···OC hydrogen bond in compounds 3−6 decreases in the order 4 > 3 > 5 > 6. This sequence is in good agreement with the measured chemical shifts of the hydroxyl group and the calculated hydrogen bond energies, which decrease in the same order (Table 3). The comparison of experimental NMR data and optimized geometries of 3 and 7 shows that NH proton in 7 is deshielded by 0.23 ppm relative to that in 3 and the bond N−H···OC is slightly shortened (1.744 Å vs 1.761 Å, Table 4). In molecules 9 and 10, the planes of the aryl and the fluorenone rings form the dihedral angle θ of 51° and 56°, respectively, arising from repulsion of the ortho hydrogens in the biphenyl motif in these molecules. A larger dihedral angle in molecule 10 is consistent with the aforementioned weaker hydrogen bond in its analogue, molecule 5 as compared to 4. In molecules 4 and 5, this dihedral angle is much smaller, 21° and 42°, respectively, most likely, due to smaller steric hindrances between the olefinic and the ortho hydrogens. Because of large dihedral angles, the C2−H···O distance increases to 2.793 and 2.840 Å and the hydrogen bond in molecules 9 and 10 is

Table 4. 1H NMR Chemical Shifts of XH and AIM Parameters of X−H···OC Hydrogen Bond

a

entry

δ (XHexp)

Δδ

r (X−H···O)

ρ(rc)BCP × 102

∇2ρ(rc) × 102

EHBa

3-Z 3-E 4-Z 4-E 5-Z 5-E 6-Z 6-E 7-Z 7-E 8 9 10 11

13.10 8.68 8.20 7.62 8.14 7.88

4.42

1.761

4.037

−3.329

6.5

0.58

2.146

1.953

−1.779

2.4

0.26

2.463

1.326

−1.125

1.6

1.656

5.021

−3.726

9.0

4.034 0.959

−3.390 −0.84

6.9 1.1

1.956

−1.671

2.7

13.33 8.89

4.44

1.744 1.758

See footnote to Table 3. 9083


Article


Figure 10. Optimized structure of 3-Z·DMSO (a) and 3-E·DMSO (b) complexes.

Figure 11. Optimized structure of 6-Z·DMSO (a) and 6-E·DMSO (b) complexes.

intramolecular hydrogen bond O−H···OC. Due to strong solvation, the length of the intramolecular hydrogen bond O− H···OC is only slightly less than the sum of the van-derWaals radii (2.7 Å). As clearly seen in Figure 11, the formation of intramolecular COOH···O bond in 6-Z·DMSO, shortens and, hence, strengthens the second component of the bifurcate hydrogen bond (2.606 Å vs 2.652 Å), as is the case in the isolated molecules.

and 5, and from a high-field shift of the olefinic proton in all studied compounds. • The relative stability of the Z- and E-isomers in gas phase is determined by the balance between the strain energy and the hydrogen bonding energy, while in solution the formation of associates may interfere and shift the equilibrium toward the E-isomers. • An unexpected strengthening of the O−H···OC component of the hydrogen bond with bifurcation on the carbonyl oxygen atom upon the formation of its C O···H−X component was demonstrated experimentally by downfield shift of the 7-OH signal of the Z-isomers relative to E-isomers. Theoretical MP2 analysis allowed to explain a remarkable strengthening of one component of the bifurcated hydrogen bond upon the formation of the second component by the presence of a roundabout way of interaction of the H-donor and H-acceptor parts of the molecule via the system of conjugated bonds including the π-system of the substituent, exocyclic C C bond and the carbonyl group. Indeed, for compounds 3 and 6 having strong intramolecular NH···OC or COOH···OC hydrogen bonds, calculations revealed much more pronounced equalization of the single and double bonds in the enone motif −CHC−CO in the Z-isomers than in compounds 4 and 5 (see Δ(1−2), Table 2).

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CONCLUSION To summarize, the following conclusions can be drawn: • A series of 7-hydroxy-2-methylidene-2,3-dihydro-1Hinden-1-ones having the 2-pyrrolyl (3), 4-dimethylaminophenyl (4), 4-nitrophenyl (5), and carboxyl group (6) as substituents at the exocyclic double bond was synthesized. All compounds except 3 are formed as Eisomers as proven by the chemical shifts of olefinic hydrogens. Compound 3 was obtained as a mixture of Zand E-isomers, the first being predominant due to more favorable complexation with boron tribromide. In solution, the 3-Z isomer is rapidly converted to the 3-E isomer. • UV irradiation converts the E-isomers of compounds 3− 6 as well as the model 7-methoxy-2-(1H-pyrrol-2ylmethylidene)-2,3-dihydro-1H-inden-1-one 7 to the corresponding Z-isomers, containing intramolecular hydrogen bonds CO···H−X, as follows both from a low-field shift of NH proton of 3 and ortho-protons of 4 9084



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EXPERIMENTAL SECTION

Article

ASSOCIATED CONTENT

S Supporting Information *

Melting points are uncorrected. 1H and 13C NMR spectra were recorded at working frequencies of 500.13 (1H) and 125.1 (13C) MHz; chemical shifts are reported in parts per million relative to TMS. HRMS measurements were carried out on LTQ XL Orbitrap mass analyzer. Geometry optimization for compounds 3−7 discussed in the article was performed by applying DFT (B3LYP, M062X) and MP2/ 6-311G+(d,p) basis set in the gas phase. For the DMSO complexes the PCM + SM (single molecule) solvation model was used at the MP2/6311G+(d,p) theory level. No restrictions were imposed on the geometry optimization. All computations were performed with the Gaussian 09 program package.28 Synthesis. (E)-2-((1H-Pyrrol-2-yl)methylene)-7-methoxy-2,3-dihydro-1H-inden-1-one (7). 7-Methoxy-2,3-dihydro-1H-inden-1-one (0.55 g, 3.4 mmol) and 2-pyrrolecarbaldehyde (0.35 g, 3.7 mmol) were added to the mixture of 5 mL ethanol and 1 mL 2N aqueous KOH, heated at reflux during 1 h, cooled and allowed to stand overnight. The precipitate formed was filtered and washed with cold ethanol. Yield 0.53 g (65%), yellowish crystals, mp 202−203 °C. Anal. Calcd for C15H13NO2: C, 75.30; H, 5.48; N, 5.85; found: C, 75.43; H, 5.58; N, 5.76. 1H NMR (CDCl3, δ, ppm): 9.17 br., 1H; 7.71t, J = 1.8 Hz, 1H; 7.58t, J = 7.7 Hz, 1H; 7.16d, J = 7.7 Hz, 1H; 7.09m, 1H; 6.90d, J = 7.7 Hz, 1H; 6.75m, 1H; 6.46m, 1H; 4.06s,3H; 3.90br., 2H. 13 C NMR, (CDCl3, δ, ppm):192.2; 158.6; 151.5; 135.7; 129.6; 127.0; 122.8; 118.0; 111.6; 109.3; 55.8; 32.2. (E)-2-((1H-Pyrrol-2-yl)methylene)-7-hydroxy-2,3-dihydro-1Hinden-1-one (3). To the solution of (7) (1 mmol) in dichloromethane (10 mL) was added 2.5 mL of 1 M BBr3 solution in dichloromethane at room temperature and stirred 1 h. The red solution was poured into ice−water mixture, the organic layer was separated, washed with water, dried with anhydrous magnesium sulfate, and evaporated to give (3) as dark yellow solid, yield 0.2 g (89%). Mp 196−198 °C, (ESI+)-HRMS: Calcd for C14H11NO2H (M + H)+ 226.0851, found 226.0863. 1H NMR (recorded after standing 1 week in solution, CDCl3, δ, ppm): 9.34s, 1H; 8.72br, 1H; 7.50t, J = 1.8 Hz, 1H; 7.47dd, J = 8.1 and 7.6 Hz, 1H; 7.07 m, 1H; 7.00dd, J = 7.6 and 0.7 Hz, 1H; 6.81dd, J = 8.1 and 0.7 Hz, 1H; 6.75m, 1H; 6.44m, 1H; 3.85br, 2H. 13C NMR, (CDCl3, δ, ppm): 196.2; 157.8; 148.4; 136.9; 129.0; 128.7; 123.1; 116.8; 115.6; 113.9; 112.2; 32.4. General Procedure (according to ref 27) for the Synthesis of Compounds 4−6. A mixture of 7-hydroxy-1-indanone 1, (1 mmol), appropriate aldehyde (1.1 mmol) and conc. H2SO4 (2−3 drops) in dioxane (10 mL) was heated at reflux for 4 h. The mixture was cooled, the precipitated product filtered off, washed with water, and dried. (E)-2-(4-(Dimethylamino)benzylidene)-7-hydroxy-2,3-dihydro1H-inden-1-one (4). Red precipitate obtained after completing the reaction was treated with 1 M aqueous potassium carbonate to give yellow solid, yield 0.18 g (64%), mp 180−182 °C, (ESI+)-HRMS: calcd. for C18H17NO2H (M + H)+ 280.1316, found 280.1332. 1H NMR (CDCl3, δ, ppm): 9.48s, 1H; 7.59 d, J = 9.0 Hz, 2H; 7.58t, 1H; 7.46t, J = 7.7 Hz, 1H; 7.01d, J = 7.7 Hz, 2H; 6.82d, J = 7.7 Hz, 1H; 6.75d, J = 9.0, 2H; 3.96br, 2H; 3.07s, 6H. 13C NMR, (CDCl3, δ, ppm): 196.8; 157.9; 151.4; 149.1; 136.5; 135.0; 132.9; 129.3; 124.2; 122.8; 116.7; 113.6; 111.9; 40.1; 32.8. (E)-7-Hydroxy-2-(4-nitrobenzylidene)-2,3-dihydro-1H-inden-1one (5). Yield 0.14 g (50%), white solid, mp 243−245 °C (decomp.), (ESI+)-HRMS: calcd. for C16H11NO4H (M + H)+ 282.0747, found 282.0761. 1H NMR (CDCl3, δ, ppm): 9.16s, 1H; 8.34d, J = 8.8 Hz, 2H; 7.89d, J = 8.8 Hz, 1H; 7.69t, J = 2.2 Hz, 1H; 7.61dd, J = 7.3 and 8.1 Hz, 1H; 7.13d, J = 7.3 Hz, 1H; 6.89d, J = 8.1 Hz, 1H; 4.11br.d, J = 2.2 Hz, 2H. 13C NMR, (DMSO-d6, δ, ppm): 192.2; 157.7; 151.6; 147.6; 142.1; 140.1; 137.5; 131.9; 129.1; 124.3; 124.2; 117.0; 115.0; 32.2. (E)-2-(7-Hydroxy-1-oxo-1H-inden-2(3H)-ylidene)acetic acid (6). Yield 0.17 g (83%), mp 237−238 °C, (ESI+)-HRMS: calcd. for C11H8O4H (M + H)+ 205.0485, found 205.0495. 1H NMR (DMSOd6, δ, ppm):13.03br, 1H; 10.53s, 1H; 7.55dd, J = 7.3 and 8.1 Hz, 1H; 7.03d, J = 7.3 Hz; 6.83d, J = 8.1 Hz, 1H; 6.47br.t, 1H; 4.02 br.d; 2H. 13 C NMR (DMSO-d6, δ, ppm): 195.2; 167.5; 151.5; 150.0; 139.1; 119.5; 117.3; 114.0; 32.6.

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b01589. 1 H and 13C NMR spectra of synthesized compounds 3− 7, optimized structures of 3−12, and their complexes with BBr2 and DMSO (for 3 and 6) (PDF) X-ray crystallographic data for compound 6E (CIF) X-ray crystallographic data for compound 7E (CIF)

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AUTHOR INFORMATION

Corresponding Author

*[email protected] ORCID

Mark V. Sigalov: 0000-0002-7609-9030 Bagrat A. Shainyan: 0000-0002-4296-7899 Notes

The authors declare no competing financial interest.

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REFERENCES

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Article

The Journal of Organic Chemistry aromatic rings and the exocyclic double bond in 4-Z and 5-Z. The lowfield shift of these signals in 4-Z and 5-Z with respect to 4-E and 5-E is substantially different (0.62 and 0.26 ppm, respectively), which is indicative of notably different dihedral angles mentioned above. Among all methods used, only MP2 predicts molecules 4 and 5 to be noncoplanar whereas other methods predict them to be planar (Table 1). In this case the values of chemical shift changes upon isomerization must be identical. (25) Afonin, A. V.; Vashchenko, A. V.; Sigalov, M. V. Org. Biomol. Chem. 2016, 14, 11199−11211. (26) Parra, R. D.; Streu, K. Comput. Theor. Chem. 2011, 977, 181− 187. (27) Ofori, E.; Zhu, X. Y.; Etukala, J. R.; Bricker, B. A.; Ablordeppey, S. Y. Bioorg. Med. Chem. 2016, 24, 5730−5740. (28) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision A.01; Gaussian, Inc.: Wallingford, CT, 2009.

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Photoinduced Intramolecular Bifurcate Hydrogen Bond: Unusual

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