ISSN 0036�0244, Russian Journal of Physical Chemistry A, 2012, Vol. 86, No. 8, pp. 1250–1253. © Pleiades Publishing, Ltd., 2012.Original Russian Text © A.N. Isaev, 2012, published in Zhurnal Fizicheskoi Khimii, 2012, Vol. 86, No. 8, pp. 1364–1367.

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INTRODUCTION

Aminals of α,α�dioxoketens are suitable initialreagents for the synthesis of nitrogen�containing het�erocycles. Enamine, enediamine, and β�dicarbonylfragments can be distinguished in the molecules ofthese compounds that are able to participate in differ�ent closures of five� and six�membered rings [1–3].The possibilities of N�heterocycles design are consid�erably extended by the approach suggested by theauthors of [4], based on the change in the reactivity ofketenaminals as a result of their chelating with boron.

For electronic and steric reasons, the highest effi�ciency in heterocyclization reactions should obviouslybe observed from ketenaminals with two unsubstitutedNH2 groups. It was found earlier that compounds ofthis type are able to react with aroylketens, forming 4�

pyrimidinone derivatives [5]. Trichloromethyl�pyrim�idines were obtained in [6] by the cyclocondensationreaction of esters of 2�(diaminomethylidene)�3�oxobutyric acid with trichloroacetonitrile (Fig. 1). It isbelieved that ketenaminals Ia,b react as N�nucleo�philes added to the C≡N bond of a nitrile, while theobtained adducts under these reaction conditionsform pyrimidines IIa,b as a result of intramolecularcondensation with the elimination of water. However,the adduct structure and mechanistic details of thisreaction and the effect of substituents in the ketogroupon the reaction rate remain unclear. Of interest is thequestion of why replacing methyl groups with oxyme�thyl groups upon transitioning from the 3�(diaminom�ethylene)�2,4�pentanedione molecule (III) to thedimethyl�2�(diaminomethylene)�malonate molecule

STRUCTURE OF MATTERAND QUANTUM CHEMISTRY

The Role of Intramolecular Hydrogen Bondsin Nucleophilic Addition Reactions of Ketenaminals

A. N. IsaevZelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, 119991 Russia

e�mail: isaevaln@ioc.ac.ruReceived June 7, 2011

Abstract—Quantum�chemical calculations of the geometries and electronic structures of molecules of keten�aminals 3�(diaminomethylene)�2,4�pentanedione and dimethyl�2�(diaminomethylene)�malonate and cal�culations of the structures of intermediates in the reaction of the nucleophilic addition of the ketenaminalsto the acetonitrile molecule are performed by B3LYP/6�31+G** method. Two possible scenarios of the pro�cess are shown, depending on the mutual orientation of reacting molecules. The nucleophilic addition pro�ceeds in two stages. It is found that the rate�limiting stage of the process is the transfer of the proton of theintramolecular hydrogen bond in a ketenaminal molecule. The experimentally observed faster reaction ofpyrimidine formation for the 3�(diaminomethylene)�2,4�pentanedione molecule relative to that for dime�thyl�2�(diaminomethylene)�malonate is explained by the hydrogen bond being stronger and the barrier ofproton transfer from the aminogroup to the ketogroup oxygen falling upon nucleophilic attack in the formermolecule.

Keywords: hydrogen bond, quantum�chemical calculation, intermediates, nucleophilic attack, ketenaminals,acetonitrile.

DOI: 10.1134/S0036024412070072

H2N NH2

O

OR

O

Me

H2N N

O

OR

O

Me

C

HH

NCl3C

Cl3CC≡N–H2O N

NH2

OR

O

Cl3C

Me

Ia,b IIa,b

N

Fig. 1. Formation of pyrimidines IIa,b in the nucleophilic addition of ketenaminals Ia,b to trichloroacetonitrile; R = Me (a),Et (b).

RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A Vol. 86 No. 8 2012

THE ROLE OF INTRAMOLECULAR HYDROGEN BONDS 1251

(IV) (Fig. 2) leads to a substantial reduction in thereaction rate. In this work, these problems are investi�gated by means of quantum�chemical calculations.

RESULTS AND DISCUSSION

At the first stage of our work, quantum�chemical cal�culations of the geometries and electronic structures ofmolecules III and IV were performed. Tables 1 and 2present the results from calculations for molecule IIIperformed with complete geometry optimization in 6�31+G** basis set with regard to electron correlation bythe B3LYP method of the density functional theory [7,8]. The calculated values for the lengths of the carbon–carbon bonds are evidence of their conjugation: theC1=C2 double bond is noticeably lengthened, while theC2–C3 bond is, in contrast, shorter than a single bond.

B3LYP/6�31+G** calculations predict virtuallythe same bond lengths for intercarbon bonds, interme�

diate between the lengths of double and single car�bon–carbon bonds. The molecules under consider�ation belong to so�called push–pull systems withstrong interaction between electron�donor and elec�tron�acceptor groups through a system of π�electronbridges. A consequence of the interaction betweendonor and acceptor groups is the so�called push�pulleffect, i.e., a low rotation barrier about the C1=C2bond. It is known that the barrier of cis–trans isomer�ization in simple ethylenes is about 62–65 kcal/mol,while the barrier is reduced to 20–25 kcal/mol inpush–pull systems [9]. The low rotation barrier aboutthe C1=C2 bond is usually explained by this bondnoticeably losing the double bond character due toconjugation in the push–pull system. In agreementwith the experimental data, B3LYP/6�31+G** calcu�lations of molecules III and IV give a barrier value of20 kcal/mol.

Another specific feature of the molecules underconsideration is the intramolecular hydrogen (H�)bond N1–H1· · ·O1 between the aminogroup nitrogenand ketogroup oxygen. It is known that the H�bonds insuch push–pull systems are exhibited as double set ofsignals in 1H NMR spectra and are rather strong [9].According to the data from our B3LYP/6�31+G**calculations, the interatomic distance N1· · ·O1 in thesix�membered cycle of molecule III is only 2.5 Å, thelengthening of the valence N1–H1 bond being about0.02 Å. It should be noted that allowing for electroncorrelation reduces the calculated O1· · ·H1 inter�atomic distance by 0.1 Å. The data on charge distribu�tion in molecule III presented in Table 2 confirm theparticipation of the H1 hydrogen atom in the forma�tion of a hydrogen bond. The calculated positivecharge value on the H1 atom is 0.1 a.u. bigger than theone for the second hydrogen atom of the aminogroup.The nitrogen and oxygen atoms of the H�bond haveconsiderable negative charges whose sum exceeds theelectron charge.

As very close geometries and charge distributionwere generally obtained for molecule IV, they are notpresented in the tables. A noticeable difference in thecalculated parameters is observed only for the inter�atomic distances O1· · ·H1 and O1· · ·H2. R(O1· · ·H1) inmolecule III is 0.1 Å less and R(O1· · ·H2) is 0.2 Å morethan in molecule IV. The calculated bond anglesC3CH2 and OCH2 in methyl and oxymethyl groupsare less than the tetrahedron angle and less than thecorresponding angles for other hydrogen atoms by6 deg, pointing to the interaction between atoms O1and H2.

Table 1. Geometry of the molecule of 3�(diaminomethyl�ene)�2,4�pentanedione (III), according to the data fromquantum�chemical calculations

BondCalculation method

HF/6�31+G** B3LYP/6�31+G**

Interatomic distance, Å

C1–C2 1.447 1.461

C2–C3 1.465 1.463

C1–N1 1.331 1.341

C3–O1 1.221 1.254

C3–C(Me) 1.521 1.524

N1–H1 0.999 1.029

N1–H 0.992 1.008

O1–H1 1.762 1.662

O1–H2 2.316 2.340

N1–O1 2.531 2.511

Bond angle, deg

C1C2C3 117.3 117.3

C3C2C 125.4 125.5

C2C1N1 122.4 121.1

C2C3O1 122.2 122.2

N1C1N 115.2 117.8

C3CH2 106.1 106.3

C3CH(Me) 112.2 112.4

Table 2. Calculated values of effective charges on atoms of molecule III (a.u.)

Calculation method С1 С2 С3 O1 N1 H1 H(N1) H2 H(Me)

HF/6�31+G** 0.47 –0.01 0.19 –0.63 –0.71 0.43 0.32 0.18 0.14

B3LYP/6�31+G** 0.32 0.11 0.22 –0.53 –0.60 0.39 0.29 0.18 0.16

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RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A Vol. 86 No. 8 2012

ISAEV

A somewhat bigger positive charge value found onthe H2 atom in the CH3 and OCH3 groups (Table 2) ismore indirect evidence for the participation of the H2atom in electrostatic interaction with the ketogroupoxygen atom. The spatial proximity of the ketogroupoxygen and the oxymethyl group hydrogen in mole�cule IV results in their stronger interaction, relative tothat in molecule III. As a result of competitionbetween oxymethyl and aminogroup hydrogens for theketogroup oxygen, the intramolecular hydrogen bondin molecule IV is weaker than one in molecule III, asindicated by an increase of 0.1 Å in the interatomicdistance O1· · ·H1.

Conjugation of carbon bonds in molecules III andIV could considerably facilitate the transfer of thehydrogen bond’s H1 proton from the aminogroup tothe ketogroup oxygen. Such proton transfer should beaccompanied by a dynamic rearrangement of the sys�tem of valence bonds in the six�membered cycle of themolecule. Our calculations show that transferring theproton of the N1–H1· · ·O1 hydrogen bond plays a keyrole in the reaction mechanism of the nucleophilicaddition of ketenaminals.

To analyze the structure of adducts in the reactionof pyrimidine synthesis (in brackets in Fig. 1), we per�formed B3LYP/6�31+G** calculations of the modelreaction of molecule III addition to acetonitrile. It wasassumed earlier that upon adding to the C≡N bond ofa nitrile, both hydrogen atoms of the attacking amino�

group are transferred to the nitrile group nitrogen [6].However, the calculations showed that only one of theaminogroup hydrogen atoms is transferred to acetoni�trile. Here, two scenarios of the process are possible,depending on the mutual orientation of the reactingmolecules (Fig. 3).

In the first scenario, the H1 hydrogen atom of thehydrogen bond is transferred to the nitrogen of aceto�nitrile, forming the structure INT2 (Fig. 3). Accordingto our calculations, the transfer of the H1 atom pro�ceeds in two stages. When the molecules approach oneanother and the interatomic distance R(N1· · ·C4)between the aminogroup nitrogen and the carbon ofC≡N group of acetonitrile decreases, lengthening theN1–H1 bond with the following transfer of H1 to theketogroup oxygen occur. According to the obtaineddata, proton transfer to the group C=O occurs at

H

OC

C2

C1N

C3O1

H1N1

H H

C CH H

H HH H2

H

OC

C2

C1N

C3O1

H1N1

H H

O OC C

H2

HH

H

HH

III IV

Fig. 2. Structures of molecules of 3�(diaminomethylene)�2,4�pentanedione (III) and dimethyl�2�(diaminomethyl�ene)�malonate (IV). A description is given in the text.

O1

H1

N1

CH3

O

CH3

H2N N2C4H2

CH3

12

3

H2N N1

O

CH3

O1

CH3

CH2CH3

N

H1

O1

H1N1

CH3

O

CH3

H2N CH3

C4H2N2

12

3 O1

H1N1

CH3

O

CH3

H2N CH3

C

H2 N

INT1 INT2

INT4INT3

Fig. 3. Structures of intermediates in the nucleophilicaddition of 3�(diaminomethylene)�2,4�pentanedionemolecule to acetonitrile. The structures of adducts INT1and INT2 correspond to the nitrile group orientation nearthe ketogroup (the first scenario of the process), whilestructures INT3 and INT4 are formed when a nitrile groupand aminogroup approach one another (second scenario;see text).

Table 3. Geometries of intermediates formed upon nucleophilic attack at different orientations of molecules (Fig. 3). Thecalculations were performed by B3LYP/6�31+G** method

Inter�mediate

Interatomic distance, Å

C1–C2 C2–C3 C1–N1 C3–O1 O1–H1 N1–H1 С4–N1 C4–N2 N2–H1 N1–O1 N2–O1 N1–H2 N2–H2 N1–N2

INT1 1.492 1.401 1.334 1.318 0.993 2.699 1.512 1.225 1.789 3.022 2.552 1.015 3.162 2.413

INT2 1.397 1.465 1.365 1.231 1.791 2.588 1.337 1.289 1.019 3.254 2.699 1.014 3.178 2.354

INT3 1.498 1.397 1.330 1.320 0.991 2.693 1.523 1.228 4.584 3.019 4.989 1.028 1.617 2.613

INT4 1.484 1.389 1.263 1.322 0.991 2.705 1.341 1.291 4.306 3.034 5.012 1.523 1.023 2.402

H2

O1

O1O1

RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A Vol. 86 No. 8 2012

THE ROLE OF INTRAMOLECULAR HYDROGEN BONDS 1253

R(N1· · ·C4) < 1.6 Å, the barrier value being about28 kcal/mol. Geometrical parameters of the formingadduct INT1 are presented in Table 3. Furtherapproach of the molecules leads to a strengthening ofthe H�bond between the oxygen atom O1 and nitrogenatom N2 of acetonitrile, making energetically favor�able the proton transfer to the nitrile group. The bar�rier for the second stage of the process was found to be20 kcal/mol. The final structure INT2 corresponds tothe interatomic distance R(N1· · ·C4) = 1.34 Å, evi�dence of the formation of a covalent bond between theaminogroup nitrogen and the carbon of the acetoni�trile.

It is seen from Table 3 that upon the formation ofintermediates INT1 and INT2, a gradual structuralrearrangement of the ketenaminal molecular frametakes place, during which the C1=C2 bond is initiallylengthened and then noticeably shortened, whilechanges in the C2–C3 bond length are of the oppositecharacter, changes in the interatomic distance C1–N1also being noted. According to the calculations, thestructure INT1 is about 7 kcal/mol more thermody�namically stable than INT2.

In the second scenario of adduct formation, it is theH2 hydrogen atom of the aminogroup that does notparticipate in the intramolecular H�bond of the kete�naminal molecule, transferred to the molecule of ace�tonitrile. Two stages can also be distinguished here(Fig. 3). At the first stage like the first scenario, the H1proton is transferred to the oxygen of the C=O groupas the R(N1· · ·C4) distance decreases. The formingadduct INT3 is structurally distinguished from INT1only by the orientation of terminal groups of acetoni�trile molecule relatively the protonated ketogroup ofketenaminal (the geometry is presented in Table 3):the ketogroup of III is spatially close to the methylgroup of acetonitrile. It is important for the secondstage of the process that the nitrile group in the struc�ture INT3 is close to the hydrogen atom H2 of theattacking amino group. Therefore, the transfer of H2to the nitrogen N2 of the C≡N group (adduct INT4 inFig. 3) is observed as R(N1· · ·C4) decreases to 1.4 Å. Itcan be seen from Table 3 that the interatomic distancesC1–N1 and C2–C3 in the structure of INT4 are closeto lengths of the corresponding double bonds. Thesecond stage barrier is about 15 kcal/mol, being con�siderably lower than the proton transfer barrier for the

N1–H1· · ·O1 H�bond. Thus, in both scenarios, thelimiting stage of the process is the transfer of the H1proton of the intramolecular hydrogen bond.

CONCLUSIONS

The experimentally observed faster reaction ofpyrimidine formation for molecule III relative to thatfor molecule IV is explained by the rate of the processbeing determined by the transfer of the proton H1 tothe ketogroup. According to our calculated data, aweakening of the intramolecular H�bond in moleculeIV raises the barrier of proton H1 transfer to the keto�group in the first stage to 32 kcal/mol (versus28 kcal/mol in molecule III), which should slow therate of formation of adducts INT1 and INT3 and, as aconsequence, the entire process rate. The results of theperformed calculations allow us to relate the reactivityof ketenaminal molecules with the effect of terminalelectron�donor groups on the strength of the intramo�lecular H�bond. Another important conclusion fol�lowing from our calculations concerns the multistagecharacter of the nucleophilic addition reaction, whichproceeds via the formation of two intermediates withthe rearrangement of the frame of the ketenaminalmolecule.

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