ORGANIC CHEMISTRY

ELECTROCARBOXYLATION OF ARYL- AND ACYLHYDRAZONES

IN

NONAQUEOUS MEDIA T. V. Troepol'skaya, G. A. Vagina, L. V. Ermolaeva, Z. S. Titova, T. A. Zyablikova, and Yu~ P. Kitaev

UDC 541.138:530.145:547.574.3: 547.467.1

The electrochemical hdyrocarboxylation of azomethines [1-3] and also of Schiff bases [4-6] has been fairly thoroughly investigated, and in a number of instances [3, 4] high yields of N-substituted amino acids have been obtained. In the present study, in order to assess the possibility of the electrosynthesis of hydrazino or hydrazido acids and of Nsubstituted amino acids, we have investigated the carboxylation of aryl- and acylhydrazines containing azomethine moieties. EXPERIMENTAL The voltamperograms %~rerecorded with a GWP-673 polarograph (GDR) in DMF with a supporting electrolyte of I • 10 -I M Et4NCIO 4 and a scanning rate of 0.5 V min -I in a two-electrode cell thermostatted at 25 ! 0.1~ The characteristics of the dropping mercury electrode in DMF were T = 0~ sec -l, m = 2.23 mg sec -I (hHg = 45 cm). The anode, serving as a comparison electrode, was a pool of mercury. Electrolysis at a controlled potential was effected with a P-5827M potentiostat in a cell with separate anode and cathode compartments; the working electrode was a pool of mercury, the comparison electrode Ag/AgNO3~0.0~ M in MeCN, and the auxiliary electrode was a platinum plate; the solvent was MeCN or DMF. Electrolysis was carried out at a potential corresponding to three quarters of the height of the first reduction wave of the hydrazone. The concentration of the depolarizer was 0.02 M. During electrolysis the solution was flushed continuously with CO 2 which had been dried by passing through concentrated H2SO ~ and calcined indicator silica gel. The duration of electrolysis was in every case 2 h, the initial current 300-400 mA, and at the end of the electrolysis about 5 mA. After electrolysis had finished the solution was treated with an excess of MeI (1-3 by weight), washed several times with water and extracted with ether. After drying over MgSO 4 the ether was evaporated off in a vacuum and the oily residue from several experiments (10-12) was fractionated on AI=O 3 and silica gel columns (eluents: chloroform, ether, and benzene). TLC was carried out on Silufol254 plates, eluents were benzene and MeOH, and development with iodine vapor. GLC employed a "Khrom-5" chromatograph, column 250 • 0.3 cm, Chromaton W-AN with 5% SE-30 Silicone, and temperature programming (120-2500C). When methylation was not employed the aqueous and ethereal layers were analyzed separately. IR spectra were recorded on a UR-20 spectrophotometer and UV spectra on a Specord UV-VIS spectrometer. NMR spectra were measured on a Varian T-60 spectrometer with a working frequency v 0 = 60 MHz at 34o5~ relative to TMS (6TMS = 0). The samples consisted of 20% solutions in DMSO-d 6. Ab initio calculations were carried out with the GAUSSIAN-80 program [7], adapted in the Institute for Theoretical and Experimental Physics, Moscow~ The model ~-phenylhydrazino and ~-phenylacetic acids were synthesized by the chemical reduction of the phenylhydrazone of phenylglyoxalic acid with Na/Hg [8]. DISCUSSION Table i shows that El/2 for compounds (1)-(X) is more positive than the potential of the first reduction wave of C02; in the presence of CO 2 the limiting currents of the waves of these compounds are increased, and their El/2 is displaced towards more cathodic values (Fig. i), i.e., the generally accepted criterion for electrocarboxylation is satisfied. An increase in the limiting current of the first wave in the presence of CO 2 is regarded as a A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Branch, Academy of Sciences of the USSR. Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1314-1318, June, 1989. Original article submitted March 30, 1988.

0568-5230/89/3806-1197512.50

9 1989 Plenum Publishing Corporation

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TABLE i. Effect of CO 2 on the Characteristics of the Electrochemical Reduction of Azomethines ln the absence of C02

I

Compound

-EI/2,V

(1) C6H~CONHN=CMe2 (II) C6HsCONHN=CHC~H5 (III) CeHsCONHN=CHMe

NOCONHN=CMe2 (IV) (~CONHN=CMe2 (V) N C6H~CH=NOH (VI) C~HsCH=N-NCHC6Hs. (VII) CeH~NHN=CHC~H5 (VIII) C6H~CH=NC~H5 (IX) C~HsCONHN=C-Me (X)

l

COOH MeCONHN=CHMe (XI) MeCONHN=CHC~H5 (XII) C02

(xIiI)

ilim,~A

2,30 2,70 2,45 2,83 2,10 2,75 t,98

0,60 0,80 t,08 0,48 0,75 t,t5 t,00

2,28

0,93

2,33 i,85 2A5 2,93 2,25 3,18

3,2 0,60 0,60 2,40 0,72 4,56

2,03 2,40 1,525 2,475

t,08 1,62 0,20 0,84

2,47 2,7t 2,22 2.39 2.73

0,82 1.00 0,72 O,68 5,50

C02 *

-EI/2,V

ilim,~/A

2,45 2,85 2,58 2,88 2,28 2,85 2,08 2,80 2,38 2,83

1,30 t.18 f,25 0,50 1,53 2,75 2.60 0,85 2.60 2,05

2,58 1,90 2,45 2,85 2,38 2,68 2,98 2,t8 3,05 t,48 2,38

4,32 0,96 0.24 2,96 t.80 3,00 4,56 3.20 t0,00 t,40 0,95

2J9

0.63 0.76 0.80 0.64

2,64 t,98 2,t6

*C02 passed through the solution for 5 sec.

Z/ 2

I/ T

2-f,v F i g . 1. Polarograms o f t h e h y d r a z o n e ( I ) i n t h e absence (1) and t h e p r e s e n c e o f CO2 ( 2 ) ; s u p p o r t i n g e l e c t r o l y t e 0 . 1 M Et4NCIO~.

criterion for the possibility of carboxylation, though this increase in ili m was not observed for the phenyl or methylphenylhydrazones of salicylaldehyde or of o-vanillin. Electrolysis at a controlled potential of the phenyl, methyl and diphenylhydrazones of benzaldehyde, and of acylhydrazones, was carried out in DMF in the presence of C02. Analysis of the catholyte after methylation with CH2N 2 or MeI (TLC, IR and UV spectra) demonstrated the absence of fission products of the N-N bond, aromatic amines or methylated amines, and also of esters of amino acids (ninhydrin reaction). This suggests that, as in the case of Schiff bases, carboxylation should probably always lead to the formation of ~-hydrazinocarboxylic acids, though N-carboxylation is by no means excluded. The phenylhydrazone of benzaldehyde (VIII) was subjected to a more detailed investigation. The following scheme is proposed for its transformations

1198

+e +H+. CO,,e.H+ CeHsNHN=CHCsH5 ---~[CeHsNHN=CHC6Hs]':--~

--. C6H~NHNH--CH--C6Hs

+ MeI

> CeH~NHNH--CH--C6H5

I COOMe

Cl,o o n

The reduction of phenylhydrazinoacetic acid at E = -2.9 V leads to the formation of aaminophenylacetic acid (phenylglycine) and aniline

CeHsNHNH--CH--CsH~

2e, 2II+

~ C6HsNH2 ~- NH2--CH--C~H5

COOH

COOH

A comparison of the IR and UV spectra of solutions of (VIII) after electrolysis at a controlled potential (ECP) in the presence of CO 2 with the spectra of model compounds established their identity. Previous investigations [9] of the mechanism of the electrochemical reduction (ECR) of aryl and acylhydrazones revealed differences in the sequence of stages, connected with differences in the stability of the N-N bonds. In the arylhydrazones the breaking of the N-N bond occurs first, while in the acylhydrazones the first step is the saturation of C=N, so that the first stage in the carboxylation of acylhydrazones is most probably the formation of hydrazino, acids. In the electrolysis of the hydrazones (I)-(III) under the conditions described in the experimental section no fission of the N-N bond was observed at the potential of the first wave. The original hydrazones were absent from the products of electrolysis, and after methylation esters of ~-hydrazinocarboxylic acids were detected. A more thorough study was carried out with the benzoylhydrazone of acetaldehyde (I). After the electrolysis of (I) the IR spectrum of the solution exhibited strong absorption at around 1650 cm -I, attributed to vC,--O, while after methylation, there was a strong band at about 1750 cm -l, characteristic of v ~ of the ester group complex, while the ~C=O band of the carboxyl group disappeared. After electrolysis the solutions did not exhibit absorption at around 3000cm -l characteristic of the valency vibrations of the groups NH and OH in associated forms of the acids~ The appearance in the UV spectrum of (I) of an absorption band in the region of 330 nm, characteristic of related compounds (phenylhydrazones of esters and of the amide of pyroracemic acid) [i0] is evidence of the introduction of a chromophore into the original molecule, while methylation leads to the expected bathochromic shift. Thus the electrochemical reduction of the benzoylhydrazone of pyroracemic acid should yield the same hydrazido acid

(C6HsCONHNH--CH--COOH)~ I

Me as the electrocarboxylation of (I) (in agreement with [9]) and a comparison of the UV spectra of the solutions after the electrolysis of these compounds demonstrates their identity. The NMR spectrum of the product of electrolysis of (I) contains signals corresponding to the phenyl protons in the region 7.20-7~ ppm with an integrated intensity of 6H~ a signal from the protons of the methoxy group with 6 = 3.76 ppm (3H), a signal from the methyl group on the N atom with 6 = 2.26 ppm (3H), a signal from the single proton of CH with 6 = 3.90 ppm (IH) and of NH with 6 = 10o76 ppm (IH). The NMR spectrum of the product of t h e electrocarboxylation is thus consistent with the structure (XIII)o Hence the electrocarboxylation of (I) involves C-carboxylation. It is therefore possible in principle to realize the electrocarboxylation of acylhydrazones according to the following scheme e,

CeHsCONHN=CHMe ~

H+

CO.~ e, H +

[C6I-IsCONHNHCHMe] "~

MeI

+ C~H~CONHNH--CH--Me COOMe

1199

No signs of the products of N-carboxylation could be detected spectroscopically. These may not be present at all, or may be formed in very small amounts, as in the carboxylation of most Schiff bases [3-6]. Although no quantitative measurements have been made, it would be expected that the yields of hydrazino or hydrazidoacids would be almost quantitative, since there were no signs of other possible products for the hydrazones investigated. On further reduction of ~-benzoylhydrazinoacetic acid the formation of u-aminoacetic acid was observed 2e, 2 H +

C~H~CONHNH--CH--Me ~

C6H~CONH2+ NH~--CH--Me

COOH

COOH

The a c e t y l h y d r a z o n e s (XI) and (XlI) (Table 1) do not undergo c a r b o x y l a t i o n , although their El/2 is close to EI/2 for CO 2. However, their ilim does not increase in the presence of C02, which would be provisional evidence for such reactions. This is confirmed experimentally by carrying out the electrolysis of (Xl) and (XlI); the presence of C02 has no effect on their ECR. We have carried out quantum-chemical calculations of the electronic structure of compounds (I) and (XI) and of their anion-radicals0 The MNDO method was used to optimize the geometry of the molecules of (I) and (Xl), the structural parameters and symmetry of the substituents Me and C6H 5 being fixed. The calculated energies showed that the EE'Z" form is less stable by 2.0 kcal mole -I than the EE'E" conformer (structures with sp 2 hybridization of the nitrogen (V) atom, valency angles N-N}{ 120.9 ~ CNN 120.9 Q) H3C

H

\/

H3C

C N

H~G/

H

\/ C

H

N

EE,E u

N

H

2 \

CHs

EE'Z ~

For the benzoylhydrazone (I) the difference between the energies of the conformers EE'Z" and EE'E" is reduced to 1.4 kcal mole -I, i.e., the introduction of the group C6H S into the acyl moiety increases the fraction of the EE'E" form. In both forms the benzene ring is outside the C-N-N=C plane. Optimization of the geometry of the anion-radical (XI)" in the "half electron" approximation [12] does not indicate any essential difference from the geometry of the uncharged molecule (the bonds N=C and C=O are lengthened and the grouping O=C-N-N~ remains planar). By using the structural results obtained by the MNDO method for compound (XI) we have carried out an ab initio calculation in a minimum basis of the electronic structure of the anion-radical of the compound O=CH-qqH-NH=CH2. The values obtained for the charges and for the distribution of spin density over the atoms are given in Table 2. Quantum-chemical calculations have been recently carried out [13] for the intermediate anion-radical of benzylideneanilines, formed during ECR, and the mechanism of electrocarboxylation on the carbon atom was confirmed. It was shown that the value of the charge determines the reaction center for protonation of the anion radical, while the distribution of electron density controls the direction of approach of the CO 2 in terms of the mechanism proposed previously [3, 5, 6]. According to the data in Table 2, C-carboxylation is the most likely, since the density of the unpaired electron is highest at this atom. The MND0 calculations for compounds (I) and (XI) show that on passing from acetylhydrazones to aroylhydrazones there is an increase in the proportion of the EE'Z" form~ The conformational behavior and the E-Z isomerization of N-acyl and N-aroylhydrazones has been considered [14], and it was shown (on the basis of NMR spectra of solutions in DMSO and CDCIs) that aroylhydrazones exist mainly (up to i00%) in the EE'Z" form, while the acetylhydrazones are present as a mixture of both conformers, the composition of which depends on the polarity of the solvent. The nucleophilicity of the imino nitrogen atom in the EE'Z" form exceeds that in the EE'E" form, thus increasing considerably the electrostatic field near the N atom. It may be assumed that the higher basicity of the N atom in the EE'Z" conformer accounts for the reactivity of the aroy!hydrazones in the ECR reaction. 1200

TABLE 2. Charges on the Atoms (q) and Distribution of the 9 2 S p i n D e n s z t y ( C i ) i n t h e A n i o n - R a d i c a l o f t h e Model F o r m y l h y d r a zone of Formaldehyde Os=C4--NI--N~=C3~H (EE'E" form) I H Parameter

q C~.(unpaired)

I H

N,

N~

C~

-0,237 -0,480

-0.298 0,343

-0.201 0,707

C4

C~ I

+0,061 J I

-0,385 0,644

CONCLUSIONS I. It is shown that a number of aryl and acylhydrazones can be electrochemically carboxylated in non-aqueous media (acetonitrile, DMF) to give ~-hydrazino (or hydrazido) acids. 2. On passing from benzoyl to acetylhydrazones electrocarboxylation no longer occurs, probably because of the predominance in the acetylhydrazones of fhe EE'E" form, in which the basicity of the imino nitrogen atom is lower than in the EE'Z" form. LITERATURE CITED i. 2. 3. 4. 5. 6. 7. 8. 9. i0. ii. 12. 13. 14.

N. Weinberg, Tetrahedron Lett., 2271 (1971). S. Kato and J. Mitzutani, Abstracts, Meeting on Electroorganic Chemistry. Kyoto, Japan (1980), p. 9. U. Hess, Z. Chem., 20, 148 (1980). D. Ko Root and W. H. Smith, J. Electrochem. Soc., 129, No. 6, 231 (1982). U. Hess and M. Ziebig, Pharmazie, 37, No. 2, 107 (1982). U. Hess and R. Tiele, J. Prakto Chem., 324, No. 3, 385 (1982). J. S. Binkley, R. Ao Whiteside, R. Krishnan, et ai., QCPE, 13, 406 (1981). A. Elber, Liebigs Ann. Chem., 227, 340 (1885). Yu. P. Kimaev, T. V. Troepol'skaya, L. V. Ermolaeva, and E. N. Munin, Izv. Akad. Nauk SSSR, Ser. Khim., No. 8, 1736 (1985). R. A. Abramovitch and I. D. Spenser, J. Chem. Soc., 3767 (1957). M. J. S. Dewar and W. Thiele, Jo Am. Chem. Soc., 99, 4899 (1977). R. C. Bingham and M. J. S. Dewar, J. Am. Chem. Soc., 94, 9107 (1972). J. Komenda, R. Fiala, and U. Hess, Z. Phys. Chem., 268, No. i, 48 (1987). G. Palla, G. Predieri, P. Domiano, et al., Tetrahedron., 42, No. 13, 3649 (1986).

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