Electrochemical behavior of nitrogen heterocycles in N,N-dimethylformamide-water and aqueous buffer solution

J. Electroanal. Chem., 102 (1979) 221--235

221

© Elsevier Sequoia S.A., Lausanne -- Printed in The Netherlands

ELECTROCHEMICAL BEHAVIOR OF NITROGEN HETEROCYCLES IN N,N-DIMETHYLFORMAMIDE-WATER AND AQUEOUS BUFFER SOLUTION

MASAO M A R U Y A M A and KAZUO M U R A K A M I

Department of Industrial Chemistry, Faculty of Science and Engineering, Chuo University, Kasuga, Bunkyo-ku, Tokyo 112 (Japan) (Received 4th S e p t e m b e r 1978; in revised form 3rd J a n u a r y 1979)

ABSTRACT

The electrochemical behavior of ten nitrogen heterocycles was investigated in DMF-water and aqueous buffer solution. On the basis of these data, the effect of p r o t o n on the reduction behavior in DMF-water media and the reduction pathway in aqueous buffer solution were phenomenologically classified. The adsorption p h e n o m e n a in aqueous buffer solution and the correlation of reduction behavior with structure and reactivity were discussed. The structure of electrolytic products was also estimated and identified by negative electron density distributions of radical anion, GC-MS and s p e c t r o p h o t o m e t r y .

In recent years several papers dealing with the polarographic investigation of nitrogen heterocycles have been published. O'Reilly and Elving [1 ] have reported the alternating current (a.c.) polarographic behavior of pyrimidine and Klatt and Rouseff [2] have examined the electroreduction of pyridazine in aqueous media. Fujinaga et al. [3] have studied the polarographic reduction of quinoline and its derivatives in N,N-dimethylformamide (DMF). Van der Meer and Feil [4--6] have examined the protonation rate constant and electrochemical reduction of eight compounds in DMF. Millefiori [ 7] has studied the electrochemical behavior of some compounds in acetonitrile. O'Reilly and Elving [ 8,9] have measured kinetic constants and the electrochemical behavior of diazines in acetonitrile. The present authors, however, feel that further work is necessary. They [10--15] have reported the further detailed electrochemical behavior of a series of nitrogen heterocycles, particularly 10 kinds of six-membered compounds, in DMF-water and aqueous buffer solution by polarography, cyclic voltammetry, controlled potential electrolysis, coulometry and spectroscopic methods. The purpose of this paper is to classify phenomenological the effect of proton on the reduction behavior of nitrogen heterocycles in DMF and the reduction pathway in aqueous buffer solution, to discuss the adsorption phenomena in aqueous buffer solution and the correlation between structure, reactivity and electrochemical behvior, and to estimate the structure of the electrolytic products on the basis of the these data.

222 EXPERIMENTAL

Chemicals The nitrogen heterocycles investigated are listed in Table 1, G.R. grade nitrogen heterocycles were used without further purification. DMF was purified by drying over anhydrous sodium carbonate and anhydrous sodium sulfate for a few days with occasional shaking, followed by vacuum distillation under a nitrogen stream. The water content of the DMF was checked by gas chromatography. The supporting electrolyte, tetraethylammonium perchlorate, was prepared by titrating perchloric acid in tetraethylammonium hydroxide, followed by recrystallizing with water three times and drying under vacuum. Britton-Robinson buffer solution was used to control pH. All other reagents were of analytical grade.

Apparatus and procedure D.c. and a.c. polarograms were measured with a Yanagimoto polarograph Model P8, and cyclic voltammograms with a Yanagimoto rapid scanner Model P8-ES and Hitachi XY recorder Model QPD 203. Controlled potential electrolysis and coulometry were performed with a Yanagimoto controlled potential electrolyzer Model V3 and a Yanagimoto coulometer Model CC-2. A Hitachi double beam spectrometer Model 124 was used to measure u.v. spectra. Mass spectra of electrolytic products were recorded with a Nichiden Varian mass spectrometer Model TE 600 and a gas chromatograph Model 1400. The reference electrode was a saturated calomel electrode (SCE). The counter electrode was made of platinum wire. The temperature was maintained at 25.0 + 0.1°C through out the experiments. All measurements except those using the a.c. method were carried out with a three electrode system. RESULTS AND DISCUSSION

(1) Electrochemical behavior in DMF-water media (1.1) Effect o f water on d.c. wave A number of organic compounds generally give two one-electron waves in aprotic solvents. The first wave represents reduction to a radical anion and the second one reduction to the dianion. It is expected that all of the nitrogen heterocycles investigated essentially show two one-electron waves in DMF. Benzene structure compounds, however, give only the one-electron wave since the lowest vacant molecular orbital (LVMO) energies of them are higher than those of other compounds, and their second wave is more negative than the reduction wave of the supporting electrolyte. Of the benzene structure compounds pyridine and pyridazine show one two-electron wave even in DMF containing as little as 0.1 vol% H~O. Napthalene and anthracene structure compounds give various electrochemical behavior according to the difference in size of the molecule or the position of the nitrogen atom in the molecule. The effect of water content on the d.c. wave of these nitrogen heterocycles in DMF is classified into five categories.

223 Pyridine t H20>0-1% Pyridazine J Pyrazine 0.1% H20

~e R

+

e~R v

0.i~.

_1 (i)

R

5%

Pyrazine

H20>I. 5%

4l
+

e~R"

R" +

(i)

(i)~(4)

H20-~RH" + OH (2)

RH" +

e CRH

RH

H20-~RH 2 + OH (4)

+

(3)

Fig. 1. Effect of water on the polarographic wave of nitrogen h e t e r o c y c l e s in DMF (Type 1).

Type 1. Pyridine, pyridazine, pyrazine. The change of d.c. waves and the reduction mechanisms at various water c o n t e n t are shown in Fig. 1. In the case of type 1, a single two-electron wave is observed above a certain a m o u n t of water. Pyrazine gives a one-electron wave at 0.1 vol% H20 corresponding to a radical anion, a one to two-electron wave b y an e.c.e, mechanism, reactions (1)--(4), in the range of 0.1 to 1.5 vol% H20, and a single two-electron wave above 1.5 vol% H20. All three c o m p o u n d s will probably show only the one-electron wave in perfectly a n h y d r o u s DMF. The reduction mechanism of the c o m p o u n d s in t y p e 1 is explained as follows: the radical anion f o r m e d at the potential of the first wave takes a p r o t o n from water to be a neutral radical, R H ' , which is further reduced at the same potential to form RH-. R H - is finally p r o t o n a t e d to dihydro compounds. Type 2. Cinnoline, quinoxaline, phenazine. The r e d u c t i o n of the c o m p o u n d s of t y p e 2 is generally similar to t h a t of m a n y organic c o m p o u n d s in aprotic solvents. They show t w o one-electron waves at 0.1 vol% H20. The first wave forms the radical anion and the second one corresponds to addition of a second electron to form the dianion. The addition of water causes the second wave to shift to less negative potentials, until it merges with the first to give a single two-electron wave by the mechanism shown in Fig. 2. Figure 3 is the typical polarogram of cinnoline in DMF-water media as the example of such a behavior. Cinnoline gives two one-electron waves at 0.1 vol% H20. A.c. polarograms corresponding to d.c. waves are observed. The first peak is reversible and sharp, whereas the second one is irreversible and small. The electrode mechanism m e n t i o n e d above is s u p p o r t e d by this behavior of the a.c. waves. In the range of 0.1 to 5 vol% H20, the height of the first step increases at the expense of the second step, according to the e.c.e, mechanism, reactions (1)--(3). The a.c. polarograms of the first step show t h a t the reversibility of the electrode reaction decreases inversely p r o p o r t i o n a l to the increase in water addition. Above 5 vol% H20, only one two-electron wave is observed. Type 3. Acridine, quinoline. As shown in Fig. 4, up to 50 vol% H20, the effect of water on d.c. waves and r e d u c t i o n mechanisms of acridine in DMF resembles

224

Phenazine 0.i%
Cinnoline ~ 0 IH 0% " 2 Quin°xalineI Phenazini~ e

Phenazine H20>I0% Cinnoline, Quinoxaline H20>5%

4 1 y

wave R + e~R" (i) 2nd wave R v + e ~ R 2- (5)

Ist

1 2e

(i)~(4) ist wave R + e ~R" (i) R= + H20=RH" + OH(2) lqI--I" + e~IRI-II~H

(3)

+ H20~RH 2 ÷ OH (4)

2ridwave R= + e ~ R 2-

(5)

Fig. 2. Effect of water on the polarographic wave of nitrogen heterocycles in DMF (Type 2).

that of type 2. Above 50 vol% H20, acridine gives two waves corresponding to the addition of one electron each. The process in the less negative wave proceeds according to reactions (1), (2) and (3). After the carboanion, R H - , is formed, the dimer anion, RRH-, is formed according to reaction (6). The dimer, RRH-, undergoes two-electron reduction at more negative potential to the dihydro form. This behvior of acridine is analogous to that of quinoline studied by Fujinaga et al. [3].

Type 4. Pyrimidine. Type 4 is more complicated than types 1--3 (Fig. 5). In the range of 0.1 to 5 vol% H20, the change of the d.c. wave of pyrimidine from a one-electron wave to a two-electron wave is the same as that of pyrazine in type 1. The two-electron reduction wave splits into two one-electron waves in the range of 5 to 70 vol% H20. The first step at the less negative potential corresponds to formation of the carboanion, reactions (1)--(3) followed by reaction

I

" 0.5

/ /

I//_I/

, 1.0

',_

, 1.5

- E/V

....

/',. I 2.0

"--;----" 2.5

3.0

vs. SCE

Fig. 3. Polarograms of cinnoline in DMF-H20 media. Concentration: (cinnoline) 1 mmol dm -3, (Et4NCIO4) 50 mmol dm -3. Water content (vol%)- (1,1') 0.1, (2) 1, (3) 4, (4) 8, (5) 20, (6) 60, (7) 100, (8) residual current.

225 Acridine 0.05%H20

0.05%
5%
H20>50%

_____9 f

I

2

e

/

J

12e

/

I

2e

............ 1st wave 2nd wave

R + e~---R" RT+ e ~ R 2-

(1) (5)

ist wave R

ist wave

+ e~R"

(i)

ist wave

(i) ~ (4)

(i) ~ (3)

R~+ H20-~RH" + OH-

RH- + R=RRH-

(2)

(6)

2nd wave

_ RH"

+ e~RH

(3)

RRH

RH- + H20-~RH 2 + OH(4) 2nd wave R ~ + e ~ R 2-

+ 2e + 3H20 --~2RH 2 + 3OH-

(7)

(5)

R2- + 2H20-'-RH2 + 20H(8) Fig. 4. Effect of water on the polarographic wave of nitrogen heterocycles in DMF (Type 3). Pyrimidine 0. I%H20 0. I%
' /

J--'l

te

Ist wave R + e~-~RT

l
2%
5%< H 2 ~

__j~~l
H20>7~

] ...I2e

Ist wave ist wave R + e~R ~ (i) (i)~ (4) R7 + H20~ RH" + OH- 2nd wave (2) RH 2 + 2e + 2H20 _ R H ' + e~RH (3) --~RH4 + OH RH- + H20--~RH2 + OH(4)

J

J 4e

ist wave(2 step) 1st wave 1st step R + 4e + 4H20 (i)~ (3) --~RH4 + 4OH- (10) RH- + R-~RRH- (6) (9) 2nd step RRH- + 2e + 3H20 --~ 2RH 2 + 3OH- (7) 2nd wave (9)

Fig. 5. Effect of water on the polarographic wave of nitrogen heterocycles in DMF (Type 4). Quinazoline H20<15%

3 % < H 2 ~

Phthalaz ine P~ Quinazoline 0.1%H20

0.1%
~ Phthal az ine

jte/~e

~'~ _.] ............

Ist wave

I ~2e

/

0"1%H20 J /T

+ e~R"

2nd wave R ~ + e ~ R 2-

R + e~R"

(5)

R T + H20--~RH" + OH(2) + e~RH

(I)

(3)

_ RH

2e

JI

1 4e t l 3e .......eJ J

ist wave

(i)

RH"

~

[

ist wave _

R

H20<5% f

I|2 ~ . ~

+ H20-~RH 2 + OH (4)

(1),'~(4)

ist wave (i)~ (4) 2nd wave(quinazoline) (5),

(9)

(8)

3rd wave (quinazoline)

Rtt2 + 2e + 2H20--~ RH 4

2nd wave (5)

2nd wave

+ 4OH

(9)

2nd wave (phthalazine)

R 2- + 2H20-~RH 2 + 2OH-

(5), (8), (9)

(8)

Fig. 6. Effect of water on the polarographic wave of nitrogen heterocycles in DMF (Type 5).

226

ii 1 i

f'~l' _", . . . . . .

1

5

.

t

2.0

1

2.5

1

3.0

- E / V v s . SCE

Fig. 7. Polarograms of phthalazine in DMF-water media. Concentration" (Phthalazine) 1 mmol dm -3, (Et4NC104) 50 mmol dm -3. Water content (vol%)" (1,1') 0.1, (2) 2, (3) 8, (4) 20, (5) 50, (6) 70, (7) 90, (8) residual current.

(6), while the second step corresponds to reduction of the dimer to dihydropyrimidine; there are similar to that of type 3. A new reduction wave at the most negative potential (--2.7 V vs. SCE), which is observed above 2 vol% H20, corresponds to a two-electron reduction to proceed from dihydro form to tetrahydro form as shown by reaction (9).

Type 5. Quinazoline, phthalazine. These compounds show the characteristic behavior at lower water content, although they finally form tetrahydro compounds in the same process as pyrimidine (Fig. 6). Phthalazine shows a reversible 1,3-electron wave and a 2.7-electron wave in DMF containing 0.1 vol% H20 as shown in Fig. 7. The first step is 1,3-electron reduction to radical anion, reaction (1), and from neutral radical to carboanion, reaction (3). The second one is 2.7-electron reduction to dianion and from dihydrophthalazine, which protonates to carboanion and dianion, to tetrahydrophthalazine. The a.c. polarogram corresponding to the second d.c. wave shows two peaks. This is evidence supporting the above ekectrode reaction mechanism. Phthalazine gives a four-electron reduction wave (two step 2e, 2e) to produce tetrahydrophthalazine in DMF containing above 5 vol% H20. These mechanisms are supported by controlled potential coulometry and the u.v. spectra of solution obtained after controlled potential electrolysis. It can be presumed that phthalazine gives two one-electron waves in perfectly anhydrous DMF. It, however, gives a four-electron wave (total process) in DMF containing 0.1 vol% H20 since the protonation rate of radical anion, carboanion and dianion of its is extremely rapid. (1.2) Effect o f benzoic acid on d.c. wave The effect of benzoic acid on d.c. wave of nitrogen heterocycles in DMF containing 0.1 vol% H20 is shown in Fig. 8. Nine compounds except phthalazine give the same behavior with changing concentration of benzoic acid. When benzoic acid is added to the DMF solution of these compounds, new waves are observed at potentials less negative than the first wave. With the increase of benzoic acid concentration, these new waves grow at the expense of the original

227 Pyrazine (imol dm-3 ) Pyrimidine (Pyridine, Pyridazine)

Benzoic acid (mmol dm-3) 0

~ .

.

.

.

~ .

e

.

Benzoic acid(retool dm 3)

i~2

0

2~3 ~ ~ ~ e

.

.

.

.

.

.

Cinnoline Quinoxaline Quinazoline(immol dm-3 ) ePhenazine e Acridine

_/"

.

,

.

Benzoic acid(retool dm ~)

l ~v0. ~ ..2.7e

i~~

2

e

Ce

Phthalazin (immoi dm:~)

Fig. 8. Effect of benzoic acid on the polarographic wave of nitrogen heterocycles in DMF.

r e d u c t i o n waves. At 2 - - 3 m m o l d m -3 o f b e n z o i c acid for 1 m m o l d m -3 nitrogen h e t e r o c y c l e s , the original waves disappear and are r e p l a c e d b y n e w t w o o n e - e l e c t r o n waves. T h e r e a c t i o n m e c h a n i s m s o f the n e w waves s e e m to proc e e d as fol~nws. T h e n e w first wave is d u e to the o n e - e l e c t r o n r e d u c t i o n o f a h y d r o g e n b o n d c o m p l e x to the n e u t r a l radical. R H A + e -~ RH" + A -

(11)

T h e r e d u c t i o n p r o d u c t , R H ' , o f c o m p l e x is also r e d u c e d at p o t e n t i a l b e t w e e n R H A and R. RH" + e ~ R H -

(3)

R H - + H A -~ RH2 + A -

(12)

T h e s e m e c h a n i s m s are t h e s a m e as in t h e case o f t h e a d d i t i o n o f p h e n o l o n the

1

1.5

1

2.0

_i

6

2.5

, i, 3 0

- E / V vs. SC E

Fig. 9. Polarograms of phthalazine with benzoic acid in DMF. Concentration: (phthalazine) 1 m m o l d m -3, (Et4NCIO4) 50 m m o l d m -3. B e n z o i c acid ( m m o l d i n - 3 ) • ( 1 , 1 ' ) ( 2 ) 0 . 5 , (3) 1.0, ( 4 , 4 ' ) 2.0, (5) 0.5 without phthalazine, (6) residual current, water content 0.1 vol%.

228

reduction of quinoline p r o p o s e d by Fujinaga et al. [3]. The effect of benzoic acid on the d.c. wave of phthalazine in DMF containing 0.1 vol% H20 is different from t h a t of the other c o m p o u n d s . When phthalazine is reduced in the presence of benzoic acid, three new waves (--1.44, --1.90 and - - 2 . 3 8 V vs. SCE) appear (Fig. 9). These waves grow in height at the expense of the original two waves (1.3 e, 2.7 e) until with sufficient acid four one-electron waves are observed. The original first wave (--2.07 V vs. SCE) disappears and the height of the second one decreases to one third at 2 m m o l d m -3 benzoic acid for 1 m m o l d m -3 phthalazine. The total wave height remains a p p r o x i m a t e l y constant as shown in Fig. 9. The new first wave is due to the one-electron reduction of acid complex, and the second one to the one-electron r e d u c t i o n of reduction product, RH', of the complex. 1st wave R H A + e-+ R H ' + A-

(11)

2nd wave RH" + e ~ R H RH-+2HA-+RH2"HA+A-

(3) (13)

The third one is due to the one-electron r e d u c t i o n of d i h y d r o p h t h a l a z i n e acid complex, and the fourth one to the one-electron reduction of the reduction product, R H 2 H ' , of the acid complex. 3rd wave RH~'HA+e-~

RH~.H'+A-

(14)

4th wave RH2"H'+e~

RH2"H-

RH2" H- + HA-+ RH4 + A-

(15) (16)

The final p r o d u c t s are expected to be the same t e t r a h y d r o p h t h a l a z i n e as t h a t in aqueous buffer solution (pH 8).

(1.3) Chemical structure and its reduction potential Organic c o m p o u n d s generally give two one-electron waves in aprotic solvent. The first wave, which is a reversible one-electron wave w i t h o u t p r o t o n a t i o n process, forms the radical anion, so t h a t the half-wave potential of its wave is regarded as a m e a n t to measure the standard reduction potential. The potential can be correlated to the LVMO energy level calculated by the simple Hfickel m e t h o d . The correlation between the E1/2's of thirteen nitrogen heterocycles and --mj is fairly notable as shown in Table 1 and Fig. 10. In this case the following e q u a t i o n is obtained with a standard deviation of 0.001. E~/2 = 2.28fl -- 0.90

(17)

The slope of this line corresponds to the effective value of ~, namely to --2.28 eV in the system of nitrogen heterocycles. This value is in fair agreement with --2.23 eV f o u n d in the case of h y d r o c a r b o n systems in dioxane-water media by Hoijtink [16] and --2.27 eV in the case of the stilbene derivative system in dioxane-water media by F u e n o et al. [ 17]. Therefore, this tendency of nitrogen heterocycles is the same as t h a t of h y d r o c a r b o n s .

229 3,0

U

2.5

/7 12/• 10

2,0

1.5

w u o3 ei > > u.~

/

1.0

0.5

0

o

!

o2

~

o4

o'6

0'8

~o

-mj

Fig. 10. R e l a t i o n b e t w e e n half-wave p o t e n t i a l of the first wave and m i value of the lowest vacant molecular orbital energy of nitrogen heterocycles.

As to the relation between the reduction potential and chemical structure of nitrogen heterocycles, the more nitrogen atoms in the molecule, the easier these compounds are reduced in the order as follows" pyridine < pyrimidine < TABLE 1 The energy level of the lowest vacant m o l e c u l a r orbital, half-wave pot ent i al and diffusion current c o n s t a n t of s i x - m e m b e r e d nitrogen heterocycles. Parameters" C o u l o m b integral aN = ~ + 0.6/~, (XC, = (X + 0.1/3 (C--N); resonance integral/3ON = /~NN =/3- Water c o n t e n t in DMF" 0.1 vol%. I = Diffusion current const ant [pA ( ( m g s -1 )2/3 81/6 m m o l dm -3 }-1 ]. Compound

The mj values of the lowest vacant M.O.

__~red

I

(1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13)

--0.783 --0.681 --0.681 --0.666 --0.586 --0.539 --0.504 --0.494 --0.433 - - 0 .4 1 1 --0.345 --0.304 --0.153

2.60 2.55 2.02 2.30 2.07 2.19 2.06 2.10 1.85 1.71 1.84 1.68 1.24

4.0 2.0 2.1 4.3 2.4 2.1 2.4 2.0 2.0 1.9 2.4 2.6 2.3

Pyridine Pyrimidine Triazine(s--) Pyridazine Pyrazine Isoquinoline Phthalazine Quinoline Quinazoline Cinnoline Quinoxaline Acridine Phenazine

~ 1 / 2 / V vs. SCE

230

pyridazine < pyrazine (benzene structure compounds with one or two nitrogen atoms), quinoline < phthalazine < quinazoline < cinnoline < quinoxaline (naphthalene structure c o m p o u n d s with one or two nitrogen atoms) and acridine < phenazine (anthracene structure c o m p o u n d s with one or two nitrogen atoms). With respect to relation between the reduction potential and the difference in position of nitrogen atom in molecule, these are reduced more easily in the sequence of meta < ortho < para. Phthalazine, however, does not follow this rule. This agrees with the specificity in physical and chemical properties of phthalazine. As to relation between the n u m b e r of condensed benzene rings and the reduction potential, the greater the number of benzene rings, the more positive the reduction potential becomes: such as the pyridine--quinoline--acridine series and the pyrazine--cinnoline--phenazine series (the compounds with one or two nitrogen atoms, in the same position). These results are in accordance with the tendency of LVMO energy levels obtained from HMO method.

(2) Electrochemical behavior in aqueous buffer solution (2.1) The pathway o f polarographic reduction in aqueous buffer solution In general, even numbers of electrons transfer when organic compounds are reduced in aqueous solution. Most of the nitrogen heterocycles investigated undergo two-electron reduction and protonation to dihydro forms. After this step, electrode reactions proceed in the various pathways according to the nature of the compound. The electrode reactions of these compounds in aqueous buffer solution may be classified into four groups as shown in Fig. 11. The classification of the reaction pathways is discussed only in the case when the n u m b e r of electrons transferred is the largest in the electrode reaction of each compound. (1) Two-electron reduction in total process: pyridine, acridine, phenazine. These three compounds undergo two-electron reduction and proton addition to the stable dihydro forms, which are n o t further reduced in aqueous buffer solution. (2) Two-electron reduction in total process, followed by hydrolysis: pyrazine, pyridazine, (pyrimidine). Pyrazine and pyridazine in aqueous buffer solution

0

R+2e+2H+(or2H20)~

}~{2 ~H
Q (PYRAZINE,PYRIDAZINE, (PYRIMIDINE))

2H20)..~ ~J/4(~YRIMIDIN£.(:~INAZOLINE.QUINOXALINE)

PYRIDINE ~ ~ 4 2 ~ L ~ ACRIDINE PHENAZINE

S + 2e + 2H+(or 2H20)_~ p (CINNOLINE, PHTHALAZINE)

Fig. 11. T h e p a t h w a y of electrochemical r e d u c t i o n for nitrogen he tero cycles in a q u e o u s buffer solution.

231 undergo two-electron r e d u c t i o n and p r o t o n addition to the d i h y d r o forms, which are rapidly h y d r o l y z e d , break the ring, and result in the f o r m a t i o n of amino carbonyl c o m p o u n d s . Pyrimidine undergoes two-electron reduction in neutral solution by controlled potential electrolysis at the m e r c u r y pool cathode, resulting in the f o r m a t i o n of the amino carbonyl c o m p o u n d just the same as the above c o m p o u n d s .

(3) Four-electron reduction (2e, 2e) in total process: pyrimidine, quinazoline, quinoxaline (two nitrogen atoms take meta or para position). Pyrimidine undergoes two-electron reduction in neutral solution to form d i h y d r o p y r i m i d i n e and four-electron reduction in alkaline solution to t e t r a h y d r o p y r i m i d i n e . Quinazoline and quinoxaline also similarly undergo two two-electron r e d u c t i o n to the t e t r a h y d r o forms in aqueous buffer solution.

(4) Six-electron reduction (2e-2e-2e, 2e-4e or 6e) in total process: cinnoline, phthalazine (two nitrogen atoms take ortho position). Cinnoline and phthalazine show from one to three waves, and these total heights correspond to sixelectron process. These are reduced to dihydro forms in the first two-electron step. The second two-electron r e d u c t i o n corresponds to reductive cleavage of nitrogen-nitrogen bond, and forms amino c o m p o u n d s . In the third two-elect r o n step, the amino c o m p o u n d s are further reduced to diamino c o m p o u n d s . The r e d u c t i o n mechanism of cinnoline in aqueous buffer solution is shown as follows:

2nd wave RH2 + 2 e + 2 H + -~ C6HgNH2CH2CH=NH

(18) (~9)

3rd wave C6H4NH2CH2CH=NH + 2 e + 2 H ÷ -~ C6H4(NH2)CH2CH2NH2

(20)

lstwave

R+2e+2H

+-~ RH2

R = CsH6N:

(2.2) Adsorption phenomena In this section, the a d s o r p t i o n of nitrogen heterocycles in aqueous buffer solution on the dropping mercury electrode is discussed, although being observed in DMF containing more than 70 vol% H20. In the case of c o m p o u n d s having naphthalene and anthracene structure m a n y factors such as d r o p 4 i m e curves, dependence of m e r c u r y head on d.c. wave height, the effect of t e m p e r a t u r e on d.c. wave and dependence of the concentration on a.c. wave height show the characteristics of a d s o r p t i o n , but these with benzene structure do not. Acridine and phenazine (anthracene structure c o m p o u n d ) exhibit an anomalous prewave at potentials less negative than the main wave. The adsorption of the reduction p r o d u c t s can be assumed from the shape of the drop-time curves. The lowering of the surface tension starts at the potential of prewave and continues t h r o u g h the whole region of the main wave. Acridine gives an irreversible a.c. peak overlapping the prewave and reduction wave and a reversible positive t e n s a m m e t r i c wave caused by a d s o r p t i o n in aqueous buffer solution containing 3 vol% ethanol (pH 8) as shown in Fig. 12. Phenazine gives t w o a.c. peaks, which are extremely reversible and sharp,

232

1 5.5 5.0

.~ ~. 4.0

0.4 mS

0 13

3

0

0'5

10

-E/V

15

vs. SCE

Fig. 12. Drop-time curves and polarograms of phenazine in Britton-Robinson buffer solution containing 4% ethanol (pH 7). Concentration" ( 1 ) w i t h o u t phenazine, (2--4) phenazine, 0.4 mmol dm -3. (KNO3) 160 mmol dm -3

corresponding to prewave and main wave, an irreversiSle one corresponding to d e s o r p t i o n as shown in Fig. 13. The existence of these two sharp peaks can be c o n t i n u e d d o w n to the c o n c e n t r a t i o n 1 X 10 -7 mol d m -3, so that t h e y are available for microanalysis of these c o m p o u n d s . In conclusion, the larger the size of nitrogen heterocycle molecule, the more easily adsorption on the dropping m e r c u r y electrode occurs.

~A 41JS AC

[:K: |

!

o

0.5

~.'o

1;5

- E / V vs. $CE

Fig. 13. Polarograms (]d.c. and a.c.) of acridine in Britton-Robinson buffer solution containing 3% ethanol (pH 8.0). Concentration" (acridine) 0.4 mmol dm -3, (KNO3) 160 mmol dm-3.

233

(3) Estimation and identification of electrolytic products Identification of the polarographic reduction products is very difficult since most of them are unstable or decompose immediately after electrolysis. It is expected that all ten nitrogen heterocycles investigated in DMF-water and aqueous buffer solution undergo two-electron reduction to the dihydro forms. However, it is difficult to identify where they two protons are located in molecule. Hoijtink [18] predicted the structure of polarographic reduction products of hydrocarbons from negative electron density distributions of radical anion based on Hiickel method. The predictions agreed with the electrolytic products. The negative electron density distributions of radical anion of ten nitrogen heterocycles are shown in Fig. 14. The highest electron density is at the 1- and 4-position in pyridine, pyrazine and naphthalene structure compounds, and at the 1- and 2-position in anthracene structure compounds, so that the attack by a proton on the radical anion will occur at this position. The highest electron density of pyrimidine is at the 4- and 6-position, but it is structurally impossible that proton attack occurs at such positions. U.v. spectra of the electrolytic products (2e reduction) of quinazoline, which is made up by condensing a benzene ring to a pyrimidine, are in agreement with those of 3,4-dihydroquinazoline. Consequently, it is expected that pyrimidine also undergoes two-electron reduction to form 3,4-dihydropyrimidine. In aqueous buffer solution, benzene structure compounds except pyridine are attacked by two protons at the higher electron density position after twoelectron reduction, and then the resulting dihydro compounds are hydrolyzed through equilibrium of 1,2 (3,4)- and 1,4-dihydro forms. The degree of hydrolysis in nitrogen heterocycles is generally reported to depend on the ratio of the carbon (C) atoms to the number of nitrogen (N) atoms. The less the C/N ratio, 0.307

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234 130

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~/e Fig. 15. Mass spectra of pyridazine and electrolytic product of pyridazine in DMF-water (2 vol%). (1) Pyridazine, (2) electrolytic product=dihydropyridazine. Fig. 16. Mass spectra of cinnoline and electrolytic products of cinnoline in DMF-water and buffer solution. (1) Cinnoline, (2) Electrolytic product=dihydrocinnoline, (3, 4) polymerized cinnoline.

the more easily benzene structure compounds are hydrolyzed. However, naphthalene and anthracene structure compounds are not hydrolyzed. The electrolytic products, which are stable and have relatively lower boiling point, in DMF containing below 10 vol% H20 are identified by gas chromatography-mass spectrometry (g.c.-m.s.). For example, when the solution electrolyzed at the mercury pool cathode is introduced immediately to g.c.-m.s., the large fragment peaks are observed at 81 (M + 1) and 82 (M + 2) in pyridazine (M = 80) and at 131 (M + 1) and 132 (M + 2) in cinnoline (M = 130) (Figs. 15 and 16). The (M + 1) fragment peak is largest because the hydrogen to carbon bond of the dihydro compounds is broken easily in the ionization chamber. In DMF-water (above 80 vol% H20) and aqueous buffer solution, polymers of cinnoline, phthalazine, quinazoline and acridine precipitate on electrolysis at the mercury pool cathode. Their mass spectra are analogous to those of the dihydro compounds although there are differences in the degree of polymerization. The u.v. spectra before and after electrolysis of ten nitrogen heterocycles at the mercury pool cathode in DMF or acetonitrile-water and aqueous buffer solution show regular changes according to the electrode reaction mechanism. In the case of forming dihydro compounds by two-electron reduction and two-proton addition, the position of the absorption maxima ~before and after electrolysis does not shift, and the molar absorptivity increases or decreases more or less. On forming tetrahydro compounds by two-electron, two-electron reduction and two proton, two proton addition (phthalazine, quinazoline), the position of absorption maxima are the same as those of the dihydro compounds, but the

235

k\ ,

2~0

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~o

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Fig. 17. U.v. spectra of phthalazine before and after electrolysis in AN-water and water. Concentration' (phthalazine) 0.1 mmo] dm -3 (before electrolysis). (1) Before electrolysis 0.1 v o l % H 2 0 ; a f t e r e l e c t r o l y s i s ( t w o - e l e c t r o n r e d u c t i o n ) , w a t e r c o n t e n t ( v o l % ) : ( 2 ) fi, ( 3 ) 50, (4) 100, (5) 100 (buffer solution, pH 12). After electrolysis (four-electron reduction)" ( 6 ) 0 . 1 , ( 7 ) 2, (S) 5 0 .

molar absorptivity reduces to about one-half that of the dihydro compounds (Fig. 17). Benzene structure compounds except pyridine in aqueous buffer solution are hydrolyzed to carbonyl compounds immediately after two-electron and two-proton addition. Their u.v. spectra show the c o m m o n characteristic that it has an intense absorption maximum (e = 2 X 104) at near 210 nm. The formation of carbenyl compounds by hydrolysis is also confirmed by the colour identification test. REFERENCES 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

J.E. O'Reilly and P.J. Elving, J. E l e c t r o a n a l . Chem., 21 ( 1 9 6 9 ) 169. L.N. K l a t t and R.L. R o u s e f f , J. E l e c t r o a n a l . Chem., 41 ( 1 9 7 3 ) 411. T. Fujinaga, K. Izutsu and K. T a k a o k a , J. Electroanal. Chem., 12 (1966) 203. D. van der Meet and D. Feil, Rec. Trav. Chim., 87 (1968) 746. D. van der Meet, Rec. Trav. Chim., 88 ( 1 9 6 9 ) 1361. D. van der Meet, Rec. Trav. Chim., 89 ( 1 9 7 0 ) 51. S. Millefiori, j . H e t e r o c y c l i c Chem., 7 ( 1 9 7 0 ) 145. J.E. O'Reilly and P.J. Elving, J. Amer. Chem. Soc., 93 (1971) 1871. J.E. O'Reilly and P.J. Elving, J. Amer. Chem. Soc., 94 ( 1 9 7 2 ) 7941. M. M a r u y a m a , K. M u r a k a m i and Y. Saito, Chuo Daigaku R i k o g a k u b u Kiyo, 17 ( 1 9 7 4 ) 1 4 7 . M. M a r u y a m a and K. Murakami, N i p p o n K a g a k u Kaishi, ( 1 9 7 6 ) 1239. M. M a r u y a m a and K. Murakami, N i p p o n K a g a k u Kaishi, ( 1 9 7 7 ) 990. M. M a r u y a m a and K. Murakami, N i p p o n K a g a k u Kaishi, ( 1 9 7 7 ) 1648. M. M a r u y a m a and K. Murakami, C h u o Daigaku R i k o g a k u b u K i y o , 20 ( 1 9 7 7 ) 271. K. Murakami and M. M a r u y a m a , N i p p o n K a g a k u Kaishi, ( 1 9 7 8 ) 700. G.J. Hoijtink, Rec. Trav. Chim., 74 ( 1 9 5 5 ) 1525. T. F u e n o , T. M o r o k u m a and J. F u r u k a w a , N i p p o n K a g a k u Zasshi, 79 ( 1 9 5 8 ) 116. G.J. Hoijtink in P. Delahay and C.W. Tobias (Eds.), Advances in E l e c t r o c h e m i s t r y and E l e c t r o c h e m i cal Engineering, Vol. 7, Wiley-inte~science, New York, 1 9 7 0 , p. 221.