Synthesis of ring-substituted phenyl hydrazinecarboxylates and study of their protonation in dimethyl sulfoxide solutions

Article abstract of DOI:10.1135/cccc19980793

The pK_a values of nineteen phenyl hydrazinecarboxylate hydrochlorides R-C₆H₄OCONHNH₂.HCl (R = H, 3-and 4-Cl, 3-and 4-O₂N, 4-Me) and their 1-methyl or 2-methyl derivatives were determined by potentiometric titration with tetrabutylammonium hydroxide in DMSO. IR spectra of the hydrazinecarboxylates and their hydrochlorides revealed that the hydrazinecarboxylate protonation occurs at N². The methods of synthesis of phenyl hydrazinecarboxylate and their N-methyl derivatives were optimized.

Full text of DOI:10.1135/cccc19980793

Protonation of Phenyl Hydrazinecarboxylates
793
SYNTHESIS OF RING-SUBSTITUTED PHENYL HYDRAZINECARBOXYLATES
AND STUDY OF THEIR PROTONATION IN DIMETHYL SULFOXIDE
SOLUTIONS
a
b1
b
b2,
Petr VLASAK , Patrik PARIK , Jiri KLICNAR and Jaromir MINDL
*
a SYMPO, a.s., 532 10 Pardubice, Czech Republic; e-mail: sympo@pce.czn.cz
b Department of Organic Chemistry, University of Pardubice, 532 10 Pardubice, Czech Republic;
e-mail: 1 parik@hlb.upce.cz, 2 mindl@hlb.upce.cz
Received July 7, 1997
Accepted February 24, 1998
The pKa values of nineteen phenyl hydrazinecarboxylate hydrochlorides R-C6H4OCONHNH2 HCl
(R = H, 3- and 4-Cl, 3- and 4-O2N, 4-Me) and their 1-methyl or 2-methyl derivatives were deter-
mined by potentiometric titration with tetrabutylammonium hydroxide in DMSO. IR spectra of the
hydrazinecarboxylates and their hydrochlorides revealed that the hydrazinecarboxylate protonation
occurs at N2. The methods of synthesis of phenyl hydrazinecarboxylate and their N-methyl deriva-
tives were optimized.
Key words: Aryl hydrazinecarboxylates; Acidity constants.
Phenyl hydrazinecarboxylates 1a–5a are bioactive substances which are hydrolytically
degraded in living organisms. Previously1, we examined the kinetics and mechanism of
alkaline hydrolysis of the substances whose general formula is given below.
1
R
3
2
R R NNCO
2
X
1
2
3
In formulae 1-5 : a, X = H
R
R
R
X = 3-Cl
b,
c,
d,
e,
f,
H
H
H
1
2
3
4
5
X = 4-Cl
H
Me Me
X = 3-NO
X = 4-NO
X = 4-Me
2
Me
H
H
2
Me Me H
g, X = 4-OMe
Me Me Me
* The author to whom correspondence should be addressed.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

794
Vlasak, Parik, Klicnar, Mindl:
We found that the reactivity and degradation pathway are substantially affected by
the presence or absence of hydrogen in the R1 position, capable of ionizing (Ka1) in the
presence of bases. During the synthesis of the substances, we observed that many of
them can be isolated from solutions in aprotic solvents as stable hydrochlorides
1a HCl–5a HCl. The hydrochlorides can be converted back to the starting hydrazine-
carboxylates by alkalization* (equilibrium Ka2), as shown in Scheme 1.
+
+
–H /NaOH, K 1
a
–H /HCl, K 2
a
[R3R2NNCO2C6H4X]–
R3R2NN(R1)CO2C6H4X
[R3R2NN(R1)CO2C6H4X] H+
1
(R = H)
1a–5a
1a HCl–5a HCl
SCHEME 1
The present paper describes the results of study of protonation of hydrazinecarboxy-
lates 1a–5a, paying attention to the site where the reaction occurs and how the equilib-
rium Ka2 is affected by the structure of the substance. We also optimized the synthesis
of phenyl hydrazinecarboxylate because the only published route2 fails to provide satis-
factory yields. This topic was not addressed by our previous paper.
Phenyl Hydrazinecarboxylate Protonation
Phenyl hydrazinecarboxylate hydrochlorides are little soluble in aprotic solvents, while
in water, in which they are well soluble, hydrolysis and decarboxylation to phenols and
hydrazinium salts takes place. Therefore, we examined the acid-based equilibria of the
phenyl hydrazinecarboxylates in anhydrous dimethyl sulfoxide (DMSO), where the
protonation equilibrium is unaffected by hydrolysis; at the same time, this approach
enabled us to follow up the work of Koppel and others3 who examined similar equili-
bria of hydrazine and amines in DMSO. Phenyl hydrazinecarboxylates contain basic
centres at N1 and N2 and at the two oxygen atoms, which must be considered in deduc-
ing the structure of the hydrochlorides.
The protonation was studied by examined the IR spectra of the model substances
1a HCl, 2a HCl and 4a HCl and comparing them with those of the bases 1a, 2a and 4a.
On the protonation of hydrazinecarboxylates 1a, 2a and 4a, the original 1H NMR signals of
both the N–H groups vanish. In the IR spectra of the dimethyl derivatives 2a and 4a,
the absorption bands of the N1H and N2H groups lie at 3 250 cm–1 and 3 330 cm–1.
* The equations (3) were presented in a wrong form in ref.1. The correct one is as follows:
log kobs = pH + log k2Kw = pH + log k1Ka = pH + log kOH – 14.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

Protonation of Phenyl Hydrazinecarboxylates
795
Table I gives the corresponding wavenumbers for the N–D groups in the deuterated
derivatives. The ν(NH)/ν(ND) ratio is 1.34 to 1.35. The IR spectra of the substances
+
1a HCl and 2a HCl exhibit broad diffuse bands of the associated N2H groups within
the range of approximately 3 200–2400 cm–1. The salts 1a HCl, 2a HCl and 4a HCl
differ in the number of hydrogen atoms at the N2 atom (3, 2 and 1, respectively), and
are consistent with the corresponding primary, secondary and tertiary amine salts,
whose spectra are identical within the above region4. The set of intense δ(+N2H3) bands
within the 1 600–1 500 cm–1 region for 1a HCl, and the weak δ(+N2MeH2) band for
2a HCl can be attributed to the bending vibrations of the hydrochlorides.
Table I also summarizes the wavenumbers of the hydrazinecarboxylate carbonyl
group bands for 1a, 2a and 4a. The spectrum of the 2,2-dimethyl derivative 2a, how-
ever, exhibits three ν(C=O) bands but a single ν(N1H) band. In carbon tetrachloride
solution, this substance displays a medium-intensity band with two shoulders, which
we took into account. In this case, we failed to decide whether these are due to a
mixture of conformers or to vibrational interactions. The strong ν(C–O) band lies at
1 211–1 212 cm–1. Due to the –I effect of the positively charged N2, the carbonyl
wavenumber for the hydrochlorides is shifted upwards by 20–43 cm–1 (Table I). Proton
exchange in the related hydrazides takes place mainly at the N2 atom, as found by
variation of substituents in the benzene rings at N1 and N2 (refs5,6).
We found that with respect to its pKa2 value (pKa2 = 5.24, see Table II), phenyl
hydrazinecarboxylate hydrochloride 1a HCl is roughly a ten times weaker acid than
hydrazine dihydrochloride (4.0), whose value has been determined by Koppel and coworkers3.
TABLE I
IR wavenumbers (cm–1) of phenyl hydrazinecarboxylates 1a–4a, their deuterated analogs and hydro-
chloridesa
Com-
pound
Com-
pound
ν(Ν1H)
ν(N2H)
ν(N1D)
ν(N1D)
ν(C=O)
ν(N2H)
ν(C=O)
1a 3 260 w 3 338 s
2 408 w 2 500 w 1 715 vs
2 480 w 1 745 vsb
1a HCl 3 120–2 660 1 763 vs
3 319 m
sb
2a 3 250 m
2 420 w
1 726 v
2a HCl 3 120–2 655 1 749 vs
1 740 shc
1 740 m
1 760 vsc
1 758 s
sb
1 775 shc
4a
3 330 wb
2 470 wb 1 727 vs
4a HCl 3 232–2 435 1 747 vs
sb
a
b
c
Solid phase (Nujol mulls, KBr disks); chloroform; tetrachloromethane.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

796
Vlasak, Parik, Klicnar, Mindl:
The presence of methyl groups at nitrogen atoms in hydrazinecarboxylates 12a HCl–5a HCl
reduces the acidity in the order H2NNHCO2Ph HCl (1a HCl) Me2NNCO2Ph HCl
(2a HCl) > H2NNMeCO2Ph HCl (3a HCl) > MeNHNMeCO2Ph HCl (4a HCl) >
Me2NNMeCO2Ph HCl (5a HCl). This order is not in accord with the acidity order of
the respective methylated hydrazine dihydrochlorides, whose acidities are enhanced by each
introduced methyl group7, MeNHNMe2 HCl > Me2NNH2 HCl > Me2NHNHMe HCl >
MeNHNH2 HCl > NH2NH2HCl HCl and, rather, approaches the acidity order of the
ammonium and alkylammonium ions8, NH4+ > Me3N+ > MeNH2+ > Me2NH+. The acid-
base properties of the last-mentioned series have been explained in terms of a simple
combination of electronic and steric effects, whereas for the methylhydrazine series, no
satisfactory explanation is available.
In the phenyl hydrazinecarboxylate series, the acidity of the hydrazinecarboxylate
hydrochlorides (1a–2g) HCl is enhanced by the presence of electronegative substi-
tuents. We determined the sensitivity of the protonation equilibrium pKa2 to the phenyl
ring substitution in DMSO solution on the basis of the reaction constants ρ in the
Hammett equation for our experimental acidity constants pKa in the hydrazinecarboxy-
late hydrochlorides series (1–3) HCl (Table II). The values are ρ = 0.80 ± 0.21, 0.52 ±
0.10 and 0.09 ± 0.04 for the series (1a–1f) HCl (2a–2g) HCl and (3a–3f) HCl, respec-
tively. Although the standard deviations are considerable, it is clear that the ρ values
are rather high, especially for the two former series. The values suggest that the confor-
mation, where the proton at N2 can be simultaneously attracted by electrons of the C=O
group in anion-bonding interaction, may be the predominating phenomenon.
Phenyl Hydrazinecarboxylate Synthesis
When reproducing the preparation procedure for phenyl hydrazinecarboxylate 1a as
reported by Merck2 by hydrazinolysis of diphenyl carbonate in ethanol, we obtained the
TABLE II
pKa2 values of phenyl hydrazinecarboxylate hydrochlorides and their 1-methyl and 2-methyl deriva-
tives in DMSO at 25 °C (standard deviations are given in parentheses)
Compound
pKa2
Compound
pKa2
Compound
pKa2
Compound
pKa2
1a HCl
1b HCl
1c HCl
1d HCl
1e HCl
1f HCl
5.24(0.05)
4.75(0.06)
4.71(0.07)
4.69(0.09)
4.56(0.02)
5.41(0.11)
2a HCl
2b HCl
2c HCl
2d HCl
2e HCl
2f HCl
5.21(0.04)
5.00(0.05)
5.22(0.07)
4.89(0.05)
4.80(0.10)
5.28(0.11)
2g HCl
3a HCl
3b HCl
3c HCl
3d HCl
3e HCl
5.30 (0.10)
5.57(0.06)
5.54(0.07)
5.48(0.05)
5.48(0.09)
5.50(0.08)
3f HCl
4a HCl
5a HCl
5.68(0.07)
5.42(0.05)
5.51(0.10)
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

Protonation of Phenyl Hydrazinecarboxylates
TABLE III
797
Analytical data of hydrazinecarboxylates R3R2NN(R1)CO2C6H4X (procedure A) and their hydro-
chlorides
Calculated/Found
R1, R2
R3, X
M.p., °C
Yield, %
Formula
M.w.
Adduct
M.p., °C
Compound
% C
–
% H % N
1a
1b
1c
1d
1e
1f
H, H
H, H
104–105a
45, 10b
C7H8N2O
–
–
1a HCl
151.2
179–181
H, H
110–111
88
C7H7ClN2O2
186.6
45.06 3.76 15.01
45.12 3.86 15.16
1b HCl
H, 3-Cl
183–185
H, H
139–141
42
C7H7ClN2O2
186.6
45.06 3.76 15.01
45.33 3.68 14.78
1c HCl
H, 4-Cl
203–205
H, H
121–123
82
C7H7N3O
197.1
42.65 3.58 21.31
42.34 3.60 21.06
1d HCl
H, 3-NO2
147–149
H, H
111–113
78
C7H7N3O
197.1
42.65 3.58 21.31
42.90 3.73 21.12
1e HCl
H, 4-NO2
149–151
H, H
115–117
40, 14b
C8H10N2O2
166.1
57.82 6.07 16.86
57.56 6.41 16.83
1f HCl
H, 4-Me
191–193
2a
2b
2c
2d
2e
2f
H, Me
Me, H
69.5–71c
28
C9H12N2O
180.2
–
–
–
2a HCl
113–115
H, Me
88–90
54
C9H11ClN2O2 50.32 5.17 13.06
214.6 50.11 4.92 13.40
C9H11ClN2O2 50.32 5.17 13.06
2b HCl
Me, 3-Cl
135–139
H, Me
129–131
41
2c HCl
Me, 4-Cl
214.6
50.07 5.23 13.25
154–155
H, Me
110–112
39
C9H11N3O4
225.2
48.00 4.92 18.66
48.22 4.92 18.59
2d HCl
Me, 3-NO2
151–152
H, Me
118–120
56
C9H11N3O4
225.2
48.00 4.92 18.66
47.96 4.91 18.52
2e HCl
Me, 4-NO2
145–147
H, Me
124–126
21
C
10H14N2O2
194.2
61.84 7.27 14.43
61.86 7.26 14.72
2f HCl
Me, 4-Me
143.5–145
2g
3a
H, Me
102–103
C10H14N2O3
210.2
57.14 6.71 13.33
56.97 6.81 13.31
2g HCl
Me, 4-OMe
15
141–143
d
Me, H
H, H
C8H10N2O2
166.1
57.82 6.07 16.86
57.49 6.18 16.56
3a HCl
162–164e
35
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

798
Vlasak, Parik, Klicnar, Mindl:
TABLE III
(Continued)
Calculated/Found
% C % H % N
R1, R2
R3, X
M.p., °C
Yield, %
Formula
M.w.
Adduct
M.p., °C
Compound
3b
3c
3d
3e
3f
Me, H
31–34f
42
C8H9ClN2O2
200.6
47.89 4.53 13.96
48.14 4.60 13.68
3b HCl
H, 3-Cl
146–148
Me, H
161–163
50, 15b
C8H9ClN2O2
200.6
47.89 4.53 13.96
47.95 4.70 13.74
3c HCl
H, 4-Cl
155–157
Me, H
83–88 (dec) C8H9N3O4
38 211.1
93–97 (dec) C8H9N3O4
45.50 4.30 19.90
45.76 4.32 19.89
3d HCl
H, 3-NO2
136.5–138
Me, H
45.50 4.30 19.90
45.42 4.47 20.14
3e HCl
H, 4-NO2
47
211.1
150–152
g
Me, H
C9H12N2O2
180.2
59.99 6.71 15.55
60.21 6.60 15.27
3f HCl
Me, 4-Me
23
164–166
h
4a
5a
Me, Me
H, H
C9H12N2O2
180.2
59.99 6.71 15.55
59.42 6.51 15.12
4a HCl
42
144–146
i
Me, Me
Me, H
C10H14N2O2
194.2
61.84 7.27 14.42
62.12 7.33 14.09
5a HCl
27
103–105
a
b
c
d
Ref.1 gives for 1a m.p. 105 °C; see procedure B; ref.2 gives for 2a m.p. 75–77 °C; for 3a b.p.
155–157 °C/1.3 kPa, n2D0 1.5298; e ref.9 gives for 3a HCl m.p. 165–167 °C; f for 3b b.p. 123–125 °C/0.1 kPa;
g for 3f b.p. 110–115 °C/0.1 kPa; h for 4a b.p. 102–103 °C/0.4 kPa, n2D0 1.5230; i for 5a b.p. 94–97 °C/0.4 kPa,
n2D0 1.5148.
product in a yield as low as 10% see Experimental, procedure A). The procedure applied
to the preparation of substance 2f and 3c resulted in similarly low yields (Table III). If ethanol
was replaced by diethyl ether and the reaction components were stirred at –35 °C (proce-
dure B), hydrazinecarboxylates 1a–1f separated from the solutions as crystalline sub-
stances when keeping the reaction mixture at room temperature. The
hydrazinecarboxylates 3a–4a were prepared by a similar procedure (C). The yields, rang-
ing from 40 to 88%, are given in Table III along with the elemental analysis data and
physical constants. The starting diphenyl carbonates were prepared in yields exceeding
90% by a new phosgene-free single-step method reacting the corresponding phenol
with trichloromethyl chloroformate in the presence of triethylamine.
Substituted phenyl 2,2-dimethylhydrazinecarboxylates (2a–2g) and phenyl 1,2,2-tri-
methylhydrazinecarboxylate (5a) were obtained by reacting aryl chloroformates with
an excess of 1,1-dimethylhydrazine and 1,1,2-trimethylhydrazine, respectively, follow-
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

Protonation of Phenyl Hydrazinecarboxylates
799
ing procedure D. The yields, along with the elemental analysis data, are given in Table III.
On analogous reaction of hydrazine with phenyl chloroformates (which are more reac-
tive than diphenyl carbonate) in the presence of sodium carbonate gives diphenyl hy-
drazine-1,2-dicarboxylate9. We found that this is the sole product at –60 °C even if
hydrazine is present in excess. This substance is also formed in aqueous formate buffer,
where hydrazine is mostly present as monohydrochloride (procedure F).
Reaction of phenyl chloroformate and hydrazine monohydrochloride in DMSO gives
roughly the same amount of hydrazinecarboxylate as hydrazine-1,2-dicarboxylate; this
is also true for the water-containing heterogeneous system (procedure G).
EXPERIMENTAL
The melting points were measured on a Kofler stage and have not been corrected. The IR spectra
were measured in Nujol mulls (1a–5a), in KBr disks (1a HCl, 2a HCl), in melts and in chloroform
or carbon tetrachloride solutions on a Zeiss IR-75 spectrophotometer. The 1H and 13C NMR spectra
in deuteriochloroform or hexadeuteriodimethyl sulfoxide were scanned at 25 °C on a Bruker AMX-
360 instrument. The chemical shifts are given relative to the solvent signals (for hexadeuteriodi-
methyl sulfoxide, δ(1H) 2.55, δ(13C) 39.6). The purity of the hydrazinecarboxylates was assessed
chromatographically on a Varian HPLC Model 5000 using a Separon SGX C1 column (80% aqueous
methanol), and on a GC Chrom-5 apparatus (Laboratorni pristroje Praha) in a 1-m column packed
with Chromosorb A (60/80 mesh)–10% SE52, using FID and nitrogen as carrier gas.
The equilibria of the phenyl hydrazinecarboxylates 1a–5a and their hydrochlorides (1a–5a) HCl
were measured by potentiometric titration of solutions (5 mmol l–1) of the hydrochlorides in anhy-
drous dimethyl sulfoxide with 0.1 M methanolic solution of tetrabutylammonium hydroxide under
argon at 25 °C, using a Radiometer Titrilab 3 instrument. For nitrophenyl hydrazinecarboxylate
hydrochlorides, where hydrolysis takes place in the presence of an excess of the titrant, the pKa2
values were determined by titrating phenyl hydrazinecarboxylates 1d, 1e, 2d and 2e in DMSO with
an alcoholic solution of hydrogen chloride. The pKa1 values of (1a–1e) HCl are given in Table II.
The equilibria were characterized by a single potentiometric wave within the pH region from 4.4 to
5.7 and compared with the pKa value of benzoic acid (11.8) and the first wave of hydrazine dihydro-
chloride pKa1 (4.0, ref.3).
Aryl Hydrazinecarboxylates 1a–1f
Procedure A. To a solution of a diphenyl carbonate (20 mmol) in diethyl ether (30 ml), 85% hy-
drazine hydrate (20 mmol)) was portionwise added at 0 °C within 5 min. The reaction was allowed
to proceed for 30 min, after which the mixture was concentrated to 20% volume. The crude product
was separated from the solution by cooling with ice. The yields of hydrazinecarboxylates 1a, 1f and
3c obtained are given in Table III.
Procedure B. To a stirred solution of a diphenyl carbonate (20 mmol) in diethyl ether (30 ml),
cooled to –35 °C, 85% hydrazine hydrate (20 mmol) was added in one portion. The mixture was
warmed to room temperature and allowed to stand for another 20 min. The crude hydrazinecarboxy-
late crystals were filtered off and recrystallized from a hexane–benzene 1 : 1 mixture. The yields,
physical properties and elemental analysis data are given in Table IV.
Procedure C. This procedure was applied to the phenyl 1-methylhydrazinecarboxylates 3a–3f and
phenyl 1,2-dimethylhydrazinecarboxylate 4f. To a stirred solution of the corresponding hydrazine (20 mmol)
in ether (15 ml), cooled to –35 °C, a solution of a diphenyl carbonate (20 mmol) in the same solvent
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

800
Vlasak, Parik, Klicnar, Mindl:
TABLE IV
1H NMR data of phenyl hydrazinecarboxylates (chemical shifts in ppm (δ-scale), J in Hz)
Compound
1H NMR (CDCl3), δ (ppm), J (Hz)
1a
3.71 b, 2 H (H-8); 6.46 b, 1 H (H-7); 7.12 d, 2 H, J = 7.6 (H-2, H-6); 7.20 t, 1 H, J =
7.4 (H-4); 7.35 t, 2 H, J = 8.0 (H-3, H-5)
1ba
1c
6.77 m, 1 H (H-6); 6.85 m, 2 H (H-2, H-4); 7.23 t, 1 H, J = 7.9 (H-5)
3.84 b, 2 H (H-9); 6.37 b, 1 H (H-7); 7.06 d, 2 H, J = 8.8 (H-2, H-6); 7.32 d, 2 H,
J = 8.8 (H-3, H-5)
1da
7.26 m, 1 H (H-6); 7.51 t, 1 H, J = 8.14 (H-5); 7.60 t, 1 H, J = 2.0 (H-2); 7.70 m, 1 H
(H-4)
1ea
1f
6.97 d, 2 H, J = 9.2 (H-2, H-6); 8.16 d, 2 H, J = 9.2 (H-3, H-5)
2.31 s, 3 H (H-11); 3.68 b, 2 H (H-9); 6.49 b, 1 H (H-7); 6.97 d, 2 H, J = 8.1
(H-2, H-6); 7.12 d, 2 H, J = 8.1 (H-3, H-5)
2a
2b
2c
2.64 s, 6 H (H-11); 6.09 b, 1 H (H-7); 7.12 m, 2 H (H-2, H-6); 7.17 t, 1 H, J = 7.15
(H-4); 7.34 t, 2 H, J = 7.6 (H-3, H-5)
2.65 s, 6 H (H-10); 6.04 b, 1 H (H-7); 6.78 m, 1 H (H-6); 6.87 m, 2 H (H-2, H-4);
7.25 t, 1 H, J = 7.9 (H-5)
2.65 s, 6 H (H-10); 6.05 b, 1 H (H-7); 7.06 d, 2 H, J = 8.75 (H-2, H-6); 7.29 d, 2 H,
J = 8.75 (H-3, H-5)
2da
2.45 s, 6 H (H-10); 7.16 b, 1 H (H-7); 7.26 m, 1 H (H-6); 7.50 t, 1 H, J = 8.15 (H-5);
7.60 t, 1 H, J = 2.2 (H-2); 7.70 m, 1 H (H-4)
2ea
2f
2.45 s, 6 H (H-10); 6.97 m, 2 H (H-2, H-6); 7.17 b, 1 H (H-7); 8.16 m, 2 H (H-3, H-5)
2.31 s, 3 H (H-11); 2.68 s, 6 H (H-10); 6.99 d, 2 H, J = 8.3 (H-2, H-6); 7.13 d, 2 H,
J = 8.3 (H-3, H-5)
2g
3a
3b
3c
2.66 s, 6 H (H-10); 3.76 s, 3 H (H-11); 6.84 m, 2 H (H-3, H-5); 7.03 d, 2 H, J = 8.6
(H-2, H-6)
3.22 b, 3 H (H-8); 3.99 b, 2 H (H-10); 7.09 m, 2 H (H-2, H-6); 7.17 t, 1 H J = 7.2
(H-4); 7.33 t, 2 H, J = 7.5 (H-3, H-5)
3.24 b, 3 H (H-8); 4.18 b, 2 H (H-9); 7.01 m, 2 H (H-6); 7.15 t, 1 H, J = 2.0 (H-2);
7.18 m, 1 H (H-4); 7.27 t, 1 H (H-5)
3.24 b, 3 H (H-7); 4.16 b, 2 H (H-9); 7.04 d, 2 H, J = 8.8 (H-2, H-6); 7.28 d, 2 H,
J = 8.8 (H-3, H-5)
3da
3ea
3f
3.14 b, 3 H (H-8); 4.11 b, 2 H (H-9); 7.24 m, 1 H (H-6); 7.49 t, 1 H, J = 8.2 (H-5);
7.59 t, 1 H, J = 2.1 (H-2); 7.71 m, 1 H (H-4)
3.14 b, 3 H (H-8); 4.12 b, 2 H (H-9); 7.14 d, 1 H, J = 9.1 (H-2, H-6); 8.19 d, 1 H,
J = 9.1 (H-3, H-5)
2.30 s, 3 H (H-11); 3.20 b, 3 H (H-8); 4.19 b, 2 H (H-9); 6.96 m, 2 H (H-2, H-6);
7.11 m, 2 H (H-3, H-5)
4a
5a
2.65 b, 3 H (H-10); 3.21 b, 3 H (H-8); 4.13 b, 1 H (H-8); 7.12 m, 2 H (H-2, H-4);
7.18 t, 1 H, J = 7.4 (H-4); 7.35 t, 2 H (H-3, H-5)
2.64 b, 6 H (H-10); 2.97 b, 3 H (H-8); 7.11 m, 2 H (H-2, H-6); 7.16 t, 1 H, J = 7.3
(H-4); 7.32 t, 2 H, J = 8.0 (H-3, H-5)
a
In (CD3)2SO.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

Protonation of Phenyl Hydrazinecarboxylates
801
(20 ml) was added over a period of 15 min. The mixture was warmed to room temperature, allowed
to stand for another 40 min, and then the system was bubbled with dry hydrogen chloride for 10 min.
The solid separated was filtered off and washed with ether (30 ml). The substance was dispersed in
ether (30 ml) and on aqueous solution of potassium carbonate (12 mmol) was added portionwise to
the stirred mixture within 15 min. The organic phase was evaporated, the crude product was distilled
in vacuum and then crystallized from a hexane–benzene 1 : 1 mixture. The results, along with
elemental analysis and physical data, are given in Table III, the NMR spectral data are given in Table IV.
Preparation of Diphenyl Carbonates from Trichloromethyl Chloroformate and Phenols
To a stirred solution containing phenol (1.9 g, 20 mmol) and triethylamine (2.0 g, 20 mmol) in tetra-
hydrofuran (20 ml), a solution of trichloromethyl chloroformate (1.0 g, 5 mmol) in tetrahydrofuran
(5 ml) was added dropwise within 5 min. The stirred mixture was heated to the boil for 10 min,
cooled, and mixed with water (100 ml). The solid (2.0 g, 93%) was filtered off, washed with water,
and crystallized from methanol; m.p. 79–80 °C. The same procedure was applied to the synthesis of
the diphenyl carbonates substituted in positions 3 or 4 by a chloro, nitro, methyl or ethoxy group; the
yields ranged from 91% to 95%.
Procedure D. Preparation of Phenyl 2,2-Dimethylhydrazinecarboxylates 2a–2g and
Phenyl 1,2,2-Trimethylhydrazinecarboxylate 5a from Phenyl Chloroformates
The substances were prepared from the corresponding hydrazine (20 mmol) in ether (20 ml) by adding,
under stirring at –35 °C, a solution of a phenyl chloroformate (10 mmol) within 10 min. After 30 min,
the separated 2,2-dimethyl- or 1,1,2-trimethylhydrazine hydrochloride was filtered off and the pro-
duct was isolated either by vacuum distillation or by recrystallization from a petroleum ether–propan-
2-ol mixture. The yields and physicochemical properties are given in Table III, the spectral
characteristics in Table IV.
Procedure E. To a stirred emulsion of 99% hydrazine hydrate (0.5 ml, 10 mmol) in chloroform (5 ml),
cooled to –60 °C, a solution of phenyl chloroformate (0.63 ml, 5 mmol) in the same solvent (3 ml)
was added within 5 min. After warming up to room temperature, the mixture was shaken with water,
the organic solution was dried and the solvent was removed by vacuum distillation. The solid (0.5 g)
was crystallized from toluene; m.p. 154–156 °C.
Procedure F. To a stirred mixture of hydrazine dihydrochloride (0.52 g, 5 mmol) in water (5 ml)
and phenyl chloroformate (0.78 g, 5 mmol) in dichloromethane (10 ml), a solution of sodium formate
(2.5 g, 30 mmol) in water (10 ml) was portionwise (over a period of 15 h) added at 10 °C. The
mixture was allowed to warm up to room temperature and allowed to stand for another 8 h. The
organic phase was separated, dried with anhydrous sodium sulfate, and the solvent was removed by
evaporation in vacuum. The residue (0.35 g) was crystallized from toluene; m.p. 155–156 °C. The
same procedure was used when adding potassium hydrogencarbonate (1.5 g, 15 mmol) instead of
sodium formate; the product yield was 0.6 g, m.p. 155–156 °C.
Procedure G. To a stirred solution of hydrazine monohydrochloride (0.42 g, 4 mmol) in DMSO (6 ml),
held at room temperature, phenyl chloroformate (0.25 ml, 2 mmol) in chloroform (3 ml) was drop-
wise added within 5 min. After 10 min, the mixture was alkalized with a saturated solution of so-
dium carbonate. The chloroform phase was separated, washed with water and analyzed by
chromatography. The product contained compound 1a (46%), diphenyl hydrazine-1,2-dicarboxylate
(42%) and two unidentified substances.
The same procedure was performed in water; after the reaction, the mixture was allowed to stand
for 24 h at room temperature. Chromatographic analysis revealed the presence of 1a (52%), diphenyl
1
hydrazin-1,2-dicarboxylate (41%) and one unidentified substance. H NMR spectrum: 7.37 t, 2 H (H-3,5);
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

802
Vlasak, Parik, Klicnar, Mindl:
7.234 t, 21 H (H-4); 7.16 d, 2 H (H-2,6); 6.95 t, 2 H (NH). 13C NMR spectrum: 154.9 (CO), 150.6
(C-1), 129.7 (C-3), 125.7 (C-4), 121.6 (C-2).
Phenyl Hydrazinecarboxylate Hydrochlorides 1a HCl–5a HCl
Dry hydrogen chloride was introduced into a 10% solution of a phenyl hydrazinecarboxylate in diethyl
ether (1a–1c, 1f–5a) or in diethyl ether–dioxane 5 : 1 (1d and 1e) at 0 °C. After saturation, the crystals
were separated by centrifugation and purified by crystallization from toluene. The yields of the
hydrochlorides were quantitative, the melting points are given in Table III.
This research work was sponsored by the Grant Agency of the Czech Republic, Grant No.
203/97/0545.
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