A simple and efficient approach to the synthesis of 1-phosphonated 5-amino-1-H-[1,2,4]-triazole from N-functionalized imidates

Article abstract of DOI:10.1080/10426507.2015.1100178

In this study, we describe a new and easy synthetic approach to variously substituted triazoles based on the reaction of imidates with phosphorylated hydrazine in good yields. A general mechanism of the reactions was also proposed. Characterization of the products was carried out by several analytical and spectroscopic tools including infrared and nuclear magnetic resonance spectroscopies (¹H,¹³C NMR,³¹P NMR).

Full text of DOI:10.1080/10426507.2015.1100178

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
A simple and efficient approach to the synthesis of
1-phosphonated 5-amino-1-h-[1,2,4]-triazole from
n-functionalized imidates
Dhiab Jabli, Khaireddine Dridi & Mohamed Lotfi Efrit
To cite this article: Dhiab Jabli, Khaireddine Dridi & Mohamed Lotfi Efrit (2016): A simple
and efficient approach to the synthesis of 1-phosphonated 5-amino-1-h-[1,2,4]-triazole from
n-functionalized imidates, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:
10.1080/10426507.2015.1100178
To link to this article: http://dx.doi.org/10.1080/10426507.2015.1100178
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A SIMPLE AND EFFICIENT APPROACH TO THE SYNTHESIS OF 1-
PHOSPHONATED 5-AMINO-1-H-[1,2,4]-TRIAZOLE FROM N-FUNCTIONALIZED
IMIDATES
Dhiab Jabli a, *, Khaireddine Dridi a,b, and Mohamed Lotfi Efrit a
aLaboratory of Organic Chemistry, Department of Chemistry, Faculty of Sciences, El Manar
University, El Manar II, Tunis 1060, Tunisia
bDepartment of Chemistry, College of Sciences and Arts, Qassim University, Al‐ Rass, 53,
Kingdom of Saudi Arabia
E-mail: jabli.dhiab@yahoo.fr; medlotfi.efrit@gmail.com Tel: +21696886540. Fax:
+21671883424
Abstract
In this study, we describe a new and easy synthetic approach to variously substituted triazoles
based on the reaction of imidates with phosphorylated hydrazine in good yields. A general
mechanism of the reactions was also proposed. Characterization of the products was carried out
by several analytical and spectroscopic tools including Infra-Red and Nuclear Magnetic
Resonance Spectroscopies (1H, 13C, 31P-NMR).
1
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TsOH (cat)
Toluene, reflux
TsOH (cat)
Toluene, reflux
Keywords: (thio)phosphohydrazides, N-functionalized imidates, 1-phosphonated-5-amino-1-H-
[1,2,4]-triazole.
2
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Introduction
Triazoles are privileged structures, which have attracted considerable attention in the
design of biologically active molecules. Moreover, these compounds are found to exhibit a
1
variety of biological activities such as anti-inflammatory , antimicrobial 2-4, and anticancer
properties5, 6. In addition, a wide variety of 1,2,4-triazole derivatives have been reported in the
7,8
literature as selective antagonists for Lotrifen an abortifacient , Rilmazafone and Anastrozole
9. On the other hand, the synthesis of 1,2,4-triazoles represents an important building block in
organic and medicinal chemistry. In addition, they show interesting pharmacological properties
10-12, and they are used in agricultural chemistry as herbicides 13, 14. Many pathways are described
in the literature for the synthesis of triazoles 15-22, but these methods are based on a multi-step
processes.
Due to their potential properties, we initiated a research program that focused on the
synthesis of some new triazole scaffolds resulting in the discovery of a simple and general path
for the preparation of triazole 4 and 5 from the corresponding N-functionalized imidates 1 and 2
and (thio)phosphorohydrazides 3a and 3b. According to the literature and as a continuation of
our interest works on heterocyclic compounds related to aminotriazole 23, we wish to report
herein the synthesis of new 1-phosphonated-5-amino-1-H-1,2,4-triazole 4 and 5 in the hopes of
obtaining compounds of diverse biological activities. The intramolecular cyclization occurring in
the reaction intermediate shows the greater reactivity of the cyano group regarding the NH
attack.
3
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Results and discussion
The characterization of the new products was carried out by many elemental analysis and
spectroscopic methods such as Infra-Red and Nuclear Magnetic Resonance Spectroscopies. The
synthetic route of the 1-phosphonated-5-amino-1-H-1,2,4-triazole 4 and 5 is outlined in the
Schemes 1 and 2. Indeed, the bis electrophilic character of the easily accessible ketene imidates
N functionalized 1 and 223-28 would allow a nucleophilic attack of (thio)phosphorohydrazides 3a
and 3b, which would give an easy access to new triazolo-N-phosphorylated derivatives such as 4
and 5. Schemes 1 and 2 depict the synthesis of triazolo-N-phosphorylated 4 and 5. N
functionalized imidates 1 and 2 were prepared according to the literature 24-29, and subsequently
refluxed with (thio)phosphorohydrazides 3a and 3b 30-36 in toluene with a catalytic amount of p-
toluene sulfonic acid to give the triazolo-N-phosphorylated 4 and 5 respectively.
The reaction was assumed to proceed by nucleophilic substitution of a Y (methylthio,
ethyloxo) group and/or methyloxo of 1 or 2 by the NH2 group of (Thio)phosphorohydrazides 3,
giving after heterocyclization the amidrazone intermediate non isolated of the reaction mixture
which then immediately yielded the triazolo-Nphosphorylated 4 and 5. The reaction can
theoretically lead to the formation of two regioisomers of the 5-amino-1-H-1, 2, 4-triazoles
derivatives 4 and 5 rather than 4' and 5'. Experimentally, only products having structures 4 and 5
were obtained. We base ourselves on spectroscopic data IR and NMR. It is interesting to report
that these products 4 and 5 can be better used in organic synthesis than in coordination
chemistry.
4
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The plausible mechanism of 5-amino-1-H-1, 2, 4-triazoles 4 and 5 formation was described
as follows and it was comparable to some mechanisms described in the literature 37. The
transformation is believed to proceed via the nucleophilic attack of –NH2 group on the imidic
carbon, giving rise to a non-isolated intermediate. A subsequent intramolecular cyclization
through the nucleophilic –NH attack of the cyano and/or thio groups, leads to the final products 4
and 5.
The structures of the compounds 4 and 5 were established on the basis of their spectral
data. The IR spectra of obtained products 4 and 5 show a large bands between 3435 and 3355
cm-1, assignable to the NH2, but no absorption frequency in the CN region or other bands at 1600
cm-1 attributed to -C=N. Other absorption bands are observed at 1249 cm-1 and 1186 cm-1, which
1
correspond to P=O and -P=S vibrations. A characteristic H NMR signal of 4 and 5 is the
presence of a broad singlet at 6.24-9.20 ppm region, ascribed to the hydrogens linked to
nitrogen atoms and disappear upon deuteration. We observed the signal of a -O-CH2-CH3 group
3
as a quadruplet at δ 3.75 ppm region with a coupling constant of JHH about 7.15 Hz and the
13
signal of -O-CH2-CH3 group as a triplet at δ 1.15 ppm region. Also, C NMR spectra of these
compounds revealed essentially the appearance of the signals at δ 156.4 and 148.1 ppm,
respectively of the signal -C=N and -C=C group. We observed essentially the total disappearance
of the signal around 120 ppm of the nitrile group. Passing thiophosphorylhydrazines 3a and of
o,o-dialkylphosphorylhydrazines 3b to 5-amino-1-H-1, 2, 4-triazoles 4 and 5. <AQ> This
sentence does not makes sense </AQ> These results are presented in the experimental section
and can be attributed to the fact that the 31P NMR (121.5MHz, DMSO-d6) spectra of these
5
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compounds revealed essentially the appearance of the signals of P=O and P=S at -1.2-2.0 and
61.0 ppm.
Experimental
General
Solvents and reagents were obtained from commercial sources and were dried and purified when
necessary by standard techniques. Melting points were taken with a Kofler hot staged apparatus
and are uncorrected. All reactions were monitored by thin layer chromatography (TLC) using
precoated aluminium sheet silica gel Merck 60 F 254 and was visualized by UV lamp. IR spectra
were carried out in the liquid state dissolved in chloroform with Perkin Elmer Paragon 1000 PC
spectrometer or in solid state dispersion in KBr with a Perkin Elmer 1600 series FT‐IR
1
spectrometer. H, 13C NMR and 31P spectra were recorded on a Varian‐Unity spectrometer at
(300 MHz, 75 MHz and 121.5 MHz), respectively) using TMS as an internal standard. Chemical
shifts of protons were reported in parts per million (ppm) downfield from TMS. Coupling
constants are reported in Hertz (Hz). Elemental analyses were determined using an elementar
vario EI III Elemental Analyser.
General experimental procedure
Synthesis of starting material imidates (1a and 1b)
These compounds were prepared by methods taken from the literature 16, 27. We recall here the
general procedure that we used:
A mixture of orthoester (0.12 mol), cyanamide (0.1 mol) and few drops of acetic acid was
refluxed for 6 h and distilled under vacuum (14 mmHg).
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Ethyl N-cyanoacetimidate (1a)
-1
-1 1
300
Yield = 78%. Bp. 108-110° C. IR (FT-IR 200 V, ν (cm )): 1655, 2220 cm . H NMR (
MHz, DMSO‐d +
CDCl3) δ: 1.20 (t, 3H, J = 7.3 Hz, OCH2CH3), 2.10 (s, 3H, CCH3), 4.10 (q,
6
2H, J = 7.20 Hz, OCH2CH3). 13C-NMR (75 MHz, CDCl3) δ: 13.1, 20.4, 65.3, 113.6, 181.5.
Analysis.-Calculated for C5H8N2O: C, 53.55; H, 7.19; N, 24.99. Found: C, 53.56; H, 7.52; N,
24.61.
Ethyl N-cyanoethimidate (1b).
°
1
Yield = 85%. Bp = 116-118 C. IR (FT-IR 200 V, ν (cm-1)): ν 2183; 1643 cm-1. H NMR (300
DMSO‐d +
MHz,
CDCl3) δ: 4.10 (q, 2H, J =7.2 Hz, OCH2CH3), 2.00 (q, 2H, CCH2CH3), 1.30
6
(t, 3H, CH3), 1.20 (t, 3H, J = 7.3 Hz, CH3). 13C-NMR (75 MHz, CDCl3) δ: 11.6, 13.0, 21.6, 71.1,
116.2, 178.4. Analysis.-Calculated for C6H10N2O: C, 57.12; H, 7.99; N, 22.20. Found: C, 56.78;
H, 8.09; N, 22.13.
Synthesis of dimethyl cyanodithioimidocarbonate (1c)
Dimethyl cyanodithioimidocarbonate was obtained according to the published method in
literature 24-25. Cyanamide (0.02 mol; 50% aqueous solution) was dissolved of water in 80 mL.
Potassium hydroxide ( 0.04 mol) was added and the solution was stirred for 45 min at room
°
temperature. Carbon disulfide was added. The reaction was heated at 40 C When all carbon
disulfide was dissolved (2h is required), methyl iodide (0.04 mol) was added and the reaction
was stirred at room temperature overnight. The precipitate was filtered and the solid was washed
with water, dried at room temperature under vacuum until constant weight, and purified by
recrystallization in EtOH.
Dimethyl cyanodithioimidocarbonate (1c)
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°
1
Yield: 71%. Mp: 58-60 C. IR (FT-IR 200 V, ν (cm-1)): 1678, 2176 cm-1. H NMR (300 MHz,
DMSO-d6) δ: 2.90 (s, 6H, 2 x SCH3). 13C-NMR (75 MHz, CDCl3) δ: 18.8, 115.3, 186.8.
Synthesis of starting material imidates (2a and 2b)
Imidates 2c and 2b: To a solution of iminoester (10 mmol), prepared according to the method
described by Pinner, 26 in ethanol and malononitrile (15/15 mL) was added by dry HCl. Then, the
iminoester was free of its salt, in 50 mL of ether, by a solution of sodium carbonate.
Phenylthioisocyanate (10 mmoL) was added dropwise at 0 °C in the thus formed iminoester. The
mixture was stirred for 4 h and the ether was evaporated. The imidate 2c-d was recrystallised
from petroleum ether.
N-(N-phenylcarbothioamido) imidates (2a)
Yield = 82%. Mp = 126-128 °C. TR = 4h. IR (FT-IR. 200 V, ν (cm-1)): νNH = 3384; νC=N = 1658
cm-1. 1H NMR (300 MHz, CDCl3) δ: 9.60 (br s, 1H), 7.50( m, 10H), 3.90 ( s, 3H). 13C-NMR (75
MHz, CDCl3): 41.1, Ph; 132.4-144.6, 148.6, 154.5.
N-(N-phenylcarbothioamido) imidates (2b)
°
Yield = 87%, Mp = 77-78 C; TR = 2.5h. IR (FT-IR. 200 V, ν (cm-1)): νNH= 3385; νC=N = 1658
cm-1.1H NMR (300 MHz, CDCl3) δ: 9.60 (br s, 1H), 7.25 (m, 10H), 4.10 (s, 2H), 3.7 (t, 3H). 13C-
NMR (75 MHz, CDCl3): 37.2, 46.7, Ph; 138.9-147.6, 154.10, 161.1.
Synthesis of starting materials 3a and 3b
Substituted thiophosphorylhydrazidates and of diethylphosphorylhydrazidates were prepared
according to procedures described in literature 30-34 (Scheme 4 and 5).
Synthesis of diethylphosphorohydrazides (3a) 32, 36
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Hydrazine hydrate (12.5 g, 0.2 mol) was added dropwise with efficient stirring to a mixture of
tetrachloromethane (120 mL ), dichloromethane (200 mL), anhydrous, finely powdered
potassium carbonate (41.4 g, 0.3 mol), and triethylbenzylaminium chloride ( 0.4 g, 1 mol %).
The addition was carried out at 20-25°C. Stirring was continued for 15 min at room temperature
and a solution of the diethyl phosphite (0.2 mol) in dichloromethane (40 mL) was then added at
20-30°C with occasional external cooling. After the addition had been completed, stirring was
continued for 4h at room temperature. Potassium carbonate was then filtered off and washed
with dichloromethane, finely, evaporated of solvent and was verified by NMR spectroscopy
(Scheme 2).
Diethylphosphorohydrazides (3a)
Yield = 84%; Bp. = 100-102 °C; IR (FT-IR. 200 V, ν (cm-1)): 1037, 1190, 1240, 1591, 3326,
3440 cm−1. 31P NMR (121.5 MHz, CDCl3) δ: -10.2. 1H NMR (300 MHz, CDCl3) δ: 4.20 (qt; 4H;
3
JHH = JHP = 7.20 Hz; CH3–CH2–O), 1.25 (t; 6H; JHH =7.2 Hz; CH3–CH2–O), δ 3.65 (s; 2H; -
NH-NH2), 6.10 (d; 1H; JPH = 30.0 Hz, -NH-NH2).
Synthesis of diphenylthiophosphorohydrazides (3b) 33-37
To hydrazine hydrate (0.3 mol) in water (10 mL), diphenyl chlorothiophosphate (0.1 mol) was
added with stirring at 35-40 °C and the reaction mixture was stirred for 1-3h at 40 °C. The
completion of the reaction was monitored by thin-layer chromatography. After completion of the
reaction, the reaction mixture was cooled; water (100 mL) and chloroform (100 mL) were added.
The chloroform layer was washed with water (3 x 100 mL), dried with sodium sulfate,
chloroform, and unreacted starting compounds were distilled off under reduced pressure and the
residue crystallized from cyclohexane ( Scheme 5).
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Diphenyl thiophosphorohydrazides (3b)
Yield = 86%. Mp = 59-61°C. IR (FT-IR 200 V, ν (cm-1)): 674, 3308, 3162, 3352 cm-1. 31P NMR
(121.5 MHz, CDCl3) δ: 65.3. 1H NMR (300 MHz, CDCl3) δ: 7.25–7.15 (m, 7H), 4.45 (d, 1H, JPH
= 30.0 HZ.-NH-NH2), 3.65 (s, 2H, -NH-NH2). 13C NMR (75 MHz, CDCl3) δ: 136.8-125.5.
Synthesis of starting material of 5-amino-1,2,4-triazoles 4
To a solution of imidates 1 and 2 (5 mmol) in absolute ethanol (20 mL) was added Phosphorus
Hydrazides 3a and/ or 3b (5 mmol) drop-wise at room temperature and stirred for 4h. The
stirring of the solution was refluxed for 8 to 10 h. After cooling about 20 min, the solvent was
evaporated. The obtained residue is a viscous yellow liquid; which was chromatographed on a
silica gel column using a mixture of (ether/ethanol) 9/2 as eluent. The solid obtained was filtered
and recrystallized from ethanol.
5-Amino-3-ethyl-[1, 2, 4] triazol-1-yl]-phosphonic acid diethyl ester (4a).
Yield = 73%. mp. = 131-133 °C. IR (FT-IR 200 V, ν (cm-1)): 3337–3439, 1648, 1604, 1241,
31
1
1043 cm−1, P NMR (121.5 MHz, DMSO-d6) δ: -1.0 ppm; H NMR (300 MHz, DMSO-d6) δ:
7.15 ppm (broad s; 2H; NH2), 4.25 ppm (q; 4H; 3JHH = 3JPH = 7.2 Hz; CH3–CH2–O), 1.45 ppm (t;
3
3
6H; JHH = JPH = 7.2 Hz; -CH3). 13C.NMR (75 MHz, DMSO-d6) δ: 12.6, 15.3, 17.2, 148.7,
157.4. Anal, Calcd for: C8H17N4O3P: C, 38.70; H, 6.92; N, 22.57. Found: C, 38.83; H, 7.06; N,
22.71.
5-Amino-3-methyl-[1, 2, 4] triazol-1-yl]-phosphonic acid diethyl ester (4b).
Yield = 81%. mp. = 129-131 °C. IR (FT-IR 200 V, ν (cm-1)): 3345–3451, 1654, 1584, 1249,
31
1
1058 cm−1; P NMR (121.5 MHz, DMSO-d6) δ: -1.3 ppm, H NMR (300 MHz, DMSO-d6) δ:
7.15 ppm (broad s; 2H; NH2), 4.10 ppm (q; 2H; 3JHH = 3JPH = 7.20 Hz; CH3–CH2–O), 2.78 ppm
10
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3
3
(s; 3H, -CCH3), 1.20 ppm (t; 3H; JHH = JPH = 7.2 Hz; CH3–CH2–O).13C.NMR (75 MHz,
DMSO-d6) δ: 11.5, 15.3, 16.0, 147.6, 154.7. Anal, Calcd for: C7H15N4O3P: C, 35.90; H, 6.47; N,
23.93. Found: C, 36.03; H, 6.52; N, 23.24.
5-Amino-3-methylsulfanyl-[1, 2, 4] triazol-1-yl]-phosphonic acid diethyl ester (4c).
Yield = 69%. mp. = 121-123 °C. IR (FT-IR 200 V, ν (cm-1)): 3326-3440; 1654; 1584; 1209,
31
1
1037cm−1; P NMR (121.5 MHz, DMSO-d6) δ: -0.7 ppm; H NMR (300 MHz, DMSO-d6) δ:
3
7.75 ppm (broad s; 2H; NH2), 4.15 ppm (q; 2H; JHH =3JPH = 7.20 Hz; CH3–CH2–O), 2.75 ppm
3
3
13
(s; 3H, -S-CH3), 1.25 ppm (t; 3H; JHH = JPH = 7.20 Hz; CH3–CH2–O). C.NMR (75 MHz,
DMSO-d6) δ: 14.2, 17.2, 21.3, 148.5, 155.3. Anal, Calcd for: C7H15N4O3PS: C, 31.57; H, 5.69;
N, 21.04. Found: C, 31.71; H, 5.81; N, 21.17.
5-Amino-3-ethyl-[1, 2, 4] triazol-1-yl]-thiophosphonic acid diphenyl (4d).
Yield = 71%. Mp = 168-170°C. IR (FT-IR 200 V, ν (cm-1)): 3317-3421; 1618; 1523, 1197 cm−1;
1
31P NMR (121.5 MHz, DMSO-d6): δ: 54.1 ppm; H NMR (300 MHz, DMSO-d6) δ: 7.44 ppm
(broad; s, 2H; NH2), 6.67-7.26 (m, 15H, CH arom), 3.54 ppm (s, 3H; -CH2), 1.21 ppm (t; 3H; -
CH3). 13C.NMR (75 MHz, DMSO-d6) δ: 12.5, 17.4, Carom, 139-142; 149.1, 153.8. Anal, Calcd
for: C16H17N4O2PS: C, 53.32; H, 4.76; N, 15.55. Found: C, 53.46; H, 4.92; N, 15.68.
5-Amino-3-methyl-[1, 2, 4] triazol-1-yl]-thiophosphonic acid diphenyl (4e).
Yield = 68%. Mp = 146-148°C. IR (FT-IR 200 V, ν (cm-1)): 3317-3421, 1618; 1523, 1197 cm−1,
1
31P NMR (121.5 MHz, DMSO-d6) δ: 52.3 ppm, H NMR (300 MHz, DMSO-d6) δ: 7.61 ppm
(broad; s, 2H; NH2), 6.76-7.72 (m, 10H, CH arom), 2.84 ppm (s, 3H; -CH3). 13C.NMR (75 MHz,
DMSO-d6) δ: 16.2, Carom, 139-142, 149.1, 153.8. Anal, Calcd for: C15H15N4O2PS: C, 52.01; H,
4.37; N, 16.18. Found: C, 52.11; H, 4.51; N, 16.27.
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5-Amino-3-phenyl-[1, 2, 4] triazol-1-yl]-thiophosphonic acid diphenyl (4f).
Yield = 81%. Mp: 174-176°C. IR (FT-IR 200 V, ν (cm-1)): 3345-3451, 1651, 1554, 1211 cm−1,
1
31P NMR (121.5 MHz, DMSO-d6) δ: 56.1 ppm; H NMR (300MHz, DMSO-d6) δ: 8.03 ppm
(broad; s, NH2), 6.81-7.64 (m, 15H, CH arom), 3.86 (s, 3H, SCH3). 13C.NMR (75 MHz, DMSO-
d6) δ: 19.4, Carom, 140-143, 148.7, 158.3. Anal, Calcd for C15H15N4O2PS2: C, 47.60; H, 4.00; N,
14.81. Found: C, 47.72; H, 4.09; N, 14.94.
Synthesis of starting material of 5-amino-1,2,4-triazoles 5
In a flask equipped with a condenser surmounted by a guard tube filled with CaCl2, under a
nitrogen atmosphere, was placed N-functionalized iminoester (0.25 mol), (thio)phosphorus
Hydrazides (0.25 mol) 3a and/or 3b and glacial acetic acid (0,015 mol) in absolute ethanol (30
mL). The reaction mixture was refluxed for about 8 h. After cooling about 20 min, the solvent
was evaporated. The obtained residue is a viscous; which was chromatographed on a gel column
using of ethanol as eluent. The solid obtained was filtered and recrystallized from hexane.
5-(N-phenyl amine)-3-phenyl-[1,2,4] triazol-1-yl-phosphonic acid diethyl ester (5a).
Yield = 78%. Mp. = 157-159 °C. IR (FT-IR 200 V, ν (cm-1)): 3345-3451; 1654; 1584; 1249,
31
1
1058 cm−1; P NMR (121.5 MHz, DMSO-d6) δ: 2.0 ppm; H NMR (300 MHz, DMSO-d6) δ:
3
3
8.65 ppm (broad s; 1H; NH), 7.20-7.45. ppm (m; 10H, Ph), 4.05 ppm (q; 2H; JHH = JPH =7.2
3
3
Hz; CH3–CH2–O), 1.24 ppm (t; 3H; JHH = JPH =7.20 Hz; CH3–CH2–O). 13C.NMR (75 MHz,
DMSO-d6) δ: 13.2, 18.3, Ph; 134-142, 149.1, 153.8. Anal, Calcd for: C18H21N4O3P: C, 58.05; H,
5.70; N, 15.05. Found: C, 58.18; H, 5.83; N, 15.13%.
5-Amino-3-phenyl-[1, 2, 4] triazol-1-yl]-thiophosphonic acid diphenyl (5b)
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Yield = 73%. Mp = 210-212 °C. IR (FT-IR 200 V, ν (cm-1)): 3351-3434; 2238; 1618; 1523, 1197
31
1
cm−1; P NMR (121.5MHz, DMSO-d6) δ: 61.0 ppm; H NMR (300MHz, DMSO-d6) δ: 9.35
13
ppm (broad; s, 1H; NH), 7.15-7.95 ppm (m, 20H; Ph). C.NMR (75 MHz, DMSO-d6) δ: Ph,
139-142, 149.6, 156.9. Anal, Calcd for: C26H21N4O2PS: C, 64.44; H, 4.38; N, 11.57. Found: C,
64.57; H, 4.43; N, 11.70%. (75 MHz, DMSO-d6) δ: 13.0, 17.1, 23.7, Ph, 141-144, 148.8, 158.4.
Anal, Calcd for: C19H23N4O3P: C, 59.05; H, 6.01; N, 14.50. Found: C, 59.18; H, 6.16; N,
14.64%.
5-(N-phenyl amine)-3-phenyl-[1,2,4] triazol-1-yl-phosphonic acid diethyl ester (5c)
Yield = 63%. Mp. = 221-223°C. IR (FT-IR 200 V, ν (cm-1)): 3345-3451; 1654; 1584; 1249, 1058
31
1
cm−1; P NMR (121.5 MHz, DMSO-d6) δ: 1.2 ppm; H NMR (300 MHz, DMSO-d6) δ: 9.17
ppm (broad s; 1H; NH), 7.23-7.46 ppm (m; 10H, Ph), 4.38 ppm (s; 2H, CCH2), 4.24 ppm (q; 2H;
3
3
3
3JHH = JPH = 7.20 Hz; CH3–CH2–O), 1.35 ppm (t; 3H; JHH = JPH = 7.20 Hz; CH3–CH2–O).
13C.NMR (75 MHz, DMSO-d6) δ: 13.0, 17.1, 23.7, Ph, 141-144, 148.8, 158.4. Anal, Calcd for:
C19H23N4O3P: C, 59.05; H, 6.01; N, 14.50. Found: C, 59.18; H, 6.16; N, 14.64%.
5-Amino-3-phenyl-[1, 2, 4] triazol-1-yl]-thiophosphonic acid diphenyl (5d)
Yield = 76%. Mp = 189-192 °C. IR (FT-IR 200 V, ν (cm-1)): 3337-3442; 2238; 1611, 1523, 1197
31
1
cm−1; P NMR (121.5MHz, DMSO-d6) δ: 58.8 ppm; H NMR (300MHz, DMSO-d6) δ: 9.25
ppm (broad; s, 1H; NH), 7.20-8.10 ppm (m, 20H; Ph), 4.37 ppm (s; 2H). 13C.NMR (75 MHz,
DMSO-d6) δ: 30.2, Ph, 140-143, 149.0, 157.8. Anal, Calcd for: C27H23N4O2PS: C, 65.11; H,
4.66; N, 11.25. Found: C, 65.21; H, 4.79; N, 11.33%.
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Conclusions
In this work, a novel series of 5-amino-1-H-1, 2, 4-triazoles derivatives 4 and 5 were synthesized
using an easy method. The cited path consists to the incorporating of triazole rings with
substituted imidates 1 and 2 as building block in one framework. It is interesting to note that
synthesized substrates 3 may be considered as target molecules for synthetic organic chemistry
as malonic derivatives.
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Table 1: Prepared synthesized 5-amino-1-H-1, 2, 4-triazoles 4
Entry
R1
Et
R
X
O
O
O
S
Products
Et
Et
Et
Ph
Ph
Ph
1
2
3
4
5
6
4a
4b
4c
4d
4e
4f
Me
SMe
Et
Me
SMe
S
S
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Table 2: Prepared synthesized 5-amino-1-H-1, 2, 4-triazoles 5
Entry
R2
Ph
R
X
O
S
Products
Et
Ph
Et
Ph
1
2
3
4
5a
5b
5c
5d
Ph
CH2Ph
CH2Ph
O
S
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Scheme 1: N-functionalized imidates- 1 and 2
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Scheme 2: The two plausible pathways and different products that could be expected
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3a
3b
Diethylphosphorohydrazidate (3a)
Diphenyl-thiophosphorohydrazidate (3b)
Scheme 3: Synthesis of Diphenyl(thio)phosphohydrazides 3a and 3b
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3a
Scheme 4: Synthesis of diethylphosphorohydrazides (3a)
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3b
Scheme 5: Synthesis of diphenylthiophosphorohydrazides (3b)
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