Experimental Section
All melting points are uncorrected. Infrared spectra (KBr-disc) were
ble); 13C-NMR: 41.1, 127.0, 128.7 (2C), 128.8, 129.5 (2C), 129.7,
136.2, 169.5; MS, m/z ( %): 270.1 (M , 13.78), 271.1 (M + 1, 1.98),
+
1
recorded using a Jasco FT/IR-300E spectrometer. H-NMR and
269.0 (M-1, 100), 268.1 (M-2, 49.0); Anal. Calcd for C10H15ClN O
6
13C-NMR spectra were measured in DMSO-d6 using Varian Mercu-
ry 500 MHz and Varian Gemini 200 MHz with chemical shifts using
TMS as standard solvent. Mass spectra were recorded on a GC/MS
Finnigan SSQ 7000 spectrometer.
(270.72): C, 44.37; H, 5.58; N, 31.04; Found: C, 44.56; H, 5.41; N,
30.87 %.
2
-Benzoyl-N-carbamimidoylhydrazinecarboximidamide
hydrochloride 5
General procedure for the synthesis of the
biguanide derivatives 1–5
Yield 85 %; mp 235–237 °C; IR: ν/cm− 1: 3 410, 3 333, 3 174 (NH2,
1
NH), 1 685, 1 639 (C = O & C = N); H-NMR: δ/ppm: 7.01–8.12 (m,
In a round-bottomed flask equipped with a magnetic stirrer, ben-
zo[1,3-d]dioxol-5-amine, phenylhydrazine, N,N-dimethylhydrazi-
necarboxamide, benzohydrazide or 2-phenylacetohydrazide
11H, 5Ar-H + NH + 4NH) 10.81 (br, 1H, NH, D O-exchangeable);
2
2
MS, m/z (%): 267.8 (M+1, 3.01), 239.9 (42.19), 223.0 (5.87), 104.6
(100); Anal. Calcd for C H ClN O (256.69): C, 42.11; H, 5.10; N,
9
13
6
(
0.1 mol) was added to aq. HCl (0.1 mol) in 50 mL ethanol, and the
mixture was stirred until it became homogeneous. Dicyandiamide
0.1mol) was then added, and the mixture was heated at reflux with
32.74; Found: C, 42.35; H, 5.03; N, 32.49 %.
(
Conflict of Interest
constant stirring for 12 h. The mixture was then cooled to room
temperature, and the resulting crystals were separated by filtration
and washed with methanol to yield an initial crop of biguanide
monohydrochloride 1–5.
The authors declare no conflicts of interest.
References
N-1,3-benzodioxol-5-ylimidodicarbonimidic diamide
hydrochloride 1
Yield 85 %; mp 232–235°C; IR: ν/cm− 1: 3 460, 3 368, 3 308, 3 197
[1] Skyler JS. Diabetes mellitus: pathogenesis and treatment strategies. J
Med Chem 2004; 47: 4113–4117
1
(
NH , NH), 2902 (CH-aliph.), 1647, 1606 (C=N); H-NMR: 5.94 (s,
2
[
2] Hundal RS, Inzucchi SE. Metformin: new understandings, new uses.
Drugs 2003; 63: 1879–1894
2
H, -CH ), 6.45 (d, 1H, J = 8.6, Ar-H), 6.80 (d, 1H, J = 8.6 Hz, Ar-H),
2
7
.02 (d, 1H, J = 4.8, Ar-H), 7.29 (br, 4H, NH , 3NH (D O-exchange-
2
2
[
3] Huttunen KM, Mannila A, Laine K et al. The first bioreversible prodrug
of metformin with improved lipophilicity and enhanced intestinal
absorption. J Med Chem 2009; 52: 4142–4148
able)), 9.75 (br, 1H, NH, D O-exchangeable); 13C-NMR: 101.6
2
(
-CH ), 104.3, 108.5, 114.9, 133.2, 144.0, 147.6, 156.2 (C = N),
2
1
61.5 (C = N); MS, m/z ( %): 221.0 (M-HCl, 14.03), 178.9 (M -
[
4] Selvi M. Insulin and hypoglycemic agents. burger’s medicinal
chemistry and drug discovery”. 6th ed. Ed. Abraham DJ. New York: A
Wiley-Interscience Publication, John Wiley & Sons, Inc; 2003: 1
[
HCl + C(NH) ], 5.69), 137.0 (benzo[1,3–d]dioxol-5-amine, 100);
2
Anal. Calcd for C H12ClN O (257.68): C, 41.95; H, 4.69; N, 27.18;
9
5
2
Found: C, 42.27; H, 4.72; N, 27.43 %.
[5] Emerick AJ, Richards MP, Kartje GL et al. experimental diabetes
attenuates cerebral cortical− evoked forelimb motor responses.
Diabetes 2005; 54: 2764–2771
N-carbamimidoyl-2-phenylhydrazinecarboximidamide
hydrochloride 2
Yield 79 %; mp > 300 °C; IR: ν/cm − 1: 3 390-3 180 (NH , NH),
[6] Milani E, Nikfar S, Khorasani R et al. Reduction of diabetes-induced
oxidative stress by phosphodiesterase inhibitors in rats. Comparative
biochemistry and physiology part C. Toxicology and Pharmacology
2
1
1
741(C = N); H-NMR: δ/ppm: 7.1–7.9 (m, 12H, 5Ar+ NH + 5NH);
2
2
005; 140: 251–255
+
MS, m/z ( %): 227.1 (M , 1.54), 191.8 (M-HCl, 1.25), 175.0 (M-[H-
[
[
7] Salama RM, Schaalan MF, Ibrahim ME et al. Effectiveness of telmisartan
as an adjunct to metformin in treating type ii diabetes mellitus in rats.
Open Journal of Endocrine and Metabolic Diseases 2013; 3: 186–196
Cl + NH ], 100); Anal. Calcd for C H ClN (228.68): C, 42.02; H,
3
8
13
6
5
.73; N, 36.75 Found: C, 41.78; H, 5.64; N, 36.58
8] Sharma SS, Ramani JV, Dalwadi DP et al. New ternary transition metal
complexes of 2-{[(2-aminophenyl)imino] methyl}-phenol and
metformin: synthesis, characterization and antimicrobial activity.
E-Journal of Chemistry 2011; 8: 361–367
2
-(N-carbamimidoylcarbamimidoyl)-N,N-dimethylhydrazi-
necarboxamide hydrochloride 3
Yield 73%; IR: ν/cm− 1: 3380-3170 (NH , NH), 1651 (C=O & C=N);
2
1
[9] LeBel O, Maris T, Duval H et al. A practical guide to arylbiguanides:
synthesis and structural characterization. Can J Chem 2005; 83:
H-NMR: δ/ppm: 4.05 (s, 6H, 2-CH ), 7.14–8.31 (m, 6H, NH , 4NH),
3
2
1
0.32 (br, 1H, NH); 13C NMR: 63.2 (2CH ), 151.1, 154.8, 155.9; MS,
3
6
15–625
+
m/z ( %): 224.4 (M , 2.43), 187.0 (M-HCl, 1.67), 98.8 (100); Anal.
Calcd for C H ClN O (223.66): C, 26.85; H, 6.31; N, 43.84; Found:
[
10] Abbas SY, Basyouni WM, El-Bayouki KAM et al. Synthesis and
evaluation of 1-substituted-biguanide derivatives as anti-diabetic
agents for type ii diabetes insulin resistant. drug res/arzneimittel-
forschung 2016; 66: 377–383
5
14
7
C, 26.57; H, 6.22; N, 43.64 %.
N-carbamimidoyl-2-(2-phenylacetyl)hydrazinecarboximid-
amide hydrochloride 4
Yield 82 %; mp 235°C; IR: ν/cm− 1: 3 460 - 3 197 (NH , NH), 1 647,
2
1
1
606 (C=O & C=N); H-NMR: δ/ppm: 3.75 (s, 2H, -CH ), 6.89–7.65
2
(
m, 11H, 5Ar-H + NH + 4NH), 10.11 (br, 1H, NH, D O-exchangea-
2 2
Abbas SY et al. Biguanides as Anti-Diabetic Agents … Drug Res