Synthesis and properties of acetamidinium salts
© Jalový et al 2011
Received: 3 October 2011
Accepted: 12 December 2011
Published: 12 December 2011
Acetamidines are starting materials for synthesizing many chemical substances, such as imidazoles, pyrimidines and triazines, which are further used for biochemically active compounds as well as energetic materials. The aim of this study was to synthesise and characterise a range of acetamidinium salts in order to overcome the inconvenience connected with acetamidinium chloride, which is the only commercially available acetamidinium salt.
Acetamidinium salts were synthesised and characterised by elemental analysis, mass spectrometry, NMR and - in the case of energetic salts - DTA. The structures of previously unknown acetamidinium salts were established by X-ray diffraction analysis. Hygroscopicities in 90% humidity of eight acetamidinium salts were evaluated.
The different values of hygroscopicity are corroborated by the structures determined by X-ray analysis. The acetamidinium salts with 2D layered structures (acetamidinium nitrate, formate, oxalate and dinitromethanide) show a lack of hygroscopicity, and the compounds with 3D type of structure (acetamidinium chloride, acetate, sulphate and perchlorate) and possessing rather large cavities are quite hygroscopic.
Acetamidines are starting materials in the synthesis of many chemical substances, such as imidazoles, pyrimidines and triazines which are further used for biochemically active compounds [1–5]. In the field of energetic materials, acetamidine is a starting material for the synthesis of 2-methoxy-2-methylimidazolidine-4,5-dione  and 2-methylpyrimidine-4,6-diol [7–9]. Both are further transformed to 2,2-dinitroethene-1,1-diamine (FOX-7, DADNE), which is an energetic material with low sensitivity to external stimuli [6, 10]. The free base acetamidine is hygroscopic. It decomposes into ammonia and acetonitrile at higher temperatures , and produces acetamidinium carbonate during one day at room temperature when stored in contact with air . Therefore, it is unsuitable as a starting material for synthesis and the use of an acetamidinium salt is necessary.
The most commonly used and commercially available salt of acetamidine is acetamidinium chloride (1). It is prepared by the Pinner method from acetonitrile and alcohol in the presence of hydrogen chloride, followed by addition of ammonia to the intermediate iminoether . Reaction of acetonitrile with cobalt or nickel nitrates and oximes gives acetamidinium nitrate (2) [14, 15]. An easily accessible acetamidine salt is acetamidinium acetate (3), prepared by the reaction of triethyl orthoacetate, ammonia and ammonium acetate . The method is convenient, both for laboratory and industrial use or the acetate may be further transformed into other salts, e.g. formate (4)  sulphate (5)  or dinitromethanide (6) . Many synthetic routes for acetamidines have been reviewed [20, 21].
The main disadvantage of acetaminium chloride is its relatively high hygroscopicity. The release of the free base in methanol by the use of sodium methoxide will produce sodium chloride, which is partly soluble in this solvent (~1 g/100 ml) . The presence of any chloride sourse is unfavourable in certain syntheses, e.g. nitrations, and its complete removal is tedious .
Results and Discussion
The method starting with acetamidinium acetate (3) based on the reaction with a stronger acid than the one we used (acetic acid) for acetamidinium sulphate (5)  was now successfully used for preparation of acetamidinium perchlorate (8). This salt was also prepared from 5 by an ion exchange reaction with barium perchlorate in water (Figure 3).
Acetamidinium formate (4) was prepared from trimethyl orthoacetate and ammonium formate. A similar method has been published earlier by Taylor for preparation of 3 .
Hygroscopicities of acetamidinium salts and other selected salts.
The nitrate (2), formate (4), dinitromethanide (6) and oxalate (7) salts are almost anhygroscopic. The chloride (1), acetate (3), sulphate (5) and hydrogensulphate (9) compounds are hygroscopic. The hygroscopicity of acetamidinium chloride (1) is almost the same as for guanidinium chloride (12), and acetamidinium acetate (3) is very similar to ammonium acetate (10).
The acetamidinium cation is frequently used as a counterion for a wide variety of anions like simple halogenides, carboxylates, complex metal anions and others. The parent acetamidine reveals large cavities and an extensive system of hydrogen bonding within the structure. The distances between the pivot carbon atom and the amino and imido nitrogen atoms are rather distinct (1.344 Å for C-NH2 and 1.298 Å for C = NH group) .
The perchlorate and oxalate structures are rather unique in the set of acetamidinium structures determined, the distances between the pivot carbon atom and the NH2 moiety are rather different - 1.323(3) Å for the C-NH2 group bonded by H-bonds only to one oxygen atom of the perchlorate ion, and 1.297(4) Å for the C-NH2 group bonded by two H-bonds to the perchlorate ion. In the oxalate structure, the differences between these groups are even greater 1.339(5) Å and 1.280(5) Å, which disagree with a delocalisation concept and the data found in the literature (1.302-1.312 Å). In these groups, the H-bonds to the oxalate moiety are equidistant.
NMR data for acetamidines 2, 4, 7 and 8.
On the other hand, the position of the equillibrium is reversed in DMSO-d6 where approximately 90% of the non-deuterated form can be found for all the samples measured.
In all cases (excluding 4 in DMSO-d6), two separated broadened signals belonging to the 2 × NHaHb arrangement were observed, probably due to the delocalisation of the positive charge throughout the amidinium group. The only exception is acetamidinium formate 4 in DMSO-d6 where one broad signal comprising all four NH protons was detected. This is in accordance with the observation published by Krechl  and similar to the results obtained by Tominey  for acetamidinium tetrazolate complexes. This may be caused by different interactions between the formate anion and amidinium group in defferent solvents. The interactions inside some acetamidinium complexes were studied by Tominey and Krechl by means of NMR, X-ray analysis and quantum chemical treatment [17, 27].
Differential thermal analysis
Acetamidinium salts were synthesised and characterised by elemental analysis, electrospray mass spectrometry, NMR and, in the case of energetic salts, by DTA. The structures of previously unknown acetamidines have been proved by X-ray diffraction analysis. Hygroscopicities in 90% humidity of eight acetamidinium salts have been evaluated. The different values of hygroscopicity are corroborated by the structures determined by X-ray analysis: acetamidinium salts with 2D layered structures are not hygroscopic while acetamidinium salts with 3D layered structures are quite hygroscopic.
Acetamidines 2, 6, and 8 are explosives, sensitive to mechanical stimuli and heat, and should be handled with care.
NMR spectra were measured using a Bruker AVANCE III spectrometer operating at 400.13 MHz (1H) and 100.61 MHz (13C). The proton spectra in deuterium oxide were calibrated on the HDO signal of the solvent (δ = 4.80) whereas the spectra in DMSO-d6 were standardised on the residual signal of the solvent (δ = 2.50). Carbon spectra in D2O were standardised on internal neat methanol (δ = 49.50, value taken from  and the spectra in DMSO-d6 were calibrated on the middle of the solvent multiplet (δ = 39.61). The carbon spectra were measured with broadband proton decoupling.
The electrospray (ESI) mass spectra were measured on a Quattro Premiere XE tandem quadrupole mass spectrometer (Waters) equipped with a T-wave™ collision cell in both positive (ESI+) and negative (ESI-) ion mode. Typical ion source conditions were as follows. ESI+: capillary voltage 3.7 kV, cone voltage: 30 V, source temperature: 100°C, desolvation temperature: 200°C, desolvation gas: N2 (100 l hr-1); ESI-: capillary voltage 2.5 kV, cone voltage: 30 V, source temperature: 100°C, desolvation temperature: 200°C, desolvation gas: N2 (200 l hr-1). Approximately 10-4 mol l-1 solutions of acetamidine salts in water were directly infused into the electrospray ion source using the built-in syringe pump at a flow rate of 5 μl min-1. Generally, in the ESI+ mass spectra, the protonated acetamidine (denoted as AH+) was observed together with the less abundant ions of the general formula MnAH+, where M is a molecule of the salt consisting of acetamidine A (CH3C(NH)NH2) and acid X (for example HNO3). Similarly in the ESI- mass spectra, the deprotonated acids (X-H)- and cluster ions Mn(X-H)- were observed.
The thermal analysis was studied using differential thermal analyzer DTA 550Ex (OZM Research). The 50 mg samples were tested in open glass microtest tubes (in contact with air) and the heating rate was 5°C min-1. The melting points were measured on a Kofler bench and are uncorrected.
Acetamidinium nitrate (2)
Sodium (3.36 g, 146.2 mmol) was gradually dissolved in ethanol (95 mL) and acetamidinium chloride (14.00 g, 148.1 mmol) in ethanol (90 mL) was slowly added. The mixture was stirred for one hour at room temperature and the precipitated sodium chloride was filtered off. To the filtrate, 65% nitric acid (14.4 g, 148.1 mmol) was then added to the solution of acetamidine in ethanol. The product immediately precipitated. It was filtered, washed with cold ethanol and dried to yield 14.01 g (79.1%). M.p. 186-188°C.
1H NMR (D2O) δ: 2.20 (s, CH3), 7.96 (brs, NH2), 8.38 (brs, NH2). 13C NMR (D2O) δ: 18.4 (CH3), 168.9 (C(NH2)2. The signals of NH2 in D2O are residual signals of non-deuterated species. 1H NMR (DMSO-d6) δ: 2.10 (s, 3H CH3), 8.39 (brs, 1.8 H, NH2), 8.90 (brs, 1.8 H NH2).
Anal. Calcd for C2H7N3O3: C, 19.84; H, 5.83; N, 34.70. Found: C, 19.60; H, 5.77; N, 34.48.
ESI+ MS: m/z 59(AH+), 117(A2H+), 180(MAH+), 301(M2AH+), 422(M3AH+). ESI- MS: m/z 62((X-H)-), 125(X(X-H)-), 183(M(X-H)-), 304(M2(X-H)-), 425(M3(X-H)-).
Acetamidinium formate (4)
A mixture of trimethyl orthoacetate (10.0 g, 83.2 mmol) and ammonium formate (10.5 g, 166.5 mmol) was heated under reflux for 2.5 hours. After cooling to room temperature the product was filtered, washed with cold methanol and dried to yield 5.83 g (67.2%) of white powder. M.p. 214-215°C (lit.  214-215°C).
1H NMR (D2O) δ: 2.18 (s, 3H CH3), 8.03 (brs, NH2), 8.41 (brs, NH2), 8.41 (s, 1H, HCOO-). 13C NMR (D2O) δ: 18.4 (CH3), 168.9 (C(NH2)2, 171.5 (HCOO-). The signals of NH2 in D2O are residual signals of non-deuterated species. 1H NMR (DMSO-d6) δ: 2.06 (s, 3H CH3), 8.42 (s, 1 H, HCOO-), 9.71 (brs, 3.6 H 2 × NH2).
Anal. Calcd for C3H8N2O2: C, 34.61; H, 7.75; N, 26.91. Found: C, 34.90; H, 7.64; N, 26.78.
ESI+ MS: m/z 59(AH+), 117(A2H+), 163(MAH+), 267(M2AH+), 371(M3AH+), 475(M4AH+). ESI- MS: m/z 45((X-H)-), 91(X(X-H)-), 253(M2(X-H)-), 357(M3(X-H)-), 461(M4(X-H)-).
Acetamidinium oxalate (7)
Acetamidinium chloride (15.60 g, 0.165 mol) in ethanol (70 mL) was slowly added to a solution of sodium ethoxide in ethanol (82.52 g of 12.95% solution ~ 0.157 mol of sodium ethoxide). The mixture was stirred for one hour at room temperature and the precipitated sodium chloride was filtered off. To the filtrate, a solution of the dihydrate of oxalic acid (9.9 g, 0.079 mol) in ethanol (150 mL) was then added. The product immediately precipitated. It was filtered off, washed with ethanol and dried to yield 12.98 g (65.6%) of acetamidinium oxalate. No melting up to 360°C.
1H NMR (D2O) δ: 2.16 (s, CH3), 8.04 (brs, NH2), 8.38 (brs, NH2). 13C NMR (D2O) δ: 18.4 (CH3), 168.8 (C(NH2)2), 173.8 (COO-). The signals of NH2 in D2O are residual signals of non-deuterated species.
Anal. Calcd for C6H14N4O4: C, 34.95; H 6.84; N, 27.17. Found: C, 34.93; H, 6.89; N, 27.26.
ESI+ MS: m/z 59(AH+), 117(A2H+), 207(MAH+), 355(M2AH+), 503(M3AH+). ESI- MS: m/z 89((X-H)-), 179(X(X-H)-), 237(M(X-H)-), 385(M2(X-H)-), 533(M3(X-H)-).
The crystals suitable for X-ray crystallography analysis were prepared by crystallisation from water using solvent evaporation at 5°C.
Acetamidinium perchlorate (8)
(A) Perchloric acid (70%, 0.42 mL, 10 mmol) was slowly added to a solution of acetamidinium acetate (1.18 g, 10 mmol) in 10 mL ethanol. The reaction mixture was allowed to stand to let the solvent evaporated slowly. The product crystallized in the form of colourless crystals. Yield 1.41 g (89%), m.p. 268-269°C. The crystals obtained were suitable for X-ray crystallography analysis.
1H NMR (D2O) δ: 2.32 (s, CH3), 8.00 (brs, NH2), 8.40 (brs, NH2). 13C NMR (D2O) δ: 18.6 (CH3), 169.0 (C(NH2)2. The signals of NH2 in D2O are residual signals of non-deuterated species. 1H NMR (DMSO-d6) δ: 2.09 (s, 3H CH3), 8.30 (brs, 1.8 H, NH2), 8.84 (brs, 1.8 H, NH2).
Anal. Calcd for C2H7ClN2O4: C, 15.15; H, 4.45; Cl, 22.36; N, 17.67. Found: C, 15.41; H, 4.18; Cl, 22.71; N, 17.76.
ESI+ MS: m/z 59(AH+), 217(MAH+), 375(M2AH+). ESI- MS: m/z 99((X-H)-), 257(M(X-H)-), 415(M2(X-H)-).
(B) Acetamidinium sulphate (1.07 g, 5 mmol) was dissolved in 5 mL water. This solution was added to a solution of barium perchlorate (1.68 g, 5 mmol) in water (5 mL). The white precipitate of barium sulphate that immediately formed was filtered off. Acetamidine perchlorate was finally isolated from the aqueous solution using vacuum evaporation to give 0.75 g (95%) of a white solid, m.p. 269-270°C.
Anal. Calcd for C2H7ClN2O4: C, 15.15; H, 4.45; Cl, 22.36; N, 17.67. Found: C, 15.80; H, 4.68; Cl, 22.70; N, 17.99.
References to procedures or availability of other salts of acetamidine
Crystallography of 7 and 8
Crystallographic data for acetamidinium oxalate (7) and acetamidinium perchlorate (8).
F d d 2
α = γ(°)
Crystal size (mm)
0.32 × 0.26 × 0.18
0.35 × 0.25 × 0.17
h; k; l range
-20, 20; -9, 8; -21, 17
-5, 6; -14, 12; -6, 7
- independent (Rint)a)
- observed [I > 2σ(I)]
R c)/wR c)
Crystallography data for structural analysis have been deposited with the Cambridge Crystallographic Data Centre, CCDC no. 834605 and 834606 for 8 and 7, respectively. Copies of this information may be obtained free of charge from The Director, CCDC, 12 Union Road, Cambridge CB2 1EY, UK (fax: +44-1223-336033; e-mail: email@example.com or www: http://www.ccdc.cam.ac.uk).
Sample preparation and hygroscopicity evaluation 
Samples weighed to within 0.1 mg were placed in bottles with cap style stopper: The weights of the samples were 5-6 g, with the exception of acetamidinium dinitromethanide and acetamidinium perchlorate where the weight was around 1.5 g, and dried over phosphorous pentoxide for two days. Then the samples were quickly removed to a desiccator containing 18.6% sulphuric acid (relative humidity of 90% is thus obtained). The samples were kept at 30°C. With 24-72 hours interval, the samples were weighed (during weighing the cap was in place).
The authors thank the Ministry of Education, Youth and Sports of the Czech Republic (within the framework of research project MSM 0021627501), the Ministry of Industry and Trade of the Czech Republic (within the framework of the research project FR-TI1/127) and the Czech Science Foundation (grant No. P206/11/0727) for financial support for this work.
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