Synthesis of N 1,N 1,N 3,N 3-tetrasubstituted diethylenetriamines

Article abstract of DOI:10.1007/s11172-018-2147-y

Preparative procedures for the synthesis of N¹,N¹,N³,N³-tetrasubstituted diethylenetriamines via aminoalkylation of N,N-disubstituted ethylenediamines with N,N-disubstituted 2-chloroethylamines were developed. A

Full text of DOI:10.1007/s11172-018-2147-y

Russian Chemical Bulletin, International Edition, Vol. 67, No. 5, pp. 840—843, May, 2018
840
Synthesis of N1,N1,N3,N3-tetrasubstituted diethylenetriamines
D. Q. Hoang, E. Ya. Borisova, N. Yu. Borisova, A. V. Krylov, and V. K. Lesnikov
Moscow Technological University (Institute of Fine Chemical Technologies),
86 prosp. Vernadskogo, 119571 Moscow, Russian Federation.
Fax: +7 (499) 600 8300. E-mail: quanghoang1510@gmail.com
Preparative procedures for the synthesis of N1,N1,N3,N3-tetrasubstituted diethylenetriamines
via aminoalkylation of N,N-disubstituted ethylenediamines with N,N-disubstituted 2-chloro-
ethylamines were developed. Aminoalkylation of N,N-dimethylethylenediamine under heating
gave simultaneously secondary N1,N1,N3,N3-tetrasubstituted diethylenetriamines and quater-
nary ammonium salts, N-(2-aminoethyl)-N-(2-dialkylaminoethyl)-N,N-dimethylammonium
chlorides. Structures of the synthesized compounds were established by IR spectroscopy, 1H and
13C NMR spectroscopy, and electrospray ionization mass spectrometry.
Key words: synthesis, aminoalkylation, ethylenediamines, diethylenetriamines, quaternary
ammonium salts.
Aliphatic polyamines and their derivatives have found
3a—i was carried out following two different experimental
routes (Scheme 1). It is known that aminoalkylation with
an excess of 2-chloroethylamines results in tetramines.20
We prevented formation of tetramines by using limiting
amount of 2-chloroethylamines. Thus, the ratios of ethyl-
enediamine 1 to 2-chloroethylamine 2 were varied in the
range from 1.5 : 1 to 2 : 1.
Molecules of N,N-disubstituted ethylenediamines
1a—c comprise two nucleophilic centers, namely, the
primary and ternary amino groups. Alkylation of these
groups can result in two type of the products, i.e., second-
ary amines and quaternary ammonium salts (the latter
being the products of the Menshutkin reaction21—24).
Optimization of the aminoalkylation reaction involved the
following factors and reaction conditions: reaction tem-
perature, the solvent nature, and the nature of haloamine
used as an alkylating agent. Two experimental procedures
were developed (methods A and B).
In method A, the reaction was carried out in 10% aque-
ous NaOH. Aminoalkylation of N,N-dimethylenediamine
(1a) with N-(2-chloroethyl)pyrrolidine (2c) at room tem-
perature for 24 h gives selectively quaternary ammonium
salt 4b in 75% yield without any formation of the target
triamine 3b. An increase in the reaction temperature results
in the appearance of the target products in the reaction
mixture. When the reaction is carried out at 60—70 °C,
secondary ethylenediamines 3a—c are formed in the yield
of 18—28%. The nature of the starting diamine signi-
ficantly affects the yields of the target products 3. Thus,
the reactions of N,N-diethylethylenediamine (1b) and
N-(2-aminoethyl)piperidine (1c) with 2-chloroethyl-
amines 2b—e at 65—70 °C for 15—18 h result mainly in
secondary triamines 3d—i not contaminated with quater-
nary ammonium salts. Products were extracted from the
wide applications in medicinal and organic chemistry.1—4
Due to wide variety of their properties, aliphatic diethyl-
enetriamines and their derivatives are used as ligands,5—9
amphiphilic reagents,10 and components of medications.11
In contrast to well-studied symmetrical analogs, non-
symmetrical aliphatic diethylenetriamines are less explored.
The present work continues our studies on synthesis
of N1,N1,N3,N3-tetrasubstituted diethylenetriamines bear-
ing secondary and ternary amino groups that can be further
transformed into different diamino amides with potential
biological activities.12
N1,N1,N3,N3-Tetrasubstituted diethylenetriamines can
be synthesized by several following pathways: basic hydro-
lysis of the corresponding N-lithio derivatives of diethyl-
enetriamines,13 reduction of the amide group of amine-
substituted carboxamides,11,14,15 hydrogenation of amino-
acetonitriles,16,17 and amination of bis(chloroethyl)amine
with secondary amines.5,18 The main drawbacks of these
methods are instability of the starting compounds, the
technical complexity of the synthetic procedure, and the
lack of generality.
Aminoalkylation of diamine to synthesize bis(2-diethyl-
aminoethyl)amine was also published.19 Among the men-
tioned approaches, aminoalkylation of diamines is the
most convenient and scalable procedure for the synthesis
of diethylenetriamines bearing different substituents at the
N(1) and N(3) atoms.
Results and Discussion
Aminoalkylation of N,N-disubstituted ethylenedi-
amines 1a—c with N,N-disubstituted 2-chloroethylamine
hydrochlorides 2a—e to give the target diethylenetriamines
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 0840—0843, May, 2018.
1066-5285/18/6705-0840 © 2018 Springer Science+Business Media, Inc.

N1,N1,N3,N3-Tetrasubstituted diethylenetriamines
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 5, May, 2018
841
Scheme 1
reasons are the intermediate formation of reactive N-(2-
iodoethyl)amines and lower stabilization of the quaternary
ammonium salts in aprotic polar MeCN by the I– counter
ion than that of Cl–. An increase in the size of the sub-
stituent at the nitrogen atom of halo-substituted amino-
alkylating agent 2 (Et2N (2b) and (CH2)5N (2d) vs. Me2N
(2a)) also does not favor the stabilization of the quaternary
ammonium salts and, therefore, these salts are almost not
formed. In turn, the reagents with the bulkier N-substitu-
ents give the higher yields of the corresponding products
3d—i than that of 3a—c.
Purity of the synthesized compounds was confirmed
by TLC, their structures were established by IR and NMR
spectroscopy and mass spectrometry.
In summary, the developed procedures enable synthe-
sis of biologically active non-symmetric N1,N1,N3,N3-
tetra-substituted diethylenetriamines and their derivatives.
Experimental
Product
NR1
NR2
Starting
compounds
1a, 2a
2
2
3a
3b
3c
3d
3e
3f
3g
3h
3i
NMe2
NMe2
NMe2
NEt2
NEt2
NEt2
NEt2
NC5H10
NC5H10
NMe2
NC4H8
NC5H10
NEt2
NC4H8
NC5H10
NC4H8O
NC4H8
NC4H8O
N,N-Dimethylethylenediamine (1a), N,N-diethylethylene-
diamine (1b), N,N-dimethyl-2-chloroethanamine hydrochloride
(2a), N,N-diethyl-2-chloroethanamine hydrochloride (2b),
N-(2-chloroethyl)pyrrolidine hydrochloride (2c), N-(2-chloro-
ethyl)piperidine hydrochloride (2d), N-(2-chloroethyl)morpho-
line hydrochloride (2e) were purchased from Sigma-Aldrich.
N-(2-Aminoethyl)piperidine (1c) was synthesized from 2-chloro-
ethylamine and piperidine following the known procedure.25
Solvents were purified and dried by the standard procedures.
Thin layer chromatography was performed with Kavalier Silufol
UV-254 plates (elution with MeOH, spots were visualized with
the iodine vapors). Melting points were measured using a Büchi
MP-520 apparatus. IR spectra were recorded for pure compounds
with a Bruker Alpha instrument operating in a single-pass at-
tenuated total reflection mode. NMR spectra were run on
a Bruker DPX-300 instrument (working frequencies of 300.13 MHz
(1H) and 75 MHz (13C)) in CDCl3, D2O, and DMSO-d6 relative
to Me4Si as an internal standard. Electrospray ionization mass
spectrometry was performed with a LC/MSD Trap SL mass
spectrometer. Samples were injected as solutions in methanol.
High-resolution electrospray ionization mass spectra were re-
corded on a LTQ OrbitrapXLTM mass spectrometer.
Synthesis of diethylenetriamines 3a—i (method A). To a stirred
mixture of ethylenediamine 1a—c (1.5—2 equiv.) and NaOH
(2 equiv.) in water (9 mL per 1 g of NaOH), 2-chloroethanamine
hydrochloride 2a—e (1 equiv.) was added portionwise. The mix-
ture was magnetically stirred at 65—70 °C for 16—18 h (TLC
monitoring, methanol as an eluent). Products 3a—i were ex-
tracted five times with equal volumes of ethyl acetate, the com-
bined organic layers were dried with Na2SO4, and concentrated
in vacuo. Vacuum distillation of the residues afforded diethylene-
triamines 3a—i as colorless liquids.
1a, 2c
1a, 2d
1b, 2b
1b, 2c
1b, 2d
1b, 2e
1c, 2c
1c, 2e
Note. NC4H8 is pyrrolidin-1-yl, NC5H10 is piperidin-1-yl, NC4H8O is
morpholin-4-yl.
Reaction and conditions: i. Method A: NaOH, H2O, 60—70 °C or
method B: K2CO3, KI, MeCN, reflux; ii. HCl, dioxane, PriOH.
aqueous reaction mixtures with ethyl acetate and purified
by vacuum distillation. Method A gives compounds 3d—i
in 38—56% yields.
To increase the yields of diethylenetriamines 3a—c, we
elaborated another method of their synthesis via generated
in situ ternary iodoethylamines (method B). The reactions
were carried out at a 2 : 1 molar ratio of N,N-dimethyl-
ethylenediamine (1a) to N-(2-chloroethyl)amine 2a,c,d in
the presence of K2CO3 and KI in refluxing MeCN for 16—18 h.
Under these reaction conditions, the formed inorganic
salts were almost insoluble in MeCN and precipitated out.
After completion of the reaction, the inorganic precipitate
was filtered off, and the filtrate was concentrated. The
target secondary diethylenetriamines 3a—c were isolated
by extraction of the residue with diethyl ether and subse-
quent vacuum distillation. Method B gives compounds
3a—c in 26—38% yields. Poorly soluble in diethyl ether
quaternary ammonium salts 4a—c were isolated in the
yields of 52—54% and converted into the corresponding
dihydrohlorides (4a—c)•2HCl in 56—72% yields.
A comparison of both methods revealed that method
B gives higher yields of the target products. The apparent
N,N-Bis(2-dimethylaminoethyl)amine (3a) was synthesized
from N,N-dimethylethylenediamine (1a) (3.67 g, 0.042 mol),
NaOH (1.67 g, 0.042 mol), and N,N-dimethyl-2-chloroethan-
amine hydrochloride (2a) (3.0 g, 0.021 mol). Yield 0.59 g (18%).
B.p. 112—115 °C (30 Torr). IR, ν/cm–1: 3312 (NH). 1H NMR
(CDCl3), δ: 1.98 (t, 4 H, 2 CH2N, J = 6.3 Hz); 2.16 (s, 12 H,
4 CH3N); 2.65 (t, 4 H, CH2NHCH2, J = 6.3 Hz).13

842
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 5, May, 2018
Hoang et al.
N,N-Dimethyl-N'-(2-pyrrolidinoethyl)ethylenediamine (3b)
was synthesized from N,N-dimethylethylenediamine (1a) (2.3 g,
0.0276 mol), NaOH (1.41 g, 0.036 mol), and N-(2-chloroethyl)-
pyrrolidine hydrochloride (2c) (3.0 g, 0.018 mol). Yield 0.8 g
Rf 0.42. IR, ν/cm–1: 3310 (NH). 1H NMR (CDCl3), δ: 0.99
(t, 6 H, 2 CH3, J = 7.1 Hz); 2.41—2.57 (m, 12 H, 6 CH2N);
2.66—2.74 (m, 4 H, CH2NHCH2); 3.07 (s, 1 H, NH); 3.68
(t, 4 H, 2 CH2O, J = 4.4 Hz). 13C NMR (CDCl3), δ: 11.30
(2 CH3); 45.46 (CH2NH); 46.48 (2 CH2N, NEt2); 46.86 (CH2NH);
51.89 (CH2N); 53.18 (2 CH2N, NC4H8O); 57.44 (CH2N); 66.49
(2 CH2O). Found: m/z 230.2220 [M + H]+, 252.2039 [M + Na]+.
C12H28N3O. Calculated: M + H = 230.2232, M + Na = 252.2052.
N-[2-(2-Pyrrolidinoethylamino)ethyl]piperidine (3h) was
synthesized from N-(2-amonoethyl)piperidine (1c) (3.39 g,
0.0264 mol), NaOH (1.41 g, 0.0352 mol), and N-(2-chloroethyl)
pyrrolidine hydrochloride (2c) (3.0 g, 0.0176 mol). Yield 2.1 g
20
(24%). B.p. 104—106 °C (12 Torr), nD 1.4625, Rf 0.36. IR,
1
ν/cm–1: 3309 (NH). H NMR (CDCl3), δ: 1.73 (m, 4 H, β-H,
NC4H8); 2.18 (s, 7 H, 2 CH3N + NH); 2.38 (t, 2 H, CH2N,
J = 6.3 Hz); 2.46 (m, 4 H, α-H, NC4H8); 2.56 (t, 2 H, CH2N,
J = 6.6 Hz); 2.65—2.74 (m, 4 H, CH2NHCH2). 13C NMR
(CDCl3), δ: 23.32 (2 β-C, NC4H8); 45.50 (2 CH3N); 47.50
(CH2NH); 48.76 (CH2NH); 54.18 (2 α-C, NC4H8); 55.99
(CH2N); 59.11 (CH2N). MS, m/z: 186.0 [M + H]+.
N,N-Dimethyl-N´-(2-piperidinoethyl)ethylenediamine (3c)11
was synthesized from N,N-dimethylethylenediamine (1a) (5.7 g,
0.066 mol), NaOH (2.64 g, 0.066 mol), and N-(2-chloroethyl)
piperidine hydrochloride (2d) (6.0 g, 0.033 mol). Yield 1.8 g
(52%). B.p. 168—174 °C (21 Torr), nD 1.4868, Rf 0.35. IR,
20
ν/cm–1: 3311 (NH). 1H NMR (CDCl3), δ: 1.40 (m, 2 H, γ-H,
NC5H10); 1.54 (m, 4 H, β-H, NC5H10); 1.74 (m, 4 H, β-H,
NC4H8); 1.95 (br.s, 1 H, NH); 2.33—2.37 (m, 4 H, 2 CH2N);
2.42 (t, 2 H, CH2N, J = 6.3 Hz); 2.48 (m, 4 H, 2 CH2N); 2.57
(t, 2 H, CH2N, J = 6.3 Hz); 2.68—2.74 (m, 4 H, CH2NHCH2).
13C NMR (CDCl3), δ: 23.48 (2 β-C, NC4H8); 24.49 (γ-C,
NC5H10); 26.04 (2 β-C, NC5H10); 46.94 (CH2NH); 48.78
(CH2NH); 54.15 (2 α-C, NC4H8); 54.72 (2 α-C, NC5H10);
56.01(CH2N); 58.66 (CH2N).
20
(28%). B.p. 118—122 °C (14 Torr), nD 1.4675, Rf 0.25. IR,
ν/cm–1: 3311 (NH). 1H NMR (CDCl3), δ: 1.39 (m, 2 H, γ-H,
NC5H10); 1.53 (m, 4 H, β-H, NC5H10); 2.19 (s, 6 H, 2 CH3N);
2.32—2.44 (m, 9 H, 4 CH2N + NH); 2.64—2.71 (m, 4 H,
CH2NHCH2). 13C NMR (CDCl3), δ: 24.36 (γ-C, NC5H10);
25.88 (2 β-C, NC5H10; 45.46 (2 CH3N); 46.83 (CH2NH); 47.43
(CH2NH); 54.70 (2 α-C, NC5H10); 58.66 (CH2N); 59.11
(CH2N). Found: m/z 200.2121 [M + H]+, 222.1942 [M + Na]+.
C11H26N3. Calculated: M + H = 200.2127, M + Na = 222.1946.
N,N-Bis(2-diethylaminoethyl)amine (3d) was synthesized from
N,N-diethylethylenediamine (1b) (6.08 g, 0.052 mol), NaOH (2.8 g,
0.07 mol), and N,N-diethyl-2-chloroethanamine hydrochloride
(2b) (6 g, 0.035 mol). Yield 3.15 g (42%). B.p. 116—120 °C (7 Torr),
nD20 1.4500, Rf 0.43. IR, ν/cm–1: 3308 (NH). 1H NMR (CDCl3),
δ: 1.01 (t, 12 H, 4 CH3, J = 7.1 Hz); 2.04 (br.s, 1 H, NH);
2.48—2.57 (m, 12 H, 6 CH2N); 2.66—2.70 (m, 4 H, CH2NHCH2).14,15
N,N-Diethyl-N´-(2-pyrrolidinoethyl)ethylenediamine (3e) was
synthesized from N,N-diethylethylenediamine (1b) (6.2 g,
0.053 mol), NaOH (2.8 g, 0.07 mol), and N-(2-chloroethyl)-
pyrrolidine hydrochloride (2c) (6.0 g, 0.035 mol). Yield 3.2 g
N-[2-(2-Piperidinoethylamino)ethyl]morpholine (3i) was syn-
thesized from N-(2-amonoethyl)piperidine (1c) (3.1 g, 0.024 mol),
NaOH (1.3 g, 0.032 mol), and N-(2-chloroethyl)morpholine
hydrochloride (2d) (3.0 g, 0.016 mol). Yield 1.9 g (49%). B.p.
187—194 °C (21 Torr), nD 1.4884, Rf 0.35. IR, ν/cm–1: 3308
20
(NH). 1H NMR (CDCl3), δ: 1.40 (m, 2 H, H(γ), NC5H10); 1.54
(m, 4 H, β-H, NC5H10); 1.98 (br.s, 1 H, NH); 2.33—2.49
(m, 12 H, 6 CH2N); 2.67—2.71 (m, 4 H, CH2NHCH2); 3.68 (t, 4 H,
2 CH2O, J = 4.6 Hz). 13C NMR (CDCl3), δ: 24.47 (γ-C,
NC5H10); 26.08 (2 β-C, NC5H10); 46.20 (CH2NH); 46.79
(CH2NH); 53.71 (2 α-C, NC5H10); 54.68 (2 CH2N, NC4H8O);
58.28 (CH2N); 58.54 (CH2N); 67.01 (2 CH2O).
Synthesis of diethylenetriamines 3a—c and quaternary ammo-
nium salt hydrochlorides (4a—c)•2 HCl (method B). To a stirred
mixture of N,N-dimethylethylenediamine (1a) (2 equiv.), K2CO3
(4 equiv.), and KI (0.1 equiv.) in MeCN (12 mL per 1 g of com-
pound 1a), 2-chloroethylamine hydrochloride 2a,c,d (1 equiv.)
was added portionwise at 50 °C. The mixture was magnetically
stirred under reflux for 16 h (TLC monitoring, methanol as an
eluent). The mixture was cooled to room temperature, inor-
ganic precipitate was filtered off. The volatiles (solvent and un-
reacted starting compound 1a) were removed in vacuo. Triamines
3a—c and ammonium salts 4a—c were separated by extraction
of the residue with diethyl ether. Ether-soluble compounds 3a—c
were isolated from the organic extracts by removal of the solvent
in vacuo and subsequent vacuum distillation of the residues.
Physicochemical properties of compounds 3a—c synthesized by
methods A and B are identical.
20
(43%). B.p. 142—144 °C (14 Torr), nD 1.4659, Rf 0.52. IR,
ν/cm–1: 3310 (NH). 1H NMR (CDCl3), δ: 0.96 (t, 6 H, 2 CH3,
J = 7.1 Hz); 1.71 (m, 4 H, β-H, NC4H8); 2.17 (br.s, 1 H, NH);
2.43—2.57 (m, 12 H, 6 CH2N); 2.62—2.73 (m, 4 H, CH2NHCH2).
13C NMR (CDCl3), δ: 11.27 (2 CH3); 22.91 (2 β-C, NC4H8);
46.55 (2 CH2N, NEt2); 47.28 (CH2NH); 48.32 (CH2NH); 52.20
(CH2N); 53.73 (2 α-C, NC4H8); 55.54 (CH2N). Found: m/z
214.2269 [M + H]+, 236.2087 [M + Na]+. C12H28N3. Calculated:
M + H = 214.2283, M + Na = 236.2103.
N,N-Diethyl-N´-(2-piperidinoethyl)ethylenediamine (3f) was
synthesized from N,N-diethylethylenediamine (1b) (6.3 g, 0.054 mol),
NaOH (2.16 g, 0.054 mol), and N-(2-chloroethyl)piperidine
hydrochloride (2d) (5.0 g, 0.027 mol). Yield 3.4 g (56%). B.p.
152—156 °C (14 Torr), nD 1.4720, Rf 0.35. IR, ν/cm–1
:
20
3307 (NH). 1H NMR (CDCl3), δ: 0.96 (t, 6 H, 2 CH3, J = 7.1 Hz);
1.39 (m, 2 H, γ-H, NC5H10); 1.51 (m, 4 H, β−H, NC5H10);
2.32—2.52 (m, 13 H, 6 CH2N + NH); 2.61—2.69 (m, 4 H,
CH2NHCH2). 13C NMR (CDCl3), δ: 11.27 (2 CH3); 23.92 (γ-C,
NC5H10); 25.47 (2 β-C, NC5H10); 46.34 (CH2NH); 46.52
(2 CH2N, NEt2); 47.17 (CH2NH); 52.15 (CH2N); 54.23 (2 α-C,
NC5H10); 58.13 (CH2N). MS, m/z: 228.1 [M + H]+.
The insoluble materials remained after diethyl ether extraction
were vacuum dried over CaCl2 to give salts 4a—c. Quaternary
ammonium salt hydrochlorides (4a—c)•2HCl were prepared by
treatment of the solutions of salts 4a—c in propan-2-ol with
a solution of HCl in dioxane. The products were washed with
anhydrous acetone, dried in vacuo over P2O5, and recrystallized
from anhydrous methanol—anhydrous acetone.
N,N-Bis(2-dimethylaminoethyl)amine (3a)13 was synthesized
from N,N-dimehylethylenediamine (1a) (6.12 g, 0.07 mol),
K2CO3 (19.3 g, 0.14 mol), and KI (0.58 g, 0.0035 mol) in MeCN
(70 mL) and 2-chloroethyldimethylamine hydrochloride (2a)
(5.0 g, 0.035 mol). Yield 1.5 g (26%).
N,N-Diethyl-N´-(2-morpholinoethyl)ethylenediamine (3g) was
synthesized from N,N-diethylethylenediamine (1b) (5.6 g,
0.048 mol) and NaOH (2.56 g, 0.064 mol) in water (23 mL) and
N-(2-chloroethyl)morpholine hydrochloride (2e) (6.0 g, 0.032 mol).
20
Yield 2.8 g (38%). B.p. 166—168 °C (22 Torr), nD 1.4698,

N1,N1,N3,N3-Tetrasubstituted diethylenetriamines
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 5, May, 2018
843
N-(2-Aminoethyl)-N,N-dimethyl-N-(2-dimethylaminoethyl)-
γ-H, NC5H10); 1.80 (br.s, 4 H, β-H, NC5H10); 3.01 (br.s, 2 H,
α-H, NC5H10); 3.26 (s, 6 H, 2 CH3N+), 3.37—3.48 (m, 4 H,
2 α-H of NC5H10 + CH2NH+, partially overlaps with the solvent
ammonium chloride (4a). Yield 3.7 g (54%), heavy oil. IR, ν/cm–1
:
3342, 3267 (NH2). 1H NMR (CDCl3), δ: 2.28 (s, 6 H, 2 CH3N);
2.51 (br.s, 2 H, NH2); 2.77 (t, 2 H, CH2N, J = 4.8 Hz); 3.27
(t, 2 H, CH2NH2, J = 6.5 Hz); 3.44 (s, 6 H, 2 CH3N+); 3.74—3.81
(m, 4 H, 2 CH2N+).
signal); 3.73 (m, 4 H, CH2NH3 + CH2N+); 4.03 (m, 2 H,
+
CH2N+); 8.87 (s, 3 H, H3N+); 11.35 (s, 1 H, HN+). 13C NMR
(DMSO-d6), δ: 21.13 (γ-C, NC5H10); 22.18 (2 β-C, NC5H10);
32.09 (CH2NH3+); 47.53 (CH2NH+); 51.33 (2 CH3N+); 52.35
(2 α-C, NC5H10); 56.21 (CH2N+); 59.48 (CH2N+).
N-(2-Aminoethyl)-N,N-dimethyl-N-(2-dimethylaminoethyl)-
ammonium chloride dihydrochloride (4a•2 HCl). Yield 2.8 g
(56%). M.p. 169—172 °C. IR, ν/cm–1: 2470—2666 (HN+). 1H NMR
(DMSO-d6), δ: 2.84 (s, 6 H, 2 CH3NH+); 3.24 (s, 6 H, 2 CH3N+);
3.40 (m, 2 H, CH2NH+, partially overlaps with the solvent signal);
References
+
3.70 (m, 4 H, CH2NH3 + CH2N+); 3.73—3.90 (m, 2 H,
CH2N+); 8.61 (s, 3 H, H3N+); 11.24 (s, 1 H, HN+). 13C NMR
(DMSO-d6), δ: 32.16 (CH2NH3+); 42.50 (2 CH3NH+); 48.33
(CH2NH+); 51.41 (2 CH3N+); 56.42 (CH2N+); 59.55 (CH2N+).
N,N-Dimethyl-N´-(2-pyrrolidinoethyl)ethylenediamine (3b)
was synthesized from N,N-dimethylethylenediamine (1a) (5.3 g,
0.06 mol), K2CO3 (16.2 g, 0.12 mol), KI (0.5 g, 0.003 mol), and
N-(2-chloroethyl)pyrrolidine hydrochloride (2c) (5 g, 0.03 mol).
Yield 2.05 g (37%).
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N-(2-Aminoethyl)-N,N-dimethyl-N-(2-pyrrolidinoethyl)am-
monium chloride (4b). Yield 3.4 g (52%), heavy oil. IR, ν/cm–1
:
3348 (br., NH2). 1H NMR (D2O), δ: 1.74 (m, 2 H, β-H, NC4H8);
2.59 (m, 4 H, α-H, NC4H8); 2.97 (m, 2 H, CH2N); 3.13 (s, 6 H,
2 CH3N+); 3.33—3.51 (m, 6 H, CH2NH2 + 2 CH2N+). 13C NMR
(D2O), δ: 21.76 (2 β-C, NC4H8); 34.50 (CH2NH2); 46.66
(CH2N); 50.48 (2 CH3N+); 52.57 (2 α-C, NC4H8); 60.97
(CH2N+); 62.64 (CH2N+).
N-(2-Aminoethyl)-N,N-dimethyl-N-(2-pyrrolidinoethyl)am-
monium chloride dihydrochloride (4b•2 HCl). Yield 2.9 g (64%).
M.p. 188—190 °C. Rf 0.19. IR, ν/cm–1: 2455—2671 (HN+).
1H NMR (DMSO-d6—D2O), δ: 1.95 (m, 4 H, β-H, NC4H8);
3.14—3.47 (m, 12 H, CH2NH+ + 2 CH3N+ + 4 α-H of NC4H8);
3.67 (m, 2 H, CH2NH3+); 3.73—3.86 (m, 4 H, 2 CH2N+). 1H NMR
(DMSO-d6), δ: 1.98 (m, 4 H, β-H, NC4H8); 3.13 (br.s, 2 H,
CH2NH+); 3.28 (s, 6 H, 2 CH3N+); 3.36—3.52 (m, 4 H, α-H,
NC4H8, partially overlaps with the solvent signal); 3.73—3.98
(m, 6 H, CH2NH3 + 2 CH2N+); 8.92 (s, 3 H, H3N+); 11.69
+
(s, 1 H, HN+). 13C NMR (DMSO-d6), δ: 22.76 (2 β-C), NC4H8);
32.14 (CH2NH3+); 45.78 (CH2NH+); 51.56 (2 CH3N+); 53.15
(2 α-C, NC4H8); 57.05 (CH2N+); 59.38 (CH2N+).
N,N-Dimethyl-N´-(2-piperidinoethyl)ethylenediamine (3c)11
was synthesized from N,N-dimethylethylenediamine (1a) (4.79 g,
0.054 mol), K2CO3 (14.9 g, 0.108 mol), KI (0.45 g, 0.0027 mol),
and N-(2-chloroethyl)piperidine hydrochloride (2d) (5 g,
0.027 mol). Yield 2.06 g (38%).
N-(2-Aminoethyl)-N,N-dimethyl-N-(2-piperidinoethyl)am-
monium chloride (4c). Yield 3.3 g (53%), white deliquescent
1
powder. IR, ν/cm–1: 3321, 3267 (NH2). H NMR (CDCl3), δ:
1.40 (m, 2 H, H(γ), NC5H10); 1.52 (m, 4 H, β-H, NC5H10);
2.40—2.50 (m, 6 H, NH2 + 4 α-H, NC5H10); 2.76 (t, 2 H, CH2N,
J = 5.5 Hz); 3.24 (t, 2 H, CH2NH2, J = 6.1 Hz); 3.43 (s, 6 H,
2 CH3N+); 3.71—3.78 (m, 4 H, 2 CH2N+).
N-(2-Aminoethyl)-N,N-dimethyl-N-(2-piperidinoethyl)am-
monium chloride dihydrochloride (4c•2 HCl). Yield 3.1 g (72%).
M.p. 182—184 °C. Rf 0.22. IR, ν/cm–1: 2376—2662 (HN+).
1H NMR (D2O), δ: 1.41 (m, 1 H, γ-H, NC5H10); 1.69 (m, 3 H,
2 β-H + γ-H, NC5H10); 1.85 (m, 2 H, β-H, NC5H10); 3.01 (m,
2 H, α-H of NC5H10); 3.22 (s, 6 H, 2 CH3N+); 3.48—3.54 (m,
4 H, 2 α-H of NC5H10 + CH2NH+); 3.63—3.75 (m, 4 H,
CH2NH3+ + CH2N+); 3.85—3.91 (m, 2 H, CH2N+). 1H NMR
(DMSO-d6), δ: 1.45 (br.s, 1 H, γ-H, NC5H10); 1.61 (br.s, 1 H,
Received November 8, 2017;
in revised form January 23, 2018;
accepted February 26, 2018