Synthesis of bicyclic N,N-enaminals by cyclization of alk-4-ynals with aliphatic diamines in DMSO upon treatment with KOH

Article abstract of DOI:10.1007/s11172-013-0351-3

A cyclization of alk-4-ynals with aliphatic diamines in DMSO upon treatment with KOH was found to lead to bicyclic N,N-enaminals. The studies of this reaction showed that 1,3-diaminopropane and N-methyl-1,3-diaminopropane gave (E)-6-(arylmethylidene)octahydropyrrolo[1,2-a]pyrimidines in 45 - 78% yields, whereas 1,2-diaminoethane gave 5-(arylmethylidene)hexahydropyrrolo[1,2-a] imidazoles as mixtures of E- and Z-isomers in up to 75% total yield. The mechanism of these new cascade cyclization reactions includes formation of the equilibrium mixtures of imines and cyclic aminals with subsequent intramolecular hydroamination of the triple bond having considerable ionic character.

Full text of DOI:10.1007/s11172-013-0351-3

Russian Chemical Bulletin, International Edition, Vol. 62, No. 11, pp. 2430—2437, November, 2013
2430
Synthesis of bicyclic N,Nꢀenaminals by cyclization of alkꢀ4ꢀynals
with aliphatic diamines in DMSO upon treatment with KOH*
V. D. Gvozdev, K. N. Shavrin, and O. M. Nefedov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: vgvozdev2006@yandex.ru
A cyclization of alkꢀ4ꢀynals with aliphatic diamines in DMSO upon treatment with KOH
was found to lead to bicyclic N,Nꢀenaminals. The studies of this reaction showed that 1,3ꢀdiꢀ
aminopropane and Nꢀmethylꢀ1,3ꢀdiaminopropane gave (E)ꢀ6ꢀ(arylmethylidene)octahydroꢀ
pyrrolo[1,2ꢀa]pyrimidines in 45—78% yields, whereas 1,2ꢀdiaminoethane gave 5ꢀ(arylꢀ
methylidene)hexahydropyrrolo[1,2ꢀa]imidazoles as mixtures of Eꢀ and Zꢀisomers in up to 75%
total yield. The mechanism of these new cascade cyclization reactions includes formation of
the equilibrium mixtures of imines and cyclic aminals with subsequent intramolecular hydroꢀ
amination of the triple bond having considerable ionic character.
Key words: alkꢀ4ꢀynals, 1,2ꢀdiaminoethane, 1,3ꢀdiaminopropanes, hexahydropyrrolo[1,2ꢀa]ꢀ
imidazoles, octahydropyrrolo[1,2ꢀa]pyrimidines, hexahydropyrimidines, imidazolidines, hydroꢀ
amination, cascade cyclization, dimethyl sulfoxide.
In the last years, researchers pay serious attention to
oxycarbonylmethylidenepyrrolidines and the correspondꢀ
ing piperidines.19 Recently, a CuClꢀcatalyzed fourꢀcomꢀ
ponent reaction between 2ꢀethynylbenzaldehyde, secondꢀ
ary amine, formaldehyde, and diaminoalkane resulted in
the synthesis of 3ꢀaminomethylꢀsubstituted annulated isoꢀ
quinoline structures.20
A distinguishing feature of the most reactions menꢀ
tioned above is obtaining of nitrogenꢀcontaining heteroꢀ
cycles with the endocyclic double bond. Formation of
products with the exocyclic double bond in the reaction of
amines with alkꢀ4ꢀynals and alkꢀ5ꢀynals was observed
only in the case when a triple bond activated by an esꢀ
ter group was present in the alkynals.19 Also note that
before our studies, no information was available on the
carrying out these cyclization reactions in the presence of
strong bases.
We discovered a oneꢀpot method for the synthesis of
bicyclic N,Nꢀenaminals — 6ꢀ(arylmethylidene)octahydroꢀ
pyrrolo[1,2ꢀa]pyrimidines and 5ꢀ(arylmethylidene)hexaꢀ
hydropyrrolo[1,2ꢀa]imidazoles, based on the cyclization
of available alkꢀ4ꢀynals with aliphatic diamines in DMSO
upon treatment with KOH.1 Compounds of these series
exhibit a wide range of biological activity,21,22 while the
presence in their structure of highly active enamine and
aminal fragments with the shared nitrogen atom makes it
possible to involve them in the selective reduction and
dehydration reactions, proceeding with both retention and
transformation of the starting bicyclic system.23 The
present work is devoted to the inꢀdepth study of the disꢀ
covered process1 leading to these compounds, its mechaꢀ
nism, and the scope of its synthetic application.
cyclization of available alkꢀ4ꢀynals, alkꢀ5ꢀynals, as well
as corresponding ketones, upon their reaction with amines
as a versatile approach to the synthesis of various nitroꢀ
genꢀcontaining heterocyclic compounds. Thus, recently
there was described a new strategy for the synthesis of
annulated isoquinolines based on the reaction of oꢀalkyꢀ
nylbenzaldehydes with aromatic amines bearing an addiꢀ
tional nucleophilic center either in the presence of AuI
(see Refs 2 and 3), AgI (see Ref. 4), and CuI salts (see Ref. 5)
or in the absence of metalꢀcontaining catalysts.6 A numꢀ
ber of works in the last years were devoted to the new
approach to the synthesis of 1,2ꢀdihydroisoquinolines
based on the reaction of oꢀalkynylbenzaldehydes with
amines and various nucleophiles in the absence of cataꢀ
lysts7 or in the presence of carbophilic Lewis acids such as
AgOTf,8,9 Au(PPh3)Cl/AgNTf2,10 In(OTf)3,10,11 CuI or
PdII salts (see Refs 12—14), CuSO4/C12H25SO3Na,15
and Mg(ClO4)2/Cu(OTf)216. A multiꢀcomponent reacꢀ
tion of 2ꢀalkynylbenzaldehyde with 1,2ꢀdiaminobenzene
and iodine in the presence of CuI opens a pathway to the
synthesis of iodoisoquinolines annulated with benzimidꢀ
azole.17 A reaction of substituted alkꢀ4ꢀynones with amines
catalyzed by AgOTf or a mixture of AuCl, AgOTf, and
Ph3P gave pyrroles.18 A condensation of chiral amines
with ꢀoxoalkynoates in the presence of alcohols effected
a diastereoselective synthesis of chiral 2ꢀalkoxyꢀ5ꢀmethꢀ
* Dedicated to Academician of the Russian Academy of Sciencꢀ
es M. P. Egorov on the occasion of his 60th birthday.
For preliminary communication, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2430—2437, Novemer, 2013.
1066ꢀ5285/13/6211ꢀ2430 © 2013 Springer Science+Business Media, Inc.

Synthesis of bicyclic N,Nꢀenaminals
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 11, November, 2013 2431
Results and Discussion
led to the formation of the corresponding (E)ꢀ6ꢀ(arylꢀ
methylidene)octahydropyrrolo[1,2ꢀa]pyrimidines 6a—j in
42—78% yields (Scheme 2, Table 1). The best yields were
observed in the case of 2,2ꢀdisubstituted aldehydes 1a—e,
apparently, because of the exception of the side processes
proceeding due to the presence of acidic hydrogen atoms
at ꢀposition to the carbonyl group. Products 6a,b having
~90% purity were isolated by simple dilution of the reacꢀ
tion mixture with a 10ꢀfold amount of water with subseꢀ
quent separation of the crystalline precipitate by filtration
and its washing with water. Additional purification of prodꢀ
ucts 6a,b, as well as isolation of compounds 6c—j, was
performed by recrystallization from hexane.
The starting alkynals 1a—e were obtained in 56—70%
yields by the reaction of 3ꢀsubstituted propargyl chlorides
2a—c with isobutyraldehyde, cyclohexanecarbaldehyde,
and tetrahydropyranꢀ4ꢀcarbaldehyde in a 30% aqueous
NaOH—toluene twoꢀphase system in the presence of
a mixture of catalytic amounts of NaI and tetrabutylꢀ
ammonium iodide according to the procedure24 suggested
for the preparation of aldehyde 1a (Scheme 1).
Scheme 1
Scheme 2
Comꢀ
pound 1
R1
R2
R3
Yield
(%)
70
58
65
a
b
c
d
e
Ph
Me
Me
Me
Me
Me
Me
Compound
R1
R2
R3
R4
4ꢀFC6H4
2ꢀthienyl
Ph
4, 5, 6
a
b
c
d
e
f
g
h
i
Ph
Ph
4ꢀFC6H4
2ꢀthienyl
Me
Me
Me
Me
Me
Me
Me
Me
H
vvvvvvvv—(CH2)5—
62
56
Me
Me
Me
H
Me
Me
H
Phvvvvvvvv—(CH2)2O(CH2)2—
1: R = H (f), F3C (g), Me (h), OMe (i)
2: R1 = Ph (a), 4ꢀFC6H4 (b), 2ꢀthienyl (c)
Ph vvvvvvv—(CH2)5—
Ph vvvvvvv—(CH2)5—
Ph vvv—(CH2)2O(CH2)2—
Ph
Ph
Reagents and conditions: i. 30% aqueous NaOH, toluene, NaI,
Bu4NI, 50 C; ii. Pd(PPh3)2Cl2, CuI, Et3N, 20 C; iii. Py•
•CrO3•HCl, CH2Cl2, 20 C.
H
H
H
H
H
H
Me
Me
j
4ꢀF3CC6H4
3: R4 = H (a), Me (b)
Alkynals 1f—i unsubstituted at ꢀposition were obꢀ
tained by a crossꢀcoupling of the corresponding iodoareꢀ
nes (iodobenzene, 4ꢀiodobenzotrifluoride, 4ꢀiodotoluene,
and 4ꢀiodoanisole) with pentꢀ4ꢀynꢀ1ꢀol upon treatment
with a mixture of Pd(PPh3)2Cl2 and CuI in anhydrous
triethylamine25 with subsequent oxidation of the alcohols
obtained with pyridinium chlorochromate in dichloꢀ
romethane (see Scheme 1).
Reagents and conditions: i. DMSO, KOH, 20 C.
It should be noted that this reaction proceeds with
high stereoselectivity: in all the cases compounds 6 were
exclusively formed as Eꢀisomers. The isomers were identiꢀ
fied using their NOESYꢀ2D proton spectra based on the
analysis of the interaction of protons at the double bond
and the protons of the methylidene fragment at position 7.
As it is seen from the data obtained (see Table 1), the
A sequential addition of aldehydes 1a—g and powꢀ
dered KOH to solutions of 1,3ꢀdiaminopropanes 3a,b in
DMSO (the molar ratio amine : aldehyde : KOH = 5 : 1 : 5)

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Russ.Chem.Bull., Int.Ed., Vol. 62, No. 11, November, 2013
Gvozdev et al.
Table 1. The products of the reaction of alkꢀ4ꢀynals 1a—i with
diaminoalkanes 3a,b and 7 in DMSO in the presence of KOH
(the molar ratio alkynal : diaminoalkane : KOH = 1 : 5 : 5)
ucts 6, both compounds 10a and 10b were obtained as
dense liquids, which were isolated by column chromatoꢀ
graphy on neutral Al2O3.
Aldehyde
Diaminoꢀ
alkane
/h
Product
Yield
(%)
Scheme 3
1a
1a
1b
1c
1d
1d
1e
1f
3a
3b
3b
3b
3a
3b
3b
3a
3b
3b
3a
3b
7
12
10
15
10
12
10
10
12
15
10
10
10
12
12
6a
6b
6c
6d
6e
6f
6g
6h
6i
77b
78b
60b
58b
52b
65b
72b
42b
51b
45b
—
1f
1g
1h
1i
1a
1d
6j
a
—
a
—
—
75d
63d
10ac
10bc
7
a No product was formed, a complete resinification of the reacꢀ
tion mixture was observed.
b The yield of the product isolated by crystallization from hexane
is given.
c The ratio of isomers was determined from the NMR spectra of
isolated products: for compound 10a E/Z = 5 : 1, for compound
10b E/Z = 4.5 : 1.
d The yield of the product isolated by column chromatography
is given.
structure of the diamine used considerably influences the
rate of the process. Thus, the reaction of 1,3ꢀdiaminoꢀ
propane (3a) with all the aldehydes 1 under study reached
completion within two hours, whereas similar processes
with Nꢀmethylꢀ1,3ꢀdiaminopropane (3b) proceeded slowꢀ
er and required stirring for 10—15 h to be completed.
No formation of the corresponding enaminals 6 was
observed when aldehydes 1h and 1i with pꢀtolyl and
pꢀmethoxyphenyl substituents at the triple bond were used
as the starting compounds. It is possible that this results
from the low polarization of the triple bond in the initial
adducts of these aldehydes with diamines because of more
donor character of the aryl substituents used, that interꢀ
feres with the intramolecular hydroamination and directs
the process along the side channels.
Unlike reactions with diaminopropanes 3a,b, similar
processes with 1,2ꢀdiaminoethane (7) proceed less selecꢀ
tively. Thus, the reaction of aldehydes 1a,d with a fivefold
molar excess of 1,2ꢀdiaminoethane (7) and powdered
KOH in anhydrous DMSO leads to the corresponding
hexahydropyrrolo[1,2ꢀa]imidazoles 10a,b as mixtures of
Eꢀ and Zꢀisomers in 75 and 63% yields, respectively
(Scheme 3, see Table 1). Most likely, such a difference
can be explained by a significantly smaller steric effect of
the fiveꢀmembered ring formed in the course of this proꢀ
cess as compared to the sixꢀmembered one. Unlike prodꢀ
8, 9, 10: R1, R2 = Me (a), R1 + R2 = —(CH2)5— (b)
Reagents and conditions: i. DMSO, KOH, 20 C.
In order to gather data on the intermediate products
emerging in the course of these reactions, a more detailed
study of their proceeding in DMSOꢀd6 with the periodical
checking of the reaction mixture by NMR spectroscopy
was performed. Thus, it was shown that the addition of
aldehyde 1a to 1,3ꢀdiaminopropane (3a) or 1,2ꢀdiaminoꢀ
ethane (7) over a short period of time (10—20 min) led to
the equilibrium mixtures of the corresponding linear imiꢀ
nes 4a and 8a and cyclic aminals 5a and 9a in quantitative
yields (Table 2). The ratio of components in the mixtures
obtained did not virtually depend on the excess of the
diamine used (in the range from 1 : 1 to 1 : 10), and no
formation of noticeable amounts of adducts at both amino
groups even at the equimolar ratio of reagents was obꢀ
served at all.
The presence of the equilibrium between compounds
8a and 9a, as well as between 4a and 5a, was confirmed by
NMR spectroscopy at different temperatures. Thus, upon
heating the reaction mixture obtained by the reaction of
aldehyde 1a with 1,2ꢀdiaminoethane to 50 C, the ratio of
components 8a and 9a changed from 1 : 5.5 to 1 : 2.3 and
was completely restored to the initial value upon subseꢀ

Synthesis of bicyclic N,Nꢀenaminals
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 11, November, 2013 2433
Table 2. The reaction of aldehydes 1a and 1f with diamines 3a,b and 7 in DMSOꢀd6 and the subsequent
reactions of the products 4a,b, 5a,i, 8a, 9a with KOH
Starting
aldehyde
Diamine
Molar ratio
aldehyde : diamine
Condensation
products
Reaction time
with KOHb/h
Product
(yield)c
1a
1a
3a
7a
1 : 1
1 : 3
1 : 1
1 : 3
1 : 10
1 : 1.5
1 : 3
1 : 10
1 : 1
4a, 5a (1 : 50)a
4a, 5a (1 : 45)a
8a, 9a (1 : 5.7)a
8a, 9a (1 : 5.6)a
8a, 9a (1 : 5.5)a
4b
2
2
2
2
2
15
15
15
15
15
6a (96%)
6a (98%)
10a (95%)
10a (94%)
10a (90%)
6b (56%)
6b (84%)
6b (90%)
6i (62%)
6i (64%)
1a
1f
3b
3b
5i
1 : 3
a The ratio was determined at 23 C.
b The molar ratio alkynal : KOH = 1 : 5.
c Determined based on the comparison of integral intensities of the signals in the 1H NMR spectrum of the
products and dioxane ( 3.56) taken as an internal standard.
quent cooling to 23 C. In similar experiment with a mixꢀ
ture of compounds 4a and 5a, heating to 50 C led to
a reversible increase in the content of linear product 4a
from ~2% (4a : 5a = 1 : 50) to 25% (4a : 5a = 1 : 3).
The reaction of aldehyde 1a with Nꢀmethylꢀ1,3ꢀdiꢀ
aminopropane (3b) in DMSOꢀd6 exclusively led to linear
product 4b in quantitative yield, whereas a similar reacꢀ
tion with aldehyde 1f unsubstituted at -position gave only
cyclic aminal 5i. Most likely, such a difference is explained
by the steric influence of two methyl groups, hindering
cyclization of imine 4b to the corresponding aminal 5b
and significantly shifting the equilibrium to the side of
the former.
corresponding cyclic product 5b in the course of the reacꢀ
tion at various conversions of the starting compound, that,
most likely, indicates that the process of its formation is
significantly slower than subsequent addition at the CC
bond, thus being a limiting step of the whole process.
As it is seen from the data given in Table 2, excess of
diamine, excluding the case of the reaction of aldehyde 1a
with Nꢀmethylꢀ1,3ꢀdiaminopropane (3b), virtually does
not affect the yields of the final products 6 and 10, which
in the case of 2,2ꢀdisubstituted aldehydes are almost quanꢀ
titative even at the equimolar ratio aldehyde : diamine.
This fact can be useful if this reaction is carried out with
expensive or hardly separable diaminoalkanes.
Compounds 4a,b, 5a,i, 8a, and 9a in the reaction mixꢀ
tures were identified by a comparison of the NMR spectra
of these mixtures with the spectra of the corresponding
products obtained by the condensation of aldehydes 1a,f
with excess of diamines 2a—c in CH2Cl2 in the presence
of anhydrous Na2SO4. In all the cases, the overall yield of
the condensation products determined based on the correꢀ
lation of the integral intensities of their signals and the
signal of dioxane taken as an internal standard has proved
to be quantitative.
Stirring the solutions of the reaction products, obtained
from aldehydes 1a,f and diamines 3a,b and 7, in DMSOꢀd6
with freshly powdered KOH led to the disappearance of
the signals for these compounds in the NMR spectra
and the appearance of the signals for the corresponding
aminals 6a,b,i and 10a, whose yields after the reaction
reached completion were determined from the correlation
of the integral intensities of the signal for the aminal proꢀ
ton ( 2.7—4.05) and that of dioxane ( 3.56) used as an
internal standard. The results obtained are given in Table 2.
In the case of cyclization of imine 4b, the NMR specꢀ
tra of the reaction mixture showed no appearance of the
It should be noted that in all the reactions of alkynals 1
with diamines in DMSOꢀd6 in the presence of KOH, the
observed integral intensity of the signal for the proton at
the double bond ( 5.1—5.3) in the NMR spectra of prodꢀ
ucts 6 and 10 was much lower than the calculated intensiꢀ
ty, that indicates a considerable extent of the deuteroexꢀ
change in the course of the process under study. Taking
into account the data of a separate experiment, which
showed that stirring compound 6b under the same condiꢀ
tions (KOH in DMSOꢀd6 at ~20 C) did not lead to the
deuteroexchange, a conclusion can be drawn that the inꢀ
tramolecular addition of the amino group at the triple
bond in aminals 5 and 9 bears considerable ionic character
and proceeds with involvement of the corresponding amide
anions 11, transforming to vinyl anions 12, which then
add a proton (or a deuterium cation) from the reaction
medium (Scheme 4).
In conclusion, we suggested a simple method for the
preparation of various 6ꢀ(arylmethylidene)octahydroꢀ
pyrrolo[1,2ꢀa]pyrimidines and 5ꢀ(arylmethylidene)hexaꢀ
hydropyrrolo[1,2ꢀa]imidazoles based on the reaction of
available alkꢀ4ꢀynals with aliphatic diaminoalkanes in the

2434
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 11, November, 2013
Gvozdev et al.
Scheme 4
fluorophenyl)propꢀ2ꢀyne (2b) was obtained similarly from
3ꢀ(4ꢀfluorophenyl)propꢀ2ꢀynꢀ1ꢀol in 82% yield, 1ꢀchloroꢀ3ꢀ(2ꢀ
thienyl)propꢀ2ꢀyne (2c) was synthesized by the reaction of
3ꢀ(2ꢀthienyl)propꢀ2ꢀynꢀ1ꢀol with SOCl2 in diethyl ether under
conditions described in the work28 (77% yield).
2,2ꢀDimethylꢀ5ꢀphenylpentꢀ4ꢀynal (1a) was synthesized from
chloride 2a and freshly distilled isobutyraldehyde according to
the procedure described in the work.24 Similar procedure was
used to obtain 5ꢀ(4ꢀfluorophenyl)ꢀ2,2ꢀdimethylpentꢀ4ꢀynal (1b),
2,2ꢀdimethylꢀ5ꢀ(2ꢀthienyl)pentꢀ4ꢀynal (1c), 1ꢀ(3ꢀphenylpropꢀ
2ꢀynyl)cyclohexanecarbaldehyde (1d), and 4ꢀ(3ꢀphenylpropꢀ2ꢀ
ynyl)tetrahydropyranꢀ4ꢀcarbaldehyde (1e).
5ꢀ(4ꢀFluorophenyl)ꢀ2,2ꢀdimethylpentꢀ4ꢀynal (1b) was obꢀ
tained from chloride 2b and isobutyraldehyde in 58% yield
and isolated by microdistillation in vacuo (bath temperature
110—120 C, 1 Torr). 1H NMR, : 1.23 (s, 6 H, 2 Me); 2.61 (s, 2 H,
CCCH2); 6.92—7.05 (m, 2 H, Ph); 7.35—7.45 (m, 2 H, Ph);
9.60 (s, 1 H, CHO). 13C NMR, : 21.3 (2 Me); 27.5 (CCCH2);
45.8 (CMe2); 82.27, 85.3 (CC); 115.5 (d, C(3), C(5), Ph,
J= 22.1 Hz); 119.5 (d, C(1), Ph, J = 3.7 Hz); 133.4 (d, C(2), C(6),
Ph, J = 8.4 Hz); 162.2 (d, C(4), Ph, J = 248 Hz); 204.6 (CHO).
2,2ꢀDimethylꢀ5ꢀ(2ꢀthienyl)pentꢀ4ꢀynal (1c) was obtained
from chloride 2c and isobutyraldehyde in 65% yield and isolated
by microdistillation in vacuo (bath temperature 120—130 C,
1 Torr). 1H NMR, : 1.22 (s, 6 H, 2 Me); 2.59 (s, 2 H, CCCH2);
6.95 (dd, 1 H, C(4)H, J = 5.2 Hz, J = 3.6 Hz); 7.14 (dd, 1 H,
C(3)H, J = 3.6 Hz, J = 1.2 Hz); 7.19 (dd, 1 H, C(5)H, J = 5.2 Hz,
J = 1.2 Hz); 9.59 (s, 1 H, CHO). 13C NMR, : 21.4 (2 Me); 27.8
(CCCH2); 45.9 (CMe2); 78.3, 89.7 (CC); 123.4 (C(2), thienyl);
126.4, 126.9, 131.5 (thienyl); 204.6 (CHO).
1ꢀ(3ꢀPhenylpropꢀ2ꢀynyl)cyclohexanecarbaldehyde (1d) was
obtained from chloride 2a and cyclohexanecarbaldehyde in 62%
yield and isolated by microdistillation in vacuo (bath temperaꢀ
ture 160—170 C, 1 Torr). 1H NMR, : 1.20—1.71 (m, 8 H,
cycloꢀC6); 1.95—2.10 (m, 2 H, cycloꢀC6); 2.56 (s, 2 H, CCCH2);
7.25—7.45 (m, 5 H, Ph); 9.64 (s, 1 H, CHO). 13C NMR, : 22.3,
25.5, 28.7, 30.5 (5 CH2, cycloꢀC6, CCCH2); 49.1 (Cquat);
83.5, 85.1 (CC); 123.4 (C(1), Ph); 127.1, 128.2, 131.6 (Ph);
206.0 (CHO).
4ꢀ(3ꢀPhenylpropꢀ2ꢀynyl)tetrahydropyranꢀ4ꢀcarbaldehyde (1e)
was obtained from chloride 2a and tetrahydropyranꢀ4ꢀcarbꢀ
aldehyde in 62% yield and isolated by microdistillation in vacuo
(bath temperature 160—170 C, 1 Torr). 1H NMR, : 1.75 (ddd,
2 H, CHHC(CHO)CHH, J = 13.9 Hz, J = 10.5 Hz, J = 4.3 Hz);
2.05 (ddd, 2 H, CHHC(CHO)CHH, J = 13.9 Hz, J = 4.3 Hz,
J = 2.8 Hz); 2.58 (s, 2 H, CCCH2); 3.49 (ddd, 2 H, CHHOCHH,
J = 12.0 Hz, J = 10.5 Hz, J = 2.8 Hz); 3.82 (ddd, 2 H,
CHHOCHH, J = 12.0 Hz, J = 4.3 Hz, J = 4.3 Hz); 7.25—7.45
(m, 5 H, Ph); 9.63 (s, 1 H, CHO). 13C NMR, : 26.9 (CCCH2);
30.3 (C(3), C(5), cycloꢀC5O); 46.9 (C(4), cycloꢀC5O); 64.3 (C(2),
C(6), cycloꢀC5O); 83.8, 84.0 (CC); 122.8 (C(1), Ph); 128.0,
128.2, 131.5 (Ph); 204.3 (CHO).
Alkynals 1f—i were obtained by the crossꢀcoupling of the
corresponding iodoarenes (iodobenzene, 4ꢀiodobenzotrifluoride,
4ꢀiodotoluene, and 4ꢀiodoanisole) with pentꢀ4ꢀynꢀ1ꢀol upon
treatment with a mixture of Pd(PPh3)2Cl2 and CuI in anhydrous
triethylamine25 with subsequent oxidation of the acetylenic alꢀ
cohol formed with pyridinium chlorochromate in dichloroꢀ
methane (the yield for the two steps was 68% for 1f, 75% for 1g,
77% for 1h, and 65% for 1i). Spectral characteristics of the comꢀ
pounds obtained agreed with the published data (see Ref. 29 for
1f, as well as Ref. 30 for 1g—i).
n = 1, 2
presence of KOH in DMSO, which gives an opportunity
to further study these polyfunctional and highly reactive
substrates. The intermediates emerging in the course of
these multiꢀstep processes were established. This approach
has the advantage over methods described earlier26 of usꢀ
ing available starting compounds, as well as of a possibility
to obtain a wider scope of bicyclic N,Nꢀenaminals, inꢀ
cluding those containing no substituents at -position to
the carbon atom of the NCHN fragment.
Experimental
GLC analysis of starting compound and products obtained
was carried out on a HewlettꢀPackard 5890 Series II instruꢀ
ment with an HPꢀ1 capillary column (30 m × 0.153 mm) and
a HewlettꢀPackard 3396A automatic integrator. 1H and 13C NMR
spectra were recorded on a Bruker ACꢀ200p spectrometer
for solutions in CDCl3, using Me4Si as an internal standard.
Mass spectra were recorded on a Finningan DSQ II GLCꢀMS
spectrometer.
1ꢀChloroꢀ3ꢀphenylpropꢀ2ꢀyne (2a) was obtained by chloriꢀ
nation of 3ꢀphenylpropꢀ2ꢀynꢀ1ꢀol upon treatment with SOCl2
in CCl4 in the presence of an equimolar amount of triethylamine
according to the procedure27 in 87% yield. 1ꢀChloroꢀ3ꢀ(4ꢀ

Synthesis of bicyclic N,Nꢀenaminals
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 11, November, 2013 2435
Synthesis of bicyclic aminals 6a—j and 10a,b from acetylenic
aldehydes 1a—g and diamines 3a,b and 7 (general procedure).
A solution of aldehyde 1 (1 mmol in DMSO (3 mL) was added
slowly to a solution of the corresponding diamine (5 mmol) in
anhydrous DMSO (3 mL) with stirring. The mixture obtained
was stirred for 30 min at ~20 C, followed by addition of freshly
powdered KOH (280 mg, 5 mmol) and stirring a suspension for
2—10 h until reaction reached completion (GLC or NMR monꢀ
itoring). Then, water (30 mL) and CH2Cl2 (30 mL) were added
to the reaction mixture, the organic layer was separated, the
aqueous layer was additional extracted with dichloromethane
(3×10 mL). The combined organic layers were washed with waꢀ
ter 4 times, dried with anhydrous K2CO3, the solvent was evapoꢀ
rated, whereas the residue was subjected to recrystallization or
column chromatography to isolate the target product, which
according to the NMR and elemental analysis data was one of
the corresponding aminals 6 or 10 with more than 95% purity
(see Table 1).
5ꢀBenzylideneꢀ7,7ꢀdimethylhexahydroꢀ1Hꢀpyrrolo[1,2ꢀa]ꢀ
imidazole (10a) was obtained from aldehyde 1a and 1,2ꢀdiaminoꢀ
ethane 7 as a mixture of Eꢀ and Zꢀisomers (the ratio of 5 : 1) and
isolated in 75% yield by chromatography on neutral Al2O3 (eluꢀ
ent hexane—diethyl ether, 10 : 1).
5´ꢀBenzylidenehexahydrospiro[cyclohexaneꢀ1,7´ꢀpyrroloꢀ
[1,2ꢀa]imidazole] (10b) was obtained from aldehyde 1d and 1,2ꢀdiꢀ
aminoethane (7) in 63% yield as a mixture of Eꢀ and Zꢀisomers
(the ratio of 4 : 1) and isolated by chromatography on neutral
Al2O3 (eluent hexane—diethyl ether, 5 : 1).
by recrystallization from hexane. Found (%): C, 96.32; H, 8.69;
N, 10.97. C15H22N2S. Calculated (%): C, 68.65; H, 8.45;
N, 10.68. 1H NMR, : 1.13 (s, 3 H, Me); 1.30 (s, 3 H, Me);
1.60—1.74 (m, 1 H, NCH2CHHCH2N); 1.76—2.00 (m, 1 H,
NCH2CHHCH2N); 2.00—2.15 (m, 1 H, MeNCHHCH2ꢀ
CH2N); 2.29 (s, 3 H, NMe); 2.44 (br.d, 1 H, =CCHH, J = 16.5 Hz);
2.50 (ddd, 1 H, MeNCHHCH2CH2N, 2J = 12.0 Hz, 3J = 12.0 Hz,
3J = 3.9 Hz); 2.69 (br.d, 1 H, =CCHH, J = 16.5 Hz); 2.75 (s, 1 H,
2
NCHN); 2.93 (ddd, 1 H, MeNCH2CH2CHHN, J = 10.9 Hz,
3
3J = 3.4 Hz, J = 3.4 Hz); 3.50—3.62 (m, 1 H, MeNCH2CH2ꢀ
CHHN); 5.48 (br.s, 1 H, ThiCH=); 6.65 (dd, 1 H, thienyl,
J = 3.4 Hz, J = 1.4 Hz); 6.88—6.98 (m, 2 H, thienyl). 13C NMR,
: 22.6 (Me); 24.0 (C(3)); 28.1 (Me); 38.5 (C(8)); 42.3 (NMe);
42.9, 45.9 (C(4), C(7)); 56.2 (C(2)); 87.4, 90.3 (NCHN, ThiCH=),
119.4, 120.2, 127.0 (thienyl); 144.1 (C(1), thienyl); 146.2
(ThiCH=C). MS, m/z: 262 [M+], 261 [M — H]+.
(E)ꢀ6´ꢀBenzylidenehexahydroꢀ1´Hꢀspiro[cyclohexaneꢀ1,8´ꢀ
pyrrolo[1,2ꢀa]pyrimidine] (6e) was obtained from aldehyde 1d
and 1,3ꢀdiaminopropane (3a) and isolated in 52% yield by reꢀ
crystallization from hexane. Spectral characteristics of this comꢀ
pound correspond to those described earlier.26
(E)ꢀ6´ꢀBenzylideneꢀ1´ꢀmethylhexahydroꢀ1´Hꢀspiro[cycloꢀ
hexaneꢀ1,8´ꢀpyrrolo[1,2ꢀa]pyrimidine] (6f) was obtained from
aldehyde 1d and Nꢀmethylꢀ1,3ꢀdiaminopropane (3b) and isolatꢀ
ed in 52% yield by recrystallization from hexane. Found (%):
C, 80.67; H, 9.69; N, 9.21. C20H28N2. Calculated (%): C, 81.03;
H, 9.52; N, 9.45. 1H NMR, : 1.10—2.00 (m, 12 H, cycloꢀC6H10
,
NCH2CH2CH2N); 2.03—2.18 (m, 1 H, MeNCHHCH2CH2N);
2.33 (br.d, 1 H, =CCHH, J = 16.4 Hz); 2.36 (s, 3 H, NMe); 2.50
(ddd, 1 H, MeNCHHCH2CH2N, 2J = 11.8 Hz, 3J = 11.8 Hz,
3J = 4.0 Hz); 2.71 (s, 1 H, NCHN); 2.88—3.00 (m, 1 H,
MeNCH2CH2CHHN); 3.12 (br.d, 1 H, =CCHH, J = 16.4 Hz);
3.52—3.64 (m, 1 H, MeNCH2CH2CHHN); 5.18 (br.s, 1 H,
PhCH=); 6.98 (br.t, 1 H, Ph, J = 6.8 Hz); 7.15—7.30 (m, 4 H,
Ph). 13C NMR, : 22.3, 23.8, 23.9, 26.4, 28.7, 37.6, 39.8 (5 CH,
cycloꢀC6; C(3´), C(7´)); 42.4 (C(1,8´)), 43.0 (C(4´)); 43.2 (NMe);
56.8 (C(2´)); 90.3 (NCHN); 93.0 (PhCH=C); 122.8, 126.3, 128.3
(Ph); 140.1 (C(1), Ph); 147.1 (PhCH=C). MS, m/z: 296 [M+],
295 [M — H]+.
(E)ꢀ6ꢀBenzylideneꢀ8,8ꢀdimethyloctahydropyrrolo[1,2ꢀa]pyrꢀ
imidine (6a) was obtained from aldehyde 1a and 1,3ꢀdiaminoꢀ
propane (3a) and isolated in 77% yield by recrystallization from
hexane.
(E)ꢀ6ꢀBenzylideneꢀ1,8,8ꢀtrimethyloctahydropyrrolo[1,2ꢀa]ꢀ
pyrimidine (6b) was obtained from aldehyde 1a and Nꢀmethylꢀ
1,3ꢀdiaminopropane (3b) and isolated in yield 78% by recrystalꢀ
lization from hexane.
Spectral characteristics of compounds 6a,b and 10a,b correꢀ
spond to those described earlier.26
(E)ꢀ6ꢀ(4ꢀFluorobenzylidene)ꢀ1,8,8ꢀtrimethyloctahydropyrroꢀ
lo[1,2ꢀa]pyrimidine (6c) was obtained from aldehyde 1b and
Nꢀmethylꢀ1,3ꢀdiaminopropane (3b) and isolated in 60% yield
by recrystallization from hexane. Found (%): C, 74.71; H, 8.21
N, 9.98. C17H23FN2. Calculated (%): C, 74.42; H, 8.45; N, 10.21.
1H NMR, : 1.12 (s, 3 H, Me); 1.27 (s, 3 H, Me); 1.60—1.74 (m, 1 H,
NCH2CHHCH2N); 1.78—2.00 (m, 1 H, NCH2CHHCH2N);
2.04—2.21 (m, 1 H, MeNCHHCH2CH2N); 2.32 (s, 3 H,
NCH3); 2.46 (br.d, 1 H, =CCHH, J = 15.6 Hz); 2.51 (ddd, 1 H,
MeNCHHCH2CH2N, 2J = 12.0 Hz, 3J = 12.0 Hz, 3J = 4.0 Hz);
2.66 (br.d, 1 H, =CCHH, J = 15.6 Hz); 2.73 (s, 1 H, NCHN);
2.94 (ddd, 1 H, MeNCH2CH2CHHN, 2J = 10.9 Hz, 3J = 3.4 Hz,
3J = 3.4 Hz); 3.50—3.62 (m, 1 H, MeNCH2CH2CHHN); 5.15
(br.s, 1 H, 4ꢀFC6H4CH=); 6.85—7.15 (m, 4 H, Ph). 13C NMR,
: 22.5 (Me); 24.1 (C(3); 28.1 (Me); 38.3 (C(8); 42.3 (NMe);
43.0, 45.8 (C(4), C(7)); 56.3 (C(2)); 90.1, 92.0 (NCHN,
4ꢀFC6H4CH=); 115.0 (d, C(3), C(5), Ph, J = 21 Hz); 127.4
(d, C(2), C(6), Ph, J = 7.2 Hz); 136.0 (d, C(1), Ph, J = 2.7 Hz);
148.6 (4ꢀFC6H4CH=C); 162.0 (d, C(4), Ph, J = 242 Hz). MS,
m/z: 274 [M+], 273 [M — H]+.
(E)ꢀ6´ꢀBenzylideneꢀ1´ꢀmethyldecahydroꢀ1´Hꢀspiro[pyranꢀ
4,8´ꢀpyrrolo[1,2ꢀa]pyrimidine] (6g) was obtained from aldehyde
1e and Nꢀmethylꢀ1,3ꢀdiaminopropane (3b) and isolated in 72%
yield by recrystallization from hexane. Found (%): C, 76.17;
H, 8.56; N, 9.23. C19H26N2O. Calculated (%): C, 76.47; H, 8.78;
N, 9.39. 1H NMR, : 1.39 (br.dd, 2 H, CH2CH2OCH2CH2,
J = 15 Hz, J = 15 Hz), 1.61—1.75 (m, 1 H, NCH2CHHCH2N);
1.77—2.25 (m, 3 H, NCH2CHHCH2N, CHHCH2OCH2CHH);
2.13—2.32 (m, 1 H, MeNCHHCH2CH2N); 2.40 (s, 3 H,
NMe); 2.43 (d, 1 H, =CCHH, J = 16.3 Hz); 2.53 (ddd, 1 H,
MeNCHHCH2CH2N, 2J = 12.0 Hz, 3J = 12.0 Hz, 3J = 4.0 Hz);
2.77 (s, 1 H, NCHN); 2.96 (ddd, 1 H, MeNCH2CH2CHHN,
2J = 11.5 Hz, 3J = 3.2 Hz, 3J = 3.2 Hz); 3.24 (br.d, 1 H, =CCHH,
J = 16.3 Hz); 3.52 (ddd, 1 H, CH2OCHH, 2J = 12.0 Hz,
3J = 12.0 Hz, 3J = 2.0 Hz); 3.53—3.63 (m, 1 H, MeNCH2CH2ꢀ
CHHN); 3.64 (ddd, 1 H, CH2OCHH, 2J = 12.4 Hz, 3J = 12.4 Hz,
3J = 2.3 Hz); 3.85—4.02 (m, 2 H, CH2OCH2); 5.22 (br.s, 1 H,
PhCH=); 7.02 (br.t, 1 H, Ph, J = 6.8 Hz); 7.15—7.35 (m, 4 H, Ph).
13C NMR, : 23.6 (C(3´)); 29.3, 37.3 (C(4), C(5), cycloꢀC5O); 39.3
(C(7´)); 40.2 (C(4, 8´)); 42.9 (C(4´)); 43.0 (NMe); 56.7 (C(2´)); 64.2,
66.6 (C(2), C(6), cycloꢀC5O), 89.5 (NCHN); 93.6 (PhCH=C);
123.1, 126.4, 128.4 (Ph); 139.7 (C(1), Ph); 145.9 (PhCH=C).
(E)ꢀ1,8,8ꢀTrimethylꢀ6ꢀ(2ꢀthienylmethylidene)octahydropyrꢀ
rolo[1,2ꢀa]pyrimidine (6d) was obtained from aldehyde 1c and
Nꢀmethylꢀ1,3ꢀdiaminopropane (3b) and isolated in 58% yield

2436
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 11, November, 2013
Gvozdev et al.
(E)ꢀ6ꢀBenzylideneoctahydropyrrolo[1,2ꢀa]pyrimidine (6h)
was obtained from aldehyde 1f and 1,3ꢀdiaminopropane (3a)
and isolated in 42% yield by recrystallization from hexane.
Found (%): C, 78.65; H, 8.23; N, 13.36. C14H18N2. Calculatꢀ
ed (%): C, 78.46; H, 8.47; N, 13.07. 1H NMR, : 1.48—1.78
(m, 3 H, NCH2CH2CH2N, =CCH2CHH); 2.03 (br.s, 1 H, NH);
2.22 (dddd, 1 H, =CCH2CHH, 2J = 11.6 Hz, 3J = 8.7 Hz,
3J = 5.8 Hz, 3J = 2.9 Hz); 2.55—3.03 (m, 4 H, =CCH2,
NCHHCH2CHHNH); 3.21 (br.d, 1 H, NCH2CH2CHHNH,
J = 13.5 Hz); 3.70 (br.d, 1 H, NCHHCH2CH2NH, J = 12.2 Hz);
3.87 (dd, 1 H, NCHN, J = 8.1 Hz, J = 5.8 Hz); 5.21 (br.s, 1 H,
PhCH=); 6.99 (br.t, 1 H, Ph, J = 6.8 Hz); 7.15—7.30 (m, 4 H,
Ph). 13C NMR, : 24.8, 27.2, 28.6 (C(3), C(7), C(8)); 43.3, 44.8
(C(2), C(4)); 75.3 (NCHN); 93.3 (PhCH=); 122.7, 126.0, 128.1
(Ph); 139.6 (C(1), Ph); 147.5 (PhCH=C). MS, m/z: 214 [M+],
213 [M — H]+.
(E)ꢀ6ꢀBenzylideneꢀ1ꢀmethyloctahydropyrrolo[1,2ꢀa]pyrimidꢀ
ine (6i) was obtained from aldehyde 1f and Nꢀmethylꢀ1,3ꢀdiꢀ
aminopropane (3b) and isolated in 51% yield by recrystallization
from hexane. Found (%): C, 78.56; H, 9.03; N, 12.01. C15H20N2.
Calculated (%): C, 78.90; H, 8.83; N, 12.27. 1H NMR,
: 1.60—1.74 (m, 1 H, NCH2CHHCH2N); 1.76—2.23 (m, 4 H,
NCH2CHHCH2N, =CCH2CH2, MeNCHHCH2CH2N);
CH2Cl2 in the presence of Na2SO4 (see below).. Results are
given in Table 2.
Solutions of the products of condensation of aldehydes 1a or
1f with diamines 3a, 3b, or 7 (see Table 2) were stirred with
freshly powdered KOH (28 mg, 0.5 mmol) at ~20 C, monitorꢀ
ing the reaction progress with 1H NMR spectra. In the case of
mixtures of products 8a and 9a, as well as 4a and 5a, the spectra
recorded after 2 h showed their complete conversion to aminals
10a and 6a, respectively. In the case of using compounds 4b and
5i, the conversion after 2 h was 65 and 73%, respectively, the
reaction reached completion within 15 h. The yields of amiꢀ
nals 6 and 10 calculated based on the comparison of integral
intensities of the signal for the proton of the NCHN fragment
and the signal for dioxane are given in Table 2.
Condensation of aldehydes 1a,f with diaminoalkanes 3a,b and
7. Independent synthesis of compounds 4a,b, 5a,i, 8a, 9a. Anhyꢀ
drous Na2SO4 (5 g) was added to a solution of one of diaminoalꢀ
kanes 3a,b or 7 (20 mmol) in CH2Cl2 (20 mL), then, a solution
of the corresponding aldehyde 1 (5 mmol) in CH2Cl2 (5 mL) was
added over 5 min. The mixture obtained was allowed to stand at
~20 C for 24 h, then, thrice washed with water, and dried with
anhydrous Na2SO4. The solvent was evaporated in vacuo to yield
dense oily compounds, which are (NMR data) either mixtures of
the corresponding adducts 8a and 9a or 4a and 5a (characterized
without separation), or derivatives 4b or 5i with the purity exꢀ
ceeding 90%.
N1ꢀ(2,2ꢀDimethylꢀ5ꢀphenylpentꢀ4ꢀynylidene)ethaneꢀ1,2ꢀdiꢀ
amine (8a). 1H NMR, : 1.15 (s, 6 H, 2 Me); 1.80 (br.s, 2 H,
NH2); 2.45 (s, 2 H, CCCH2); 2.88 (t, 2 H, CH2NH2, J = 5.8 Hz);
3.43 (br.t, 2 H, =NCH2, J = 5.8 Hz); 7.17—7.43 (m, 5 H, Ph);
7.59 (br.s, 1 H, CH=N). 13C NMR, : 24.6 (2 Me); 30.5
(CCCH2); 39.2 (C(Me)2); 42.2 (CH2NH2); 61.1 (=NCH2);
82.6, 87.2 (CC); 123.7 (C(1), Ph); 127.6, 128.1, 131.5 (Ph);
171.4 (CH=N).
2ꢀ(2ꢀMethylꢀ5ꢀphenylpentꢀ4ꢀynꢀ2ꢀyl)imidazolidine (9a).
1H NMR, : 1.04 (s, 6 H, 2 Me); 1.80 (br.s, 2 H, 2 NH); 2.41
(s, 2 H, CCCH2); 2.84—2.92 (m, 4 H, NCH2CH2N); 3.62 (s, 1 H,
NCHN); 7.17—7.43 (m, 5 H, Ph). 13C NMR, : 23.0 (2 Me);
29.7 (CCCH2); 37.3 (C(Me)2); 46.8 (NCH2CH2N); 81.7
(NCHN); 82.5, 88.0 (CC); 123.8 (C(1), Ph); 127.5, 128.1,
131.4 (Ph).
2.29 (s,
3
H, NMe); 2.57—2.81 (m,
2
2
H, =CCHH,
H, =CCHH,
MeNCHHCH2CH2N); 2.91—3.07 (m,
MeNCH2CH2CHHN); 3.08 (dd, 1 H, NCHN, J = 7.5 Hz,
J = 5.9 Hz); 3.60—3.72 (m, 1 H, MeNCH2CH2CHHN); 5.25
(br.s, 1 H, PhCH=); 7.00 (br.t, 1 H, Ph, J = 6.8 Hz); 7.15—7.30
(m, 4 H, Ph). 13C NMR, : 23.8, 27.5, 27.7 (C(3), C(7), C(8));
41.5 (NMe); 42.7 (C(4)); 55.2 (C(2)); 82.5 (NCHN); 93.8
(PhCH=); 122.9, 126.2, 128.2 (Ph); 139.8 (C(1), Ph); 148.2
(PhCH=C). MS, m/z: 228 [M+], 227 [M — H]+.
(E)ꢀ1ꢀMethylꢀ6ꢀ(4ꢀtrifluoromethylbenzylidene)octahydroꢀ
pyrrolo[1,2ꢀa]pyrimidine (6j) was obtained from aldehyde 1g and
Nꢀmethylꢀ1,3ꢀdiaminopropane (3b) and isolated in 45% yield
by recrystallization from hexane. Found (%): C, 65.21; H, 6.21;
N, 9.69. C16H19F3N2. Calculated (%): C, 64.85; H, 6.46; N, 9.45.
1H NMR, : 1.60—1.74 (m, 1 H, NCH2CHHCH2N); 1.76—2.23
(m, 4 H, NCH2CHHCH2N, =CCH2CH2, MeNCHHCH2ꢀ
CH2N); 2.26 (s, 3 H, NMe); 2.57—2.80 (m, 2 H, =CCHH,
MeNCHHCH2CH2N); 2.88—3.08 (m, 2 H, =CCHH, MeNꢀ
CH2CH2CHHN); 3.16 (dd, 1 H, NCHN, J = 7.2 Hz, J = 5.7 Hz);
3.60—3.73 (m, 1 H, MeNCH2CH2CHHN); 5.20 (br.s, 1 H,
PhCH=); 7.21 (br.d, 2 H, Ph, J = 8.3 Hz); 7.43 (br.d, 2 H, Ph,
J = 8.3 Hz). 13C NMR, : 23.7, 27.4, 28.3 (C(3), C(7), C(8));
41.4 (NMe); 42.5 (C(4)); 55.2 (C(2)); 82.5 (NCHN); 93.8
(4ꢀF3CC6H4CH=); 123.9 (q, C(4), Ph, J = 32 Hz); 124.8
(q, CF3, J = 270 Hz); 125.0 (q, C(3), C(5), Ph, J = 3.7 Hz);
125.6 (C(2), C(6), Ph); 143.8 (C(1), Ph); 150.5 (4ꢀF3CC6H4ꢀ
CH=C). MS, m/z: 296 [M+], 295 [M — H]+.
Reaction of aldehydes 1a and 1f with diamines in DMSOꢀd6.
A solution of aldehyde 1a or 1f (0.1 mmol) was added to a soluꢀ
tion of diamine 3a, 3b, or 7 (amounts are given in Table 2) and
dioxane (~10 mg) (used as an internal standard) in anhydrous
DMSOꢀd6 (0.3 mL), followed by a shortꢀtime heating to ~50 C.
The NMR spectra recorded after cooling the tubes to ~20 C
showed the absence of the signal for the aldehyde proton in
all the cases. The composition of the mixture formed was deꢀ
termined by a comparison of its spectrum with the spectra
of products obtained by an alternative method by the reacꢀ
tion of aldehydes 1a,f with the corresponding diamines in
N1ꢀ(2,2ꢀDimethylꢀ5ꢀphenylpentꢀ4ꢀynylidene)propaneꢀ1,3ꢀ
diamine (4a). 1H NMR, : 1.14 (s, 6 H, 2 Me); 1.43—1.57 (m, 2 H,
NCH2CH2CH2N; 1.55 (br.s, 2 H, NH2); 2.51 (s, 2 H, CCCH2);
2.57 (t, 2 H, CH2NH2, J = 6.7 Hz); 3.38 (br.t, 2 H, =NCH2,
J = 6.8 Hz); 7.20—7.45 (m, 5 H, Ph); 7.64 (br.s, 1 H, CH=N).
2ꢀ(2ꢀMethylꢀ5ꢀphenylpentꢀ4ꢀynꢀ2ꢀyl)hexahydropyrimidine
1
(5a). H NMR, : 1.12 (s, 6 H, 2 Me); 1.44 (br.s, 2 H, 2 NH);
1.43—1.57 (m, 2 H, NCH2CH2CH2N); 2.50 (s, 2 H, CCCH2);
2.76—2.94 (m, 2 H, NCHHCH2CHHN); 3.19—3.32 (m, 2 H,
NCHHCH2CHHN); 3.41 (s, 1 H, NCHN); 7.27—7.51 (m, 5 H,
Ph). 13C NMR, : 22.8 (2 Me); 27.6, 29.6 (CCCH2; C(5),
cycloꢀC4N2); 37.4 (C(Me)2); 46.2 (C(4), C(6), cycloꢀC4N2); 77.9
(C(2), cycloꢀC4N2); 82.3, 87.7 (CC); 123.7 (C(1), Ph); 127.2,
127.9, 131.2 (Ph).
N1ꢀ(2,2ꢀDimethylꢀ5ꢀphenylpentꢀ4ꢀynylidene)ꢀN3ꢀmethylproꢀ
paneꢀ1,3ꢀdiamine (4b). 1H NMR, : 1.19 (s, 6 H, 2 Me); 1.50
(br.s, 1 H, NH); 1.75 (tt, 2 H, NCH2CH2CH2N, J = 6.8 Hz,
J = 6.8 Hz); 2.35 (s, 3 H, NMe); 2.49 (s, 2 H, CCCH2); 2.57
(t, 2 H, CH2NHCH3, J = 6.8 Hz); 3.43 (br.t., 2 H, =NCH2,
J = 6.8 Hz); 7.20—7.45 (m, 5 H, Ph); 7.61 (br.s, 1 H, CH=N).

Synthesis of bicyclic N,Nꢀenaminals
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 11, November, 2013 2437
13C NMR, : 24.6 (2 Me); 30.5, 30.8 (CCCH2, NCH2CH2ꢀ
CH2N); 36.4 (NMe); 39.2 (C(Me)2); 49.9 (MeNCH2); 59.3
(=NCH2); 82.5, 87.2 (CC); 123.8 (C(1), Ph); 127.5, 128.1,
131.4 (Ph); 169.9 (CH=N).
11. R. Yanada, S. Obika, H. Kono, Y. Takemoto, Angew. Chem.,
Int. Ed., 2006, 45, 3822.
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50, 6791.
1ꢀMethylꢀ2ꢀ(4ꢀphenylbutꢀ3ꢀynyl)hexahydropyrimidine (5i).
1H NMR, : 1.35—1.50 (m, 1 H, NCH2CHHCH2N); 1.55—1.76
(m, 3 H, CCCH2CH2, NH); 1.89—2.11 (m, 1 H, NCH2CHHꢀ
CH2N); 2.18 (s, 3 H, NMe); 2.27 (ddd, 1 H, NCHHCH2ꢀ
CH2NMe, 2J = 12 Hz, 3J = 3.2 Hz, 3J = 3.2 Hz); 2.36—2.67
(m, 3 H, CCCH2, NCHHCH2CH2NMe); 2.83—2.96 (m, 1 H,
NCH2CH2CHHNMe); 2.93 (dd, 1 H, NCHN, J = 8.3 Hz,
J = 3.2 Hz); 2.96—3.08 (m, 1 H, NCH2CH2CHHNMe); 7.15—7.40
(m, 5 H, Ph). 13C NMR, : 15.1 (CCCH2); 26.8 (C(5),
cycloꢀC4N2); 32.4 (CCCH2CH2); 40.1 (NMe); 45.0 (C(4),
cycloꢀC4N2); 55.6 (C(6), cycloꢀC4N2); 77.3 (C(2), cycloꢀC4N2);
80.5, 90.0 (CC); 123.8 (C(1), Ph); 127.4, 128.0, 131.4 (Ph).
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This work was financially supported by the Council on
Grants at the President of the Russian Federation (Proꢀ
gram of State Support for Leading Scientific Schools of
the Russian Federation, Grant NShꢀ604.2012.3) and the
Russian Academy of Sciences (Program OKhꢀ01).
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Received March 5, 2013;
in revised form July 3, 2013