Solid-state interaction of trimethylammonioalkylferrocene iodides with primary amines

Article abstract of DOI:10.1023/B:RUCB.0000011870.91892.43

The syntheses of several aminoalkylferrocenes by the solid-state reactions of trimethylammoniomethylferrocene iodides and (S)-(-)-(1-trimethylammonio) ethylferrocene with primary amines are described. New ferrocenylalkylamines were synthesized: 1-(4-tolui

Full text of DOI:10.1023/B:RUCB.0000011870.91892.43

2146
Russian Chemical Bulletin, International Edition, Vol. 52, No. 10, pp. 2146—2148, October, 2003
Solidꢀstate interaction of trimethylammonioalkylferrocene iodides
with primary amines
N. S. Khrushcheva,ꢀ O. V. Shakhova, and V. I. Sokolov
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5085. Eꢀmail: sokol@ineos.ac.ru
The syntheses of several aminoalkylferrocenes by the solidꢀstate reactions of trimethylꢀ
ammoniomethylferrocene iodides and (S)ꢀ(–)ꢀ(1ꢀtrimethylammonio)ethylferrocene with priꢀ
mary amines are described. New ferrocenylalkylamines were synthesized: 1ꢀ(4ꢀtoluidino)ethylꢀ
ferrocene, 1ꢀ(2ꢀpyridylamino)ethylferrocene, 2ꢀpyridylaminomethylferrocene, and
N,Nꢀbis(ferrocenylmethyl)ꢀ2ꢀpyridylamine.
Key words: solidꢀstate interaction, trimethylammonioalkylferrocene iodides, primary
amines, aminoalkylferrocenes.
Scheme 1
One of the methods of introduction of the ferrocenylꢀ
alkyl group into nucleophilic compounds is their interacꢀ
tion with quaternary salts of dimethylaminoalkylferroꢀ
cenes. Among these salts, dimethylaminomethylferrocene
methoiodide is most accessible and widely used. Its hoꢀ
mologs, in particular, 1ꢀtrimethylammonioethylferrocene
iodide, are used much more rarely because of their affinꢀ
ity to thermal elimination with the formation of vinylꢀ
ferrocene. However, these are precisely the compounds
that are of interest from the point of view of stereochemꢀ
istry, because they can be obtained in the enantiomeric
form and used for introduction into compounds of optiꢀ
cally active organometallic fragments. In addition, in reꢀ
cent years researchers are greatly interested in electronꢀ
active dendrimers containing ferrocenyl groups in the peꢀ
ripheral layer. Solidꢀstate methods can be very helpful in
the syntheses of these compounds.1
Ar = 4ꢀCHOC6H4, Ph, 3ꢀCHOC6H4, 3ꢀNO2C6H4,
2ꢀCHOꢀ4ꢀMeOC6H3
Scheme 2
In this work, we studied the solidꢀstate reactions of
dimethylaminomethylferrocene methoiodide and enantioꢀ
merically pure (S)ꢀ(–)ꢀ(1ꢀdimethylamino)ethylferrocene
with several primary aromatic amines. We have previously
shown2 that optically active (S)ꢀ(–)ꢀ(1ꢀtrimethylammoꢀ
nio)ethylferrocene iodide (1) reacts easily with substiꢀ
tuted phenols in the solid state, i.e., in the absence of a
solvent, to form the corresponding ethers (Scheme 1).
The conditions of the solidꢀstate reaction (duration,
temperature regime, ratio of reactants, amount of used
K2CO3) were studied in detail. The most substantial facꢀ
tors were the rather narrow temperature interval of the
reaction (60—70 °C) and the use of tenfold K2CO3 excess
to obtain the maximum yield of the product.
Ar = Ph (a), 4ꢀNO2C6H4 (b), Tol (c),
(d)
The reaction occurred on heating of a mixture of the
starting reactants in the absence of a solvent for 2 h. In all
cases, the starting methoiodide was almost completely
converted within this time. The products formed were
extracted with chloroform and chromatographed.
The resulting amines 3 were orange oily or crystalline
substances stable in air. As the corresponding products of
the reaction of compound 1 with phenols, amines 3 are
optically active, indicating that the solidꢀstate reaction is
stereoselective.
Based on these data, we carried out the solidꢀstate
reactions of methoiodide 1 with several aromatic amines
(Scheme 2).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2033—2035, October, 2003.
1066ꢀ5285/03/5210ꢀ2146 $25.00 © 2003 Plenum Publishing Corporation

Solidꢀstate synthesis of aminoalkylferrocenes
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 10, October, 2003
2147
Our further studies were aimed at studying the possiꢀ
bility of the solidꢀstate interaction of dimethylaminoꢀ
methylferrocene methoiodide (4), which is less reactive
in nucleophilic substitution (Scheme 3), with amines.
ture of secondary and tertiary amines with a great preꢀ
domination of the first one is formed and can difficultly
be separated by chromatography.
The reaction of compound 1 with enantiomerically
pure 3ꢀmethoxyꢀ1ꢀphenylꢀ2ꢀpropylamine (7) demonꢀ
strated the possibility of the solidꢀstate interaction of
methoiodides with aliphatic primary amines (Scheme 4).
Scheme 3
Scheme 4
In the first experiment, the reaction of 4 with 2b was
carried out under conditions developed for enantioꢀ
merically pure compound 1. However, heating of the reꢀ
action mixture at 70 °C for several hours (2—4 h) did not
give the desirable product. The high thermal stability of
methoiodide 4 (unlike 1) made it possible to increase the
reaction temperature to 110 °C, after 2 h resulting in the
complete conversion of the starting compounds. After the
standard treatment of the reaction mixture followed by
chromatography, a mixture of two products was obtained:
secondary amine 5b and tertiary amine 6b. The attempt of
their complete separation failed. When this reaction is
carried out in a solution (H2O, 100 °C, 7 h), no formation
of tertiary amine was detected.3
Under standard conditions, the solidꢀstate reaction of
methoiodide 1 with 7 occurs within 2 h with the complete
conversion of the starting methoiodide. The single prodꢀ
uct was isolated by chromatography in 79% yield. Its
1Н NMR spectrum showed one set of signals correspondꢀ
ing to structure 8. We failed to isolate compound 8 in the
analytically pure state. Taking into account the presence
of two chiral centers in molecule 8, we can consider the
formation of the single diastereomer as an evidence favorꢀ
ing that the enantiomeric purity is retained during the
solidꢀstate reaction at the chiral αꢀferrocenyl carbon atom.
In all reactions studied in this work, the reaction mixꢀ
ture remains solid and friable during the whole interacꢀ
tion due to a great excess of K2CO3 used. As we have
shown previously,2 a decrease in the amount of K2CO3
results in oiling of the reaction mixture and a decrease in
the yield of the products. Melting of crystalline organic
compounds during the interaction in the absence of a
solvent was observed so often by us in the previous works
and by other authors4 that this fact was specially studied
and discussed.5 Note that using the term "solidꢀstate reꢀ
action" we imply organic reactions of solid starting comꢀ
pounds in the absence of a solvent.
Probably, compound 6b is a product of the reaction of
formed amine 5b with methoiodide 4, which suggests that
secondary amines also can react with 4 in the solid state.
We studied the influence of the ratio of
4/2b 5b/6b
the starting reactants under the standard
3/1
1/1
2/1
4/1
solidꢀstate conditions on the relative
yield of secondary and tertiary amines
5b and 6b.
1/3 7.5/1
The relative yields were determined from the ratio of
integral intensities of the well discernible signals from
aromatic protons (6.58 ppm for 5b and 6.76 ppm for 6b)
in the proton spectra of samples of the reaction mixtures.
In all cases, secondary amine 5b is mainly formed. Even
the use of threefold methoiodide excess does not suffiꢀ
ciently increase the yield of tertiary amine 6b. Probably,
more drastic reaction conditions should be selected for
the ∼100% interaction of methoiodide with secondary aroꢀ
matic amines.
Experimental
1
Н NMR spectra were recorded on Brukerꢀ200ꢀWP and
The reaction of compound 4 with 2ꢀaminopyridine 2d
occurs analogously (see Scheme 3). In this case, a mixꢀ
BrukerꢀAMXꢀ400ꢀST instruments. The optical rotation values
[α]D were determined on an EPOꢀ1 polarimeter in acetone.

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Russ.Chem.Bull., Int.Ed., Vol. 52, No. 10, October, 2003
Khrushcheva et al.
Iodides 1 and 4 were synthesized by a previously described proꢀ
cedure6 from (S)ꢀ(–)ꢀN,Nꢀdimethylꢀ1ꢀferrocenylethylamine
(Fluka) and dimethylaminomethylferrocene (Aldrich). Reacꢀ
tion mixtures were homogenized in an MLꢀ1 vibratory ball mill
(Ekoniks State Scientific Production Enterprise) with a freꢀ
quency of 50 Hz in a hermetically sealed titanium 62ꢀcm3 reacꢀ
tor using titanium balls as the activating packing (2 balls, diamꢀ
eter 1.3 cm, weight 10 g).
Solidꢀstate reactions of methoiodides 1 and 4 with amines
2а—d and 7 (general procedure). A mixture of methoiodide
(0.1 mmol), amine (0.1 mmol) or amine hydrochloride (for 2а),
and K2CO3 (1 mmol) was stirred for 1 min in a ball mill.
A uniform powder formed was placed in a roundꢀbottom flask
and heated for 2 h in an oil bath at 70 °C (110 °C for 4). Then
the reaction mixture was extracted with chloroform and filtered,
and a residue was chromatographed on a column with silica gel
(CHCl3—MeOH, 100 : 0—90 : 10). The products obtained were
crystallized if necessary from an appropriate solvent.
2ꢀPyridylaminomethylferrocene (5d). Orange crystals, 30%
yield (0.0089 g), m.p. 138—140 °C. H NMR (acetoneꢀd6), δ:
4.07 (m, 2 H, C5H4); 4.16 (s, 5 H, C5H5); 4.25 (m, 4 H, C5H4
and CH2); 5.71 (m, 1 H, NH); 6.50 (m, 2 H, C5H4N); 7.35, 8.01
(both m, 1 H each, C5H4N). Found (%): C, 65.18; H, 5.42;
N, 9.36. C16H16FeN2•0.1H2О. Calculated (%): C, 65.37;
H, 5.55; N, 9.53.
1
N,NꢀBis(ferrocenylmethyl)ꢀ2ꢀnitroaniline (6b). Orange crysꢀ
tals, 7.5% yield (0.0020 g), m.p. 213—215 °C (Ref. 3: m.p.
1
217—219 °C). H NMR (CDCl3), δ: 4.17 (m, 4 H, 2 C5H4);
4.20 (m, 14 H, 2 C5H5 and 2 C5H4); 4.40 (s, 4 H, 2 CH2); 6.76
(d, 2 H, C6H4, J = 9.4 Hz); 8.10 (d, 2 H, C6H4, J = 9.4 Hz).
N,NꢀBis(ferrocenylmethyl)ꢀ2ꢀpyridylamine (6d). Orange crysꢀ
tals, 7.5% yield (0.0019 g), m.p. 165—167 °C. 1H NMR (acꢀ
etoneꢀd6), δ: 4.08 (m, 4 H, 2 C5H4); 4.17 (s, 10 H, 2 C5H5); 4.29
(m, 4 H, 2 C5H4); 4.50 (s, 4 H, 2 CH2); 6.48, 6.68, 7.40 (all m,
1 H each, C5H4N); 8.10 (m, 1 H, C5H4N). Found (%): C, 66.13;
H, 5.57; N, 5.67. C27H26Fe2N2. Calculated (%): C, 66.02;
H, 5.54; N, 5.70.
1ꢀAnilinoethylferrocene (3а). Yellow oil (Ref. 3: m.p.
20
50—52 °C), 86.8% yield (0.0265 g), [α]D +18.9 (с 0.66, acꢀ
Nꢀ(1ꢀFerrocenylethyl)ꢀ3ꢀmethoxyꢀ1ꢀphenylꢀ2ꢀpropylamine
etone). 1H NMR (acetoneꢀd6), δ: 1.56 (d, 3 H, Me, J = 6.4 Hz);
4.05 (m, 2 H, C5H4); 4.16 (m, 7 H, C5H5 and C5H4); 4.42 (m,
1 H, CH); 4.69 (m, 1 H, NH); 6.47—7.39 (m, 5 H, C6H5).
1ꢀ(4ꢀNitroanilino)ethylferrocene (3b).7 Orange crystals,
93.1% yield (0.0326 g), m.p. 115—116 °C (hexane—benzene),
(8). Orange oil, 79% yield (0.0298 g). H NMR (C6D6), δ: 1.36
1
(d, 3 H, Me, J = 7.0 Hz); 1.71 (m, 1 H, NH); 2.28 (m, 2 H,
CH2Ph); 3.12 (s, 3 H, ОMe); 3.28 (m, 3 H, CH and CH2); 3.65
(q, 1 H, CHFe, J = 7.0 Hz); 3.97 (m, 2 H, C5H4); 4.08 (s, 5 H,
C5H5); 4.10, 4.14 (both m, 1 H each, C5H4).
20
[α]D –23.3 (с 0.82, acetone). 1H NMR (C6D6), δ: 1.53
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 02ꢀ03ꢀ
33355).
(d, 3 H, Me, J = 7.1 Hz); 4.17 (m, 9 H, C5H5 and C5H4);
4.41 (m, 1 H, CH); 4.76 (m, 1 H, NH); 6.53, 8.07 (both m,
2
H each, C6H4). Found (%): C, 62.37; H, 5.52;
N, 8.25. C18H18FeN2O2•0.1C6H6. Calculated (%): C, 62.40;
H, 5.24; N, 7.82.
References
1ꢀ(4ꢀToluidino)ethylferrocene (3с). Orange crystals, 67%
20
yield (0.0214 g), m.p. 85—87 °C, [α]D +9.4 (с 0.54, acetone).
1H NMR (acetoneꢀd6), δ: 1.37 (d, 3 H, Me, J = 7.2 Hz); 2.11 (s,
3 H, Me); 4.07 (m, 2 H, C5H4); 4.17 (m, 7 H, C5H5 and C5H4);
4.37 (m, 2 H, CH and NH); 6.62, 6.89 (both m, 2 H each,
C6H4). Found (%): C, 71.16; H, 6.66; N, 4.31; Fe, 17.37.
1. S. Nlate, J. Ruiz, V. Sartor, R. Navarro, J. C. Blais, and
D. Astruc, Chem. Eur. J., 2002, 8, 171.
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3. H.ꢀJ. Lorkowski and P. Kieselack, Chem. Ber., 1966, 3619.
4. F. Toda and K. Tanaka, Chem. Rev., 2000, 100, 1025.
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1972, 37, 3052.
C
19H21FeN. Calculated (%): C, 71.49; H, 6.63; N, 4.39;
Fe, 17.49.
1ꢀ(2ꢀPyridylamino)ethylferrocene (3d). Orange crystals, 85%
yield (0.0259 g), m.p. 82—83 °C. 1H NMR (CDCl3), δ: 1.54
(d, 3 H, Me, J = 6.0 Hz); 4.15 (m, 2 H, C5H4); 4.21 (m, 7 H,
C5H5 and C5H4); 4.71 (m, 2 H, CH and NH); 6.40, 6.57,
7.42, 8.12 (all m, 1 H each, C5H4N). Found (%): C, 66.56;
H, 5.91; N, 9.21. C17H18FeN2. Calculated (%): C, 66.69;
H, 5.93; N, 9.15.
7. Y. Yamazaki, K. Hosono, H. Matsuda, N. Minami, M. Asai,
and H. Nakanishi, Biotechnology and Bioengineering, 1991,
38, 1218.
4ꢀ(Nitroanilino)methylferrocene (5b). Orange crystals,
7.4% yield (0.0025 g), m.p. 142—144 °C (Ref. 3: m.p.
1
143.5—145.5 °C). H NMR (CDCl3), δ: 4.07 (m, 2 H, C5H4);
4.21 (m, 7 H, C5H5 and C5H4); 4.25 (m, 2 H, CH2); 4.70 (br.s,
1 H, NH); 6.58 (m, 2 H, C6H4, J = 9.0 Hz); 8.12 (d, 2 H, C6H4,
J = 9.0 Hz).
Received October 30, 2002;
in revised form June 18, 2003