Effect of atmosphere on solid-state amine-aldehyde condensations: Gas-phase catalysts for solid-state transformations

Article abstract of DOI:10.1039/c2cc36357g

The presence of water or organic solvent vapour accelerates the solid-state condensation of solid aromatic amines and aromatic aldehydes into Schiff bases; we show the important role of catalytic triethylamine in the vapour phase in such vapour digestion

Full text of DOI:10.1039/c2cc36357g

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Effect of atmosphere on solidꢀstate amineꢀaldehyde condensations: gasꢀ
ꢀphase catalysts for solidꢀstate transformations†‡
Dominik Cinčić*, Ivana Brekalo and Branko Kaitner
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
The presence of water or organic solvent vapour accelerates
the solidꢀstate condensation of solid aromatic amines and
aromatic aldehydes into Schiff bases; we show the important
role of catalytic triethylamine in the vapour phase in such
10 vapour digestion synthesis, as well as in the liquid phase in
synthesis via liquidꢀassisted grinding.
Mechanochemical methods, such as liquidꢀassisted grinding
(LAG)1 or ionꢀ and liquidꢀassisted grinding (ILAG)2 have
shown great potential as efficient methods for supramolecular
15 and covalent synthesis.3 However, many supramolecular and
covalent reactions in the solid state can occur readily simply
by mixing solid reactants and without excessive input of
mechanical energy.4 Also, it has been shown that such
reactions can proceed efficiently and selectively in the
20 presence of solvent vapour.5 During the past decade it has
been shown that solventꢀfree synthesis and mechanochemistry
are effective for the efficient and rapid synthesis of a wide
range of imines.6 However, the effect of ambient humidity and
vapour environment on the reactivity of aromatic amines and
25 aldehydes in the solid state has scarcely been explored.
We now demonstrate a surprising effect of the surrounding
atmosphere on the course of solidꢀstate synthesis of Schiff
bases.7 We focused on two different sets of imines: Schiff
bases derived from 2ꢀhydroxyꢀ1ꢀnaphthaldehyde (napht) and
30 compounds derived from 5ꢀaminosalicylic acid (mesalazine;
5asa)8. All solidꢀstate reactions were compared by means of
powder Xꢀray diffraction (PXRD), differential scanning
calorimetry (DSC) and FTꢀIR spectroscopy.9 We have
previously reported the mechanosynthesis of the Schiff base
35 (1) derived from napht and 2ꢀaminobenzonitrile (abn)10 (Fig
1a). While ascertaining the reproducibility of synthesis of 1,
by grinding solid reactants in the air, we noticed that the rate
of this relatively slow solidꢀstate reaction significantly
depends on the ambient relative humidity (RH). We have
40 observed that experiments performed in the different season
of the year have different rates of reaction. Tentatively, we
associated this to the annual variation in the relative humidity
(20%RHꢀ80%RH). Indeed, relative humidity was found to
have profound impact on the syntheses of metalꢀorganic
45 frameworks from a metal oxide.11
50 Fig. 1 a) Reaction scheme of preparation of 1 and relevant calculated and
experimental PXRD patterns for reaction at 98% RH (b) and 0% RH (c).
Characteristic reflections for napht are indicated by "*".
reactants, obtained by gentle grinding of napht and abn for
10 min in agate mortar under normal laboratory conditions
55 (temperature ca 25 °C, 40%ꢀ50% RH) for 3 days at 98% RH
quantitatively afforded 1, according to DSC and PXRD (Fig
1c). In contrast, at 0% RH over the same period the reaction
mixture still contained a noticeable amount of reactants (Fig
1b). The observation that humidity accelerates the solidꢀstate
60 reaction of napht and abn was unexpected since water is a
product of the imine condensation. More surprisingly, the
reaction appears to be inhibited at 0% RH.
4ꢀaminobenzonitrile (4abn) and 4ꢀaminobenzoic acid
(4aba) (Scheme 1) have shown considerably lower reactivity
65 with napht in the solid state compared to abn. (Table 1).
However, these reactions also proceed efficiently in the
presence of water vapour. When a reaction of napht and 4abn
is carried out at 98% RH, almost quantitative reaction is
Guided by these observations, we turned to explore
reactivity of solid napht and abn at 0%, 43%, 75% and 98%
RH (Fig 1., Fig S3ꢀS6, ESI†). Ageing of a mixture of
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Table 2 Synthesis of 4 and 5 in the solid state in the absence and presence
30 of humidity and solvent vapour.
Reactants
5asa + ovan
Conditions
0% RH
98% RH
Reaction time
28 days
1 day
Observed results
traces of 4
traces of 4
Scheme 1 Reaction scheme of preparation of 2 and 3.
98% RH
EtOH vapour
0% RH
98% RH
98% RH
28 days
1 hour
28 days
5 days
28 days
15 days
1 day
complete reaction
complete reaction
no reaction
Table 1 Synthesis of 1ꢀ3 in the solid state under different humidity
conditions.
5asa + napht
traces of 5
Reactants RH conditions / % Reaction time
Observed results
uncomplete reaction
uncomplete reaction
complete reaction
napht + abn
0
18 days
8 days
18 days
3 days
13 weeks
3 weeks
13 weeks
13 weeks
4 weeks
13 weeks
uncomplete reaction
complete reaction
complete reaction
complete reaction
traces of 2
EtOH vapour
EtOH/TEA vapour
43
75
98
0
98
98
0
reactions in the solid state proceed efficiently in the presence
of a small amount of solvent vapour. Indeed, after only 1 hour
of such vapour digestion5 of the ground mixture using ethanol
napht + 4abn
napht + 4aba
traces of 2
complete reaction
no reaction
35 vapour the quantitative formation of
4
is observed.
98
98
traces of 3
Furthermore, LAG of 5asa and ovan in a ball mill for 5 min
in the presence of a small amount14 of ethanol quantitatively
afforded 4, whereas neat grinding yielded a mixture of solid
reactants and traces of 4 (Fig 2b).
Solid state synthesis of 5 by reaction of 5asa with napht
(Fig 3a) proceeds with significantly lower rate than previously
described reaction with ovan (Table 2). Ageing of the mixture
obtained by gentle grinding of 5asa and napht for 10 min in
agate mortar for 28 days at 98% RH provided a mixture of
45 solid reactants and 5 in very poor yield, Fig 3b. It was
expected that, as with the synthesis of 4, ethanol vapour
digestion would result in a higher rate of reaction than that
with water vapour. However, such experiment did not make
the reaction quantitative, after 15 days ageing it was obtained
50 the same mixture of reactants and 5 as after 28 days ageing at
98% RH. Instead, we found that the rates of solidꢀstate
reaction were significantly improved by ageing of the ground
uncomplete reaction
5
observed after 13 weeks. Ageing of the ground mixture at 0%
RH for the same period afforded small amounts of 2 as
evidenced by weak signals in the PXRD pattern of the mixture
(Fig S7ꢀS9, ESI†). At 0% RH reaction of napht and 4aba is
10 prevented and even after 13 weeks no traces of 3 are
detectable. Ageing of the ground mixture at 98% RH for the
same period afforded a mixture of 3 and reactants in traces
(Table 1, Fig S10 and S11, ESI†). Overall, ageing at
conditions of high humidity favours the condensations (Table
15 1).
Neat grinding of 5asa and oꢀvanillin (ovan) for 10 min in
agate mortar under normal laboratory conditions also provided
a mixture of solid reactants (Fig 2a). At 0% RH reaction is
prevented and after 28 days only traces of 4 are detectable
20 (Fig 2b). Ageing of the ground mixture at 98% RH for the
same period quantitatively affords 4 with a PXRD pattern
identical to the one calculated from single crystal data (CCDC
code VIKLAD)12, Fig 2b. We found additional inspiration in
the work of Toda et al.,5a who demonstrated that some organic
40
25
Fig. 3 a) Reaction scheme of preparation of 5, b) relevant calculated and
55 experimental PXRD patterns. Characteristic reflections for 5 are indicated
by "*".
Fig. 2 a) Reaction scheme of preparation of 4, b) relevant calculated and
experimental PXRD patterns. Characteristic reflections for 4 are indicated
by "*".
2
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mixture in a vapour mixture of ethanol and an organic base
triethylamine (TEA), (5% v/v of TEA), despite the fact that
conventional synthesis of Schiff bases by condensation of
primary amines with carbonyl compounds in solution
generally requires acid catalysis. Ageing for 3 hours revealed
a partial reaction, and complete reaction, yielding 5, was
observed after only 1 day (Fig 3b). Guided by the results of
the previously described synthesis of 4, we explored the
mechanosynthesis of 5 in a ball mill (Table 3). Neat grinding
10 of 5asa and napht for 45 min resulted in a mixture of solid
reactants. Similarly, LAG for 45 min of 5asa and napht in the
presence of a small amount13 of ethanol gave the same result
as vapour digestion: a mixture of solid reactants and 5 in a
poor yield. Encouraged by the fact that a catalytic amount of
15 TEA in EtOH vapour can significantly increase the efficiency
of the reaction we turned to LAG. Indeed, LAG of 5asa and
napht for 45 min in the presence of a small quantity of
EtOH/TEA mixture14 quantitatively afforded 5, of PXRD
pattern identical with one calculated from single crystal data,
20 Fig 3b.
This research was supported by grants from the Ministry of
Science and Technology of the Republic of Croatia (Grant No.
119ꢀ1193079ꢀ3069).
5
Notes and references
50 aDepartment of Chemistry, Faculty of Science, University of Zagreb,
Horvatovac 102a, HR-10000 Zagreb, Croatia. Fax: 00385-14606341;
Tel: 00385-14606362; E-mail: dominik@chem.pmf.hr.
† This article is part of the ChemComm 'Mechanochemistry' web themed
issue.
55 ‡ Electronic Supplementary Information (ESI) available: experimental
details for solutionꢀbased synthesis, instrumental experimental details and
PXRD, FTIR, and DSC data. CCDC 898504 and 898505 contains the
supplementary crystallographic data for this paper. See DOI:
10.1039/b000000x/
60
1
a) T. Friščić, A. V. Trask, W. Jones, and W. D. S. Motherwell,
Angew. Chem. Int. Ed., 2006, 45, 7546; b) D. Braga and F. Grepioni,
Angew. Chem. Int. Ed., 2004, 43, 4002; c) V. Štrukil, L. Fábián, D.
G. Reid, M. J. Duer, G. J. Jackson, M. EckertꢀMaksić and T. Friščić,
Chem. Commun., 2010, 46, 9191.
65
2
3
T. Friščić, D. G. Reid, I. Halasz, R. S. Stein, R. E. Dinnebier, M. J.
Duer, Angew. Chem. Int. Ed., 2010, 49, 712; b) T. Friščić, Chem.
Soc. Rev, 2012, 41, 3493.
a) S. L. James, C. J. Adams, C. Bolm, D. Braga, P. Collier, T. Friščić,
F. Grepioni, K. D. M. Harris, G. Hyett, W. Jones, A. Krebs, J. Mack,
L. Maini, A. G. Orpen, I. P. Parkin, W. C. Shearouse, J. W. Steed and
D. C. Waddell, Chem. Soc. Rev., 2012; b) D. Cinčić, M. Juribašić, D.
Babić, K. Molčanov, P. Šket, J. Plavec and M. Ćurić, Chem.
Commun., 2011, 47 11543; c) M. Cindrić, M. Uzelac, D. Cinčić, I.
Halasz, G. Pavlović, T. Hrenar, M. Ćurić and D. Kovačević,
CrystEngComm, 2012, 14, 3039.
70
Scheme 2 Reaction scheme of preparation of 6.
Table 3 Synthesis of 4ꢀ6(H2O) by NG and LAG in a ball mill.
75
4
5
a) K. Chadwick, R. J. Davey, W. Cross, CrystEngComm., 2007, 9,
732; b) K. Tanaka and F. Toda, Chem. Rev., 2000, 100, 1025; c) G.
Kaupp, Topics Curr. Chem., 254, 2005, 95.
a) S. Nakamatsu, S. Toda, W. Jones and F. Toda, Chem. Commun.,
2005, 3808; b) D. Braga, S. L. Giaffreda, F. Grepioni, M. R.
Chierotti, R. Gobetto, G. Palladino and M. Polito, CrystEngComm,
2007, 9, 879.
a) J. Schmeyers, F. Toda, J. Boy and G. Kaupp, J. Chem. Soc., Perkin
Trans., 1998, 2, 989; b) G. Rothenberg, A. P. Downie, C. L. Raston
and J. L. Scott, J. Am. Chem. Soc., 2001, 123, 8701; c) O. Dolotko, J.
W. Wiench, K. W. Dennis, V. K. Pecharsky and V. P. Balema, New
J. Chem., 2010, 34, 25; d) G. Kaupp and J. Schmeyers, Angew.
Chem., Int. Ed., 1993, 32, 1587.
Reactants
5asa + ovan
Conditions
NG
LAG, EtOH
NG
LAG, EtOH
LAG, EtOH/TEA
LAG, TEA
NG
LAG, EtOH
LAG, EtOH/TEA
LAG, TEA
Reaction time
5 min
Observed results
no reaction
complete reaction
no reaction
5 min
5asa + napht
45 min
45 min
45 min
20 min
30 min
30 min
30 min
20 min
traces of 5
80
complete reaction
(solvolysis) no reaction
no reaction
traces of 6(H2O)
complete reaction
(solvolysis) no reaction
5asa + van
6
85
25
To confirm our results we finally turned to milling
mechanosynthesis of 6(H2O), a monohydrate of 6 derived
from 5asa and vanillin (van) (Scheme 2). Neat grinding of
5asa and van for 30 min and LAG for 30 min in the presence
of small amount of ethanol resulted only in a mixture
30 containing solid reactants (Table 3). In contrast, LAG of 5asa
and van for 30 min in the presence of a small quantity of
EtOH/TEA mixture quantitatively afforded 6(H2O) (Fig S20,
ESI†).
In conclusion, we demonstrated that ageing reactions of
35 ground mixtures of different solid aromatic amines and
aromatic aldehydes are accelerated in the presence of water or
organic solvent vapour. We have shown the importance of
catalytic amounts of triethylamine in the vapour phase for
such vapour digestion synthesis as well as in the liquid phase
40 for Schiff base synthesis via liqiudꢀassisted grinding. To the
best of our knowledge, this is the first demonstration of
ageing reactions catalyzed by a catalytic additive in the gas
phase. The described results are important for the
understanding of solid state reactivity as well as, we believe,
45 covalent mechanosynthesis in general.
7
8
9
A. Blagus, D. Cinčić, T. Friščić, B. Kaitner and V. Stilinović, Maced.
J. Chem. Chem. Eng. 2010, 29, 117.
90
Mesalazine is an antiꢀinflammatory drug used to treat inflammatory
bowel disease, such as ulcerative colitis and Crohn's disease.
To observe solidꢀstate experiments, as well as to facilitate the
characterisation of new materials (5 and 6) by singleꢀcrystal Xꢀray
diffraction, conventional solutionꢀbased experiments were performed.
95
10 D. Cinčić, I. Brekalo and B. Kaitner, Cryst. Growth Des., 2012, 12,
44.
11 a) M. J. Cliffe, C. Mottillo, R. S. Stein, D.ꢀK. Bučar and T. Friščić,
Chem. Sci., 2012, 3, 2495; b) F. C. Strobridge, N. Judaš and T.
Friščić, CrystEngComm 2010, 12, 2409; c) T. Friščić, I. Halasz, F. C.
Strobridge, R. E. Dinnebier, R. S. Stein, L. Fábián and C. Curfs,
CrystEngComm 2011, 13, 3125.
12 R.ꢀT. Xue and M.ꢀJ. Niu, Acta Cryst. E, 2007, E63, o3812.
13 In all LAG experiments no formation of intermediate liquid phase
was observed. The amount of liquid used was very small, so as to
avoid significant physical role of solvent, acting as lubricant for the
reaction. For all LAG experiments the mixture of solid reactants (ca
200 mg) was milled in the presence of 30 ꢁL of solvent.
14 LAG in the presence of small amount of pure TEA yielded a slurry
material which, according to PXRD, contained a significant amount
of reactants. We believe this can be attributed to the fact that milling
was hindered because the milling media were fixed with the obtained
sticky material due to solvolysis of reactants or formed product.
100
105
110
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