Solventless mechanochemical metallation of porphyrins

Article abstract of DOI:10.1039/c6gc02420c

A fast solvent-free method for the metallation of porphyrins is presented. ZnTPP, NiTPP, CuTPP and FeTPP have been prepared mechanochemically by ball milling hydrated metal acetate salts with meso-tetraphenylporphyrin (H₂TPP) in a shaker mill for as little as 20 min with no added solvent, avoiding the need for undesirable solvents and long reaction times normally used in such reactions.

Full text of DOI:10.1039/c6gc02420c

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Solventless mechanochemical metallation
of porphyrins†
Cite this: DOI: 10.1039/c6gc02420c
Received 30th August 2016,
Accepted 13th November 2016
Kathryn Ralphs, Chen Zhang and Stuart L. James
DOI: 10.1039/c6gc02420c
www.rsc.org/greenchem
A fast solvent-free method for the metallation of porphyrins is
Methods for the metallation of porphyrins typically involve
presented. ZnTPP, NiTPP, CuTPP and FeTPP have been prepared undersirable and highly toxic solvents such as DMF (dimethyl-
mechanochemically by ball milling hydrated metal acetate salts formamide), benzene, methanol and chloroform23 and heating
with meso-tetraphenylporphyrin (H2TPP) in a shaker mill for as to reflux for up to and 5 days.24,25 The need to resort to these
little as 20 min with no added solvent, avoiding the need for solvents and methods may reflect the generally low solubilities
undesirable solvents and long reaction times normally used in of porphyrins and slow kinetics of metallation. In addition to
such reactions.
its high toxicity, DMF can decompose on heating to dimethyl-
amine and can cause complicated side reactions. Herein, we
describe a simple, direct and potentially more sustainable
solvent-free mechanochemical route for the preparation of
metallo-porphyrins by ball milling of solid reactants.
Analytically pure products are obtained with no work-up other
than heating to remove volatile by-products (water and acetic
acid).
Mechanochemical synthesis is the induction of chemical reac-
tions through the input of mechanical energy, often with little
or no added solvent.1–3 Current environmental concerns over
the use of solvents make it very timely to investigate the full
scope of this technique, especially in cases where solvents are
particularly problematic. As well as being potentially more
sustainable than solvent-based synthesis, other advantages of
mechanochemical synthesis can include lower reaction temp-
eratures, increased reaction rates, reduced cost and operational
simplicity.1–3 The potential applications for mechanochemical
synthesis are wide and include organic synthesis,2 inorganic
materials,3 pharmaceuticals,4 catalysis,5–7 co-crystals,8 discrete
metal complexes,9 macrocycles10 and extended metal organic
frameworks (MOFs).11,12 Recent work has shown that screw
extrusion techniques can be used to scale-up mechano-
chemical synthesis.12–15
To date, however, despite their general importance, the syn-
thesis of macrocyclic metal complexes has not been explored
mechanochemically to our knowledge. Porphyrins and
metallo-porphyrins are amongst the most important macro-
cyclic complexes and are widely encountered in nature e.g. they
form the active sites of proteins such as haemoglobin, myoglo-
bin and cytochromes as well as pigments such as chlorophyll.
Applications of metallo-porphyrins include catalysis,16,17 fuel
cells,18 medicine19,20 and biomimetic chemistry.21,22
meso-Tetraphenylporphyrin (H2TPP) and a range of metal
acetate monohydrate salts were milled together in 1 : 1 molar
ratios without solvent for 20–90 min at 25–30 Hz (Fig. 1 and
Table 1) using a small commercial shaker mill (Retsch
MM400). Following milling, the products were heated in an
oven for 2 h at 100 °C to remove any remaining acetic acid and
water formed as by-products (Fig. 1) During the milling clear
colour changes from dark purple to magenta were observed.
To establish the extent of reaction induced by the milling
alone, analysis of the products was carried out prior to
heating.
The products were characterized by IR, 1H-NMR and
UV-visible spectroscopies (NMR spectra could not be obtained
School of Chemistry and Chemical Engineering, Queens University Belfast,
David Keir building, Stranmillis Road, Belfast, BT9 5AG N. Ireland, UK.
E-mail: s.james@qub.ac.uk, k.ralphs@qub.ac.uk
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c6gc02420c
Fig. 1 Solvent-free mechanochemical metallation of meso-tetraphe-
nylporphyrin (H2TPP).
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Table 1 Milling conditions used to prepare metalloporphyrins
Small scale
(25.2 mg)
Large scale
(151.2 mg)
Time
(min)
Speed
(Hz)
Time
(min)
Speed
(Hz)
Complex
Precursor
ZnTPP
NiTPP
CuTPP
FeTPP
Zn(OAc)2·2H2O
Ni(OAc)2·4H2O
Cu(OAc)2.H2O
Fe(OAc)2
20
40
20
20
25
25
30
20
90
20
—
20
30
25
—
180
for CuTPP and FeTPP due to their paramagnetism). ZnTPP,
CuTPP and NiTPP were each successfully prepared on two
different scales (∼25 mg and ∼150 mg). In all cases the analyti-
cal data were consistent with quantitative reactions to give ana-
lytically pure products at both scales. FeTPP was only prepared
at the smaller scale and required considerably longer milling.
Example spectra are provided here for ZnTPP. Spectra for other
products are provided in the ESI.†
IR spectra (see ESI†) of the products following milling
confirmed that de-protonation of the N atoms in the ring had
occurred through the absence of the N–H stretch in H2TPP at
∼3300 cm−1. Co-ordination of the metal was also supported by
the shift of the porphyrin ring vibration from ∼980 cm−1 to
∼1002–1007 cm−1. The fingerprint regions for the metallo-por-
phyrins prepared matched the data reported in the literature.26
1H-NMR spectra taken after milling showed only peaks
corresponding to the target metallo-porphyrins and matched
literature data.25 Fig. 2 shows spectra for the solid state ZnTPP
synthesis and shows that clean quantitative conversion
occurred (note the absence of the N–H signal at −2.73 ppm in
the product).
Fig. 2 1H-NMR spectra (CDCl3, SiMe4) of (A) TPPH2 (B) ZnTPP taken
after milling and before heating.
UV-visible analysis was carried out in dichloromethane
solution. Metallation of H2TPP is known to simplify its UV-
visible absorption spectrum, mainly due to the increased sym- these reactions to occur, potentially by acting as an internal
metry of the product.26–29 The Q band regions of spectra for solvent. Metallations were also attempted in the ball mill with
H2TPP and ZnTPP are given in Fig. 3. The Soret band remains Au(III), Mg(II), Ag(I), Pt(IV), Li(I), Mn(II) and Co(II) as detailed in
unaffected (as expected, not shown) and the number of the ESI (Table S7†). However, despite using acetate salts in
Q bands has been reduced consistent with literature data.26,27,29 some cases, varying the milling speed and duration as well as
Analysis of FeTPP complexes is known to be complicated adding small amounts of solvents such as DMF or methanol,
due to the possibility of varied oxidation states. 1H-NMR no reactions were observed for those metal ions. This is sur-
spectra could not be obtained for the complex due to the pres- prising given that some of these metal ions are highly labile
ence of paramagnetic Fe(III). However, the absorption spec- and highlights the fact that much still remains to be under-
trum consisted of a Soret band at 417 nm and Q bands at 509 stood regarding mechanochemical synthesis.
and 580 nm which is similar to data reported for FeTPPCl,30
For the successful metallations, these simple and efficient
suggesting that metallation had also occurred in this case. methods contrast with conventional methods to metallate por-
IR analysis also revealed the absence of the N–H stretch at phyrins which include refluxing a divalent metal salt (typically
∼3317 cm−1 indicating de-protonation and metallation of the an acetate, halide or hydroxide) with H2TPP in DMF. Alder24
porphyrin.
has reported preparing numerous metalloporphryins via this
Preparation of ZnTPP and CuTPP was attempted with method including ZnTPP, NiTPP and CuTPP. More recently
various alternative metal precursors including ZnO, Maqueira et al.31 described the synthesis of ZnTPP and CuTPP
[Zn5(CO3)2(OH)6] and [Cu(CH3CN)4]PF6. However, these metal- by the same process but using a reaction time of 20 min. She
lations proved unsuccessful even upon the addition of small et al.30 have described the synthesis of FeTPPCl by refluxing
amounts of solvent such as DMF, MeOH and H2O. Therefore it FeCl2 for 6–8 h in DMF. Grant et al.25 prepared ZnTPP and
seems that elimination of acetic acid may be beneficial for NiTPP by refluxing in chloroform and methanol for 2 h
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