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Early Model Complexes That Mimic Molybdenum Enzymes
MOLYBDENUM: the Answer to Life, the Universe and Everything! Element #42 is an essential
trace element for all forms of life where key biochemical systems utilize molybdenum enzymes.
There are ~40 molybdoenzymes known to date—and new ones are discovered every year. Three
molybdoenzymes can be identified in various human tissues (e.g., mammalian livers and breast
milk) and these are sulfite oxidase, aldehyde oxidase and xanthine oxidase. Of these three,
sulfite oxidase is the single most important enzyme—a lack of properly functioning sulfite oxidase
is fatal.
The compounds to be prepared in this experiment are among the first molybdenum complexes that
were useful models for the reactivity and structure displayed by the molybdenum-oxo enzymes.
Key features of these compounds are the molybdenum-oxygen double bonds, Mo=O, called
molybdenyl groups. Besides Mo, other transition metal-oxo compounds, notably those containing
Mn and Fe, are found in biological catalysis involving oxygen reactions (oxidases and
hydroxylases). Metal oxides are additionally important industrial catalysts for a variety of
catalytic reactions. In fact, the high-valent chemistry of the early transition metals is dominated by
oxo complexes. The oxo ligand, formally O2-, stabilizes high-valent complexes by both  and 
interactions (Figure 1).
pz
O
px
py
dxz
dyz
Figure 1. The  and  bonding
interactions of the filled p orbitals
of O2- with empty metal d
orbitals.
M
dz2
M-O  bonds
M-O  bond
A M=O bond is susceptible to both nucleophilic and electrophilic attack, exemplified for Mo
chemistry in equations 1 and 2, respectively. Equation 1 is an oxygen atom transfer reaction
(OAT) which is accompanied by a change in the oxidation states of the reactants .
MoVI=O
+
:PIIIR3

MoIV
+
O=PVR3
(1)The
OAT reaction in reverse is possible when suitable oxygen atom donors are reacted with MoIV.
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Equation 2 represents a simple two-step protonation which is not accompanied by a redox change.
MoVI=O
H+
+

[MoVI-OH]+
H+

[MoVI]2+
+ H2O
(2)
In the absence of other ligands, such [Mo=O] protonations lead to polyoxomolybdate formation,
[Mo7O24]6-. In the presence of suitable ligands various complexes are formed. This reaction may
be used to selectively replace oxo ligands by anionic ligands.
These reactions are exploited in the synthesis of innumerable Mo complexes and they account for
much of the chemistry of such complexes. Finally, they are important in catalytic oxygen atom
transfer reactions such as those mediated by industrial oxidation catalysts and the major
molybdoenzymes sulfite oxidase, xanthine oxidase and nitrate reductase (the last is required in all
plants).
In this experiment various oxo-Mo complexes containing the N,N-diethyldithiocarbamate ligand
(Figure 2) are prepared and studied by a variety of techniques. The synthesis of the dioxo-Mo(VI)
complex cis-MoO2(S2CNEt2)2 (Figure 3) is central to the experiment. From cisMoO2(S2CNEt2)2 a number of other, colorful oxo-molybdenum complexes are prepared and these
are characterized by a variety of analytical and spectroscopic techniques. Their structures and role
in oxygen and sulfur atom transfer reactions are also explored.
S
C
Na
+
N
S
S
Na
Na
+
+
C
S
S
C
N
N
Figure 2. Structure of the
N,N- diethyldithiocarbamate
ligand, detc. It coordinates
through the S atoms.
S
This project highlights:
(1) A variety of synthetic strategies to Mo complexes based on equations (1) and (2).
(2) The study of complexes with a variety of coordination numbers, geometries and nuclearities.
(3) Analysis of infrared , electronic and 1H NMR spectra of the complexes.
(4) Experience using mass spectral data for species identification
(5) Experience with 3-dimensional structure determination by X-ray crystallography.
(6) An examination of stoichiometric and catalytic oxygen atom transfer reactions.
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Figure 3. Molecular structure of cis -MoO2(S2CNEt2)2.
Experimental Procedure
Syntheses
While most syntheses can be performed on an open bench, the dispensing of malodorous (smelly!)
or toxic substances such as concentrated HCl, chlorinated solvents and propylene sulfide must be
done in the fume hood. Record YIELDS (both mass and %) in all cases.
cis -MoO2(S2CNEt2)2. Success depends on VIGOROUS stirring during the addition of
hydrochloric acid - so use a large (1.5 inch) stir-bar and an effective stirrer unit. Sodium
diethyldithiocarbamate [Nadetc] (5.18 g) is dissolved in water (25 mL) in a 250 mL Erlenmeyer
flask. In a separate small flask sodium molybdate(VI) dihydrate (3.5 g) is dissolved in 25 mL water
then added slowly to the Nadetc solution while stirring. The detc-/MoO42- solution is treated
dropwise (about 3-4 drops/sec from a dropping funnel (separatory funnel) over about a 10 min
period) with a solution of 6 mL of concentrated hydrochloric acid in water (100 mL). Maintain
vigorous stirring during the dropwise addition as the dense yellow-brown product precipitates. The
solid is isolated by vacuum filtration on filter paper in a Buchner funnel. (Be careful not to tear the
filter paper during the washing procedure.) The crude product should be washed with cold water
(2 x 60 mL), chilled ethanol (2 x 30 mL) then diethyl ether (3 x 60 mL) and dried on the aspirator.
For a complete washing to remove water and excess acid, remove the filter paper with the product
now stuck on the filter paper fromthe funnel, transfer the filter paper and product to a large beaker
and add the first solvent (ethanol) to remove the product off the filter paper. Use a glass rod or
rubber policeman to swirl the solid around in the washing solvent, then replace the funnel on the
flask, place a fresh piece of filter paper and filter the washing solvent off the product. The solid
can be left on the filter paper during the final ether washing. **It is extremely important to remove
all the water and HCl from the crude product to prevent decomposition so be thorough during the
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washing steps. The crude material is sufficiently pure to be used in the subsequent syntheses. A
portion (less than 1 gram) of the crude product can be further purified by recrystallization by
dissolving it in dichloromethane (15 mL/g), filtering, and adding diethyl ether (20 mL/g) to the
clear filtrate. **Note that if there is any water left on the crude product, this will interfere with the
dissolution in methylene chloride. Therefore, the crude product is best left to dry overnight or for a
week before the recrystallization procedure is attempted
Waste Disposal:: The initial reaction filtrate, the water and ethanol washings may go down the
sink. All other liquid wastes should be discarded in the METAL-CONTAINING WASTE
container. Filter paper goes in the designated container in the hood.
The Purple Compound (P). A solution of cis-MoO2(S2CNEt2)2 (0.5 g) in dichloromethane (5
mL) is filtered with a small Hirsh funnel to remove insoluble impurities, then the filtrate is treated
with a solution of triphenylphosphine (0.16 g) in methanol (10 mL). (Helpful hint: the PPh3 will
dissolve more quickly if it is first crushed to a powder with a spatula before adding to the
methanol.) The mixture is swirled for a few seconds then left to stand for 15 minutes. The purple
solid formed is vacuum filtered using a Hirsch funnel, washed with cold methanol and dried on the
fritted funnel. **Note: If you don't believe the compound is purple crush some on a piece of white
paper!
Waste Disposal All liquid wastes should be discarded in the METAL-CONTAINING WASTE
container. MeOH washings can go down the sink. Filter paper may go in the trash.
The Yellow Compound (Y).
Note: You will prepare this twice. Once according to the bulk synthesis immediately following.
Then once again to grown crystals suitable for X-ray diffraction.
Synthesis (bulk, or large scale). A solution of crude cis-MoO2(S2CNEt2)2 (0.5 g) in acetone (35
mL) is filtered to remove any impurities. The filtrate is then treated with 2.5 mL of concentrated
hydrochloric acid and the mixture stirred for 20 min. The product is isolated by filtration, washed
with 10 mL of acetone and dried on the vacuum.
Single Crystal growth. Large crystals of the product can be obtained by allowing the reaction
mixture ( as prepared above) to stand undisturbed for 2-3 h (or overnight) following the initial
mixing of the acid into the cis -MoO2(S2CNEt2)2 solution. Best results have been obtained by
pouring the HCl into the initial mixture all at once then transferring two aliquots to smaller vials.
Waste Disposal: All liquid wastes should be discarded in the METAL-CONTAINING WASTE
container. Filter paper may go in the trash.
The Red Compound (R). **Note: This compound is air-sensitive (i.e., decomposes in the
presence of oxygen and moisture) and all work should be performed quickly and efficiently, and the
final isolated product must be immediately stored in an inert atmosphere glove box.
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In the hood, bring the oil bath to the correct temperature before adding the solvent dichloroethane
to the solid reagents. In a small round bottom flask connected with an air (or reflux) condenser, a
mixture of cis-MoO2(S2CNEt2)2 (1.0 g) and powdered triphenylphosphine (1.0 g) in 1,2dichloroethane (bp 82 °C, 10 mL) is refluxed for 15 min. Make sure that reflux (in the pre-heated
bath) is commenced immediately after adding the solvent to the starting materials and that the
temperature is maintained so that the reaction refluxes for a full 15 min. Upon completion of the
reflux pour the reaction mixture, with swirling, into ice-cold ethanol (50 mL) contained in a 125
mL Erlenmeyer flask. Filter the crystals and wash with ethanol, then ether and vacuum dry (see
Figure 4).
Waste Disposal: All liquid wastes should be discarded in the METAL-CONTAINING WASTE
container.
The Blue Compound (B). WORK IN THE HOOD!! VERY STINKY REAGENT!! Use an
efficient fume hood when using propylene sulfide and wash all glassware (with dichloromethane)
in a fume hood, placing the washings into a Waste bottle so marked. In a small scintillation vial, a
solution of the Red Compound (0.25 g) in dichloromethane (5 mL) is treated with propylene sulfide
(0.25 mL). The flask is capped and the mixture stirred for 1 h (the reaction can be left overnight if
necessary). Thin layer chromatography can be employed to monitor the formation of the blue
product using dichloromethane as the eluant. After stirring, the reaction mixture is loaded onto the
top of a silica gel column and eluted with dichloromethane.
[One method of preparing the column is as follows: Silica gel (about 100 mL) is slowly poured
into a chromatography column filled with dichloromethane. Tap the column to remove air
bubbles from the silica slurry as it settles to the bottom of the column. Drain the solvent until
the solvent level reaches the top of the column of silica gel to produce a uniformly packed
column free of air bubbles (more tapping may be required). Gently pour a 1 cm layer of white
quartz sand on top of the column. Using a Pasteur pipette, slowly, carefully and evenly apply
the reaction mixture to the top of the column (it is best to run it down the walls of the column to
prevent excessive penetration into the top of the silica column). Drain the column until the
solvent level again reaches the top of the silica, then add about 5 mL of fresh solvent to the
column and again drain to the level of the silica.]
The blue fraction is collected, concentrated if necessary to about 0.5 mL on a rotary evaporator. The
solution is transferred to a 20 mL vial and placed in the hood with the lid ajar to allow the
remaining solvent to evaporate. Waste Disposal: : Unused fractions go in the METALCONTAINING WASTE container.
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Rubber stopper
Figure 4. Vacuum drying on a filter frit.
Fritted funnel
Compound
tubing to
aspirator
Oxygen Atom Transfer Chemistry - Qualitative Reaction Study
You have already observed the reactions which take place when cis-MoO2(S2CNEt2)2 is reacted
with one-half mole equivalent and excess PPh3 (the preparations of P and R, respectively). Do the
following test tube experiments to reveal more about these and related reactions. Use a very small
spatula of compound and about 5-10 mL of solvent . **You will need to take careful note of your
observations . Record initial observations then allow the test tubes to sit for several minutes before
recording observations.
TEST A.
Using dichloromethane as solvent, dissolve roughly equal amounts cisMoO2(S2CNEt2)2 and R in separate test tubes, then mix the two solutions.
Test B.
Test C.
Allow a solution of R to stand in air.
Add a drop or two of hydrogen peroxide solution to a solution of R in dichloromethane,
swirl for a minute. Add excess (use a large spatula) PPh3 to the yellow solution
formed.
Characterization of the Compounds
The series of molybdenum-oxo compounds synthesized in this experiment can be characterized by
a wide variety of techniques. For this lab course, you will perform three different types of
spectroscopy (infrared, ultraviolet/visible electronic and proton NMR), interpret mass spectral data
and observe the process of x-ray crystallography at the Univ. of Pennsylvania. Using these data
you will determine the identity of the derivative complexes, Y, P, R and B.
The spectroscopic analysis required in this experiment will generate much data. To help you
organize this data collection we suggest that you make a chart like the one below to keep track of
what compounds have been analyzed by which techniques. Be sure that each person in your team
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gets experience running each type of spectroscopy (IR, UV/vis, NMR) on at least one, if not
several, compounds.
compound
IR
MoO2detc2
.
UV/vis
NMR
Y
P
R
B
Spectroscopic Analyses: Some key characteristics to look for
A. Infrared spectroscopy.
The IR spectra of the compounds are dominated by bands due to the C=N stretching vibration of
the dithiocarbamate ligands, but bands due to the other ligands, e.g. oxo, chloro and sulfur based
ligands, are also present.
Dithiocarbamate bands. The spectrum of MoO2(S2CNEt2)2, shown in Figure 5, allows the bands
due to the dithiocarbamate ligand to be identified. These may be assigned in the usual manner: the
(CN) band is the most obvious. The M-S bands for coordinated dithiocarbamate ligands are
around 380 cm-1and are unlikely to be observed on our instrument.
Oxo ligand bands. Terminal oxo ligands are associated with bands in the 1000-850 cm-1 region.
Combined with other information, the number and structural relationship of the oxo ligands may be
derived from IR data. To summarize:
1.
Two strong bands are associated with a cis dioxo moiety within a molecule (a symmetric and
asymmetric stretch).
O
O
Mo
O
symmetric stretch
 sym
2.
Mo
O
asymmetric stretch
as ym
A single Mo=O band is associated with a single terminal oxo ligand or a trans dioxo moiety
(rare!). The position of the band depends on the strength of the M=O bond which is
determined by the electron donation from the ligand to the metal. Accordingly, many
compounds with a low coordination number have a stronger M=O band
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(Mo=O > 960 cm-1) than compounds of higher coordination number (Mo=O < 960 cm-1),
since the M=O bond in the former must provide more electron density to the coordinatively
unsaturated metal center compared to the latter types of compound.
-oxo (i.e., bridging oxo) ligands may exhibit weak bands due to the asymmetric
Mo-O-Mo stretch (around 750 cm-1). If the bridge links identical Mo=O fragments then two
(Mo=O) bands (one stronger than the other and very close in energy) may be seen in the
900-1000 cm-1 region in the same spectrum.
Other ligand bands. Other possible ligands contained in the oxo-Mo compounds exhibit the
following IR bands.
1.
3.
Chloro ligands. In the region 200-350 cm-1. The number of bands is determined by the
number and symmetry relationship of the chloro ligands. Compound Y exhibits two bands
at 294 and 220 cm-1.
2.
Thio Ligands, Mo=S. The sulfur analog of the oxo ligand, S2- forms Mo=S
compounds that exhibit bands between 460 and 510 cm-1, the number of which
depends on the number and relative geometry of the ligands as was true for M=O.
Disulfido Ligands, Mo(S2). For the side-on bonded disulfido ligand, formally an S22fragment, a strong band at 550 cm-1 (with smaller bands between 550 and 600 cm-1) is
observed.
B. NMR Spectra.
1H NMR spectroscopy is a powerful tool for the determination of molecular structure.
The oxo-Mo compounds may exhibit a variety of structures based on a) five-coordinate square
pyramidal, b) six-coordinate octahedral, c) seven-coordinate pentagonal bipyramidal geometries.
Use the information in this section to determine the exact molecular structure of the compounds.
The 1H NMR spectrum of the S2CNEt2- ligand alone consists of a triplet resonance ( 1.0-1.5) and
a quartet resonance ( 3.5-4.0) assigned to the CH3 and CH2 protons, respectively, typical of the
ethyl substituents.
This simple CH3 and CH2 ethyl pattern is observed in many dithiocarbamate
complexes due to stereochemical non-rigidity and the averaging of the ethyl group environments
on the NMR timescale. These spectra do not provide stereochemical information. At low
temperatures, such molecules may become rigid and the NMR spectra would then contain
stereochemical information. In some cases, this simple pattern is produced due to symmetry
equivalence of the ethyl groups in rigid complexes.
When the molecules are stereochemically rigid but there are n sets of symmetry
inequivalent ethyl groups one may expect to observe n triplet and n quartet resonances. These will
have an integration which reflects the number of ethyl groups in each set.
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The molecular symmetry must be further explored in other cases. Distinctive, complex
spectra are exhibited by some molecules, especially those which are chiral (i.e., those which have
non-superimposable mirror images). In chiral molecules, the methyl groups are often inequivalent
in addition to the protons of the CH2 groups that are always diastereotopic. Two groups (in this
case protons) are diastereotopic if they have identical atom connectivities but cannot be exchanged
by any symmetry elements. In chiral molecules geminal groups are always diastereotopic and the
CH2 group falls into this category. Diastereotopic CH2 groups constitute an AB spin system and
produce an AB quartet resonance when coupling to other protons is absent. In the case of an ethyl
group, the inequivalent AB protons of the CH2 group will each couple to the CH3 protons, and thus
each peak of the AB quartet would be split into a quartet resonance. These may overlap to give
complex spectra but in some cases one or more of the CH2 groups may have a chemical shift which
separates it from complex regions of the spectra, thus allowing interpretation. Diasterotopic protons
may also be observed in achiral molecules. In such cases the molecular symmetry dictates that the
two protons on any one diastereotopic CH2 group cannot be exchanged by any symmetry operation
although in many cases the CH2 groups within the molecule may be exchanged by symmetry
elements. Molecules with no h symmetry element fall into this category.
Oxygen Atom Transfer Catalysis.
As part of your characterization of compounds P and R, consideration of equation (1)
on (and its reverse) along with the test-tube reactions, will permit you to identify the components of
a catalytic cycle for the oxidation of PPh3 by oxidizing agents, using MoO2(S2CNEt2)2 as catalyst.
Diagrammatically represent the cycle in your report.
Report
Because of the large amount of data collected in this experiment, you may work together as a team
to interpret your data and a team report that includes only the Experimental and Results sections.
This experiment consists of two related parts, experimental and deductive and closely represents
how one approaches new compound identification in a research lab. Firstly, a number of
compounds have been synthesized. Experimental observations, percent yields and characterization
data (spectra) should be reported. You should use the information presented here and by your
instructors to interpret your results and verify the identity of the compounds you have synthesized.
For example, how do the infrared spectra of MoO2detc2 and P,Y, R and B compare? Secondly,
you are asked to combine your knowledge of the compounds and their chemistry to account for the
qualitative reactions you have observed.
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You have also learned several analytical techniques : UV/vis, IR, NMR and MS. You should
mention what information in general can be discerned from these techniques and what aspects of
the molecule we will be studying in our compounds.
This lab experiment is adapted from C. Young, J. Chem. Educ. 1994 .
Additional Reading.
If you want to learn more about Mo chemistry and track down some of the literature reports
concerning the chemistry involved in Experiment 2, have a look at:
Cotton and Wilkinson, "Advanced Inorganic Chemistry," Mo/W Section, 5th Edition.
E. I. Stiefel, Progress in Inorganic Chemistry, 22, 1 (1977).
E. I. Stiefel, in "Comprehensive Coordination Chemistry," Edited by G. Wilkinson, R. D.
Gillard and J. A. McCleverty, Chapter 36.5, p. 1375, Pergamon.
S. J. N. Burgmayer and E. I. Stiefel, J. Chem. Ed. 1985, 49, 227.
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Starting Material:
MoO2(dtc)2.CH2Cl2, C11H22N2S4Cl2
2.4 mL HNEt2
= 0.0232 mol (den 0.707, 73.14)
1.4 mL CS2
= 0.0403 mol (den 11.266, 44.01)
3.5 g Na2MoO4.2H2O = 0.0144 mol (241.95)
This will give 0.0116 mol of product as HNEt2 is the limiting reagent.
Product molar mass is 424, so 100 % yield corresponds to 4.91 g.
Purple Compound:
0.5 g of complex (424) = 0.00118 or 1.18 x 10-3 mol. Two moles of complex gives one mole of
dimer, therefore yield = 5.89 x 10-4 mol x 832 g.mol-1 = 0.49 g.
Red compound:
1.0 g of complex (424) = 0.00236 or 2.36 x 10-3 mol), so max yield for mol mass 408 is 0.963 g.
Yellow Compound:
0.5 g of complex (424) = 0.00118 or 1.18 x 10-3 mol. Therefore yield for mol mass of 479 is 0.565
g.
Blue Compound:
0.25 g (408) = 6.13 x 10-4 mol, giving maximum yield of 472 = 0.289 g.