Dichlorobis(1,4-diazabicyclo[2.2.2]octane)(tetrahydroborato)zirco- nium(IV), [Zr(BH4)2Cl2(dabco)2](ZrBDC), as a new, stable, and versatile bench top reducing agent: Reduction of imines and enamines, reductive amination of aldehydes and ketones and reductive methylation of amines

Article abstract of DOI:10.1246/bcsj.76.143

The reducing agent is easily prepared in an almost quantitative yield from commercially available starting materials. This compound is stable under mild aqueous acidic conditions (pH 4-6) and survives in H₂O for several days without losing its reducing abilities. ZrBDC has been successfully used for the reduction of imines and enamines, reductive amination of aldehydes and ketones, and reductive methylation of amines.

Full text of DOI:10.1246/bcsj.76.143

c. Jpn.
© 2003 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 76, 143–151 (2003)
143
e Chemical
ciety of Ja-
n
e Chemical
ciety of Ja-
n
Dichlorobis(1,4-diazabicyclo[2.2.2]octane)(tetrahydroborato)zirco-
nium(Ⅳ), [Zr(BH4)2Cl2(dabco)2](ZrBDC), as a New, Stable, and
Versatile Bench Top Reducing Agent:1 Reduction of Imines and
Enamines, Reductive Amination of Aldehydes and Ketones and
Reductive Methylation of Amines
03
3
1
SJA8
09-2673
110
[Zr(BH4)2Cl2(dabco)2] a New Stable Reducing Agent
H. Firouzabadi et al.
Habib Firouzabadi,* Nasser Iranpoor,* and Heshmatollah Alinezhad
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
(Received April 26, 2002)
02
The reducing agent is easily prepared in an almost quantitative yield from commercially available starting materi-
als. This compound is stable under mild aqueous acidic conditions (pH 4–6) and survives in H2O for several days without
losing its reducing abilities. ZrBDC has been successfully used for the reduction of imines and enamines, reductive am-
ination of aldehydes and ketones, and reductive methylation of amines.
02
3.6
Transition metal tetrahydroborates such as copper(Ⅱ) tet-
rahydroborate, Zn[BH4]2, Zr[BH4]4, and Ti[BH4]3 are very re-
active, volatile, unstable, and difficult to handle and can not be
easily used in organic synthesis as reducing agents without
modification.2 The use of the ligand can induce considerable
stabilities in these transition metal tetrahydroborates. One of
the examples is Zn[BH4]2, which is not stable at room temper-
ature and inflames with explosion when it is exposed to mois-
ture; yet its metal-ligand complexes; [Zn(BH4)2(dabco)] and
[Zn(BH4)2(Ph3P)], are highly stable, white powders that can be
used as bench top reagents for the reduction of varieties of
functional groups.3 Therefore, such modified tetrahydroborate
complexes constitute a class of hydride transfer agents, but
their reducing abilities in organic syntheses are not properly
explored. There are moreover, very few examples in the litera-
ture of the use of such compounds in organic synthesis.
[Cu(BH4)(Ph3P)2]4 is an example in which the BH4− moiety is
deactivated to the extent that it only reduces acyl chlorides to
the aldehydes, whereas NaBH4 reduces acyl chlorides to their
corresponding alcohols. The other reported compounds are
[Cu2(BH3CN)(Ph3P)4]5 and [Zr(BH4)(Cp)2(Cl)],6 these have
been used for the reduction of a limited number of carbonyl
compounds. The use of poly(vinylpyridine) supported zinc
tetrahydroborate as a stable polymeric metal tetrahydroborate
has been reported.7 The other reported modified zinc tetrahy-
droborate is [Zn(BH4)2(pyz)]n which is stable to heat but ex-
plodes violently into flames when put in contact with water.8
Very recently, the preparation of zinc tetrahydroborate-crown
ethers has been appeared in the literature9 but to the best of our
knowledge, their applications have not been reported yet. Ac-
cording to the literature, Zr[BH4]4 is a highly volatile colorless
solid, melting around room temperature, inflaming in air, and
hydrolyzing with explosive rapidity. When allowed to stand at
25 °C it slowly decomposes liberating hydrogen gas.2 There-
fore, it cannot be considered as an easily applied bench top re-
ducing agent. Recently, it is reported that a mixture of ZrCl4
and NaBH4 in THF can be used as a versatile system for the re-
duction of variety of organic substrates. In this report, the au-
thors have claimed that in situ generation of Zr[BH4]4 is re-
sponsible for the reductions they have studied.10
Preparation of amines from easy available precursors is im-
portant in organic synthesis. Amines and their derivatives are
known to show biological activities and are important precur-
sors that are used in pharmaceutical and agricultural indus-
tries.11 Preparation of amines via transformation of carbonyl
compounds to their imines or enamines, and their subsequent
reduction to the corresponding amines by tetrahydroborate
agents has been studied.
Sodium cyanotrihydroborate
(Na[BH3CN]) is a well-known reagent for the reduction of
enamines and for reductive amination of aldehydes and ke-
tones. Even though this reagent has been popular for carrying
out these transformations, it suffers seriously from high toxici-
ty and usually low yields of the products.12 Zinc-modified cy-
anotrihydroborate has also been employed for the reductive
preparation of amines from enamines and for amination of car-
bonyl compounds.13 Na[BH3CN] in the presence of TiCl4 has
been also applied for the reductive preparation of amines from
carbonyl compounds.11
Triacetoxyhydroborate Na[BH-
(OAc)3]14 is a reagent of choice for this purpose. This reagent
should be used in acetic acid, a corrosive compound, and en-
counters drawbacks for the preparative protocols.15 Some oth-
er methods used for this purpose include borane–pyridine,16
BH3S(Me)217 and Ti(OiPr)4/NaBH4.18 Recently, NaBH4 on wet
clay under solvent-free conditions has been used for the reduc-
tive amination of carbonyl compounds under microwave irra-
diation.15 Tetrahydroborate exchange resin has also been used
for the reductive amination reaction.19
It is reported that zirconium and its salts generally have low
systemic toxicity.20 In continuation of our studies on the prep-
aration of stabilized transition metal tetrahydroborates, we

144 Bull. Chem. Soc. Jpn., 76, No. 1 (2003)
[Zr(BH4)2Cl2(dabco)2] a New Stable Reducing Agent
have recently prepared a stable modified zirconium(Ⅳ) tet-
rahydroborate: dichlorobis(1,4-diazabicyclo[2.2.2]octane)(tet-
rahydroborato)zirconium(Ⅳ), [Zr(BH4)2Cl2(dabco)2] (ZrB-
DC). This compound has been employed for the efficient and
selective reduction of carbonyl functionality to their alcohols
in organic solvents and also in aqueous media.1 Now we re-
port that ZrBDC can be easily applied for the efficient prepara-
tion of amines by the reduction of imines and enamines, reduc-
tive amination of aldehydes and ketones, and reductive methy-
lation of amines.
Here we report a facile preparation of amines from imines
and enamines using ZrBDC as a reductant. In order to opti-
mize the reaction conditions, the reduction of morpholine
enamine of cyclohexanone as a model compound in CH3OH
was studied. The reaction proceeded under neutral conditions
and the pH of the media was adjusted by the addition of a 10%
aqueous solution of HCl in methanol. We have observed that
lowering the pH of the reaction media (pH 5–6) increases the
rate of the reaction. The reaction was very slow at room tem-
perature but was performed well under reflux conditions to
produce the desired amine in 91% isolated yield. We have
found that hydrolytic cleavage of the iminium cation to its car-
bonyl compound did not occur under such reaction conditions.
In order to show the general application of the method, we
have converted structurally different enamines and imines to
their amines under similar reaction conditions. The results are
shown in Table 1. We have also compared some of our results
with those reported for Na[BH3CN]/ZnCl213 and Na[BH3CN]12
in Table 2.
Results and Discussion
Dichlorobis(1,4-diazabicyclo[2.2.2]octane)(tetrahydrobora-
to)zirconium(Ⅳ), [Zr(BH4)2Cl2(dabco)2] (ZrBDC) was pre-
pared by the addition of an ethereal solution of LiBH4 to anhy-
drous ZrCl4 under inert atmosphere with stirring. After 12 h,
an ethereal solution of dabco was added dropwise to the result-
ing slurry21 and the stirring was continued for another 10 h to
produce a dark brown solid. The resulting precipitates were
filtered, washed with ether, and dried under vacuum to afford a
white powder. For further purification, the resulting powder
was washed with dry THF and Et2O respectively and was left
under vacuum overnight. ZrBDC was isolated as a white, sta-
ble, non-hygroscopic powder in 97% yield. ZrBDC could be
stored at room temperature for months without significant
change in its reducing power as determined by iodometric ti-
tration.22 This modified tetrahydroboratozirconium is much
more stable than NaBH4 in H2O, CH3OH, and C2H5OH, and in
mild aqueous acidic media (pH 4–6). The proposed chemical
formula of the compound was established by IR, NMR, iodo-
metric, potentiometric, and UV/vis spectroscopic studies.22–26
IR (KBr, dabco species) ν (cm−1) 2974s, 2963s, 2897s,
Reductive Amination of Aldehydes and Ketones.
In
biological and chemical systems, the reductive amination of al-
dehydes and ketones is an important transformation which al-
lows the direct conversion of carbonyl compounds into
amines.29 Reports describing the synthesis of amines using re-
ductive amination procedures include tetrahydroborate ex-
change resin,19 borane-pyridine in AcOH,16 Ti(OiPr)4/NaBH4,18
Na[BH(OAc)3],14 Li[BH3CN],30 Na[BH3CN],12 Na[BH3CN] in
11
combination with TiCl4 and ZnCl2,13 and NaBH4/wet clay/
microwave irradiation.15 NaBH4 has been also used for N-
alkylation of primary aromatic amines in a highly acidic
(H2SO4) medium.31 The most widely used reagents for this
aim are: a) the highly toxic Na[BH3CN] such reactions should
be conducted in highly acidic conditions (5 M HCl/CH3OH)
and suffer from low to moderate yields and sometimes from
long reaction times.12a This reagent is also sluggish for the re-
ductive amination of aldehydes with anilines bearing electron-
withdrawing groups.14a,32 b) Na[BH(OAc)3] in the presence of
acetic acid which is corrosive; such reactions also suffer from
moderate yields of the amine products and long reaction
times.14b Therefore, introduction of new reagents in order to
improve or eliminate some of the above-mentioned problems
is a useful contribution to synthetic organic chemistry.
−
1623m, 1458s, 1324s, 1056s, 993s, 846s, 702b, and for BH4
species, ν (cm−1) 2383s, 2373s, 2306s, 2268s, 1155s. 1H
NMR (CDCl3, 250 MHz) δ 1.42 (broad band, 8H, two BH4−),
that its coupling constant and the pattern are similar to the re-
ported data for Zr(BH4)4,23b 2.9 (AAꢀBBꢀ pattern,24 24H of
CH2 groups). 13C NMR (CDCl3, 63 MHz) δ 51.7, 52.1 (two
−
different CH2 groups). Determination of BH4 content was
conducted by iodometric titration method,22 quantitative mea-
surement of chloride content was proceeded by potentiometric
titration technique,25 and quantitative measurement of Zr was
conducted by UV/vis spectrophotometric method.26 Salts of
zirconium show low human toxicity,20 therefore, the presented
reagent is a good competitor with the highly toxic Na[BH3CN]
for the reduction of CwN.
The generally accepted reaction steps for a reductive amina-
tion are shown by the following reactions (1–3, Scheme 2).
Reactions 3 and 4 show that two competitive reductive reac-
tions (CwN vs CwO) are inevitable and will occur in the reduc-
tive amination of carbonyl compounds.16
Now, we report that in the presence of ZrBDC, efficient and
smooth reductive amination of a variety of carbonyl com-
pounds proceeded well in the presence of amines under neutral
conditions. The pH of the media was adjusted to neutrality by
the addition of 10% aqueous solution of HCl in methanol. Un-
der such a condition, ZrBDC did not reduce the carbonyl com-
pounds in the reaction mixture, whereas the imine intermediate
was converted easily to the corresponding amines. However,
the absence of formation of any hydroxy compound in these
reductions suggests that the overall process would proceed
successfully if a reasonable concentration of imines is avail-
able and the reaction conditions could discriminate between
Reduction of Imines and Enamines. Efficient reduction
of imines and enamines to their corresponding amines is of
practical importance. It is generally accepted that the enamine
reduction occurs through the iminium-type intermediate,
which can be generated via protonation of the enamine by pro-
tic acids (Scheme 1).12a
Scheme 1.

H. Firouzabadi et al.
Bull. Chem. Soc. Jpn., 76, No. 1 (2003) 145
Table 1. Reduction of Imines and Enamines with ZrBDC in Methanola)
Entry
1
Substrate
Productb)
Time/h
0.5
Isolated yieldRef./%
9413
2
3
4
5
8727
9014c
4
7
9113
5
6
7
10
6
8813
8613
8228
7.5
a) All reactions were carried out under reflux and neutral conditions; the molar ratio of
reagent/substrate was 1:1. b) All compounds gave satisfactory spectral analyses.
Table 2. Comparison of the Results Obtained by Using ZrBDC with Na[BH3CN]/ZnCl2 and Na[BH3CN] for
the Reduction of Enamines
13
ZrBDC
Yielda)
Na[BH3CN]/ZnCl2
Na[BH3CN]12
Time
Yielda)
Entry
Enamine
Product
Time
h
Time
h
Yielda)
%
%
h
%
1
2
3
7
6
91
0.5
0.5
1
73
90
85
0.2
80
86
88
0.5
—
81
—
10
a) Isolated yield.
Scheme 2.
the reduction of the imine intermediate (reaction 3) and the
carbonyl compound present in the reaction mixture (reaction
4). In general, the reactions were carried out with 4 equiv of
the primary amine or 2 equiv of the secondary amine by use of
1 equiv of ZrBDC in refluxing methanol. The results of this
study are summarized in Table 3. We have observed that re-
ductions under acidic conditions (pH 5) proceeded with faster
reaction rates.
We have also studied the catalytic roles of different Lewis
acids such as ZrCl4, AlCl3, FeCl3, CeCl3•7H2O, and
ZrOCl2•8H2O for the reductive anilation of benzaldehyde as a
reaction model. It was found that ZrCl4 was the most effective
catalyst among the Lewis acids we have used for this purpose.
The reaction proceeded easily in CH3OH under reflux condi-
tions in the presence of 0.5 molar equivalents of ZrCl4. In or-
der to show the general applicability of this method, we have

146 Bull. Chem. Soc. Jpn., 76, No. 1 (2003)
[Zr(BH4)2Cl2(dabco)2] a New Stable Reducing Agent
Table 3. Reductive Amination of Aldehydes and Ketones Using ZrBDC in Methanola)
Method ꢁ
Method Ⅱ
Entry Compound Amine
1
Productb)
Time/h Yieldc) Ref./%
Time/h Yieldc)/%
4
24
24
13
10
16
10
7
8713
8514a
8833a
9633
9834
9015
9115
9715
8435
8812a
8413
8012b
8914b
8314b
8412a
8614b
7812
0.4
0.1
0.1
0.2
1
90
97
94
92
96
94
95
96
85
86
87
80
92
87
—
—
—
2
3
4
5
6
0.2
0.4
0.6
2
7
8
9
24
36
2
10
11
12
13
14
15
16
17
24
0.5
0.3
1.8
36
2.5
8
48
1
—
12
1
—
—
18
8
8212
—
—
a) All reactions were carried out under reflux conditions and molar ratio of reagent/carbonyl com-
pound/amine was 1/1/4 (primary amine) and 1/1/2 (secondary amine). b) All compounds gave satis-
factory spectral analyses. c) All yields are isolated yields. Method ꢁ: Reactions were carried out
under neutral conditions using 10% HCl/CH3OH for the pH adjustment. Method Ⅱ: Reactions were
carried out in the presence of 0.5 molar equivalents of ZrCl4.
applied this procedure for the reductive amination of structur-
ally different carbonyl compounds with different amines
(Method Ⅱ). Reactions conducted in the presence of this cata-
lyst produced amines in higher yields with shorter reaction
times in comparison with the similar reactions conducted by
method ꢁ, as shown in Table 3. By this method, varieties of

H. Firouzabadi et al.
Bull. Chem. Soc. Jpn., 76, No. 1 (2003) 147
carbonyl compounds in the presence of different amines were
converted easily and smoothly to the secondary and tertiary
amines in high yields. Weakly acidic anilines like nitro- and
cyanoanilines do not usually undergo clean reductive amina-
tion reactions. Na[BH3CN], the most widely used reagent for
the reductive amination of aldehydes and ketones, is a sluggish
and inefficient reagent for this purpose.14a We have found that
4-nitroaniline and 4-cyanoaniline react efficiently with aromat-
ic aldehydes within 0.1 h in the presence of ZrBDC and 0.5
molar equivalents of ZrCl4 in refluxing CH3OH to produce
their corresponding amines in 97 and 94% yields, respectively.
Similar reactions proceeded in lower yields (85 and 88%) and
in much longer reaction times (24 h) when the pH of the reac-
tion media was adjusted by HCl in methanol. The mildness of
the reaction media, low toxicity of the reagent, and high reac-
tion rates accompanied with high yields of the products make
this protocol a useful addition to the tetrahydroborate category
of reagents used for this purpose.
In order to show the merit of the presented method, we have
compared the results with some other methods used for this
purpose in Table 4.
Reductive Methylation of Amines. Introduction of meth-
yl groups into primary or secondary amines by reductive alkyl-
ation (Scheme 3) is a useful method for the preparation of ter-
tiary methylated amines.13,16,36 Na[BH3CN] has been used for
this transformation in methanol but a mixture of starting mate-
Table 4. Comparison of ZrBDC and the Other Reducing Agents in Reductive Amination of Carbonyl Compounds
ZrBDC
Carbonyl
Amine
Other Reducing Agentsa)–f)
compound
Method ꢁ
Method Ⅱ
Entry
Time
h
Yield
%
Time
h
Yield
%
Time
h
Yield
%
Time
h
Yield
%
Time
h
Yield
%
1
2
1
78
82
84
80
97
83
86
87
85
88
—
—
—
87
80
92
87
—
90
97
86
—
—
1
41a)
43a)
42e)
79a)
74f)
44f)
73f)
88e)
85f)
83c)
18
20
2
73b)
75d)
93c)
—
3
98c)
—
—
—
—
—
—
—
—
—
8
—
—
—
—
—
—
—
—
—
—
3
2
0.5
4
2.5
8
0.3
1.8
—
96
192
27
1
—
—
—
—
2
5
—
6
48
36
—
7
12
4
—
—
8
0.4
93c)
—
9
24
36
0.1
1.5
—
—
10
24
1
—
11
1
84
—
—
—
78a)
—
—
—
—
a) Na[BH3CN]12. b) Ti(iOPr)4, CH3NH2•HCl, Et3N, and NaBH4.18a c) Zinc-modified cyanotrihydroborate.13 d) Ti(OiPr)4 and
NaBH4.18b e) Tetrahydroborate exchange resin.19 f) Na[BH(OAc)3].14
Scheme 3.

148 Bull. Chem. Soc. Jpn., 76, No. 1 (2003)
[Zr(BH4)2Cl2(dabco)2] a New Stable Reducing Agent
rial and partially methylated products has been produced. This
drawback has been eliminated by using this reagent in aprotic
solvents.37 We here report the preparation of methylated
amines by the reaction of amines with 37% aqueous solution
of formaldehyde in the presence of ZrBDC by two methods: a)
in refluxing methanol under neutral conditions, and b) by using
ZrCl4 (0.5 molar equiv) in methanol at room temperature. The
results of this study are tabulated in Table 5.
Table 5. Reductive Methylation of Amines with ZrBDC in Methanola)
Method ꢁ
Method Ⅱ
Entry
1
Compound
Productb)
Time/h Yieldc) Ref./%
Time/h Yieldc)/%
0.1
8012b
0.1
83
2
3
4
0.1
8112b
0.1
85
0.75
1
9512b
0.1
0.1
95
90
9238
5
6
7
1.7
3.5
1
8912b
9138
0.7
1
97
94
85
8236c
0.3
8
9
0.1
0.1
0.3
0.3
1.5
0.5
1.5
8839
8539
8713
9036c
9740
9512b
9413
0.1
0.1
0.1
0.1
88
87
91
95
—
—
—
10
11
12
13
14
—
—
—
15
2
8941
—
—
a) The molar ratio of the reagent/amine/37% aqueous formaldehyde in all reactions were 1/1/5.
b) All compounds gave satisfactory spectral analysis. c) All yields are isolated yields. Method ꢁ:
Reactions were carried out in refluxing methanol under neutral conditions using 10% HCl/CH3OH
for the pH adjustment. Method Ⅱ: Reactions were carried out in the presence of 0.5 molar ratio of
ZrCl4 in CH3OH at room temperature.

H. Firouzabadi et al.
Bull. Chem. Soc. Jpn., 76, No. 1 (2003) 149
Table 6. Comparison of the Results Obtained by ZrBDC, Na[BH3CN]/ZnCl2, and Na[BH3CN] for the Reductive Methylation of
Amines
13
ZrBDC
Na[BH3CN]/ZnCl2
Na[BH3CN]12
Entry
Amine
Product
Time
h
Yield
%
Time
h
Yield
%
Time
h
Yield
%
Time
h
Yield
%
1
2
3
4
5
6
0.1
1.5
0.3
0.5
1.7
0.75
80
0.1
—
83
—
91
—
97
95
2
2
86
90
83
—
—
—
2
—
—
1
92
—
—
85
86
87
94
87
95
89
95
0.1
—
2
—
—
—
0.7
0.1
3
1
7
0.1
81
0.1
85
—
—
2
84
solution of LiBH4 (0.344 mol) to anhydrous ZrCl4 (0.069 mol) un-
der inert atmosphere and the resulting slurry21 was stirred for 12 h.
Then an ethereal solution of DABCO (0.138 mol) was added
dropwise to the slurry and stirring was continued for 10 h to pro-
duce a dark brown solid. The resulting solid was filtered, washed
with Et2O, and dried under vacuum to afford a white powder. For
further purification, the resulting powder was washed with dry
THF and dry Et2O, respectively, and was left under vacuum over-
night. ZrBDC was isolated as a white, stable, non-hygroscopic
powder in 97% yield.
A Typical Procedure for the Reduction of Imines and
Enamines with ZrBDC: In a round-bottomed flask (25 mL)
equipped with a magnetic stirrer and a condenser, a solution of N-
benzylideneaniline (0.18 g, 1 mmol) in methanol (5 mL) was pre-
pared and acidified to neutral conditions with 10% aqueous solu-
tion of HCl in methanol. The reducing agent (0.416 g, 1 mmol)
was added to the solution. The mixture was refluxed with stirring
(0.5 h), and then silica-gel (2 g) was added to the resulting mix-
ture. Methanol was evaporated and the resulting mass was applied
on a silica-gel column and eluted with petroleum ether (bp 60–
80 °C)/EtOAC: 10/1 (150 mL). Evaporation of the solvent afford-
ed almost pure N-benzylaniline (0.172 g, 94% yield, Table 1, entry
1).
A Typical Procedure for Reductive Amination of Aldehydes
and Ketones, Method ꢀ: The preparation of N-cyclohexyla-
niline is representative. To a stirred solution of cyclohexanone
(0.196 g, 2 mmol) and aniline (0.745 g, 8 mmol) in methanol
(5 mL), the reducing agent (0.832 g, 2 mmol) was added and the
pH was adjusted to neutral conditions by the 10% aqueous solu-
tion of HCl in MeOH. The mixture was refluxed (2 h) and then
silica-gel (2 g) was added. Methanol was evaporated and the re-
sulting material was applied on a silica-gel column and eluted
with hexane/EtOAc: 10/1 (100 mL). After evaporation of the sol-
vent, almost pure N-cyclohexylaniline was obtained (0.27 g, 84%
yield; Table 3, entry 11).
Method ꢁ: The preparation of N-benzylaniline is representa-
tive. To a stirred solution of benzaldehyde (0.212 g, 2 mmol) and
aniline (0.745 g, 8 mmol) in methanol (5 mL), the reducing agent
(0.832 g, 2 mmol) and ZrCl4 (0.233 g, 1 mmol) were added. The
mixture was refluxed (0.4 h) and then silica gel (2 g) was added.
We have also compared some of the results obtained by
ZrBDC with other methods used for this purpose in Table 6.
Conclusion.
Dichlorobis[1,4-diazabicyclo[2.2.2]oc-
tane](tetrahydroborato)zirconium(Ⅳ), [Zr(BH4)2Cl2(dabco)2]
(ZrBDC), a stable and a versatile bench top reducing agent is
easily prepared in an almost quantitative yield from commer-
cially available starting materials. ZrBDC is a white powder
and unlike its mother compound Zr[BH4]4, is thermally stable
and so safe that it could be stored for months without apprecia-
ble loss of its reducing ability. This reagent tolerates acid con-
ditions and is stable in protic organic solvents and water. The
preparation of the reagent is easy (in 97% yield) and unlike its
polymer supported analogue [cross-linked PVP4-Zr (BH4)4] is
quite reproducible by different hands.42 ZrBDC is a good sub-
stitute for Na[BH3CN] for the preparation of amines from imi-
nes, enamines, reductive amination of carbonyl compounds,
and reductive methylation of amines. The use of ZrBDC elim-
inates the problem encountered by using Na[BH3CN] such as
residual cyanide in the product and in the waste stream. More-
over, the mildness, easy reaction work up, efficiency, selectivi-
ty, high reaction rates and yields, and lack of requirement of an
inert atmosphere, make this new stabilized transition-metal tet-
rahydroborate a useful addition to the category of reagents
used for the reductive preparation of amines.
Experimental
General: All products are known compounds. All yields re-
fer to isolated products. The products were purified by column
chromatography and the purity determinations of the products
were accomplished by GLC on a Shimadzu model GC-8A instru-
ment or by TLC on Silica-gel polygram SIL G/UV254 plates, and
mass spectra were run on a Shimadzu GC MS-QP 1000EX at
20 eV. IR spectra were recorded on a Perkin-Elmer 781 spectro-
photometer. The NMR spectra were recorded on a Bruker Avance
DPX 250 MHz instrument.
Preparation of Dichlorobis(1,4-diazabicyclo[2.2.2]octane)-
(tetrahydroborato)zirconium(Ⅳ),
[Zr(BH4)2Cl2(dabco)2],
(ZrBDC): A slurry was produced by the addition of an ethereal

150 Bull. Chem. Soc. Jpn., 76, No. 1 (2003)
[Zr(BH4)2Cl2(dabco)2] a New Stable Reducing Agent
Methanol was evaporated and the resulting material was applied
on a silica-gel column and eluted with hexane/EtOAc: 10/1
(75 mL). After evaporation of the solvent almost pure N-benzyl-
aniline was obtained (0.33 g, 90% yield; Table 3, entry 1).
14 a) A. F. Abdel-Magid and C. A. Maryanoff, Synlett, 1990,
537. b) A. F. Abdel-Magid, C. A. Maryanoff, and K. G. Carson,
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15 R. S. Varma and R. Dahiya, Tetrahedron, 54, 6293 (1998).
16 A. Pelter and R. M. Rosser, J. Chem. Soc,. Perkin Trans. 1,
1984, 717.
A Typical Procedure for Reductive Methylation of Amines,
Method ꢀ: The preparation of 4-bromo-N,N-dimethylaniline is
representative. In a round-bottomed flask (25 mL) equipped with
a magnetic stirrer and a condenser, a solution of 4-bromoaniline
(0.172 g, 1 mmol) and 37% aqueous formaldehyde (0.4 mL,
5 mmol) in methanol (5 mL) was prepared and neutralized with a
10% aqueous solution of HCl in methanol. The reducing agent
(0.416 g, 1 mmol) was added and refluxed with stirring (0.75 h)
and then silica-gel (2 g) was added. Methanol was evaporated and
the resulting solid was applied on a silica-gel column and eluted
with petroleum ether (bp 60–80 °C)/EtOAC: 10/1 (130 mL).
Evaporation of the solvent afforded almost pure 4-bromo-N,N-
dimethylaniline (0.19 g, 95% yield; Table 5, entry 3).
Method ꢁ: The preparation of 3-chloro-N,N-dimethylaniline
is representative. A solution of 3-chloroaniline (0.127 g, 1 mmol)
and 37% aqueous formaldehyde (0.4 mL, 5 mmol) in methanol
(5 mL) was prepared. The reducing agent (0.416 g, 1 mmol) and
ZrCl4 (0.116 g, 0.5 mmol) were added and after stirring (0.7 h),
silica-gel (2 g) was added to the mixture. Methanol was evaporat-
ed and the resulting mass was applied on a silica-gel column and
eluted with petroleum ether (bp 60–80 °C)/EtOAC: 10/1
(130 mL). Evaporation of the solvent afforded almost pure 3-
chloro-N,N-dimethylaniline (0.15 g, 97% yield, Table 5, entry 5).
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We are thankful to Prof. M. Rashidi for his comments, the
Shiraz University Research Council and the Ministry of Sci-
ence, Research and Technology of Iran for grant 80-SC-9-RM
in support of this work.
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