Easy and direct conversion of tosylates and mesylates into nitroalkanes

Article abstract of DOI:10.3762/bjoc.9.58

Tosylates and mesylates were directly converted into the corresponding nitroalkanes, by their treatment with tetrabutylammonium nitrite (TBAN) under mild conditions.

Full text of DOI:10.3762/bjoc.9.58

Easy and direct conversion of tosylates and
mesylates into nitroalkanes
Alessandro Palmieri, Serena Gabrielli and Roberto Ballini*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2013, 9, 533–536.
“Green Chemistry Group”, School of Science and Technology,
Chemistry Division, University of Camerino, Via S. Agostino 1, 62032
Camerino (MC), Italy
doi:10.3762/bjoc.9.58
Received: 17 December 2012
Accepted: 19 February 2013
Published: 14 March 2013
Email:
Roberto Ballini* - roberto.ballini@unicam.it
Associate Editor: T. J. J. Müller
* Corresponding author
© 2013 Palmieri et al; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
mesylates; nitroalkanes; nucleophilic substitution;
tetrabutylammonium nitrite; tosylates
Abstract
Tosylates and mesylates were directly converted into the corresponding nitroalkanes, by their treatment with tetrabutylammonium
nitrite (TBAN) under mild conditions.
Introduction
Nitroalkanes have proven to be one of the most valuable, versa- tained from different sources [4], the displacement of alkyl
tile classes of substances in organic synthesis. In this sense, the halides with metal nitrite, thanks to the large number of
chemical literature continuously reports progresses in their commercially available halides, remains the most used, espe-
utilization for the preparation of a variety of target molecules, cially for the primary ones [18-23]. The classical reaction
such as dyes, plastics, perfumes, pharmaceuticals and many conditions require the usage of MNO2 (M = Na, K, Ag) in polar
natural products [1-7]. In fact, thanks to the high electron-with- aprotic solvents (DMF, DMSO). Recently, owing to the impor-
drawing effect of the nitro group, nitroalkanes are prone to tance of this transformation, new innovative and more eco-
afford, under basic conditions, stabilized carbanions, which are friendly procedures have been developed with success [24-27].
commonly used as nucleophiles with a variety of electrophiles Unfortunately, despite the advantages introduced with these
[8-11] leading to carbon–carbon bond formation. Furthermore, new methodologies, the usefulness of the reaction remains
by making use of the possibility to transform the nitro group restricted to the use of alkyl halides, and the research of alter-
into other functionalities, the obtained adducts can be employed native sources is surely welcomed. In this regard, alcohols are a
as strategic starting materials for the preparation of more com- broad class of molecules easily available from both commercial
plex structures [12,13]. In this context, primary nitroalkanes are sources and nature and, as a direct source for nitroalkanes, have
the most used nitro derivatives [3-5,14-17], and thus, their unsuccessful been explored in the past [28]. In fact, the conver-
availability is crucial. Although these molecules can be ob- sion of alcohols into nitroalkanes requires a three-step se-
533

Beilstein J. Org. Chem. 2013, 9, 533–536.
quence, as reported in Figure 1, that necessitates [29-33] (i)
conversion of alcohols a into their tosylates or mesylates b, (ii)
transformation of b into the corresponding halo derivatives c
(mainly iodide), and (iii) displacement of the halides by metal
nitrite into the nitro compounds d.
Table 1: Optimization studies.
Entry Nitrating agent
Solventa Time (h) Yield (%)b
1
2
3
4
5
6
7
8
NaNO2 (1.5 equiv)
DMF
6
traces
27
Bu4NNO2 (1.5 equiv) DMF
Bu4NNO2 (1.5 equiv) CPMEc
Bu4NNO2 (1.5 equiv) Et2O
Bu4NNO2 (1.5 equiv) DCM
6
6
traces
traces
24
6
Figure 1: Classical conversion of tosylate and mesylate into the
corresponding nitroalkanes via halides.
24
Bu4NNO2 (1.5 equiv) toluene 2.5
Bu4NNO2 (1.0 equiv) toluene
Bu4NNO2 (2.0 equiv) toluene 2.5
61
5
45
However, although the first step (a into b) can be usually
performed in quantitative yields, the main drawbacks, in terms
of waste production and energy consumption, are in the two-
step conversion of b into d.
59
aUsed 4 mL/mmol. bYield of pure isolated product. cCyclopentyl methyl
ether.
Thus, an important advancement could be the development of
an easy, direct and mild procedure for transforming tosylates
and mesylates into the corresponding nitroalkanes. In fact, with
the exception of a couple of examples reporting the conversion
of 1-BuOTs [26] and homoallylic tosylates [34] into the corres-
ponding nitro compounds, to the best of our knowledge, no
general methods are available in literature.
Table 2: Synthesis of primary nitroalkanes 2a–j.
Entry
R
R1
Product
Yield (%)a
1
CH3(CH2)13
CH3(CH2)13
CH3(CH2)8
CH3(CH2)18
CH3(CH2)5
CH3(CH2)5
PhCH2CH2
PhCH2CH2
CH2=CH(CH2)8
Cl(CH2)5
Ts
Ms
Ts
Ts
Ts
Ms
Ts
Ms
Ts
Ts
Ts
Ts
2a
2a
2b
2c
2d
2d
2e
2e
2f
61
55
65
66
53
50
58
53
60
59
55
48
Results and Discussion
2
Following our studies in the development of new processes for
the preparation of nitroalkanes [24,27,35], we have now elabo-
rated a general protocol for the direct transformation of ali-
phatic tosylates and mesylates into the corresponding nitro com-
pounds. In order to optimize the reaction conditions we studied,
as a test reaction, the conversion of tosylate 1a into nitropenta-
decane 2a (Table 1). As an initial trial we submitted 1a to the
use of NaNO2 as the nitrating agent and DMF as the solvent.
Under these conditions, we observed the formation of a mix-
ture of products with traces of compound 2a. Thus, we switched
our attention to a different class of nitrating agent, i.e., the
commercially available tetrabutylammonium nitrite (TBAN).
The application of 1.5 equiv of this compound in DMF
produced 2a in 27% yield. With this result in our hand we
3
4
5
6
7
8
9
10
11
12
13
2g
2h
2i
NC(CH2)4
AcO(CH2)3
(Z)-CH3(CH2)3C
H=CHCH2
2j
Ts
57
aYield of pure isolated product.
tested both (i) different amounts of TBAN and (ii) different mildness of our reaction conditions permits the survival of
reaction media. As reported in Table 1, we obtained the best important functionalities, such as cyano, ester, chlorine and (Z)-
result (61% yield) using 1.5 equiv TBAN in toluene as the C–C double bond, giving easy access to polyfunctionalized
solvent (Table 1, entry 6).
nitroalkanes.
In order to verify the generality of our method we examined a Finally, we investigated our reaction conditions on secondary
variety of substrates and, as showed in Table 2, the procedure substrates, but, as reported in Table 3, the procedure is not
works well with a variety of primary substrates, including the general and, for the right substrates, the corresponding nitro-
functionalized ones giving access to a huge typology of alkanes 2k–n were isolated in lower yields and after longer
primary nitroalkanes in 48–66% overall yields. Moreover the reaction times with respect to the primary ones.
534

Beilstein J. Org. Chem. 2013, 9, 533–536.
the formation of two phases. The solvent phase (upper phase)
was carefully separated, while the other phase was treated with
fresh MTBE (5 mL) and extracted under stirring for 10 min,
then, the solvent phase was once again separated (the extrac-
tion process was repeated four times). Finally, the combined
solution was concentrated under vacuum, to afford the crude
product 2, which was purified by flash column chromatography
(heptane/ethyl acetate).
Table 3: Synthesis of secondary nitroalkanes 2k–n.
Yield (%)a
(Time, h)
Entry
R
R1
Product
1
2
3
4
CH3CH2
CH3
CH3(CH2)5
PhCH2CH2
CH3(CH2)5
CH3(CH2)2
2k
2l
41 (28)
33 (39)
Supporting Information
CH3
2m
2n
<10 (37)
<10 (40)
CH3(CH2)2
All synthesized products were characterized by IR, NMR,
GC–MS and elementary analysis. The data is reported in
Supporting Information File 1, while copies of 1H and
13C NMR spectra are attached as Supporting Information
File 2.
aYield of pure isolated product.
Conclusion
In conclusion, our method can be considered an important
contribution for the preparation of nitroalkanes, making alco-
hols a strategic source for their availability. Moreover, the
mildness of our reaction conditions permits the survival of
important functionalities. Furthermore, our protocol presents an
interesting peculiarity from the sustainability point of view,
since (i) it overcomes the need to convert the alcohol deriva-
tives (tosylates and mesylates) into halides, (ii) low-impacting
solvents [36,37] such as toluene and methyl tert-butyl ether
(work-up) were used, and (iii) any aqueous work-up was
avoided, with evident restriction of waste production and
energy consumption.
Supporting Information File 1
Spectroscopic data of synthesized compounds.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-9-58-S1.pdf]
Supporting Information File 2
Copy of 1H and 13C NMR spectra of synthesized
compounds.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-9-58-S2.pdf]
Experimental
Acknowledgements
General Information: Compounds 2a [38], 2b [24], 2c [15], The authors thank the University of Camerino and MIUR-Italy
2d [25], 2e [39], 2f [24], 2g [40], 2h [40], 2i [24] and 2j [41] (FIRB National Project “Metodologie di nuova generazione
are known, and their spectroscopic data are in agreement with nella formazione di legami carbonio-carbonio e carbonio–etero-
those reported in the literature. Compounds 1 were synthesized atomo in condizioni eco-sostenibili”) for financial support.
by Ghosh and Nicponski’s methodology [42]. 1H NMR was
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