Download Cyanogen bromide

Cyanogen bromide
Product Code: FC02319
CAS Number: 506-68-3
Chemical Formula: CBrN
Molecular Weight: 105.92
Br
CN
Product Name/Grade
Product Code
Cyanogen bromide
FC02319
Cyanogen bromide 30% w/w in acetonitrile
FC04239
Cyanogen bromide 34% w/w in dichloromethane
FC03962
Cyanogen bromide 50% w/w in acetonitrile
FC07135
Cyanogen bromide 50% w/w in toluene
FC07908
Cyanogen bromide is a versatile solid reagent which is used widely in organic synthesis and
biochemistry. Cyanogen bromide is usually written as CNBr, though this is misleading as the
carbon atom has a triple bond to nitrogen and a single bond to bromine (N�C-Br). The
electronegative bromine and nitrogen atoms shift electron density away from the carbon atom in
this linear molecule, making it particularly electrophilic and susceptible to nucleophilic attack.
The reagent has many uses in synthetic organic chemistry, being useful for the synthesis of
guanidines, hydroxyguanidines, heterocyclic systems, ureas and thioureas.1
CNBr is a source of electrophilic cyanide, and reacts with primary and secondary amines to yield
cyanamides (1), which can be reacted further with amines or hydroxylamines to yield guanidines
(2) and hydroxyguanidines (3) respectively (Scheme 1).
NH
R1
R3NH2
R1
CNBr
R1
NH
R2
N
N
R2
N
H
R3
CN
R2
NH
R1
H2NOH
N
R2
N
H
R3
Scheme 1
Snider and O’Hare have used this technique to synthesize hindered guanidine 4 as a model for
the naturally occurring bradykinin receptor antagonist Martinellic acid.2 Attempts to form the
guanidine directly from a pyrrolidine precursor resulted in poor yields, and the success of the
two step process using cyanogen bromide is attributed to the lower steric hindrance (CNBr is a
small, linear molecule) and higher electrophilicity than reagents such as N-butyl-N’-Boc-thiourea
which can form guanidines directly.
Carbosynth Limited
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- Berkshire
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HN
O
HN
HN
i) CNBr, NaHCO3, EtOH
ii) Prenylamine, (CF3)2CHOH, 120oC
O
O
N
O
O
O
4
Scheme 2
Cyanogen bromide is a convenient reagent for the synthesis of amino-heterocycles (Scheme 3).
For example, amino 1,3,4-oxadiazoles (5) can be readily formed from hydrazide precursors3 and
aminobenzoxazoles (6) and aminobenzimidazoles (7) synthesized by treatment of the oaminophenol or o-diamine respectively with CNBr.4
H
N
S
N
CNBr, MeOH
NH2
N
S
O
O
NH2
NH2
N
CNBr, MeOH, DCM
NH2
6, X = O
7, X = NH
X
X
Scheme 3
Reaction of a tertiary amine with CNBr results in the formation of a disubstituted cyanamide with
the loss of one of the original substituents on nitrogen as an alkyl bromide (the von Braun
reaction), as illustrated in Scheme 4 for the synthesis of N-methyl-1-napthylcyanamide.5 The
alkyl group that cleaves is usually the one which yields the most reactive alkyl halide,6,7 and the
von Braun reaction has also been used to cleave aziridine rings.8
N
N
CNBr, reflux
CN
+
MeBr
Scheme 4
Von Braun has additionally reported that dialkyl thioethers can be cleaved by CNBr to yield alkyl
thiocyanates and an alkyl bromide (Scheme 5).1,9 The reaction has been used to cleave peptides
at the C-terminus of methionine residues and has utility in the reduction of polypeptides for
identification and sequencing. The nucleophilic sulfur in methionine attacks the electrophilic
carbon of cyanogen bromide, but the sulfur in cysteine residues does not react, making the
technique selective for cleavage at methionine residues. Cleavage yields are frequently high
except where the methionine residue is followed by a serine or threonine residue. In these cases
modified buffer conditions have been reported which produce greater yields.10,11
Carbosynth Limited
8&9 Old Station Business ParkCarbosynth
- ComptonLimited
- Berkshire - RG20 6NE - UK
8&9 Old
Station Business Park - Compton
- Berkshire
- RG20
UK 579444
www.carbosynth.com
[email protected]
Tel: +44 1635
578444
Fax: 6NE
+44 -1635
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CNBr, 60oC
S
S
CN
+
MeBr
Scheme 5
In biochemistry, cyanogen bromide is frequently used to immobilize proteins for affinity
chromatography by coupling them to reagents such as agarose (a polymer based on alternating
monomers of β-D-galactopyranose and 3,6-anhydro-α-L-galactopyranose). Cyanogen bromide
activation is one of the most common methods for preparing affinity gels, and is useful because
it reacts with the hydroxyl groups on agarose to form cyanate esters and imidocarbonates,
which are attacked by primary or secondary amine nucleophiles from the protein, resulting in
immobilization of the protein on the agarose matrix.12,13
Sokolova and colleagues have reported the use of cyanogen bromide as a coupling reagent for
the formation of phosphoroamidate or pyrophosphate internucleotide bonds in DNA duplexes.14
Compared to alternative reagents such as water-soluble carbodiimide that are often used for this
process, CNBr is advantageous as it is highly reactive and yields no modified products.
Carbosynth supplies cyanogen bromide in solid form (product code FC02319) and as solutions in
CH2Cl2, toluene and acetonitrile (FC03962, FC07908 and FC07135 respectively.
References:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Kumar, V. Synlett 2005, 10, 1638.
Snider, B. B.; O’Hare, S. M. Tetrahedron Lett. 2001, 42, 2455.
Somani, R. R.; Shirodkar, P. Y. Der. Pharma Chemica 2009, 1, 130.
Luzzio, F. A.; Wlodarczyk, M. T. Tetrahedron Lett. 2009, 50, 580.
Cressman, H. W. J. Organic Syntheses 1955, Collect. Vol. No. 3, 608.
th
March, J. Advanced Organic Chemistry, 4 Edition; Wiley: New York, 1992; 436.
Cooley, J. H.; Evain, E. J. Synthesis 1989, 1.
Furuya, S.; Okamoto, T. Heterocycles 1988, 27, 2609.
von Braun, J.; Engelbertz, P. Ber. Dtsch. Chem. Ges. 1923, 56, 1573.
Kaiser, R.; Metzka, L. Anal. Biochem. 1999, 266, 1.
Schroeder, W. A.; Shelton, J. B.; Shelton, J. R. Arch. Biochem. Biophys. 1969, 130, 551.
Porath, J.; Aspberg, K.; Drevin, H.; Axén, R. J. Chromatogr., A 1973, 86, 53.
March, S. C.; Parikh, I.; Cuatrecasas, P. Anal. Biochem. 1974, 60, 149.
Sokolova, N. I.; Ashirbekova, D. T.; Dolinnaya, N. G.; Shabarova, Z. A. FEBS Lett. 1988, 232, 153.
Carbosynth Limited
8&9 Old Station Business ParkCarbosynth
- ComptonLimited
- Berkshire - RG20 6NE - UK
8&9 Old
Station Business Park - Compton
- Berkshire
- RG20
UK 579444
www.carbosynth.com
[email protected]
Tel: +44 1635
578444
Fax: 6NE
+44 -1635
www.carbosynth.com [email protected] Tel: +44 1635 578444 Fax: +44 1635 579444