organoborane2ketone-3

organoborane2ketone-3, biotransformation

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6891
it is apparent that in this reaction the primary and
secondary alkyl groups migrate with equal facility.
More sterically hindered trialkylboranes react some-
what .more sluggishly and give lower yield^.^ The re-
sults are summarized in Table
I.
Moreover, that tri-
arylboranes also undergo this reaction was demon-
strated by the conversion of triphenylborane to phenyl-
acetonitrile
(52
%).
occurring. In such a complex, a secondary process,
namely isomerization to trans-propenylbenzene, occurs.
The free olefin may compete for ligand positions in
separate or mixed sets
of
complex ions. However, it is
required that the nature of the olefin complex be differ-
ent from that of the cyclopropane complex as the prod-
ucts of each reactant are different.
When the ratio of palladium(I1) chloride to phenyl-
cyclopropane is 4:
1,
the yield of propiophenone is
approximately 95x after
2
hr. No phenylacetone or
trans-propenylbenzene is observed. Therefore, the
oxidative cleavage reaction
of
phenylcyclopropane is
enhanced, and this fact is consistent with the expected
mass law effect on the formation
of
a complex ion con-
taining one cyclopropane moiety.
Studies of the effect of structure are being undertaken
in addition to experiments designed to elucidate further
the structures of postulated intermediates. Deuterium-
labeling experiments are being carried out in order to
determine the origin and ultimate destination of the
postulated hydride shifts in both the oxidation and isom-
erization reaction.
(8) Sinclair Oil Fellow, 1967-1968.
Robert J. Ouellette, Charles Levin*
Department
of
Chemistry, The Ohio State Unioersity
Columbus, Ohio 43210
Received October
IO,
1968
Table I.
Functionalization of Olefins into Nitriles by Reaction
of the Corresponding Trialkylboranesa with Diazoacetonitrile
Yield,c
z
Product?
Z
Olefin
1-Hexene
Octanenitrile, 95
100
3-Methylheptanenitrile,
5
1-Heptene
Nonanenitrile, 93d
93
Cyclopentene
Cyclopentylacetonitrile
99
ZMethyl-1-pentene
4Methylheptanenitrile
91
trans-3-Hexanee
3-Ethylhexanenitrile
54
Hydroboration was conducted such that complete conversion to
RaBwas ensured.a Structures were secured by direct comparison,
comparison with literature constants, or acceptable compositional
analyses and compatible spectral data. By glpc analysis. Yield
based on the utilization
of
one alkyl group of RIB.
A
50%
excess
of diazoacetonitrile was employed although we have not yet deter-
mined that this amount is necessary. A 1:1 molar ratio gives
somewhat lower yields.‘
d
Approximately
5z
of another product,
presumably 3-methyloctanenitrile, was also detected.
(1
Reaction
was conducted at
25”
for
2
hr followed by a 4-hr reflux.
The method illustrated for the conversion of cyclo-
pentene to cyclopentylacetonitrile is representative.
To an ice-cooled, magnetically stirred solution of tri-
cyclopentylborane (prepared in the usual manner
from cyclopentene (63 mmol) in
15
ml of tetrahydro-
furan and a solution of borane
(20
mmol) in tetra-
hydrofuran) was added a solution of diazoacetonitrile5
(30 mmol) in
15
ml of tetrahydrofuran over a period
of 30 min. The solution was stirred for
2
hr at room
temperature and then cooled in an ice bath, and
25
ml of a 3
N
potassium hydroxide solutions was added.
The reaction mixture was stirred at room temperature
an additional
0.5
hr. After the addition of brine
solu-
tion, glpc analysis of the organic extract indicated a
99
%
yield of
cyclopentylacetonitrile.
Evaporation of
solvent and distillation of the residue afforded 1.76 g
(81
%)
of
cyclopentylacetonitrile,
bp 85-86’ (16 mm).
Esters.
As
in the nitrile synthesis, organoboranes
derived from 1-alkenes liberate nitrogen smoothly at
ice-bath temperature on treatment with ethyl diazo-
acetate. However, the organoborane-diazoacetic ester
reaction appears to be considerably more sensitive to
steric factors, as evidenced by the variation of yield
(40-83
%)
with olefin struct~re.~Moreover, the tri-
(3)
(a)
G.
Zweifel and H.
C.
Brown,
Org. Reacfions,
13,
1 (1963);
(b) H.
C.
Brown, “Hydroboration,”
W.
A.
Benjamin, Inc., New York,
N.
Y.,
1962.
(4)
A
side reaction takes place which consumes diazo compound.
We
are investigating this in greater detail in an attempt to circumvent
this difficulty.
(5)
Caufion!
Although no difficulties were ever encountered in
numerous reactions of this substance with a variety
of
organoboranes,
the
isolation of this diazo compound is occasionally fraught with
capricious explosions. It is recommended that adequate safety pre-
cautions be observed in preparing this material.
Cf,
S.
H. Harper and
K. C.
Sleep,
J.
Sci.
Food Agr., 6,
116 (1955), and
T.
Curtius,
Ber.,
31,
2489 (1898).
(6) Subsequent experiments have indicated that the intermediate
a-borylnitrile may
be
conveniently hydrolyzed by water in the absence
of base, as described below for the ester synthesis.
The Alkylation of Diazoacetonitrile and Ethyl
Diazoacetate
by
Means of Organoboranes.
A
New Synthesis of Nitriles and Esters
Sir
:
We wish to report that trialkylboranes react with
diazoacetonitrile and ethyl diazoacetate, respectively,
with expulsion of nitrogen and provide, after hydrolysis,
novel and facile routes to the corresponding homol-
ogated nitriles (1) and ethyl esters’
(2).
In concert
RaB
+
NzCHCN
--t
-N2
hydrolysis
(1)
RCHzCN
-
Ng
RaB
+
NzCHCOOCzHj
+
-
+
RCHzCOOCzHs
(2)
with hydroboration, these reactions permit the over-all
conversion of olefins into two-carbon-atom chain-
extended derivatives possessing useful functionality.
These reactions probably proceed by a mechanism
analogous to that described earlier. Both processes,
however, occur with varying efficiency, and the follow-
ing salient features have been noted.
Nitriles.
The reactions of organoboranes derived
from terminal olefins as well as cyclopentene proceed
rapidly
(as
evidenced by complete nitrogen evolution)
at ice-bath temperatures. Yields are excellent (93-
100%).
The product obtained from the organoborane
derived from I-hexene contained 95 octanenitrile and
5
%
3-methylheptanenitrile. Since hydroboration of
monosubstituted terminal olefins produces approxi-
mately 94
%
primary and 6 secondary alkyl gro~ps,~
(1) For alternative ester syntheses based on organoborane homo-
logation,
see:
J.
J.
Tufariello, L. T. C. Lee, and P. Wojtkowski,
J.
Am.
Chem.
Soc.,
89,
6804(1967); H.
C.
Brown,
M. M.
RogiC, M.
W.
Rathke,
and
G.
W. Kabalka,
ibid.,
90,
818, 1911 (1968).
(2)
We
have previously reported the functionalization of olefins into
ketones
via
hydroboration;
cf.
J.
Hooz and
S.
Linke,
ibid.,
90,
5936
(1968).
hydrolysis
Communications to
the
Editor
6892
alkylborane derived from
I
-hexene gave rise exclusively
to ethyl octanoate; no product corresponding to re-
action of the 2-hexyl groups was observed.' Reactions
with hindered organoboranes require a reflux period
in order to complete the nitrogen evolution.
to the corresponding carboxylic acids.
2,3
In each case,
reactions catalyzed by these enzymes are susceptible to
inhibition by reagents which react with thiol groups
of
the enzymes. This behavior has led to the suggestion
that thiol groups of the enzymes may function as nucleo-
philic catalysts in these reactions. Among the various
nitriles acted upon by these enzymes is 3-cyanopyri-
dine.2b An investigation of the catalysis of hydrolysis
of
a related nitrile, N-benzyl-3-cyanopyridinium ion,
by a simple thiol, mercaptoethanol, reveals a substantial
number of parallels between the mercaptoethanol-
promoted reaction and the enzyme-promoted reactions.
Since the nonenzymatic reaction mechanism may shed
substantial light on that of the enzymatic reactions, we
are prompted to report our findings at this time.
Catalysis of hydrolysis of N-benzyl-3-cyanopyri-
dinium bromide by mercaptoethanol is characterized
by the following. First, under neutral or slightly acidic
conditions, the predominant reaction product is the
corresponding amide. Under conditions more acidic
than pH 3 appreciable amounts of the corresponding
acid are formed as well. Second, first-order rate con-
stants for disappearance of the nitrile at fixed concen-
trations of mercaptoethanol exhibit a rate maximum
near
pH
7. Third, between pH 3.6 and pH 8.9 first-
order rate constants for disappearance of the nitrile
exhibit saturation with respect to mercaptoethanol
concentration. This point and that developed just
above are illustrated by the collection of rate constants
for this reaction in Table
I.
The re-
sults are summarized in Table
11.
Table
11.
of
the Corresponding Trialkylboranes with Ethyl Diazoacetate
Conversion of Olefins into Ethyl Esters by Treatment
Yield;
Olefin Product*,
z
1-Hexene Ethyl octanoate 83
1-0ctene Ethyl decanoate 78
Cyclopentenec Ethyl cyclopentylacetate 58
2-Methyl-1-pentened Ethyl 4methylheptanoate 40
a
Structures were proven by direct comparison
or
satisfactory
elemental analyses.
*
By glpc analysis. Yield based on the con-
sumption of one alkyl group
of
RIB using a 1
:
1 molar ratio
of
ethyl diazoacetate
to
RIB. An additional 3C-min reflux period
was required for complete nitrogen evolution.
d
An additional
2-hr reflux period was necessary to liberate nitrogen completely.
The procedure for the functionalization of 1-hexene
into ethyl octanoate is representative.
A
solution of
ethyl diazoacetate (20 mmol) in 15 ml of tetrahydro-
furan was added, over a period of 20 min, to an ice-
cooled, magnetically stirred solution
of
trihe~ylborane~
(20 mmol) in tetrahydrofuran. The solution was kept
at ice-bath temperatures for an additional 30 min,
then stirred at room temperature for
2
hr. The ice
bath was replaced, and water (5 ml) was added drop-
wise (exothermic). The reaction mixture was re-
fluxed for
1
hr. Glpc analysis indicated an 83% yield
of ethyl octanoate. The solution was concentrated,
then poured into water and extracted with pentane.
Distillation of the dried (Drierite) organic extract
yielded 2.40 g
(70z)
of ethyl octanoate, identical in all
respects with an authentic sample.
The reactions of organoboranes with functionally
substituted diazoalkanes thus appear to possess very
broad synthetic potential, and we are continuing to
pursue these possibilities.
We wish to thank the National
Research Council of Canada for financial support of
this work.
Fourth, at the values of pH
near
10
excess
mercaptoethanol
causes
inhibition
of the reaction.
Table I.
First-Order Rate Constants for the Disappearance
of
N-Benzyl-3-cyanopyridinum
Bromide in the Presence of
Mercaptoethanol in Aqueous Solution at 25" and Ionic
Strength 0.60~
----Mercaptoethanol
concentration,
M--
pH
0.04
0.08
0.15
3.63
0.061
3.88
0.112
4.28
0.075
0.154
0.277
4.90
0.25
0.56
1.03
Acknowledgment.
1.05
4.04
5.45
2.09
6.26
3.77
6.28
8.63
6.54
3.50
6.90
9.20
7.00
4.76
7.15
8.20
(7) We could have detected
<1
%
ethyl 3-methylheptanoate under
(8) Postdoctoral Research Fellow, 1967-1968.
7.31
4.95
5.96
5.8
our analytical conditions.
7.88
4.29
5.32
5.6
7.46
4.66
6.33
7.6
Siegfried Link@
Department
of
Chemistry, Unicersity
of
Alberta
Edmonton, Alberta, Canada
Receiced September
12,
1968
John
HOOZ,
7.64
3.84
5.45
6.55
7.66
3.02
3.83
7.85
2.65
3.90
4.57
8.25
2.63
3.52
4.10
8.55
2.43
3.23
4.06
8.89 2.06 2.58
a
Rate constants in units of min-1, multiplied by lo2. The
reaction was followed spectrophotometrically at 332
mp
by the
periodic withdrawal
of
aliquots of the reaction mixtures and addi-
Catalysis of
H
ydrolysis of N-Benzyl-3-cyanopyridinium
Bromide.
A Model for the Nitrilase Reaction'
tion of these to
a
0.1
M
solution
of
mercaptoethanol, at pH 10.3
*
0.1. Under these conditions, only the nitrile adds mercaptoethanol
to form
a
332"
Sir:
A
substantial variety of plant and bacterial species
are known to possess enzymes, nitrilases, capable of
catalyzing the hydrolysis of a variety of organic nitriles
(1) Supported by Grant
GE
3277 from the National Science Founda-
tion and by Grant AM08232-05 from the National Institutes of Health.
Publication No. 1626 from the Department of Chemistry, Indiana
University.
chromophore.
(2) (a) K. V. Thimann and
S.
Mahadevan,
Arch.
Biochem.
Biophys.,
105,
133 (1964);
(b)
S.
Mahadevan and
K. V.
Thimann,
ibid.,
107,
62
(1964).
(3) R. H.
Hook
and W. C. Robinson,
J.
Bid.
Chem.,
239,
4263,
4257 (1964).
November 20,
1968
Journal
of
the American Chemical Society
90:24
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