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Strecker Degradation Of Amino Acids To Ketones
H.L. Slates, D. Taub, C.H. Kuo, N.L. Wendler
. Org. C!em. "#, $%"% &$#'%(
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Degradation of al)!a*+et!,l*-,%*di!,dro.,)!en,lalanine
The transformation of alphamethyl!"#A diethyl ether to $%&dimetho'yphenylacetone
(/) was effected o'idatively with sodium hypochlorite
*
in +,- yield. Thus% the total
se.uence (C!art 0) from alphamethyl!"#A to $%&dimetho'yphenylacetone%
consistin/ of the four steps% acetylation% methylation% hydrolysis% and hypochlorite
o'idation% can be effected with a potential overall yield of +,-.
The direct hypochlorite o'idation of alphamethyl!"#A itself proceeds in the desired
manner to /ive $%&dihydro'yphenylacetone in ca. 0,- yield. The latter substance is
hi/hly water soluble and sensitive as well to manipulation% althou/h it can be
methylated to / in reasonable yield. To a lar/e and competitive e'tent% however% the
direct hypochlorite o'idation of alphamethyl!"#A involves nuclear attac1 as
evidenced by accompanyin/ resinification. The use of tbutyl hypochlorite was found to
be superior to sodium hypochlorite in this instance and su//ests% thereby% that the
brea1down reaction to 1etone is faster than nuclear involvement. The hypochlorite
de/radation of the $monomethyl ether of alphamethyl!"#A to $metho'y&
hydro'yphenylacetone also can be accomplished in at least 2,3,- yield.

The o'idative de/radation 0/ 4 / would appear clearly to be initiated by 5
chlorination (compare a b c) inasmuch as the 5acetate derivative 000 is
unchan/ed under the conditions of hypochlorite o'idation% whereas the latter (000) is
o'idi6ed smoothly by lead tetraacetate% a rea/ent 1nown to attac1 carbo'yl functions.

1.)erimental
-,%*Dimet!o.,)!en,lacetone &/( from 0/
To a stirred solution% (7,708) of +02 m/. (&.,, mmoles) of alphamethyl$%&
dimetho'yphenylalanine (0/) in 70 ml. of water was added *, ml. of ben6ene. 9odium
hypochlorite solution (*& ml.% ,.$ 5 active chlorine)
7
was added dropwise over 7, min.
The reaction was followed by spottin/ ali.uots on starchiodide paper. After each
addition of hypochlorite% a ne/ative test was obtained in about $, sec. At the reaction:s
completion% a positive test was obtained 0 min. after addition of the last drop of
hypochlorite. The layers were separated and the basic a.ueous layer was e'tracted twice
with 0,- ben6eneether; the combined or/anic phase was dried over ma/nesium sulfate
and concentrated to dryness in vacuo. The neutral residue (370 m/.% +7-) consisted of
$%&dimetho'yphenylacetone; infrared spectrum was identical with standard; v.p.c.
showed it to be +3- pure.
9emicarba6one. The semicarba6one crystalli6ed from etherchloroform and had m.p.
*3**3&8; mi'ture meltin/ point was undepressed with an authentic sample of mp *30
*328C.
-,%*Di!,dro.,)!en,lacetone &/0(
A. Sodium H,)oc!lorite
To a stirred solution of <&& m/. (&.,, mmoles) of alphamethyl$%&
dihydro'yphenylalanine (0) in 7, ml. of ,.0 M bora' buffer (pH <.0)
$
was added *, ml.
of ben6ene. 5itro/en was bubbled throu/h the solution and *7., ml. of ,.$& 5 sodium
hypochlorite solution added dropwise. The red solution was acidified with dilute
hydrochloric acid and e'tracted with ethyl acetate. The latter e'tract was dried and
concentrated to dryness. The residue was triturated with chloroform% the latter
suspension filtered% and the filtrate concentrated to dryness in vacuo to /ive $%&
dihydro'yphenylacetone% 7$0 m/ ($2-)% with additional material still in the a.ueous
mother li.uors. Acetylation of a probe (pyridineacetic anhydride% 708C% *< hr.) /ave
$%&diaceto'yphenylacetone. The latter was identified as the diacetate by comparison
with an authentic sample.
2. t*2ut,l H,)oc!lorite
To a stirred suspension of <&& m/ (&., mmoles) of alphamethyl$%&
dihydro'yphenylalanine in *, ml. of water (under nitro/en) was added $&, m/. (&.,,
mmoles) of sodium bicarbonate. t=utyl hypochlorite (,.0, /.% &.0 mmoles) in *, ml. of
tbutyl alcohol was added dropwise over $, min. The deep red reaction mi'ture was
acidified with 0 ml. of 7 5 hydrochloric acid and e'tracted thorou/hly with ethyl
acetate. >urther wor1up as in A led to $$0 m/. (0,-) of $%&dihydro'yphenylacetone;
infrared spectrum was identical with that of an authentic sample.
-,%*Diaceto.,)!en,lacetone &30/( from 00
To a stirred solution of *2.<0 /. (0, mmoles) of 5acetylalphamethyl$%&
diaceto'yphenylalanine (00) in *70 ml. of acetonitrile was added &.,, mL (0, mmoles)
of pyridine followed by 77.*0 /. (0, mmoles) of lead tetraacetate. The mi'ture was
warmed cautiously to reflu' temperature at which point lead acetate precipitated rapidly
from solution. The mi'ture was reflu'ed /ently for $, min.% cooled% filtered% and the
filtrate concentrated to dryness. The residue% consistin/ mainly of the intermediate
decarbo'ylated imine triacetate (3000)% was hydroly6ed by heatin/ on the steam bath
(+,+08) with *0 ml. of acetic acid and *, ml. of water for 0, min. The mi'ture was
cooled% water was added% and it was e'tracted with chloroform. The chloroform e'tract
was washed with dilute potassium bicarbonate solution and salt solution% dried over
ma/nesium sulfate% and concentrated to dryness to /ive $%&diaceto'yphenylacetone
(30/)% +.& /. (30-); bp *&0*0,8C (,.,0 mmH/).
The diaceto'y 1etone was converted in /ood yield by the appropriate processes to the
correspondin/ dimetho'y1etone / and to the dihydro'y hydantoin and alphamethyl
!"#A. 9imilar lead tetraacetate treatment of the 5acetyldimetho'yamino acid 000c in
CH$C5pyridine led to the dimetho'y 1etone /.

4eferences
*. >or the employment of hypochlorite in the de/radation of natural amino acids%
see?
*. @. Lan/held% =er.% &7% $+7 (*+,+)
7. H. #. !a1in =iochem. A.% *,% $*+ (*+*2); **% 3+ (*+*3)
3. !. !. van 9ly1e% !. A Mcfayden% and !. Hamilton% A. =iol. Chem.% *&*%
273 (*+&*)
4. B. !. 9penser% A. C. Crowhall% and !. C. 9myth% Chem. Bnd. (London)%
3+< (*+02)
7. Commercial D0-D sodium hypochlorite was used. A 0.,, ml ali.uot was added
to 7., / of potassium iodide in $,ml of ,.0 5 hydrochloric acid and the iodine
formed titrated vs. ,.* 5 sodium thiosulfate; $,.0, ml. of ,.* 5 sodium
thiosulfate was re.uired.
$. =ora' buffer? $.* /. of boric acid in 0, ml. of water% <.0 ml. of * 5 sodium
hydro'ide% and enou/h water to brin/ the total to *,, ml.

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