8/12/2019 Amino Acid to Ketones - With Sodium Hypochlorite

http://slidepdf.com/reader/full/amino-acid-to-ketones-with-sodium-hypochlorite 1/4

This file is a part of the Rhodium site archive. This Aug 2004 static snapshot is hosted by Erowidas of May 200 and is not being updated. ! ! "ac# to Rhodium Archive $nde% ! !

[www.rhodium.ws] ☯[Chemistry Archive] 

Strecker Degradation Of Amino Acids To Ketones

H.L. Slates, D. Taub, C.H. Kuo, N.L. Wendler

. Org. C!em. "#, $%"% &$#'%(

HTML by Rhodium

Degradation of al)!a*+et!l*-,%*di!dro)!enlalanine

The transformation of alphamethyl!"#A diethyl ether to $%&dimetho'yphenylacetone

(/) was effected o'idatively with sodium hypochlorite*

 in +,- yield. Thus% the totalseuence (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 t butyl 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)!enlacetone &/( from 0/

8/12/2019 Amino Acid to Ketones - With Sodium Hypochlorite

http://slidepdf.com/reader/full/amino-acid-to-ketones-with-sodium-hypochlorite 2/4

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/ aliuots 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 aueous 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)!enlacetone &/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 aueous

mother liuors. 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*2utl 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. oftbutyl alcohol was added dropwise over $, min. The deep red reaction mi'ture was

8/12/2019 Amino Acid to Ketones - With Sodium Hypochlorite

http://slidepdf.com/reader/full/amino-acid-to-ketones-with-sodium-hypochlorite 3/4

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)!enlacetone &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 thefiltrate 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 inCH$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. .% *,% $*+ (*+*2); **% 3+ (*+*3)

3. !. !. van 9ly1e% !. A Mcfayden% and !. Hamilton% . =iol. Chem.% *&*%

273 (*+&*)

4. B. !. 9penser% . C. Crowhall% and !. . 9myth% Chem. Bnd. (London)%

3+< (*+02)

7. Commercial D0-D sodium hypochlorite was used. A 0.,, ml aliuot 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 reuired.

8/12/2019 Amino Acid to Ketones - With Sodium Hypochlorite

http://slidepdf.com/reader/full/amino-acid-to-ketones-with-sodium-hypochlorite 4/4

$. =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.