Oxidation of α,β-un saturated aldehydes

Te~mludron Vol37. pp. 2091 [o xR6.1981 Prmrcd ,nGrear Britam. All nghts reKrved

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OXIDATION OF s,o-UNSATURATED ALDEHYDES PALXRISHNA S. EAL, WAYNE E. CHILDERS, JR. and HAROLD W. PIWWICK* Department of Chemistry, University of Georgia, Athens, Georgia 30602 (Received in USA 23 February 1981) Abstract - A variety of methods for the conversion of O,6-unsaturated aldehydes to the corresponding acids have been explored.

The best approach uses sodium

chlorite and gives the desired transformation even in systems where steric hindrance and/or sensitive functionality are present. In a recent investigation,

1

the oxidation

of o-methylenc aldehydes to the corresponding acids was required (cq

1).

The first method which was examined was 5a Consequently,

R&OOH(I)

citral was converted into the corresponding

methyl ester without difficulty; however, when

sensitivity of the molecules of interest, strong oxidizing agents like Jones reagent2 and potassium permanganate3 were not appropriate. In addition, the use of silver oxide 4,5 was to of

the high initial invest-

the a-methylene aldehyde 1 (R=C6H5CH2) was allowed to react according to the prescribed directions,

a variety of products resulted.

These included compounds derived from conjugate addition

ment and the bothersome recycling of silver

of cyanide ion.

which is necessary for economic reasons.

(54 f

Several methods have been developed for the oxidation of o,6-unsaturated aldehydes to the corresponding acids or esters. 5.6 The 6a has been approcedure employing Care's acid

OR

E

&CHo

plied to acrolein, methacrolein and crotonaldehyde only.

and oxime.6e

We now wish to report the results of a detailed

that developed by Corey.

CHO

bc avoided because

6d

study of the reaction of equation 1.

Because of the

+

R

corresponding dithiane anion

In addition, the necessary

I

reagent is prepared with concentrated sulIn view of the unusual regioselectivity

furic acid and this may cause problems with sensitive molecules.

A second very clever 5a based on the

method was developed by Corey

in situ formation of a cyanohydrin which -undergoes oxidation by manganese dioxide to give an acyl cyanide.

In the presence of an

alcohol, the ester is isolated_

Alternatively,

A recent modifica-

dlzed

of

these

are

methods using cyano-

Another approach

uses selenium

dioxide6c but requires 90% hydrogen peroxide and thus presents some danger particularly

a modification of Corey's procedure

Indeed, TMSCN reacts with a variety of alde-

silyl-protected cyanohydrins which react with 9. in methanol containing ace-

esters (see Table I). In many cases, a cleaner

No a-methylene aldehydes were oxi-

by either

hydrins.

that

tic acid to yield the corresponding methyl

cyanohydrins of a,(3-unsaturated aldehydes 6b with pyridinlum dichromate. Allylic oxi-

isolated.

felt

may improve its general synthetic utility by 8 increasing the scope of the reaction.

manganese dioxide

tion treats the trimethylsilyl protected

dation also occurs so that AZ-butenolides

silyl cyanide (TMSCN) with enones, ’ it was

hydes to give good yields of the trimethyl-

sllvcr (II) oxide converts the cyanohydrin into the unsaturated acid.

for 1,2-addition in the reaction of trimethyl-

product can be obtained if the oxidation is run in benzene as a solvent.

tion of the mSCN

product and then allowed

to react with manganese dioxide. These changes reduce the amcunt OC 'Jnreacted aldehyde which sometimes is obtained.

with large scale reactions.

In addition,

the cyanohydrin can be liberated by deprotec-

Nevertheless, all

Finally, cinattempts to oxidize aldehyde 1 (R'C~H~CH~)~'

namaldchyde has been oxidized via the TETVol 37.No.II-D

H.W. Pinnick et

2092

al

(typically 50%) of recovered starting

of E and '2 isomers) gives the corresponding 15 acid as a 71/29mixture of E/Z isomers.

material in addition to the desired methyl

Consequently, the oxidation reaction is

ester.

stereospecific.

6a was The annnonium persulfate procedure 11 studied next. Despite the use of concen-

chlorite are summarized in Table II.

trated sulfuric acid to prepare the reagent,

dation

a 90% yield of methyl cinnamate is obtained

explored.

from cinnamaldehyde.

with sensitive substrates containing the

via the cyanohydrin gave significant amounts

of

Oxidation of aldehyde 1

21.l'

of

ol,&unsaturated aldehydes have been Only sodium chlorite works well

Ci-methylene aldehyde unit.

the desired ester and isomerized

starting material (eq

results using sodium

In summary, numerous methods for the oxi-

(R=C6H5CH2) gives an 83% yield of a 1:l mixture

The

This reagent

efcects clean oxidations quickly and in a

The free alco-

In addition, it is

stereospecific manner.

hol 1 (R=H) gives an 87% yreld of the

very inexpensive. This method has considerable synthetic potential. EXPERX.mNTAL SECTION All reactions involving air-sensitive reagents were run under nitrogen in flamed-out apparatus.

Proton NMR spectra were r-22on

Varian T-60 or EM-390 spectrometers.

Infrared

spectra were recorded on Perkin-Elmer model 297 or 599B spcctrophotometers.

Mass spectra

were obtained with a Finnigan 4023 GC/MS. Typical procedures for oxidations are provided. Oxidation of E- 2,4-dimethyl-2-hexenal via the cyanohydrin The aldehyde (1.26 g, 10.0 mmol) was recorrespondinq ester contaminated with the a-methylene lactone (eq

fluxed with 1.4 g (14 mmol) of freshly dis-

31.13

tilled TMSCN and 1 mg overnight.

I

3\,

H2S04

ACHO

1

H

(m, 8H), 1.6-1.8 Cm, 4H), 4.6 (s, lH), 5.2

CH30H

(3) 1

@+-‘CO&H3

The siloxynitrile

stirred

j-&

results with alde-

Another method for the oxidation of alde-

this has never been applied to a-methylene With 2-methyl-2-butene as the 14b a 95% yield of cinnamic Even more significant is the

90%

where

(2.15 g, 9.50 mmol)

was

temperature overnight with The

extracted with three 20 ml portions of ether which

gave

1.5

CJ (98%)

of the cyanohydrin

after drying and concentration: NMR (CC14) 6 0.8-1.5 (m. 8~), 1.6-2.0 (m, 4H), 4.3 (br s, lH), 4.7 (s, IH), 5.5 (d, J = 8 Hz,

1H);

IR (NaCl) 3420, 2960, 2240, 1460, 1040, -1 1020 cm . The cyanohydrin (1.5 q, 9.5 mm011 was

chlorine trap,

(R=C6H5CH2f

room

10 ml of 10% HCl and 50 ml of THF.

hydes employs sodium chlorite in the pre14 but sence of various chlorine scavengers

result from aldehyde l

at

reaction mixture was poured into water and

hyde 1 are acceptable for the intended goals.

acid is isolated.

(m, 1H); IR (NaCl) 2950, 2220, 1460, 1250, 1070, 860, 840 cm-l.

c-747 V’Q

Neither of these latter

gave

BP 52-57OC

(0.2 mm): NMR (CC14) 6 0.1 (s, 9H), 0.8-1.4

---‘$-OH

aldehydes.

anhydrous zinc iodide

2.15 (95%) of the siloxynitrile:

(NH4)2S208 >

5

of

Distillation of the product

a

yield of pure acid is obtained.

dissolved in 70 ml of dry benzene and 3 ml of methanol acetic acid.

containing

5 drops of glacial

Manganese dioxide (6.0 q, 69

mmol) was added and the reaction mixture was In addition, oxidation of citral (65/35 mixture

2093

Oxidation of a,#j-unsaturated aldehydes

allowed to stir overnight at room temperature.

were washed with 50 ml of cold water, dried

'5~~ reaction mixture was filtered throitgh celite, diluted with water and extracted with

and concentrated to give 0.20 g (90%) of a pale yellow oil which was identified as the

three 30 ml portions of ether.

desired acid:

ether

layers

were

The combined

dried and concentrated to

give, after distillation, 1.4 g (90%) of methyl E-2,4-dimethyl-2-hexenoate:

BP lOO-llO" (40

mm); NMR (Ccl,) 6 0.8-1.5 (m, 8H1, 1.6-2.0 (m, 4H), 3.6 (s, 3H1, 6.4 (d, J = 10 Hz, 1H); IR (N&l)

NMR (CC14) 6 0.8-2.8 (m, llH),

3.2-3.8 (m, 1X1, 4.3 (AB q, Ja = 5 Hz, 3

=

0 28 Mz, 2H1, 5.4 (s, lH1, 6.2 (s, lH), 7.1 (St 5H1, 9.4 (br s, lH>; IR (NaCl) 3600-2400, 1690, 1620, 1450, 1280, 1100, 1060, 690 cm-1 . A~~~LE~M~NT

We thank Professor R. EC. Hill

2960, 1715, 1650, 1430, 1270, 1240, for providing a generous sample of E-2.4-

1150, 1090. 740. dimethyl-2-hexenal as well as spectral data Oxidation of Aldehyde 1 (R=H) with Carols Acid

on the corresponding oxidation product.

Care's acid was prepared by adding 3.0 g REFERENCES

AND

NVTES

(13 mmoll of ammonium persulfate in portions to 3.5 g of concentrated sulfuric acid such

1.

This solution was added dropwise to

W.

Pinnick, submitted

to J. Org. Chem.

that the temperature was maintained below 15OC.

B. S. Bal and H.

2.

K. Bowden, I. M. Heilbron, E.R.H. Jones

a solution of aldehyde 1 (0.83 g, 5.0 mm011

and B.C.L. Weedon, J. Chem. Sot., 39

dissolved in 15 ml of methanol at O'C.

11946). Ci,%-Ensaturated aldehydes are

The

fairly resistant to Jones oxidation1

reaction mixture was stirred for 6 hours at O°C, diluted with 50 ml of water and extracted

(K. E. Harding and R. C. Liqon, Sun.

with three 30 ml portions

a.

of

ether.

The com-

I Q, 297 (1974)).

In fact, primary

bined ether layers were dried and concentrated

allylic alcohols and benzylic alcohols

to give, after bulb to bulb distillation, 0.71

give aldehydes when reacted with Jones

g of a mixture of the corresponding ester and

reagent: K. E. Harding, L. M, May and K. F. Dick, J. Org. Chem., 40_, 1664 (1975).

the cis-o-methylene lactone: BP 170-173°C (3.1 mm); NMR (CC141 6 3.7 (s, 3H, CO2CH31, 5.5

3.

aliphatic and aromatic aldehydes to acids

(s, IH, Qi=CC02CH3f, 6.1 (s, lH, CH=CC02CH3f, 5.3 (s, lH, CH-C-C02),

Potassium permanganate oxidizes both

but also

5.9 (s, 1H, CH=CCOQ;

will

IR (NaCl) 3450, 2930, 2850, 1773, 1720, 1628,

a,&unsaturated

attack the double bond of acids: I).G. Lee and

1435 cm-l; GC/MS m/e (ester) 198, 181, 166,

3. R. Brownridge, J.Am.Chem.Soc., 9$,

149, 138, 120, 110, 44, 81, 67, 53, 41 (lac-

3033 (1973); K. 13.Wiberg, C. J. Deutsch

tone) 166, 138, 94, 67, 53, 41, 39.

and J. Rocek, J.Am.Chem.Soc., 95_, 3034

The ratio

(1973).

of ester to lactone was approximately 80:20 4.

by Gc and NMR.

-30, 3475 (19651. Note that the preparation of silver oxide where the product

Oxidation of Aldehyde 1 (R=C6HgCH2) with sodium Chlorite

is washed free of base (as in A,G.h.

The aldehyde (0.30 g, 1.2 mmolf was dis-

Busch, J.W.Clark, L-B. Genung, E.F.

solved In 25 ml of tert-butyl alcohol and 6 16 A solution of

Schroeder and W.L.Evans, J.Org.Chem.,

ml of 2-methyl-2-butene. sodium

chlorite

(1.0

dihydrogenphosphats

CJ, I1

1, 1 (193611 is not of any value here.

mmol) and sodium

The mixture of silver oxide and base as

(1.0 g, 0.3 mm011 in 10 ml

in Marshall's paper and in E.Campaigne

of water was added dropwise over a 10 minute period.

J. A. Marshall and N. Cohen, J. Org. Chem.,

and B.F.ntllar, Org.Syn., Coll.Vol.IV,

The pale yellow reaction mixture was

stirred at room temperature overnight. Volatile

921 (1963) is necessary. 5.

(al E. J. Corey, N. W. Tilmman and 8. E.

components were then removed under vacuum,

Ganern, J.Am.chem.soc.,

the residue was dissolved in 30 ml of water

(bl Cinnamaldehyde is oxidized to cin-

90, 5616 (1968).

and this was extracted with two 15 ml portions

namic acid by reaction with silver (II)

of hexane.

oxide and sodium cyanide.

The aqueous layer was acidified to

pH 3 with HC1 and extracted with three 20 ml portions of ether.

The

combined ether layers

H.U.

Plxmick

(a) A Nishihara and I. Kubota, 3. Org. Chem ., 21, 2525 (1968).

et

al 9.

Ib) E. J. Corey

Prepared by the method of Attenburrow: J. Attenburrow, A.F.0. Cameron, J. H.

and G. Schmidt, Tetrahedron Lett., 731

Chapman, R. H. mans,

(1980).

Jansen and T. Walker, J.Chezu.Soc., 1094

(c) C. H. Smith and R. T. HOI.@,

J. Org. Chem., 2,

746 (1957); R.

Kazlauskas, 3. T. Pinhey, J. J. H. Simes

f1952f. 10.

C~mm., 945 (1969).

(cl) R.

A.

Org. Chem., 2,

Ellison,

2757 (1972).

z,

alcohol 1 (R-H)

forms

an uniden-

with TMSCN.

pointing out this method. 12.

The structural assignments are based on

13.

These assignments are based on ccanparison

'H NMR. IR and GC/MS data.

629 (1962).

D. A. Evans, 6. L. Carroll and I.. X.

of the 'H NMR spectrum of the mixture 1 with spectra of authentic ccnnpcunds.

Truesdale, J. Org. Chem., -39, 914 (1974). (a) The aldehyde i fails to oxidize when the Corey procedure5a is used: G. H.

14.

(al B. 0. Lindgren and T. Nilsscn, Acta Chem. Stand,, 27, 888 (1973).

Morton, Ph.D. dissertation, University of Georgia, 1980, p. 7.

free

13.. We thank"Picfessor Wolfgang Kreiser for

(e) H.

Rapoport and W. Nilsson, J. Org. Chem.,

The

tified compound when allowed to react

and T. G. Watson, J. Chem. Sot., Chem.

W. D. Woessner and C. C. Williams, 2.

B. A. Hems, A.B.A.

(b) Kraus has recently reported the use

fb) Another

of 2-methyl-2-butene to take up the

hindered aldehyde (ii) can be oxidized to the corresponding methyl ester in 80%

chlorine: G.A. Kraus and M.J.Taschner,

crude yield.

J,Org.Chem.,

This is the only example

known to the authors of successful oxidation of a hindered aldehyde by this method. We thank Dr. Annand B. Pepperman

45, 1175 (1980);

G. A. Xraus and B. Roth, J. Org. Chem., 2, 15

for details of this conversion.

4825 (19801.

The amounts of E and 2 isomers were determined by GC analysis on a @+l/carbowax column. The acids were analyzed as the methyl esters. We thank Dr. Richard R. Hautala for determinlng these ratios.

16

We thank the Shell Chemical Company for a generous sample of n~-amylene".

OXIDATION OF ALDEHYDES VIA CYANOHYDRINSa

TABLE I.

sIIiOXYNYTRILE f% YIELD) b

ALDEHYOE

ESTER f% YIEmf

(90)

TM

CHO

\ o-

/

C02CH3

(98)

CHo

(PO)

)ip\

(83)

~co*CHJ (8B)c

&CHO

(95)

n

+-o-c :

(871

H 65

ACHO

All yields refer to products purified by distillation. Prepared from the aldehydes with TPSCN under ZnIZ catalysis. The cyanohydrin was prepared by deprotectlon with dilute HCl (98%) and oxidation with !4n02 in benzene containing methanol qave the ester (90%). This ester was contaminated with at least 500 of the starting aldehyde.

B.W. Pinnick

et al

TABLE II. O~IDAPION OF RtDEHYDES WITH SODIUM CHIBRITE"

ACID (a YIELD)

ALDEHYDE

r3

CHU

rCOzH 1951

(90)

\/ tk

0 \/

&HO

@-CO2H

:

/Si

Y

: ;

o/sl

(87)

Y

(901

*CHO

&CO,

2

(92)

)-?I,,“,

a

~11 products are distilled or recrystallized.

b

E/Z = 65/35

'

E/Z = 71,/29 {determined on methyl est%?rs)

c