Preparation of Aldehydes from Carboxylic Esters by Reductive Oxidation with Lithium Aluminum Hydride and Pyridinium Chlorochromate

Notes Bull. Korean Chem. Soc. 1999, Vol. 20, No. 11 1373

Preparation of Aldehydes from Carboxylic Esters by Reductive Oxidation with Lithium Aluminum Hydride and Pyridinium Chlorochromate

or Pyridinium Dichromate

JinSoon Cha,* JoongHyun Chun, Jong MiKim,DaeYonLee,andSungDongCho'

Department of Chemistry, Yeungnam University, Kyongsan 712-749, Korea 'Department of Chemistty, Chosun University, Kwangju501-759, Korea

Received August4, 1999

Thereduction of carboxylic esterstoaldehydes is one of the most useful synthetic transformation in organic synthe­ sis. Therefore, many useful reduction methods have been reported for such conversions.1However, common reducing agents such as aluminumhydride usually reducecarboxylic esters to alcohols.2,3 Very recently, we reported that the oxi­

dation of alkoxyaluminumintermediates, which areformed by reductionof primary alcohols4 or carboxylic esters5 with aluminumhydride,by pyridinium chlorochromate (PCC) or pyridinium dichromate (PDC) gives almost quantitative yields of the corresponding aldehydes (Eq. 1). These results indi­ cate that both alkoxyaluminum intermediates (1 and2) are structurallysame : theintermediates are composed of primary alkoxy groupbonded to aluminum atom. Therefore, wecan assume that any primary alkoxy moiety attached to alumi­ num atommayundergotheoxidation toafford

3RCH2OH AlH3 >(RCH2O)sAl+ H2

T

1 RCOOR’ AlH3 >［RCH2O-AK］

2 1 or 2 PCC or PDC >RCHO

~100%

(1) thecorresponding aldehyde function. Fromthis structural point ofview, we decided to utilize lithium aluminum hydride (LAH) insteadofaluminum hydride in suchprocedure for the conversion of carboxylic esters toaldehydes. Herein, we introduce anew method,whicheffectsthetransformation of carboxylic estersto aldehydesin highyields at roomtemper­

ature.

ResultandDiscussion

First of all,we examinedthe possibilityof thealkoxyalu­ minateintermediate (3), whichis formedby thereaction of primaryalcohols with LAH,beingoxidized by PCC or PDC to the corresponding aldehydes (Eq. 2). Benzyl alcohol and 1-hexanolwere examined as representative ofprimary alco­

hol.

4RCH2OH O^o>> >［卩얠²。₎4用］淄紂RCHO ⑵

Tetraalkoxyaluminatesare readily prepared fromthe reac­

tionofalcohols with LAH at 0 oC. Both aromaticand ali­ phatic alkoxyaluminatesexamined were readily oxidized with

PCCor PDCin a mixedsolventof THF and methylenechlo­ ride at room temperature, providing essentially quantitative yields ofaldehydesdetermined by GCanalysis.

Such results accelerated us to examine the conversion of carboxylic ester to aldehydebythisprocedure.Ifcarboxylic esteris reduced to the alcohol stage by LAH under these reaction conditions,6 the resulting intermediate in the reac­

tionmixture wouldcontainalkoxy moietyas in3. Actually, carboxylicesterswere readily reduced tothecorresponding alcohol stage byLAH (0.5 equiv)atroomtemperature (Eq.

3).6 Even though the final reduction intermediate has not been identified, it is believed that4 could be the possible structure.

RCOOR’ 0.5 LiNH4 > ［RCH2O-A-］旦으］RCH2OH (3) 4

The method involves the rapid reduction of carboxylic ester with LAH, followed by oxidation of the resultant alkoxyaluminate intermediate (4) (without isolation) with PCC or PDCatroomtemperature(Eq. 4).

4 PCC 变DC > RCHO

rt

3

6 h

As listed inTable 1, theprocedureconvertsaliphaticesters to aldehydesin 6 h at roomtemperaturein yields of92-97%.

Actually, there is no difference in the yields of aldehydes with PCC orPDC. Similarly, o;,^-unsaturatedcarboxylic esters, such asethyl crotonate and ethylcinnamate, affordtheole­ finic aldehydes in 94-96% yields. The conversion of aro­

matic esters by this procedure provides the corresponding aldehydes in 92-99% yields. The unsubstituted benzoates with avariety ofalcoholportionsare converted to benzalde­

hyde inyields of 96-99%, showing no bias in the yields.

Alkyl-substituted benzoate, such as 3- and4-methylbenzoates, afford thecorrespondingaldehydesin94-96% yields. Finally, chloro and nitro groups on the benzene ring are readily accommodated and gavealdehydesin better than92% yield.

This reactionis broadly applicable tolerating many sub­ stituents,such as chloro,nitro, and alkenegroups.The reac­

tivities of LAH toward a carboxylic ester function and of PCC and PDC toward alkoxyaluminateintermediate (4) are quite similar to thecase ofaluminumhydride. However, the general reductionpatterns of these tworeducingagents are quite different.2,5,7 The difference is basically derived from the fact that lithium aluminumhydride is basicand alumi-

1374 Bull. Korean Chem. Soc. 1999, Vol. 20, No. 11 Notes Table 1. Conversion of Carboxylic Esters to Aldehydes by Oxidation

of Alkoxyaluminate Intermediate (4) with Pyridinium Chlorochromate (PCC) or Pyridinium Dichromate (PDC) at Room Temperature"

Ester Product t

Reac- ion time

(h)

PCC PDC

Yield (%)c

Yield (%)c

Ethyl butyrate Butyraldehyde 6 92 93

Ethyl caproate Hexanal 6 95(80) 95

Ethyl caprylate Octanal 6 96 97

Ethyl isobutyrate Isobutyraldehyde 6 95 94 Ethyl isovalerate Isovaleraldehyde 6 94 96

Ethyl crotonate Crotonaldehyde 6 96 94

Ethyl cinnamate Cinnamaldehyde 6 95 95

Methyl benzoate Benzaldehyde 3 97 99

Ethyl benzoate Benzaldehyde 3 98(82) 97(78)

Phenyl benzoate Benzaldehyde 3 96 98

Methyl 3-methylbenzoate 3-Methylbenzaldehyde 3 96 94 Ethyl 4-methylbenzoate 4-Methylbenzaldehyde 3 95 95 Methyl 4-chlorobenzoate 4-Chlorobenzaldehyde 3 97 95 Ethyl 4-nitrobenzoate 4-Nitrobenzaldehyde 3 94 92 aEster: oxidant = 1: 2.2.”In a THF-methylene chloridemixture solvent.

cGCyields. The numeralsin parentheses areisolated yields.

num hydride is acidic.8 For example,thereduction of caproni- trile with AlH3 resultsin thecleanconversion to hexylamine withoutanyhydrogenevolution, whereasthereductionwith LAHevolves ca. 0.2 equivof hydrogen andundesirable side reaction occurs. Therefore, when a carboxylic ester function in a complexmolecule is applied to thisreductive oxidation procedure, one must consider which reducing agentis ame­

nable. However, in thecase where thedifferencein the reduc­

tion pattern between lithium aluminum hydrideand aluminum hydrideisnot a problem,the use of lithiumaluminum hydride must be more convenient and economical than the use of aluminum hydride: all fourequivalents of hydridein lithium aluminumhydrideare utilized for thereduction.

It isworthwhile to comparethis reductive oxidation proce­ dure with thereduction procedure using diisobutylaluminum hydride(DIBAH),1-a themostwidely used methodin organic synthesis:thepresentprocedure isperformedatambient tem­

perature, buttheDIBAHreduction runsat -70o.Furthermore, thealdehyde yields obtained byDIBAHare not general(50­ 90%), whereasthe yields achievedbythe present procedure arehigher than95%. Consequently, thisreductive oxidation proceduremust befarsuperiortotheDIBAH reduction.1-a

Experiment지 Section

Allreactionswere performed underadry N2 atmosphere.

All chemicals used werecommercialproductsof thehighest purity available; THFwas dried over 4 A molecularsieve and distilledfrom sodium-benzophenone ketyl prior to use.

Methylene chloride was also driedover P²O⁵ and distilled.

1HNMR spectra wererecordedona Bruker AMX 300spec­ trometer. Gas chromatographic analyses were carried out with a Varian3300Chromatograph.

Reduction of EsterswithLithiumAluminum Hydride. Thefollowing procedure for the reaction ofethylbenzoate with PCC is representative. An oven-dried, 250 mL flask, fitted with a side arm and a reflux condenser connected to a mercury bubbler, was flushed with dry nitrogen and then maintained under a static pressure of nitrogen. Theflask was charged with a1.0 Msolutionof lithiumaluminumhydride (31 mL, 31 mmol) in THF. To the stirred solutionat 0 oC, ethyl benzoate (9.61 g, 61 mmol)was added dropwise and the reaction mixturewas stirred furtherfor 3 hat room tem­ perature. To a well-stirred suspension of PCC (29 g, 134 mmol) in methylene chloride (200mL) taken in a 500 mL flask equipped as described above, is added dropwise the above solution of alkoxyaluminate intermediate (4) in THF using a cannula. The mixture was stirred for 3 h at room temperature. The small portion ofthis mixture was trans­

ferred toa vial and dodecane was addedas an internal stan­ dard. GCanalysis using acapillary columnofCarbowax20 M indicated thepresenceof benzaldehyde in a yield of 98%.

Isolation ofAldehyde Products. The rest ofthe reac­

tion mixture (60 mmol) was diluted with ethyl ether (120 mL). The supernatant liquid isfiltered through Florisil® (120 g)containedin a 300mL sinteredglassfunnel;the solid res­

idue is triturated with ethyl ether (3 x 30 mL) and passed throughthesame Florisilcolumn. Thefiltrateis concentrated and distilledunder reduced pressure to givepure benzalde­

hyde (5.22 g, 82%):bp 62-63 oC (15 mm). The 1H NMR spec­

trumagreed withthat of an authenticsample.

Analogous procedures are used for the synthesis of the other aldehydes listedin Table 1. In the case of PDC as an oxidant used, actuallythesameprocedurewasadopted.

Acknowledgment. Theauthorswishtoacknowledgethe financialsupportedoftheKoreaResearchFoundationmade in the program year of1997.

References

1. (a) Zakharkin, L. I.; Khorlina, I. M. Tetrahedron Lett. 1962, 619. (b) Idem. Izv. Akad. Nauk. SSSR, Ser Khim. 1964, 465.

(c) Muraki, M.; Mukaiyama, T. Chemistry Lett. 1975, 215.

(d) Yoon, N. M.; Shon, Y S.; Ahn, J. H. Bull. Korean Chem.

Soc. 1992, 13, 199. (e) Yoon, N. M.; Ahn, J. H.; An, D. K.

Ibid. 1992, 13, 339. (f) Yoon, N. M.; Ahn, J. H.; An, D.

K.; Shon, Y. S. J. Org. Chem. 1993, 58, 1941. (g) Cha, J.

S.; Min, S. J.; Lee, J. C.; Lee, H. S.; Lee, S. E. Org. Prep.

Proced. Int. 1992, 24, 359. (h) Cha, J. S.; Kim, J. M.;

Jeoung, M. K.; Kwon, O. O.; Kim, E. J. Ibid. 1995, 27, 95.

2. Brown, H. C.; Yoon, N. M. J. Am. Chem. Soc. 1966, 88, 1464.

3. Cha, J. S.; Brown, H. C. J. Org. Chem. 1993, 58, 3794.

4. Cha, J. S.; Kim, M. G.; Kim, J. M.; Kwon, O. O.; Chun, J.

H.; Cho, S. D. Bull. Korean Chem. Soc. 1998, 19, 724.

5. Cha, J. S.; Kim, J. M.; Chun, J. H.; Kwon, O. O.; Lee, J.

C. Bull. Korean Chem. Soc. 1998, 19, 1301.

6. (a) Brown, W. G. Org. React. 1951, 6, 469. (b) Brown, H.

C.; Weissman, P. M.; Yoon, N. M. J. Am. Chem. Soc.

1966, 88, 1458.

7. (a) Yoon, N. M.; Brown, H. C. Ibid. 1968, 90, 2927. (b) Cha, J. S.; Brown, H. C. J. Org. Chem. 1993, 58, 3974.

8. Jorgenson, M. J. Tetrahedron Lett. 1962, 559.