1260 Bull. Korean Chem. Soc. 2000, Vol. 21, No. 12 Notes
Reductive Oxidation of Acid Chlorides to Aldehydes with Sodium Borohydride and Pyridinium Chlorochromate
JinSoonCha* andDaeYonLee
DepartmentofChemistry and Institute of Natural Science, YeungnamUniversity, Kyongsan 712-749, Korea Received July 19, 2000
The establishment ofa simple, generaland practical method toget aldehydesfromacidchloridesisoneof the most desir- able objects in organicsynthesis.Recently,we reportedthat the oxidation ofalkoxyaluminum intermediates, whichare formed by reductionof acid chlorideswithaluminum hydride, with pyridinium chlorochromate (PCC) or pyridinium di chromate (PDC), affordsaldehydes inexcellentyields.1 But this methoddid not provide areally simple and practical pro cedure. The reducing agent, aluminum hydride, exhibits a very strong reducing power which results in attacking almost all of the organic functional groups.2 Inaddition to this, thereagentshould be prepared just prior to use.2a
Recently, we successfully applied sodiumborohydride, a very mild andeconomical reducing agent, to the reductive oxidation for conversion of carboxylic acids to aldehydes.3 Onthe basis of these results, we decidedto utilize sodium borohydrideas a reducing agent tocarry out reductive oxi
dation to convert acid chlorides to aldehydes. Herein, we introducea new method,whicheffectsthetransformation of acid chlorides to aldehydesinexcellent yields.
NaBH4 / PCC
RCOCI ---a [RCH2O-B—] ---a RCHO
Although there has already been reported that sodium borohydride reduces acidchlorides to alcohols readily,4 we reexamined such reductions in THF or THF-DMF. The reagent reduce both aromatic and aliphatic acid chloridesto thecorresponding alcohols inrefluxingTHF(ProcedureA) or in THF-DMF(1 : 1) at 25o (Procedure B) both in24h : the yields ofalcohols from both procedures were higher than 98%. We appliedsuchprocedurestoreductionof acidchlo rides to the corresponding alkoxyborates stage, and the resultant borates are then subjected tothe oxidationproce dure with PCC.
As shown in Table 1, thisprocedure provides a cleanand convenient conversion of acid chlorides to aldehydes. Both aliphatic and aromatic acid chlorides arereadilyconvertedto thecorresponding aldehydes in excellentyields. The oxida tion of aliphatic borates requires 2.5 equivalents ofPCC, while the oxidation of aromatic borates needs only 10%
excess. However,theoxidationinTHF-DMF-CH2Cl2 (1 : 1 :2) appearstobemoreeffectivethantheprocedureinTHF- CH2Cl2 (1 : 1). Therefore, it appears that the reduction of acid chloridesinTHF-DMF(1 : 1) at25o (ProcedureB) fol lowedby oxidation oftheresultantalkoxyborates with PCC in THF-DMF-CH2Cl2 (1 : 1 : 2) isrecommendable for con
versionof acid chlorides to aldehydes.
This reaction is broadly applicable as many substituents, such as chloro, methoxy, nitro and alkenyl groupsare toler ated. The tolerance of sodium borohydride toward a wide variety of functional groups as wellas its ease of handling and low cost, combined with themildnature of PCCas an oxidizing agent, makes this method simple, general and practical. It is noteworthy that the use of sodium boro- hydride canprovidemoreselectivereactionsthantheuse of aluminum hydride, because sodium borohydride is milder and hence more selective than aluminum hydride.2 More
over, we are nowfree from preparinga solution of alumi
num hydride prior to use. Consequently, this method providesanother useful procedurefor direct conversion of acid chlorides to thecorresponding aldehydes.5,6
Experiment지 Section
All glassware used was driedthoroughly in adryingoven at 130o, assembled hot, and cooled under a stream of dry nitrogen priorto use. Allreactions and manipulations of air and moisture-sensitive materials were carried out under a dry nitrogen atmosphere. All chemicals were commercial products of the highest purity which werecarefully purified by standard methods before use. The acid chlorides were commercial products and purified by distillation. Tetra hydrofuran(THF)was distilledfrom benzophenone-sodium ketyl. Sodiumborohydride(NaBHQ and pyridiniumchloro chromate (PCC)wereused as received fromAldrich Chemi
cal Co. Yields reported in all cases are of analyticallypure compounds. GC analyseswere carried out on a Varian3300 FIDchromatographequipped with a Varian4400 integrator using Carbowax20Mcapillarycolumn.
Reduction of Acid Chlorides (Formation of Alkoxy borate Intermediates). The following two different proce dures for the reduction of acid chlorides to alkoxyborate intermediatesarelisted in Table 1.
ProcedureA: Into on oven-dried,100-mL, round-bottomed flask with aside-arm,fitted with asilicon rubber cap,a mag
netic stirring bar, and a refluxcondenser connected to a mer
cury bubbler was introduced 0.38 g (10 mmol) of sodium borohydride,followed by 18mLofTHF. To thisslurry, 1.40 g (10 mmol) ofbenzoyl chloride was added. The reaction mixture was then brought to a gentle reflux for 24h with vigorous stirring. The reaction mixture was subjected to oxidation (yide infrd).
ProcedureB: Into a 100-mL flask equippedasdescribed above (Procedure A), was added 0.38 g (10 mmol) of sodiumborohydride,followed by 9 mLof THF and 9 mL of
Notes Bull. Korean Chem. Soc. 2000, Vol. 21, No. 12 1261 Table 1. Conversion of Acid Chlorides to Aldehydes by Reductive Oxidation with Sodium Borohydride (NaBHq) and Pyridinium Chlorochromate (PCC)
Acid Chloride Product Reduction Procedurea," Oxidationcd Yield
A or B Time (h) (%)e
Butyryl Isobutyryl Hexanoyl
Trimethylacetyl Trichloroacetyl Cyclopropanecarbonyl Cyclohexanecarbonyl Cinnamoyl
Benzoyl
Butyraldehyde Isobutyraldehyde Hexanal
Trimethylacetaldehyde Trichloroacetaldehyde Cyclopropanecarboxaldehyde Cyclohexanecarboxaldehyde Cinnamaldehyde
Benzaldehyde
1- Naphthoyl 2- Naphthoyl o-Toluoyl
^-Toluoyl
2-Chlorobenzoyl 4-Chlorobenzoyl o-Anisoyl
^-Anisoyl 4-Nitrobenzoyl
1- Naphthaldehyde 2- Naphthaldehyde o-Tolualdehyde
^-Tolualdehyde
2-Chlorobenzaldehyde 4-Chlorobenzaldehyde o-Anisaldehyde
^-Anisaldehyde p-Nitrobenzaldehyde
b b a
b a b b b b b a
b
b b b a b a b a b a b a b a b
6 6 6 2 4 6 6 6 6 6 6 6 6 2 4 6 2 4 6 6 6 6 6 6 6 6 6 6 6 6 6 6
95 96 92 94 71 匕 97(80)
93 61〈 96
95 97 98 97 98 99 94, 9V 99(81)
98 97 96 94 99 91 97 90 98 90 97 90 98 92 97 aTreated with1 equivNaBH4. "Procedure A: reacted for 24h inrefluxing THF;Procedure B:reacted for24hat25o in a THF-DMF (1 :1) mixture solvent.cIn a THF-CH2CZ (1 : 1) or THF-DMF-CHzCh(1 :1:2) mixturesolvent. 'Reacted with 2.5 equivPCC for aliphaticacid chlorides and 1.1 equivfor aromaticacid chloridesatroom temperature. eGC yields; the valuesin parentheses areisolatedyields. fReacted with 2equivPCCatroom temperature.
DMF. Finally, 1.40 g (10 mmol) of benzoyl chloride was added to this solutionofsodiumborohydride with stirring.
The reactionmixture was stirred for 24h at room tempera
ture, and thensubjected to oxidation(vide infrd).
Oxidation of Alkoxyborate Intermediate. To a well- stirred suspension ofPCC (2.4 g, 11 mmol) in methylene chloride (18mL) taken in a 100-mLflask,was added drop
wise the above reaction mixture (from procedure A or B) usinga cannula. The mixture was stirred for 24h at room temperature. GCanalysis ofanaliquot using tridecaneasan internalstandardindicated a yieldof99%.
Isolation of Product Aldehydes. The procedure for the isolation of benzaldehyde in the reaction mixture is illustra
tive. In the usual setup, 60 mmol ofbenzoyl chloride was reduced with 60 mmol ofsodium borohydride in a THF- DMF (1 : 1)mixture solvent (108 mL)atroom temperature for 24h, the same as the procedure B described above. The reactionmixture was then oxidized with PCC (14.3 g, 66 mmol) inmethylene chloride(108 mL) at roomtemperature
for 24h. The mixture was dilutedwith ethyl ether(200mL) and the supernatant liquidwas filtered throughFlorisil®(110 g) contained in a 300-mL sintered glass funnal. The solid residue was triturated with ethyl ether (3 x 50 mL) and passed through the same Florisil column. The filteratewas then concentrated and distilled under reduced pressure to give 5.16 g (81%) of pure benzaldehyde, bp. 63-65o (16 mm). The 1H NMR spectrumagreedwith that ofanauthen tic sample.
Acknowledgment. This work was supported by Korea Research Foundation Grant(KRF-99-005-D00054).The 1H NMR spectrawere recorded on aBruker AMX 300 spec trometer attheYeungnamUniversityInstrumentalAnalysis Center.
References
1. Cha, J. S.; Kim, J. M.; Chun, J. H.; Kwon, O. O.; Kwon, S.
Y; Han, S. W. Org. Prep. Proced. Int. 1999, 31, 204.
1262 Bull. Korean Chem. Soc. 2000, Vol. 21, No. 12 2. (a) Brown, H. C.; Yoon, N. M. J. Am. Chem. Soc. 1966,
88, 1464. (b) Cha, J. S.; Brown, H. C. J. Org. Chem. 1993, 58, 4732.
3. Cha, J. S.; Lee, D. Y; Kim, J. M. Org. Prep. Proced. Int.
1999, 31, 694 .
4. (a) Chaikin, S. W.; Brown, W. G. J. Am. Chem. Soc. 1949, 71, 122. (b) Babler, J. H.; Invergo, B. J. Tetrahedron Lett.
Notes
1981, 22, 11. (c) Babler, J. H. Syn. Commun. 1982, 12, 839.
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1948, 4, 362. (b) Cha, J. S. Org. Prep. Proced. Int. 1989, 21, 451.
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