Acetyl transfer reactions on A1P04-A1203

ANTONIO COSTA AND JUAN MARTIN RIEGO Department of Chemistry, Utliversitat de les Illes Bnlenrs, E-07071 Palmn de Mallorca, Spain

Received March 10, 1987

ANTONIO COSTA and JUAN MARTIN RIEGO. Can. J. Chem. 65, 2327 (1987). An efficient acetylation of alcohols and aliphatic amines promoted by the AlP0,-AI2O3/ethyl acetate system is described.

The solid catalyst acts, at least in part, as the acetyl carrier.

ANTONIO COSTA et JUAN MARTIN RIEGO. Can. J. Chem. 65, 2327 (1987). On dtcrit une mtthode efficace d'acCtyler les alcools et les amines aliphatiques qui est catalysCe par le systkme AlP04-

A1203/acCtate d'Cthyle. Le catalyseur solide agit, au moins en partie, comme porteur de groupements acttyles. [Traduit par la revue]

Introduction Derivatization of hydroxy and amino groups to the corres-

ponding acetates and acetamides is a very common transforma- tion in organic chemistry. Among the plethora of published methods, one of the most convenient is that of Posner et al. ( I ) , which allows the chemoselective acetylation of primary alco- hols under heterogeneous conditions, i.e., with ethyl acetate over commercial at room temperature.'

Continuing our work on solid acids (for a general discus- sion, see ref. 3), we would here like to report the use of synthetic A1P04-A1203 for the mild and efficient acetylation not only of aliphatic primary and (or) secondary alcohols but also of aliphatic amines.

Experimental The typical experimental procedure involves stirring a solution of

the substrate (10mmol) in dry ethyl acetate (150mL) over 10g of A ~ P O , - A ~ ~ O ~ . ~ After 24 h at room temperature (or reflux in the case of secondary alcohols or aliphatic amines) work-up is simply carried out by filtration, solvent evaporation, and final distillation or recrys- tallization.

TABLE 1. AlP0,-A1203 promoted acetylation of alcohols

Temperature Yield Entry Alcohol ("c) (%la

- -

n-C6Hl 30H tt-C16H330H PhCH20H HO(CHZ)ZO(CHZ)ZOH HO(CH2),0H Cyclohexanol Cholesterol Cholesterol CH3CH(OH)CH20H CH3CH(OH)CH2CH2CH20H CH3CH(OH)CH2CH2CH(OH)CH3 (Z)-CH3CH2CH=CHCH2CHaH Geraniol

CH20H I

OMe

Results and discussion $H,OH As shown in Table 1, room temperature acetylation works

well for primary monoalcohols and diols (entries 1-5). Reflux- ing is, however, required to drive the reaction of secondary alcohols to completion (entries 6-8). This difference in reac- tivity may be of utility for the chemoselective acetylation of primary alcohols. In accordance with this, in a competitive experiment camed out with an equimolar mixture of 1- and 2-pentanol under standard conditions (room temperature) only 1-pentyl acetate4 was isolated in 75% yield (based on 1-pentanol). Not unexpectedly, however, 1,2- and 1,4-diols gave the cor- responding diacetates (entries 9 and lo), probably because of the easy intramolecular migration of the acetate group.

Mild acetylation of labile molecules such as allylic and homo- allylic alcohols (entries 12 and 13) was also successful, as it was with MOM (methyl-oxy-methyl) protected hydroxyalkyl phenol ethers (entry 14).

o or an excellent review covering organic reactions at alumina surfaces, see refs. 2 and 8.

'For recent applications of the A1P04-A1203 system, see ref. 4n; for synthesis and applications of other aluminophosphates, see ref. 46.

3 ~ 1 ~ ~ , - ~ 1 2 0 3 can be handled in open atmosphere without appre- ciable loss of activity. See directions for preparation in ref. 5.

,2-pentyl acetate could not be detected by gc or I H nrnr analysis of the crude mixture.

I

OMe

16 H2N(CH2)20H 17 H2N(CH2)50H 18 tl-C4H9NH2 19 PhNHz 20 p-MeO-PhNHr

"Isolated yields of spectroscopically pure acetates. bThe product was the corresponding diacetate. 'After column chromatography of crude product. dThe product was 3-hydroxy-4-methoxy-benzyl acetate.

On the other hand, whilst our catalyst does not promote the acetylation of phenols (entry 15) and aromatic arnines (entries 19 and 20), it did facilitate, however, the conversion of ali- phatic amines and aminoalcohols (6) to the corresponding acetyl derivatives (entries 16- 18).

These results are in sharp contrast with those reported by Posner (1), who describes A1203 as being capable of acylating aromatic arnines but inefficient for aliphatic amines.

Although the understanding of the mechanism of acetyl transfer is restricted by lack of information about the nature of the actual acetylating agent (7), we felt that acyl transfer might

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CAN. J. CHEM. VOL. 65, 1987

FIG. 1. Suggested mechanism for transesterification over AIP0,- AI2o3.

5 4 3 2 1 0 PPH

TMS

1 FIG. 2. The 'H nmr spectrum of supernatant CDCI3 over an acety-

lated catalyst before and after addition of CD30D.

Evidence in support of this mechanistic hypothesis was ob- tained by examining (gc, ' H nmr) the behaviour of a sample of "acetylated catalyst" before and after the addition of alcohols. Thus treatment of a sample of AlP04-A1203 with n-butyl ace- tate (12 h , reflux) allowed us to unambiguously demonstrate (gc, 'H nmr) the presence of n-butanol in the supernatant. Furthermore, filtration of the mixture followed by thorough drying of the solid under high vacuum (0.003 Torr, 1 0 h ; 1 Torr = 133.3Pa) yielded an acetylated catalyst that reacted with benzyl alcohol in toluene (room temperature, 2 4 h) providing the expected benzyl acetate (gc, ' H nrnr, ir). The presence of some n-butanol was also observed in the reaction mixture.

In a further experiment a sample of thoroughly dried acetylated catalyst (obtained as above by treatment of the solid catalyst with ethyl acetate) was suspended in CDC13. Its ' H nmr spec- trum (bottom, Fig. 2) indicated the presence of only trace amounts of ethyl acetate. After addition of C D 3 0 D to the mixture, the spectrum (top, Fig. 2) clearly showed signals corresponding to residual ethanol5 and ethyl acetate. It there- fore appears that acetylations promoted by A1P04-A1203 take place, at least to some extent, by a mechanism of acetyl transfer mediated by the solid catalyst acting as a carrier.

In summary, acetylation of alcohols and aliphatic amines can be carried out efficiently by the mild A1P04-A1203/ethyl acetate heterogeneous system, thus complementing the acylat- ing capacity of alumina (1).

1. G. H. POSNER, S. S. OKADA, K. A. BABIAK, K. MIURA, and R. K. ROSE. Synthesis, 789 (1986); G. H. POSNER and M. ODA. Tetrahedron Lett. 22, 5003 (1981).

2. G. H. POSNER. Angew. Chem. Int. Ed. Engl. 17, 487 (1978). 3. K . TANABE. Solid acids and bases. Their catalytic properties.

Academic Press, New York. 1970. 4. ( a ) J. M. CABELLO, J . M. CAMPELO, A. G A R C ~ A , D. LUNA, and

J. M. MARINAS. J . Org. Chem. 49, 5195 (1984); J . RIEGO, A. COSTA, and J . M. SAA. Chem. Lett. 1565 (1986). (b) S. T. WILSON, B. M. LOK, C. A. MESSINA, and E. M. FLANIGEN. J. Am. Chem. Soc. 104, 1 146 (1982).

5. A. COSTA, P. M. DEYA, J. V. SINISTERRA, and J . M. MARINAS. Can. J . Chem. 58, 1266 (1980).

6. R. B. MARTIN and A. PARCEL. J . Am. Chem. Soc. 83, 4835 (1961); G. H. PORTER, H. M. RYDON, and J. A. SCHOFIELD. J . Am. Chem. Soc. 82, 2686 (1960); A. P. PHILLIPS and R. BALTZLY. J . Am. Chem. Soc. 69, 200 (1947).

7. J . C. BUCHHOLZ and G. A. SOMORJAI. ACC. Chem. Res. 9, 333 (1976).

8. A. MCKILLOP and D. W. YOUNG. Synthesis, 481 (1979), and references cited therein.

take place first on the hydroxyl groups of the catalyst surface (8), thus generating a mixed anhydride-like structure that would eventually transfer the acetyl group to incoming nucleophiles (see Fig. 1).

S~nambiguous evidence for the presence of residual ethanol ad- sorbed on the surface of the catalyst has been obtained by examining the 'H nmr spectrum (before and after addition of CD30D) of a sample of thoroughly dried catalyst previously treated with ethanol.

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