Method of preparing 3-(3-methyl-2-buten-1-yl)-2,4-pentanedione and related dicarbonyl compounds

A method for preparation of a dicarbonyl compound of the following formula ##STR1## by reacting a conjugated alkadiene compound of the formula ##STR2## with a 1,3-dicarbonyl compound of the formula ##STR3## in the presence of an acid catalyst. The products of the method are useful in the preparation of compounds such as vitamins A and E, various carotenoids, Retin A, dehydrolinalool, pseudoionone, citral, and linalool.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention describes a method for preparing dicarbonyl compounds 
of the general formula: 
##STR4## 
In one embodiment, "R" is CH.sub.3 and "Z" is COCH.sub.3, and a product 
known as 3-(3-methyl-2-buten-1-yl)-2,4-pentanedione is formed, shown in 
the following formula: 
##STR5## 
In another embodiment, "R" is CH.sub.3 and "Z" is CO.sub.2 CH.sub.2 
CH.sub.3, and the product, ethyl 2-(3-methyl-2-buten-1-yl)-3-oxobutanoate, 
is formed, shown in the following formula: 
##STR6## 
2. Description of Related Art 
(a) Prior Art Processes for Preparation of Dicarbonyl Compounds (7) 
The invention relates to a new method for conversion of isoprene (or other 
2-alkyl-1,3-butadienes) to dicarbonyl compounds of the general structure 
(7). For previous syntheses of 3-(3-methyl-2-buten-1-yl)-2,4-pentanedione 
(7a), see the following: 
(a) European Patent Appl. EP 44,771 (Jan. 27, 1982) [Chem. Abstracts 1982, 
96, 199115b]. 
(b) J. A. Miller, et al., J. Chem. Soc. Perkin I 1972, 692. 
(c) H. Pommer, et al., Justus Liebigs Ann. Chem. 1969, 729, 52. 
(d) German patent 1,914,376 (Oct. 1, 1970) [Chem. Abstracts 1970, 73, 
120090h]. 
(e) U.S. Pat. No. 3,998,872 (Dec. 21, 1976) [Chem. Abstracts 1977, 86, 
89179m]. 
(f) J. Marquet and M. Moreno-Manas, Synthesis 1979, 348. 
(g) Chem. Abstracts 1980, 93, 26559j. 
(h) M. Moreno-Manas and A. Trius, Tetrahedron 1981, 37, 3009. 
(i) J. Marquet, et al., Tetrahedron Lett. 1988, 29, 1465. 
All of the above routes involved multi-step processes and/or costly 
reagents; and all involved the formation of substantial amounts of 
undesirable isomeric by-products. Furthermore, most of these previous 
syntheses of 3-(3-methyl-2-buten-1-yl)-2,4-pentanedione (7a) involved the 
preparation of expensive intermediates [e.g., (CH.sub.3).sub.2 
C.dbd.CHCH.sub.2 Cl or (CH.sub.3).sub.2 C.dbd.CHCH.sub.2 OH] from isoprene 
prior to the chemical step used to generate diketone (7a). For two notable 
exceptions, see references (a) and (e) cited above. However, both of the 
latter processes afforded unattractive mixtures of products and required 
costly metallic catalysts. 
For previous syntheses of ethyl 2-(3-methyl-2-buten-1-yl)-3-oxobutanoate 
(7b), see: 
(a) H. Pommer, et al., Justus Liebigs Ann. Chem. 1969, 729, 52. 
(b) European Patent Appl. EP 44,771 (Jan. 27, 1982) [Chem. Abstracts 1982, 
96, 199115b). 
(c) French patent 2,567,511 (Jan. 17, 1986) [Chem. Abstracts 1986, 105, 
171857a]. 
(d) A. A. Petrov, et al., Zh. Obshch. Khim. 1963, 33, 427 [Chem. Abstracts 
1963, 59 431c]. 
(e) U.S. Pat. No. 3,420,827 (Jan. 7, 1969) [Chem. Abstracts 1969, 70 
67626x]. 
(f) S. Julia and G. Linstrumelle, Bull. Soc. Chim. France 1966, 3490. 
(g) Czech. patent 112,243 (Oct. 15, 1964) [Chem. Abstracts 1965, 62, 
13049e]. 
(b) Utility of Dicarbonyl Compounds (7) 
The dicarbonyl compounds (7) may be used in the synthesis of pseudoionone 
(2) (systematically named as 6,10-dimethyl-3,5,9-undecatrien-2-one), 
according to the following reaction sequence: 
##STR7## 
Pseudoionone (2) is a costly specialty chemical that is used in the 
manufacture of .alpha.-ionone (3), used in perfumery, and .beta.-ionone 
(4), used in perfumery as well as in the manufacture of vitamin A, the 
anti-acne drugs tretinoin (sold by Ortho Pharmaceutical Corp. under the 
registered trademark Retin-A) and isotretinoin (sold by Hoffmnan-LaRoche 
Inc. under the registered trademark Accutane), and several widely used 
carotenoids, including beta-carotene and canthaxanthin. Pseudoionone can 
also be used in the manufacture of vitamin E [see: U.S. Pat. No. 5,349,071 
(Sep. 20, 1994)] since it is easily converted to isophytol. 
One of the earliest routes to pseudoionone involved a crossed-aldol 
condensation between citral (1) and acetone as shown below: 
##STR8## 
References: Organic Syntheses, Collective Volume 3, page 747; H. Hibbert 
and L. T. Cannon, J. Am. Chem. Soc., 46, 119-130 (1924). The major 
disadvantage to this route is that it involves use of the costly specialty 
chemical citral (1), systematically named as 3,7-dimethylocta-2,6-dienal, 
which is manufactured in a multi-step process generally involving at least 
five transformations. Once pseudoionone (2) has been obtained, however, it 
can be converted in high yield and in one step to either .alpha.-ionone 
(3) or .beta.-ionone (4) with little additional cost. 
##STR9## 
A very attractive alternative route to a structural analogue (18) of 
pseudoionone that avoids the use of citral has been developed by BASF and 
is outlined below: 
##STR10## 
Although BASF's C-13 polyenone (18) can be converted to .beta.-ionone, 
polyenone (18) does not possess the correct structure one would need to 
prepare carotenoids such as lycopene, the red coloring matter of tomatoes. 
Lycopene has recently been shown to have many useful properties, 
especially in giving protection against prostate cancer, heart disease, 
and degenerative eye diseases. Furthermore, the C-8 unsaturated ketone 
(14) in BASF's route does not possess the proper structure for manufacture 
of the specialty chemicals linalool (widely used in perfumery) and citral 
(used extensively in the flavor and fragrance industries). Both of the 
latter specialty chemicals can be manufactured using known industrial 
processes starting with the unsaturated ketone (9) obtained in the route 
of the presently disclosed invention (see section 2(c), below). Likewise, 
carotenoids such as lycopene are readily prepared from our unsaturated 
ketone intermediate. An additional advantage of the disclosed process for 
obtaining C-8 unsaturated ketone (9) from isoprene is that fact that the 
overall yield is higher and the process is easier to conduct (e.g., 
atmospheric pressure, room temperature) than the one developed by BASF. 
(c) Other Uses of Unsaturated Ketone (9), Produced as an Intermediate in 
the Synthesis of Pseudoionone 
Unsaturated ketone (9), shown as a product in step (b) of Scheme I above, 
may also be used to produce linalool (19) (3,7-dimethyl-1,6-octadien-3-ol, 
widely used in perfumery) and citral (1) (used extensively in the flavor 
and fragrance industries), according to the following reaction sequence: 
##STR11## 
SUMMARY OF THE INVENTION 
The present invention describes a method for preparing dicarbonyl compounds 
(7), which provides step "(a)" of Reaction Scheme I for the preparation of 
pseudoionone (2). The method is summarized by the following: 
##STR12## 
In one embodiment, R.dbd.CH.sub.3 and compound (5) is isoprene, 
##STR13## 
and compound (6) is 2,4-pentanedione (acetylacetone), and the product (7) 
is 3-(3-methyl-2-buten-1-yl)-2,4-pentanedione (7a): 
##STR14## 
Acetylacetone (6a) is used industrially to remove trace metals during waste 
water treatments. It also may be used to form various organometallic 
additives, or as drying agents for varnishes and printer's inks. 
Acetylacetone (6a) can be prepared by either of the following methods: 
##STR15## 
In another embodiment, R.dbd.CH.sub.3 and compound (5) is isoprene, 
Z.dbd.CO.sub.2 R', R'.dbd.CH.sub.3 CH.sub.2, and compound (6) is ethyl 
acetoacetate, and the product is ethyl 
2-(3-methyl-2-buten-1-yl)-3-oxobutanoate (7b): 
##STR16## 
Ethyl 2-(3-methyl-2-buten-1-yl)-3-oxobutanoate (7b) may be converted to 
compound (9) according to the following reaction: 
##STR17## 
The mechanism of the disclosed process is believed to involve the 
protonation of isoprene (5) (R.dbd.CH.sub.3) by a suitable acid catalyst 
followed by trapping of a thereby generated "prenyl cation" with a 1,3 
dicarbonyl reagent (6) that has an appreciable "enol" content to afford 
dicarbonyl compound (7) in good yield. 
The formation of the enol form of compound (6) is illustrated by the 
following equations: 
##STR18## 
The formation of the prenyl cation is illustrated by the following 
reaction: 
##STR19## 
The "prenyl cation," formed by the addition of a proton to isoprene, is 
trapped by the "enol form" of reactant (6) (see keto-enol equilibrium 
reactions, above) to give the desired product (7). If the prenyl cation 
reacts with isoprene, "polymeric" terpene products (i.e., C-10, C-15, 
etc.) are obtained. 
The novel process requires the following reagents and reaction conditions: 
(a) a conjugated alkadiene of general structure (5). Isoprene 
(R.dbd.CH.sub.3) is the preferred diene. 
(b) a 1,3-dicarbonyl compound possessing a significant "enol" content. Such 
a reactant must be used in molar excess and serves as the solvent. No 
other solvent is required. Suitable dicarbonyl compounds (6) include 
acetylacetone (2,4-pentanedione) (6a) and ethyl acetoacetate (6b). Since 
the latter compound exhibits a smaller enol content than does 
acetylacetone, it is not as effective at trapping the "prenyl cation," and 
the process proceeds more slowly in ethyl acetoacetate than in 
acetylacetone. Furthermore, use of ethyl acetoacetate as the solvent for 
this process requires the absence of significant amounts of water since 
its ester functionality is subject to hydrolysis. Hence, acetylacetone is 
the preferred solvent/reactant. If one uses ethyl acetoacetate as a 
reactant, polyphosphoric acid is a preferred catalyst. 
(c) The process requires an acid catalyst selected from one of the 
following categories: 
(i) an inorganic acid possessing a K.sub.a (relative to water) that is 
greater than 10.sup.-3. Phosphoric acid (85-100%) and polyphosphoric acid 
are preferred catalysts. Aqueous sulfuric acid (H.sub.2 SO.sub.4) can also 
be used to catalyze this process, although it is not a preferred catalyst. 
(ii) an organic acid possessing a K.sub.a (relative to water) that is 
greater than 10.sup.-1. Sulfonic acids (RSO.sub.3 H) are useful catalysts 
for this process--e.g., p-toluenesulfonic acid monohydrate (Example VI). 
(iii) The acid catalyst does not have to be soluble in the reaction 
mixture. For example, strongly acidic resins can be used to catalyze the 
process (Example VII). 
(iv) Hydrochloric acid (HCl), although it is a strong acid, cannot be used 
to catalyze this process (Example V). Although the "prenyl cation" is 
generated when HCl protonates isoprene, the chloride anion traps the 
intermediate--thereby generating (CH.sub.3).sub.2 C.dbd.CHCH.sub.2 Cl, not 
the desired product (7). 
(d) Dropwise addition of isoprene over a period of several hours to the 
dicarbonyl compound (containing an acid catalyst) is required for a good 
yield (see discussion of formation of prenyl cation, above). 
(e) The reaction occurs at room temperature if one uses a strong acid 
catalyst such as p-toluenesulfonic acid or even the more weakly acidic 
polyphosphoric acid. If phosphoric acid is used in the presence of H.sub.2 
O (e.g., 85% H.sub.3 PO.sub.4), the reaction is slower and requires gentle 
heating (60-90.degree. C.). Temperatures that exceed 140.degree. C. (i.e., 
the boiling point of acetylacetone) are not useful in this process--i.e., 
too many side-reactions occur. 
Advantages of the disclosed process include the following: 
(a) No costly raw materials are utilized. 
(b) The process avoids the use of organic halides. 
(c) Mixtures of isomeric products are not a serious problem in the 
conversion of isoprene to dicarbonyl compound (7). The latter product is 
easy to purify since (7a) is soluble in dilute aqueous NaOH (in contrast 
to the by-products). 
(d) The disclosed process generates a product (7), and subsequently (9) 
that possesses the correct structure for the preparation of valuable 
specialty chemicals such as linalool, citral, pseudoionone, and lycopene. 
BASF's route to "methyl-heptenone" generates an isomeric compound (14) 
that can only be used to prepare .alpha.- or .beta.-ionone. 
The disclosed reaction is surprisingly useful in producing dicarbonyl 
compound (7) in high yield. The results are unexpected and nonobvious for 
a number of reasons: 
(a) J. A. Miller and coworkers have reported [J. Chem. Soc. Perkin I 1972, 
692] that diketone (7a) readily cyclizes, even under mildly acidic 
conditions, to give 5-acetyl-3,4-dihydro-2,2,6-trimethyl-2H-pyran (8) in 
high yield, according to the following reaction: 
##STR20## 
This prior art teaches away from attempting to prepare compound (7) under 
acidic conditions. Miller et al. reported an 84% yield of (8) after a 
reaction time of 90 minutes at 0.degree. C. The disclosed process 
surprisingly produces very little, if any, of this heterocyclic compound 
(8) even after prolonged reaction times. 
(b) The conversion of (5) to (7) is acid-catalyzed. However, carboxylic 
acids such as oxalic acid dihydrate (K.sub.a =5.4.times.10.sup.-2) and 
dichloroacetic acid (K.sub.a =5.5.times.10.sup.-2) that are stronger than 
phosphoric acid (K.sub.a =7.1.times.10.sup.-3) failed to catalyze the 
process even at 80.degree. C.--i.e., no reaction occurred! (References for 
these acidity values: "The Merck Index," Ninth Edition, page 956; Organic 
Chemistry, Third Edition, page 600, by Morrison and Boyd.) 
DETAILED DESCRIPTION OF THE INVENTION 
The following examples are presented for purposes of illustration and 
should not be construed as limiting the invention which is delineated in 
the claims.

EXAMPLE I 
Preparation of 3-(3-Methyl-2-buten-1-yl)-2,4-pentanedione by Treatment of 
Isoprene with 2,4-Pentanedione Containing Polyphosphoric Acid as a 
Catalyst 
Polyphosphoric acid (600 mg), 2,4-pentanedione (5.0 mL), and isoprene (0.25 
mL, 2.5 mmoles), all of which were purchased from Aldrich Chemical Co., 
Milwaukee, Wis., were added to a 10 mL, 1-neck reaction flask fitted with 
a lightly-greased glass stopper [to minimize loss of the volatile isoprene 
(bp 34.degree. C.)]. This mixture was subsequently stirred at room 
temperature for 24 hours. The product was isolated by dilution of the 
reaction mixture with 40 mL of 15% (w/v) aqueous sodium chloride and 
extraction with 30 mL of hexane. [NOTE: If one intends to recycle 
unreacted 2,4-pentanedione, a fractional distillation of the organic layer 
can be done at this point.] After subsequent washing of the organic layer 
with 3% (w/v) aqueous sodium chloride (10.times.50 mL, to ensure removal 
of 2,4-pentanedione) and saturated aqueous sodium chloride (1.times.25 
mL), it was dried over anhydrous magnesium sulfate and filtered. Removal 
of the hexane by evaporation at reduced pressure and subsequent 
evaporative distillation afforded 247 mg (59% yield) of the named 
diketone: boiling point 89.degree.-98.degree. C. (bath temperature, 0.35 
mm). The identity of this compound was ascertained by IR and proton NMR 
analysis (recorded at 400 MHz). The latter spectrum exhibited a broad 
triplet at .delta. 4.98 (CH.dbd.C), a triplet (J=7.2 Hz) at .delta. 3.65 
(H bonded to C-3), a doublet (J=6.4 Hz) at .delta. 2.91 (CH.sub.2 bonded 
to C-3 in the "enol form" of the named diketone), and a triplet (J=6.8 Hz) 
at .delta. 2.53 (CH.sub.2 bonded to C-3 in the "keto form" of the named 
diketone). Approximately 20% of the distilled product consisted of a 
mixture of unidentified by-products (presumably C-10 and/or C-15 
hydrocarbons obtained by reaction of the initially generated 
"prenyl-cation" with isoprene instead of the enol form of 
2,4-pentanedione). The latter by-products were readily separated from the 
named diketone by dissolving the distillate in 20 mL of hexane and washing 
the organic layer with 1 M aqueous sodium hydroxide (3.times.15 mL)--from 
which aqueous washes the named diketone can be recovered by subsequent 
acidification and extraction with ether. The proton NMR spectrum of this 
unidentified mixture of by-products (wt.: approximately 50 mg) exhibited a 
singlet at .delta. 1.26 [C(CH.sub.3).sub.2 ] but lacked any signals in the 
region of .delta. 2.0-2.1--an indication that 
5-acetyl-3,4-dihydro-2,2,6-trimethyl-2H-pyran was not one of the 
by-products. The proton NMR spectrum of the latter heterocyclic compound 
is known to exhibit a singlet at .delta. 2.05. See: J. A. Miller, et al., 
J. Chem. Soc. Perkin I, 692 (1972). 
If one desires to maximize the yield of the named diketone, the controlled 
addition of isoprene (perhaps dissolved in a small amount of 
2,4-pentanedione) over a period of several hours to a mixture of 
polyphosphoric acid and excess 2,4-pentanedione at 40.degree.-50.degree. 
C. is recommended. The reaction mixture would have to be maintained under 
sufficient pressure to ensure that isoprene (bp 34.degree. C.) remains in 
the liquid phase. 
EXAMPLE II 
Preparation of Ethyl 2-(3-Methyl-2-buten-1-yl)-3-oxobutanoate by Treatment 
of Isoprene with Ethyl Acetoacetate Containing Polyphosphoric Acid as a 
Catalyst 
Polyphosphoric acid (530 mg), ethyl acetoacetate (6.0 mL), and isoprene 
(0.25 mL, 2.5 mmoles), all of which were purchased from Aldrich Chemical 
Co., Milwaukee, Wis., were added to a 10-mL, 1-neck reaction flask fitted 
with a glass stopper (to minimize loss of the volatile isoprene). This 
mixture was subsequently stirred at room temperature for 19 hours. The 
product was isolated by dilution of the reaction mixture with 60 mL of 15% 
(w/v) aqueous sodium chloride and extraction with 40 mL of hexane. After 
subsequent washing of the organic layer with 2:1 (v/v) water:methyl 
alcohol (7.times.50 mL, to ensure removal of ethyl acetoacetate) and 
saturated aqueous sodium chloride (1.times.25 mL), it was dried over 
anhydrous magnesium sulfate and filtered. Removal of the hexane by 
evaporation at reduced pressure and subsequent evaporative distillation 
afforded 134 mg (27% yield) of the named keto ester: boiling point 
90.degree.-102.degree. C. (bath temperature, 0.35 mm). The identity of 
this product was ascertained by IR (v.sub.max 1740, 1715 cm.sup.-1) and 
proton NMR analysis (recorded at 400 MHz). The latter spectrum exhibited a 
broad triplet at .delta. 5.02 (CH.dbd.C), a triplet (J=7.6 Hz) at .delta. 
3.43 (H bonded to C-2), a singlet at .delta. 2.22 (CH.sub.3 C.dbd.O), and 
a broad triplet (J=7 Hz) at .delta. 2.54 (CH.sub.2 bonded to C-2 of the 
named keto ester). The distillate also contained a minor amount of 
unidentified by-products similar to those obtained in Example I 
(presumably C-10 and/or C-15 hydrocarbons obtained by reaction of the 
initially generated "prenyl cation" with isoprene instead of the enol form 
of ethyl acetoacetate. 
If one desires to maximize the yield of the named keto ester, the 
controlled addition of isoprene (perhaps dissolved in a small amount of 
ethyl acetoacetate) over a period of several hours to a mixture of 
polyphosphoric acid and excess ethyl acetoacetate at 50.degree.-60.degree. 
C. and several atmospheres pressure is recommended. 
EXAMPLE III 
Preparation of 3-(3-Methyl-2-buten-1-yl)-2,4-pentanedione by Treatment of 
Isoprene with 2,4-Pentanedione Containing Aqueous Phosphoric Acid as a 
Catalyst 
2,4-Pentanedione (12.0 mL), isoprene (0.25 mL, 2.5 mmoles), and 85% 
phosphoric acid (1.00 mL) were added to a 35 mL pressure vessel (heavy 
glass wall, catalog #CG-1880-02, purchased from Chemglass, Vineland, 
N.J.). After adding a small spin bar and sweeping the system briefly with 
nitrogen, the vessel was closed; and the mixture was heated, with 
continuous stirring, at 80.degree. C. (external oil bath temperature) for 
14 hours. After cooling the mixture to room temperature, the product was 
isolated by dilution of the reaction mixture with 100 mL of 15% (w/v) 
aqueous sodium chloride and extraction with 50 mL of hexane. After 
subsequent washing of the organic layer with 3% (w/v) aqueous sodium 
chloride (10.times.100 mL, to ensure removal of 2,4-pentanedione) and 
saturated aqueous sodium chloride (1.times.50 mL), it was dried over 
anhydrous magnesium sulfate and filtered. Removal of the hexane by 
evaporation at reduced pressure and subsequent evaporative distillation 
afforded 135 mg (32% yield) of the named diketone: boiling point 
82.degree.-90.degree. C. (bath temperature, 0.35 mm). The spectral 
properties of this material were virtually identical to those exhibited by 
the product prepared in accordance with the procedure of Example I. 
EXAMPLE IV 
Attempt To Prepare 3-(3-Methyl-2-buten-1-yl)-2,4-pentanedione by Treatment 
of Isoprene with 2,4-Pentanedione Containing Dichloroacetic Acid as a 
Catalyst 
0.50 mL (6.1 mmoles) of dichloroacetic acid (purified-grade, purchased from 
Fisher Scientific Co.), 6.0 mL of 2,4-pentanedione, and 0.25 mL (2.5 
mmoles) of isoprene were added to a 15-mL, 1-neck reaction flask fitted 
with a double-jacketed, coiled reflux condenser connected to an apparatus 
similar to that described by Johnson and Schneider [Org. Synth., 30, 18 
(1950)] so that the mixture in the flask could be protected from 
atmospheric moisture throughout the course of the reaction. This mixture 
was subsequently heated, with continuous stirring, at 80.degree. C. 
(external oil bath temperature) for 25 hours, after which it was cooled to 
room temperature. [NOTE: The odor of unreacted isoprene was detected prior 
to diluting the reaction mixture with aqueous sodium chloride.] Isolation 
of the product as described in the procedure of Example I afforded only 21 
mg of crude material, the proton NMR spectrum of which detected only a 
trace amount of the named diketone. Hence the conversion of isoprene to 
the desired product was less than 2%. 
Treatment of 0.25 mL of isoprene in 6.0 mL of 2,4-pentanedione containing 
0.50 mL (7.35 mmoles) of 85% phosphoric acid in an identical reaction 
apparatus at 80.degree. C. for 21 hours afforded 191 mg (45% yield) of 
crude material, proton NMR analysis of which indicated that the major 
component was the desired named diketone. Hence the conversion of isoprene 
to diketone exceeded 20%. 
EXAMPLE V 
Use of Concentrated Aqueous Hydrochloric Acid as a Catalyst 
2,4-Pentanedione (12.0 mL), concentrated aqueous hydrochloric acid (1.0 mL, 
12.4 mmoles), and isoprene (0.25 mL, 2.5 mmoles) were added to a 25-mL, 
1-neck reaction flask fitted with a glass stopper (to minimize loss of the 
volatile isoprene). This mixture was subsequently stirred at room 
temperature for 18 hours. Isolation of the product as described in the 
procedure of Example III afforded 161 mg of crude material, the proton NMR 
spectrum of which indicated the presence of little (if any) of the desired 
product: 3-(3-methyl-2-buten-1-yl)-2,4-pentanedione. Instead, the major 
product was shown to be 1-chloro-3-methyl-2-butene, the IR and proton NMR 
spectral properties of which were identical to those exhibited by an 
authentic sample of the latter compound (purchased from Aldrich Chemical 
Co., Milwaukee, Wis.). Although isoprene was protonated by HCl under these 
reaction conditions, the thereby-generated "prenyl cation" was trapped by 
chloride anion and not by the "enol form" of 2,4-pentanedione. 
EXAMPLE VI 
Preparation of 3-(3-Methyl-2-buten-1-yl)-2,4-pentanedione by Treatment of 
Isoprene with 2,4-Pentanedione Containing p-Toluenesulfonic Acid as a 
Catalyst 
2,4-Pentanedione (6.0 mL), p-toluenesulfonic acid monohydrate (1.1 g, 5.8 
mmoles, purchased from Fisher Scientific Co.), and isoprene (0.25 mL, 2.5 
mmoles) were added to a 10-mL, 1-neck reaction flask fitted with a glass 
stopper [to minimize loss of the volatile isoprene]. This mixture was 
subsequently stirred at room temperature for 20 hours. Isolation of the 
product as described in the procedure of Example I afforded 162 mg (39% 
yield) of the named diketone, the spectral properties of which were 
identical to those exhibited by the product prepared in accordance with 
the procedure of Example I. As in the latter experiment, approximately 20% 
of the product consisted of a mixture of unidentified by-products, 
presumably obtained by reaction of the initially generated "prenyl cation" 
with isoprene instead of the enol form of 2,4-pentanedione. Slow addition 
of isoprene to the reaction mixture is advisable to maximize the yield of 
the named diketone. 
EXAMPLE VII 
Preparation of 3-(3-Methyl-2-buten-1-yl)-2,4-pentanedione by Treatment of 
Isoprene with 2,4-Pentanedione in the Presence of a Strongly Acidic 
Ion-Exchange Resin 
2,4-Pentanedione (10 mL), 1.02 g (weight of resin after drying it in an 
oven at 140.degree. C. for 2 hours to remove surface water) of Dowex.RTM. 
50X8-400 ion-exchange resin, purchased from Aldrich Chemical Co., catalog 
#21,751-4), and isoprene (0.25 mL, 2.5 mmoles) were added to a 15-mL, 
1-neck reaction flask fitted with a double-jacketed, coiled reflux 
condenser connected to an apparatus similar to that described by Johnson 
and Schneider [Org. Synth., 30, 18 (1950)] so that the mixture in the 
flask could be protected from atmospheric moisture throughout the course 
of the reaction. This mixture was subsequently heated, with continuous 
stirring, at 45.degree. C. (external oil bath temperature) for 22 hours, 
after which it was cooled to room temperature. After removal of the resin 
by filtration through a plug of glass wool, isolation of the product as 
described in the procedure of Example III afforded 155 mg (37% yield) of 
the named diketone accompanied by the usual mixture of unidentified 
by-products obtained when the initially generated "prenyl cation" reacts 
with isoprene instead of with 2,4-pentanedione. 
EXAMPLE VIII 
Preparation of 3-(3-Methyl-2-buten-1-yl)-2,4-pentanedione by Slow Addition 
of Isoprene to 2,4-Pentanedione Containing Polyphosphoric Acid as a 
Catalyst 
Polyphosphoric acid (580 mg) and 2,4-pentanedione (6.0 mL) were added to a 
15-mL, 1-neck reaction flask containing a magnetic stirring bar and fitted 
with a septum cap (to allow addition of isoprene to be made using a 
syringe). This mixture was stirred at room temperature for 30 minutes, 
after which reaction was initiated by addition of 300 microliters (.mu.L) 
of a 4:1 (v/v) mixture of 2,4-pentanedione:isoprene. Every 3 hours, an 
additional portion (300 .mu.L) of 4:1 (v/v) 2,4-pentanedione:isoprene was 
added to the stirred reaction mixture until 4 such portions [4.times.300 
.mu.L; the equivalent of 4.times.60 .mu.L (2.4 mmoles) of isoprene] had 
been added over 9 hours. The mixture was subsequently stirred at room 
temperature for an additional 20 hours. The product was isolated by 
dilution of the reaction mixture with 60 mL of 15% (w/v) aqueous sodium 
chloride and extraction with hexane. After subsequent washing of the 
organic layer with 15% (w/v) aqueous sodium chloride (9.times.50 mL, to 
ensure removal of most of the 2,4-pentanedione), it was dried over 
anhydrous magnesium sulfate and filtered. [NOTE: If one washes the organic 
layer thoroughly with 3% (w/v) aqueous sodium chloride, all residual 
2,4-pentanedione is removed from the product; however, small amounts 
(approximately 3-5%) of the named ketone (i.e., the desired product) are 
removed during each wash. Hence a significant amount (perhaps 30-40%) of 
the desired product was lost during the isolation procedure used in 
Examples I, III, IV, VI, and VII.] Removal of the hexane by evaporation at 
reduced pressure afforded 462 mg of material shown by proton NMR analysis 
to contain (approximately 35% of the mixture) some residual 
2,4-pentanedione. The latter was removed by evaporative distillation at 
40-65.degree. C. (bath temperature, 2.0 mm)--during which process a minor 
amount of the desired product was probably lost via co-distillation. 
Subsequent distillation afforded 245 mg (61% yield) of the named diketone: 
boiling point 80-90.degree. C. (bath temperature, 0.20 mm). 
The spectral properties of this product were consistent with those 
exhibited by the product prepared in accordance with the procedure of 
Example I. More significantly, proton NMR analysis indicated that the 
unidentified by-products obtained in Example I comprised less than 10% of 
the distilled product. Hence, controlled addition of isoprene to the 
reaction mixture improves the process.