Prenyl chloride

Synthesis of P-Methylheptenone from Petrochemical Sources. p-MethyUieptenone (1) is an important intermediate in the total synthesis of terpenes. Continuous hydrochlorination of isoprene [78-79-5] produces prenyl chloride [505-60-6] which then reacts with acetone with a quaternary ammonium catalyst and sodium hydroxide to give P-methyUieptenone (6-methyIhept-5-en-2-one [110-93-0]) (eq. 1) (16—19). 

The reaction temperature should be kept below 20°C to prevent side reactions. If the temperature exceeds 20°C, one should stop both the addition of the prenyl chloride and the ultrasound irradiation, and wait for the reaction temperature to fall below 15°C. 

The cathodic coupling of prenyl chloride with diethyl fumarate and methyl crotonate proceeds with different regios-electivities as shown in Fig. 17 [94]. Also in this case, the change in the regioselectivity appears to be due to the reduction of the diethyl fumarate to a radical anion that undergoes a nucleophilic substitution at the prenyl chloride, and in the other case there is a 2e reduction of the prenyl... 

Fig. 17 Regioselective cathodic addition of prenyl chloride to a, yS-unsaturated esters [94].

C11H22O2, Mr 186.30, Z>/>i,6kPa 82°C, Uq 1.441, is a colorless to pale yellow liquid with a fresh fruity citrus grapefruit-peel-like odor. It has not been found in nature. It is prepared by reaction of 2,2,5-trimethyl-4-hexenal (from isobutyraldehyde and prenyl chloride) with methanol in the presence of calcium chloride [21]. 

In the first route, methylbutenol is made from acetone and acetylene followed by hydrogenation. Reaction with methyl isopro-penyl ether yields methylheptenone (6). The second route involves the reaction of isobutylene, formaldehyde and acetone (7 ). Methyl vinyl ketone is an intermediate. Finally, methylheptenone is made by alkylation of acetone with prenyl chloride which is derived from isoprene (8). The initial product is the terminal olefin which is isomerized to the desired isopropylidene compound. 

An important intermediate for synthetic p-ionone (36) is the C8 building block methyl heptenone (37). In addition to the synthesis shown above, two further processes are known for its industrial production. In the process of Rhodia INC 36), the starting material is isoprene, and methyl heptenone (37) is obtained via prenyl chloride. At BASF, methyl heptenone (37) is produced, for economic reasons, in the form of its double bond isomer (37 a) by thermal condensation of isobutylene, formaldehyde and acetone 37) (see page 13). By suitable choice of the reaction conditions, various side-reactions, such as the Cannizzarro reaction of formaldehyde, the oligomerization of isobutene and aldol condensation between formaldehyde and acetone, can largely be suppressed. 

The most remarkable result of all is that prenyl chloride gives rearranged products in good yield. This is about the only way in which these compounds suffer attack at the tertiary centre by Sn2 reaction when there is the alternative of an S 2 reaction at a primary centre. 

Isoprene reacts with dimethylallyl chloride in the presence of CuC1-A1203 to yield geranyl chloride, neryl chloride, lavandulyl chloride, and myrcene(12) 111 reaction of (39 X = C1) with antimony trichloride gives (E)- and (Z)-2,6-dimethylocta-2,5,7-trien-4-one.111 (E)- and (Z)-3,7-Dimethylocta-3,6-dien-l-ols, geraniol (8), nerol (18), and the dienol (40) are prepared from isopentenyl acetate and prenyl chloride... 

New naturally occurring monoterpenes having the artemisia skeleton include artemisia ketone epoxide (208), isolated from Artemisia vulgaris and synthesized from prenyl chloride (15, R = Cl), and senecioic acid (59) chloride under Grignard conditions.( + )-Artemisia alcohol (209) has been isolated from A. herba alba [the usually encountered form is the (- )-(S)-isomer (- )-209]. An incompletely characterized triacetate 210 is also reported from the Brazilian plant Calea oxylepis. ... 

Construction of the suitably substituted geranic acid for making the furan ring has been effected too. For example, Poulter et al. have prepared the substituted geranate 865 by reaction of 4-methyl-3-pentenylcopper with the acetylenic ester 866. The ester 865 then underwent cyclization in the presence of acid to the lactone 867, related to scobinolide (161), and the action of acid on the lactol produced from 867 with diisobutylaluminum hydride gave perillene (849). The lactone 867 has also been prepared by a slightly different method the C9 alcohol 868 was made (in poor yield) from isobutenol and prenyl chloride with butyllithium. The extra carbon atom was introduced by the action of sodium cyanide on the epoxide of 868, and hydrolysis of the cyano group followed by dehydration yielded the lactone 867. The dimethylthioacetal of 867 has been used to synthesize perillene (849). This thioacetal was made from the suitably substituted ketene thioacetal 869 and dimethylsulfonium methylide. Thus the ketene thioacetal 870 (readily prepared from acetone, carbon disulfide, and sodium amylate, followed by methylation °) can be prenylated with lithium... 

An ingenious reaction by Stork and Mook consists of forming the C-3,C-4 bond of the furan ring, all the other carbon atoms being built beforehand. The starting material is the acetylenic alcohol 873 (propynol and prenyl chloride). 

Addition of hydrogen chloride to isoprene gives prenyl chloride, together with some of the allylic isomer 2-chloro-2-methylbut-3-ene. The presence of this tertiary chloride is not deleterious since, whilst prenyl chloride reacts with acetone via an SN2 reaction, it reacts by an Sn2 mechanism to give the same product, methylheptenone (Scheme 4.8). Further elaboration to linalool, etc., is the same as in the processes... 

A small number of hemiterpenes are used in perfumery, the most important of which are prenyl acetate and benzoate. Thioesters, such as those shown in Scheme 4.11, have extremely intense green odours reminiscent of galbanum, in which they occur naturally. The esters are usually prepared from prenyl chloride and the thioesters from the corresponding thiol and acid chloride. 

The material is prepared by alkylation of diisopropylketone with prenyl chloride [23b]. 

Terpenoid Synthesis from Isoprene.—Some prenylation procedures have been reported earlier. An efficient conversion of prenyl chloride into prenyl acetate has been described and the synthon (31 X = OH) (Vol. 7, p. 10) has... 

The acetate shown in acetone containing potassium carbonate (with some, 18-crown-6), then after Ih reflux the prenyl chloride added and refluxing ( Ah) continued to give the 5-0-prenyl ether... 

Claisen had reported that the proportion of C- to O-alkylation could be greatly enhanced by the use of sodium phenoxides in benzene suspension and indeed this method has been beneficially employed for o-C-isoprenylation. In a general procedure (ref.9), an ethereal solution of the phenol (0.05 mole), was treated with metallic sodium (0.2 mole) and after 1.5 hours the prenyl chloride (RCI) was introduced. Upon refluxing for 10 hours, removal of excess sodium and acidic work-up, monohydric phenols afforded yields from 66-90%. For example, 2-methylphenolwith3-methylbuten-2-ylchloridegave2-methyl-6-(3-methylbuten-2-... 

Although the dipotassium salt of hydroquinone in refluxing xylene with 3-methylbut-2-enyl bromide (ref. 10) similarly gave 4-hydroxy-2-(3-methylbuten-2-yl)phenol in 50% yield, reactions were not described for the dipotassium salt of resorcinol with a prenyl chloride. The potassium salt of 3-methoxyphenol with allyl chloride gave 2-allyl-3-methoxyphenol in 42% yield. 

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