2- Methylbut-2-enal

FIGURE 6.1 Structure of 2-methylbut-2-enal, the rabbit mammary pheromone. 

A stream of nitrogen gas was passed through freshly collected mother s milk and the effluent collected by adsorption on a Tenax TA resin (2,6-diphenylene oxide based). Subsequent desorption into a GC-MS instrument led to the identification of 21 volatile components (low-molecular-weight aldehydes, ketones, alcohols, and lactone) in the milk headspace. When each was screened for behavioral activity, one, 2-methylbut-2-enal (34), was clearly the main compound responsible for eliciting searching—grasping responses in the rabbit pup test subjects. 

Products from the cyclisation of sulfur-containing substrates can depend on the reaction conditions. Thus, although the P-keto thioamides 29 yield piperidine-2-thiones when boiled with 2-methylbut-2-enal in ethanol containing triethylamine, thiopyrans are formed in pyridine <03T4183>. 

The condensation between dimethyl (lithiomethyl)phosphonate and methyl glycouronides yields carbohydrate-derived -0x0 phos-phonates" The anion from diethyl (but-2-en-l-yl)phosphonate and Ida reacts with ethyl formate to give 4-(diethoxyphosphinyl)-2-methylbut-2-enal . The di-/3-oxo phosphonates (633) were prepared in a similar fashion, and when these are acted upon by a base, they undergo intramolecular cyclization to give the unsaturated and functionalized phosphonate esters (634) . ... 

A BASF patent [30] describes the transformation of 81 into 4-chloro-2-methylbut-2-enal (88), which is an ideal precursor for the preparation of (3-methyl-4-oxobut-2-enyl)-triphenyl-phosphonium chloride (89). The phosphonium salt 89 is usually acetalized before being used in Wittig condensations [19,31]. Acetylation of 88 with potassium acetate in anhydrous ethanol furnished the acetoxyaldehyde 73 in high yield [32]. 

The Wittig olefination was employed industrially for the first time by BASF for linking the Ci5-p-ionylidene-ethyltriphenylphosphonium salt (49) and the C5 unit 4-acetoxy-2-methylbut-2-enal (50), (Scheme 14). The reaction was carried out in one step to give the end product vitamin A acetate (26). The process has impressive simplicity and gives high yield [40,41]. 

The Wittig reaction of the /1-ionylidenethyltriphenylphosphonium salt with ( )-4-acetoxy-2-methylbut-2-enal leads in high yields directly to ( /Z)-retinol acetate, which subsequently has to be isomerised and crystallised. [55]... 

A third synthetic route follows the C5 -1- C5 strategy. In principal, ( )-4-acetoxy-2-methylbut-2-enal is on the one hand oxidised to a dialdehyde, and on the other hand, the same precursor is converted into the correspondingphosphoni-um salt. A Wittig reaction of both of these intermediates gives then the desired... 

Thus, the aldehyde function of ( )-4-acetoxy-2-methylbut-2-enal is protected as an acetal by reaction with 2,2-dimethylpropane-l,3-diol, and then the acetoxy-group undergoes alkaline methanolysis. While the phosphonium salt is accessible by reaction with thionyl chloride, and subsequently with triphe-... 

Citral is prepared starting from isobutene and formaldehyde to yield the important C intermediate 3-methylbut-3-enol (29). Pd-cataly2ed isomeri2ation affords 3-methylbut-2-enol (30). The second C unit of citral is derived from oxidation of (30) to yield 3-methylbut-2-enal (31). Coupling of these two fragments produces the dienol ether (32) and this is followed by an elegant double Cope rearrangement (21) (Fig. 6). 

The reaction of citral, dihydrocitral, or 3-methylbut-2-enal with strong base to yield aldol-type dimers (79) has been thoroughly re-investigated (79) may iso-... 

The formation of dihydrocyclogeranyl acetate via thiyl radical addition to geranyl acetate and aldol-type condensations of citral, of dihydrocitral, and of 3-methylbut-2-enal have been discussed already. a-Cyclocitral behaves... 

A phenylboronic acid-mediated synthesis of chromenes from naphthols and 3-methylbut-2-enal features in two short routes to 3-lapachone <99S1875>. 

The condensation of a,/3-unsaturated carbonyl compounds with phenols has received much attention as a route to chromenes. Problems associated with the instability of alkenals have been largely overcome by the use of masked forms of these reagents. The derived acetals have proved particularly useful in this respect. It is also advantageous to use the acetals of hydroxyalkanals and to introduce the double bond during the course of the reaction. Thus, 4,4-dimethoxy-2-methylbutan-2-ol serves as the equivalent of the unstable 3-methylbut-2-enal. 

It has been thought that the use of 3-methylbut-2-enal derivatives in the synthesis of chromenes was restricted to the reaction with electron rich phenols. Not so The reaction is efficiently catalysed by pyridine and 3-methylpyridine and is most successful with the more acidic phenols, indicating the need for a careful balance between acid and base catalysis (95JOC3397). 

Two short syntheses of P-lapachone from readily available naphthols and 3-methylbut-2-enal via a mild phenyl-boronic acid mediated cyclization to 2//-chromenes have been reported. Catalytic hydrogenation of 2H-chromenes with H /Pd-C in ethyl acetate afforded the corresponding naturally occurring chromanes (72) and (73). Oxidation of the adequate chromane with an excess of cerium ammonium nitrate (CAN) furnished P-lapachone in 62% yield [153]. 

There is no direct experimental evidence for this complex decomposition and it may well occur by several steps [107]. However, substantial yields of unsaturated carbonyl compounds are formed particularly at high pressures [78] under initial reaction conditions where cool flames propagate. For example, the cool-flame oxidation of 2-methylpentane at 525 °C and 19.7 atm in a rapid compression machine [78] yields no less than 14 unsaturated carbonyl compounds viz acrolein, methacrolein, but-l-en-3-one, pent-2-enal, pent-l-en-3-one, pent-l-en-4-one, trans-pent-2-en-4r one, 2-methylbut-l-en-3-one, 2-methylpent-l-en-3-one, 4-methylpent-l-en-3-one, 2-methylpent-l-en-4-one, 2-methylpent-2-en-4-one, 2-methyl-pent-2-enal and 4-methylpent-2-enal. Spectroscopic studies of the preflame reactions [78] have shown that the unsaturated ketones account for ca. 90 % of the absorption which, occurs at 2600 A. At lower initial temperatures and pressures acrolein and crotonaldehyde are formed from n-pentane [69, 70] and n-heptane [82], and acrolein is also formed from isobutane [68]. 

A high-yield synthesis of flindersine (15), involving base-catalysed reaction of 4-hydroxy-2-quinolone with 3-methylbut-2-enal, has been reported. ... 

C.34) (C.34) 2-Butenal, 3-methyl-, 3-methylbut-2-enal, 3-methylcrotonaldehyde, 3,3-dimethylacrolein, senecialdehyde, prenal [107-86-8] FEMA 3646... 

Although strictly outside the reactions of prenyiphenolic compounds the extensive work on the regiospecific general synthesis of chrom-3-enes (2H-benzo[b]pyrans), in particular2,2-dimethylchromenes, from the reaction of metal phenoxides with 3-methylbut-3-enal is very noteworthy. In the general procedure a solution of titanium tetraethoxide (0.025 mol) in toluene was treated with the phenol (0.1 mol) in toluene and the ethanol formed removed by distillation over... 

A further example is the reaction of the magnesium salt of olivetol with 3-methylbut-2-enal when the yield of the 4-substitited product was 77% and that of the 2- was 3%. By contrast in the reaction of resorcinols with a,p-unsaturated carbonyl compounds in pyridine solution 2-substitution occurs as will be seen in the synthesis of deoxybruceol in section 12.6.5. 

Chromenes.- Continuing interest in the precocenes and their biological action has stimulated further work on their synthesis. Precocene III (82) has been synthesized from a phenol, 3-methylbut-2-enal and titanium(IV) ethoxide93 and precocenes I and II were obtained by cyclization of the relevant 3-methoxyphenol with isoprene and dehydrogenating the resultant chroman with DDQ.94 Several new positional isomers of precocenes and related compounds have been synthesized and screened for insecticidal activity in a rice crop. Chromanones [such as (83)] were reduced with LAH to the chromanol which was efficiently dehydrated with a trace of toluene-4-sulphonic acid. Under some conditions, reduction gave dimeric... 

A synthetic example of this reaction is taken from Evan s synthesis of (+)-miyakolide.l 3 Ketone 279 was treated with B-chlorodicyclohexylhorane in the presence of triethylamine, and this generated boron enolate 280. 4-Methylbut-2-enal was also present in the reaction and they condensed to give a 98% yield of 281, with a diastereoselectivity of 88 12. 

A second industrial process for preparing j/-ionone (2) starts form wo-butene (10) and formaldehyde (11) to give 12 and is based on linking 3-methylbut-2-en-l-ol (13) and 3-methylbut-2-enal (14) o give citral (15) (Scheme 2) [12]. The dienol ether formed from the acetal 76 by elimination of 13 undergoes a sigmatropic rearrangement [13]. V /-Ionone (2) results from aldol condensation of 15 with acetone (3). 

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