Ketones, preparative uses

Ketone, aralkyl, selective a-bromina-tion of,53, 111 Ketone, heptyl phenyl, 53,78 Ketones, preparation using 1,3-dithiane, 50,74 51,80... 

T. Shimoda and H. Hachiya. Process for preparing a polyether ether ketone membrane. US Patent 5 997 741, assigned to Asahi Kasei Kogyo Kabushiki Kaisha (Osaka, JP), December 7,1999. 

Organolithium and organomagnesium compounds find their- chief use in the preparation of alcohols by reaction with aldehydes and ketones. Before discussing these reactions, let us first exanine the reactions of these organometallic compounds with proton donors. 

D. S. Treybig and R. G. Martinez. Compositions prepared from hydrocarbyl substituted nitrogen-containing aromatic heterocyclic compounds, an aldehyde and/or ketone and an amine. Patent US 4871848, 1989. 

Interestingly, we were intrigued by the ESI mass spectrum of the compound, as the observed base peak consisted of [M-S02+Na]+. This led us to explore a thermal retro-Diels-Alder reaction that could afford the desired enone 69. It is noteworthy that the chemistry of cyclic enol-sulfites would appear to be an under-explored area with a few references reporting their isolation being found [57]. At last, we were also able to prepare epoxy ketone 70 from 69 in three steps, albeit epoxidation did not take place unless the TES group was removed. Spartan models reaffirmed our initial conformational assessment of enone 69 and epoxy ketone 70, which contain sp3-hybridized C8a and s/r-hybridized C8b (p s e u d o-. v/r - h y b r i d i zed C8b for 70) at the AB-ring junction (Fig. 8.12) and displayed the desired twisted-boat conformation in A-ring. 

This gives us a clue as to how to proceed, since the acetylenic ketone may be prepared from the starting acetylenic alcohol. 

This method, also named immediate (direct) interaction of ligands and sources of metal center [2], is the oldest and most widespread, in most cases the safest, preparative method. It is comparatively accessible with, in general, high yields of final products - metal complexes. Precisely as a result of its use, the majority of Werner coordination compounds with the simplest ligands water (aqua complexes), ammonia (amino complexes), halides, (5-di ketones, etc. - have been obtained. At present, the above method allows us to obtain practically all types of complexes (see Sec. 1.2) with all types of ligands (see Chap. 2). 

The residue is the hydrochloride of m-hydroxyphenyl-a-aminoethyl ketone. This is purified by recrystallization from absolute alcohol. It is then dissolved in 200 parts of water and agitated with a further quantity of the palladium catalyst in an atmosphere of hydrogen until saturated. The product thus recovered from the solution is the hydrochloride of m-hydroxyphenylpropanol amine. After recrystallization from absolute alcohol this melts at 177°C. The corresponding free base can be prepared from the hydrochloride by treatment with ammonia, according to US Patent 1,995,709. 

Let us now consider the synthesis of isoxazole 4.28, a drug for the treatment of bronchial asthma. The most direct preparation of isoxazolyl ketone 4.24 is the cycloaddition of unstable bromonitrile oxide 4.22 (prepared in situ by dehydrobromination of 4.21) with acetylenic ketone 4.23. Observe the regioselectivity of this reaction. Both electron-donating and electron-withdrawing groups on the acetylenic components in such cycloadditions tend to occur at the C5 position in the final isoxazole and not at C4. Bromination of ketone 4.24 affords bromoketone 4.25 which is 4.23 n... 

We shall cleave the bond shown. This shows us that we need the ketone D and the Grignard reagent E. D is a permitted starling material and E can be prepared by reacting ethyl bromide and Mg. 

What procedures are available for preparing aliphatic ketones Answer Procedures X-4 and X-5. Let us use procedure X-5. (The preparation of X-b via procedure X-4 will be left to... 

Reaction of succinylhydrazide derived from (A)-amino-2-methoymethylpyrrolidine (SAMP) with benzylmagne-sium chlorides allows us to prepare a number of enantiopure 5-arylmethyl-pyrrolidones and -pyrrolidines.265 An enantioselective desymmetrization of anhydrides was reported by Fu. Arylmagnesium chlorides react in toluene in the presence of 1 equiv. of (—)-sparteine with 3-substituted glutaric anhydrides, giving aryl ketones with 87-92% ee (Scheme 90).266... 

A versatile approach to spiro-oxacycles is the use of cyclic a-methylene enol ethers employed by us in an efficient and short enantioselective total synthesis of the mycotoxin talaromycin B (see Sect. 7.1). Later Pale and Vogel [148] employed the same protocol for the preparation of spiroacetals 2-145 using e.g. acrolein 2-78, methyl vinyl ketone and 2-pentenal, respectively with the enol ether 2-143 (Fig. 2-39). In most cases the yields were only modest, however, reaction of 2-143 and 2-78 in benzene in the presence of the mild Lewis acid ZnCl2 gave 2-145 in 70% yield as a single adduct. 

As in the Grignard reaction we may use any aliphatic aldehyde, ketone, ester or acid chloride, or an aryl compound of the same type and also, we may use either alkyl magnesium halides or aryl magnesium halides the synthesis makes possible the preparation of practically any desired secondary or tertiary alcohol either aliphatic or aromatic. Also if formaldehyde, in the form of its polymer, tri-oxy methylene, is used in the second reaction we will obtain primary alcohols. In the third reaction formic acid esters yield secondary instead of tertiary alcohols. These syntheses of alcohols by the Grignard reaction give us an idea of its importance in synthetic work. 

Let us try to get a broader picture of the synthesis of complicated alcohols. We learned (Sec. 15.12) that they are most often prepared by the reaction of Grignard reagents with aldehydes or ketones. In this chapter we Have learned that aldehydes and ketones, as well as the alkyl halides from which the Grignard reagents are made, are themselves most often prepared from alcohols. Finally, we know that the simple alcohols are among our most readily available compounds. We have available to us, then, a synthetic route leading from simple alcohols to more complicated ones. 

A few of the many laboratory methods of preparing aldehydes and ketones are outlined below most of these are already familiar to us. Some of the methods involve oxidation or reduction in which an alcohol, hydrocarbon, or acid chloride is converted into an aldehyde or ketone of the same carbon number. Other methods involve the formation of new carbon-carbon bonds, and yield aldehydes or ketones of higher carbon number than the starting materials. 

The ketone formed on oxidation of cholesterol-5 ,6/S-dibromide rapidly darkens on exposure to strong light or when heated to 70° but nevertheless was prepared in high yield by one of us as follows. A suspension of the dibromide in 2 1. of acetic... 

Another well known example of successful application of Beta zeolite is the substitution of AICI3 for Friedel-Crafts acylation. This reaction is an important industrial process, used for the preparation of various pharmaceuticals, agrochemicals and other chemical products, since it allows us to form a new carbon-carbon bond onto an aromatic ring. Friedel-Crafts acylations generally require more than one equivalent of for example, AICI3 or BF3. This is due to the strong complexation of the Lewis acid by the ketone product. 

Bioactive compounds that contain the difluoromethylene group adjacent to the carbonyl functionality have been the subject of increased research efforts in recent yearsf 59). The most widely utilized methods that have been employed to introduce this group into organic molecules have been (a) Reformatsky reaction of halodifluoroacetates (60-66) (b) elaboration of difluoroketene silyl acetals (67-69) (c) metal catalyzed addition of 3-bromo-3,3-difluoropropene to aldehydes and ketones (70) and (d) alkylation of CuCF2COOR(77). The modest yields associated with these methods prompted us to explore alternative methodology for the preparation of this useful building block. 

Retrosynthetic considerations suggested that the obvious inducement for us was the opportunity to transform the known optically pure ketone 82 [49] into 83 in advance of an anionic Cope rearrangement (Scheme XI) [50]. Although 1,2-addition of the cerate prepared from 3-furyllithium proceeded with appropriately high facial selectivity, subsequent isomerization of the potassium salt of 83... 

The method has been extended to the preparation of 4-cyclohepteneones, such as karahanaenone (8) (equation II). In this case the reaction involves reaction of isobutyraldehyde with a mixture of cis- and fra . -l-lithio-2-methyl-2-vinylcyclopropane (4) followed by oxidation with pyridinium chiorochromale to give a mixture of ketones (5). Silylation and thermal rearrangement us before lead to (7) the ketone (8) is obtained on desilylation. 

V. Jansons, H. C. Gors, S. Moore, R. H. Reamey, and P. Becker. Preparation of poly(arylene ether ketones). EP Patent 0174207, assigned to Raychem Corp. (US), March 12,1986. 

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