Carbon halo acetates

The reaction is very general. The aldehyde or ketone may be aliphatic, alicyclic, or aromatic (including diaryl ketones) it may contain double or triple bonds it may contain various functional groups, such as OH, OR, NR2, aromatic nitro or halo, acetal, or even ester groups.643 Double or triple bonds conjugated with the carbonyl also do not interfere, the attack being at the 0=0 carbon. 

As an extension of this new procedure for carbon-carbon bond formation, the reaction between silyl enol ethers and acetals 50, a typical protecting group of aldehydes, is performed to afford j5-alkoxy carbonyl compound 51 in the presence of titanium(IV) chloride (Eq. (24)) [27]. A variety of substituted furans are readily prepared by application of the TiCU-promoted reaction of a-halo acetals 52 with silyl enol ethers (Eq. (25)) [27]. 

Madorsky, S. L., Thermal Degradation of Organic Polymers , Interscience, New York, 1964. A compilation of the existing knowledge on polymers and copolymers of styrene, alkenes, halo-carbons, vinyl acetate, acrylonitrile, butadiene, isoprene, poly(ethylene terephthalate), polybenzyl, polyxylene, phenol, formaldehyde resin and cellulosic polymers Polym, Rev, vol. 7). 

Labeled heterocyclic systems of the imidazopyridine type are accessible from halo [ " ]-acetates. For example, the reaction between 2-aminopyridine and chloro[2- C]acetic acid produced (2-imino-l,2-dihydropyridin-l-yl)[2- C]acetic acid (1411 in 76% yield (Figure 6.46). Treatment of 141 with POCI3 induced cyclization and chloro-dehydration to furnish 2-chloro[3- C]imidazo[l,2-a]pyridine (1421 in 99% yield. The latter was a key intermediate in the synthesis of the carbon-14-labeled herbicide MON 37500 (1431. ... 

When unsymmetrical ketones were used in this reaction (with BF3 as catalyst), the less highly substituted carbon preferentially migrated. The reaction can be made regioselective by applying this method to the a-halo ketone, in which case only the other carbon migrates. The ethyl diazoacetate procedure has also been applied to the acetals or ketals of a, P-unsaturated aldehydes and ketones. ... 

Propiolaldehyde diethyl acetal has found numerous synthetic applications in the literature which may be briefly summarized. The compound has been utilized in the synthesis of unsaturated and polyunsaturated acetals and aldehydes by alkylation of metal-lated derivatives, " by Cadiot-Chodkiewicz coupling with halo acetylenes, " and by reaction with organocuprates. Syntheses of heterocyclic compounds including pyrazoles, isoxazoles, triazoles, and pyrimidines have employed this three-carbon building block. Propiolaldehyde diethyl acetal has also been put to use in the synthesis of such natural products as polyacetylenes " and steroids. ... 

Organoboranes can also be used to construct carbon-carbon bonds by several other types of reactions that involve migration of a boron substituent to carbon. One such reaction involves a-halo carbonyl compounds.20 For example, ethyl bromoac-etate reacts with trialkylboranes in the presence of base to give alkylated acetic acid derivatives in excellent yield. The reaction is most efficiently carried out with a 9-BBN derivative. These reactions can also be effected with (3-alkenyl derivatives of 9-BBN to give (3,y-unsaturated esters.21... 

Nucleophilic reactions at the carbon atoms of 1,3,4-thiadiazoles occur readily owing to the electron-deficient nature of this ring. Halo-substituted thiadiazoles are therefore highly activated and react with a wide range of nucleophiles. Carbon-based nucleophiles such as malonates have been used in the synthesis of 2-substituted thiadiazoles. When chlorothiadiazole 52 was treated with ethyl acetate in the presence of NaHMDS, the 2-phenyl-1,3,4-thiadiazol-5-ylacetic ester 53 was obtained (Equation 6) <20060L1447>. 

Halogenation of dibenzofuran produces the 2-halo compounds. Bromina-tion can be achieved in good yield with bromine in acetic acid " or with N-bromosuccinimide in boiling carbon tetrachloride. The 2,8-dibromo compound has been made, using dioxane dibromide. Chlorination of dibenzofuran in acetic acid in the presence of iron powder can be controlled to yield the 2-chloro or the 2,8-dichloro compounds. 2-Chlorodi-benzofuran is best prepared by reaction of dibenzofuran with phosphorus pentachloride. 2-Iododibenzofuran (45%) results from treatment of dibenzofuran with iodine in boiling chloroform in the presence of nitric acid. 2,8-Diododibenzofuran is best prepared by reaction of dibenzofuran with iodine and iodic acid in aqueous acetic acid. ... 

Alkyl carbon atoms attached in a position a, / , or y to a carboxy function give rise to tx, [1. and y effects which shift the carboxy carbon resonances by 10, 4 and — 1 ppm, respectively. This trend is illustrated by the 13C shift values collected for formic, acetic, propionic, and butyric acids among others in Table 4.34 [305-309], Further, carboxy carbons of x halo acids and dicarboxylic acids with closely spaced carboxy groups arc shielded relative to those of parent alkanoic acids (Table 4.34). On the other hand, the x, j3 and y carboxy increments Z, = hi(RCOon)- — krh) f°r the carbon shifts of an alkyl chain are... 

Ozone oxidizes phenothiazine and some of its substituted derivatives to 5-oxides. Selective oxidation of V-alkylphenothiazines to 5-oxides is conveniently performed by means of sodium nitrite in acetic acid. - < In some cases, for example that of 3,7-dinitro -phenothiazine and octachlorophenothiazine, nitric acid may be used as a selective oxidant for obtaining pure 5-oxides. Chlorine oxidizes octachlorophenothiazine in nitrobenzene in the presence of water to the corresponding 5-oxide. Almost quantitative yields of 5-oxides have been reported in the oxidation of V-methylphenothia-zine, and of 10-dialkylaminoalkylphenothiazines in which there are three carbon atoms in the side chain, with ammonium persulfate " (see also Section VI, A). Some halo- and halonitrophenothiazines may be converted into 5-oxides by dichromate. - - ... 

An acyl and an acyloxy group can be added to a double bond by treatment with an acyl fluoroborate and acetic anhydride. As expected, the addition follows Markovnikov s rule, with the electrophile Ac going to the carbon with more hydrogens. In an analogous reaction, an acyl and an amido group can be added to give 183, if a nitrile is used in place of the anhydride. Similarly, halo acetoxyla-tion is known.This reaction has also been carried out on triple bonds, to give the... 

Halo-ajS-unsaturated ketones and esters are highly susceptible to 8 2 displacement at the carbon attached to halogen, so strong bases are undesirable for such substrates [60, 91, 92]. However, relatively weak bases, such as sodium acetate and even triethylamine, are effective when the reaction is conducted in alcohol solvents [60]. Sodium acetate suspended in methanol, and aqueous or solid carbonate in ethanol give best results for haloenones (Scheme 2-33) [60] and haloesters [91], respectively. 

The results, a-halo esters of (S) configuration, are consistent with an electrophilic addition of the halonium on the less hindered Si face of the [3-carbon of the keten acetals. Obviously, a-halo esters with (R) configuration are obtained if the antipode of the aforementioned chiral auxiliary is used. It is noteworthy that this procedure not only affords crude a-halo esters in high diastereoisomeric excess but, allows, by a simple crystallisation, to obtain them, in quantitative diastereoisomeric excess. 

Of the various methods of preparing ketenes,167 only those that involve introduction of the C=C double bond have their place in this Section. The oldest of these methods is dehalogenation of a-halo carbonyl chlorides by zinc in boiling ether or boiling ethyl acetate 168 but this gives only poor yields, except for some oxoketenes, which are obtained in 90-95% yield,169 and carbon suboxide. 

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