Mechanism acid chloride formation with

Interactive mechanism for acid chloride formation with SOCIj... 

A new method of cyclization has been developed, through the reaction of suitably or//ru-substituted diethyl benzoylphosphonates (41), or their acid chloride precursors, with trialkyl phosphites. An analogous reaction takes place with (42) to give the fluorenylphosphonate (43). The mechanism suggested involves initial attack on carbonyl oxygen, and gains support from the formation of the benzofuranylphosphon-ate (45) in the reaction of (44) with triethyl phosphite. 

From the mechanism of the acid chloride formation, one can see that it is the C-OH bond of the carboxylic acid that is broken to form the C-Cl bond. Subsequently, the C-Cl bond is cleaved to form the C-OR bond with the alcohol oxygen. 

The first step of this new mechanism is exactly the same as that seen earlier for the reaction of tert butyl alcohol with hydrogen chloride—formation of an alkyloxonmm ion by proton transfer from the hydrogen halide to the alcohol Like the earlier exam pie this IS a rapid reversible Brpnsted acid-base reaction... 

The interaction of acid chlorides (167 X = Cl) with imines in the presence of bases such as triethylamine may involve prior formation of a ketene followed by cycloaddition to the imine, but in many cases it is considered to involve interaction of the imine with the acid chloride to give an immonium ion (168). This is then cyclized by deprotonation under the influence of the base. Clearly, the distinction between these routes is a rather fine one and the mechanism involved in a particular case may well depend on the reactants and the timing of mixing. Particularly important acid chlorides are azidoacetyl chloride and phthalimidoacetyl chloride, which provide access to /3-lactams with a nitrogen substituent in the 3-position as found in the penicillins and cephalosporins. 

Thebainone (Schopf), CigHjjOgN. This substance, which must be distinguished from Pschorr s thebainone (metothebainone of Schopf (see p. 248) ), is formed, along with the latter in the reduction of thebaine by stannous chloride in hydrochloric acid, and was isolated by Schopf and Hirsch. Its prior isolation by Pschorr, as confirmed by Morris and Small, has been referred to already. It crystallises with 0-5 HjO, has m.p. 151-2°, yields a hydriodide, m.p. 258-9°, methiodide, m.p. 223°, and an oxime, m.p. 185-6°. On catalytic hydrogenation it yields dihydrothebainone (LI), and can be degraded to 3 4 6-triacetoxyphenanthrene, m.p. 165-7°. On this basis formula (XLIX) is assigned to it. The mechanism of the formation of codeinone, thebainone and mefathebainone from thebaine is discussed by Schopf and Hirsch. ... 

McLafferty, Fred Warren, 732 McLafferty rearrangement. 416, 732 Mechanism (reaction), 139 acetal formation, 717-718 acetylide alkylation, 272 acid chloride formal ion with SOCl2, 795... 

Thionyl chloride is another activating agent employed for reactions between aromatic carboxylic acids and phenols in pyridine solution. The mechanism suggested does not involve the formation of an acid chloride but assumes the existence of an intermediary mixed sulfinic anhydride which undergoes reaction with phenolic endgroups (Scheme 2.32).311... 

The mechanism of the condensation in Part D probably involves thioformylation of the metallated isocyanoacetate followed by intramolecular 1,1-addition of the tautomeric enethiol to the isonitrile. This thi2izole synthesis is analogous to the formation of oxazoles from acylation of metallated isonitriles with acid chlorides or anhydrides. " Interestingly, ethyl formate does not react with isocyanoacetate under the conditions of this procedure. Ethyl and methyl isocyanoacetate have been prepared in a similar manner by dehydration of the corresponding N-formylglycine esters with phosgene and trichloromethyl chloroformate, respectively. The phosphoryl chloride method described here was provided to the submitters by Professor U. Schollkopf and is based on the procedure of Bohme and Fuchs. The preparation of O-ethyl thioformate in Part C was developed from a report by Ohno, Koi/.uma, and Tsuchihaski. " ... 

The mechanism of the formation of compound 67 has been studied by Higa and Krubsack [41] in detail, as shown in Scheme 15. Namely, the initial step of the reaction of the cinnamic acid derivative 66 with thionyl chloride is an electrophilic addition of thionyl chloride across the double bond of cin-namoyl chloride to form the sulfinyl chloride intermediate (66a), which is then converted to 68 by the Pummerer reaction. Dehydrochlorination of 68... 

With propene, n-butene, and n-pentene, the alkanes formed are propane, n-butane, and n-pentane (plus isopentane), respectively. The production of considerable amounts of light -alkanes is a disadvantage of this reaction route. Furthermore, the yield of the desired alkylate is reduced relative to isobutane and alkene consumption (8). For example, propene alkylation with HF can give more than 15 vol% yield of propane (21). Aluminum chloride-ether complexes also catalyze self-alkylation. However, when acidity is moderated with metal chlorides, the self-alkylation activity is drastically reduced. Intuitively, the formation of isobutylene via proton transfer from an isobutyl cation should be more pronounced at a weaker acidity, but the opposite has been found (92). Other properties besides acidity may contribute to the self-alkylation activity. Earlier publications concerned with zeolites claimed this mechanism to be a source of hydrogen for saturating cracking products or dimerization products (69,93). However, as shown in reaction (10), only the feed alkene will be saturated, and dehydrogenation does not take place. 

This process is similar to the formation of an ester by the action of an acid anhydride on an alcohol (described in the earlier section Acid anhydride plus an alcohol ). Half the acid anhydride forms the amide the other half is a leaving group. Ammonia, primary amines, and secondary amines react to produce amides. Figure 12-27 shows the industrial preparation of phenacetin by the reaction of an amine with an acid anhydride. The mechanism for this reaction is similar to the mechanism for the reaction of an acid chloride with an amine (refer to Figure 12-26). 

Amines also react with esters by a method similar to the reaction of an acid chloride with an cimine (which was described in the previous section, From acid chlorides ). Figure 12-28 illustrates the formation of benzamide by this type of reaction, using ammonia and methyl benzoate. Again, the mechanism is similar to the reaction of an acid chloride with an amine (Figure 12-26). 

Preparation of acid chlorides The best way to make acid chlorides is the reaction of a carboxylic acid with either thionyl chloride (SOCI2) or oxalyl chloride (COCl)2 in the presence of a base (pyridine). The mechanism of formation of acid chloride is similar to the reaction of alcohol with SOCI2. 

A concerted elimination-cyclization mechansim, involving a sulfenyl halide in a 1,3-butadiene-1-thio system, is the most probable mechanism for the formation of benzo[6 Jthiophenes from cinnamic acids or 4-aryl-2-butanones by treatment with thionyl chloride. The reactions shown in Scheme 5 have been carefully worked out, and the intermediates isolated (75JOC3037). The unique aspect of this synthesis is the reduction of the sulfinyl chloride (a) by thionyl chloride to form the sulfenyl chloride (b). The intermediate (b) was isolated and converted in pyridine to the 3-chlorobenzo[6]thiophene-2-carbonyl chloride in 36% yield (73TL125). The reaction is probably initiated by a sulfenyl ion attack on the aromatic ring, since it is promoted by electron-releasing groups para to the site of ring closure. For example, when X in (36) was N02, a 23% yield of (37), a mixture of 5-and 7-nitro derivatives, was obtained, but when X in (36) was OMe, a 54% yield of (37) was obtained, contaminated with some 3,4-dichloro-5-methoxybenzo[6]thiophene-2-carboxylic acid. 

Treatment of an a-amino acid with an anhydride in the presence of pyridine, known as the Dakin-West reaction,[1431 gives access to a racemic a-amido ketone.1 44 1451 The mechanism involves formation of an oxazolinone (98)J146 In the modified Dakin-West reaction, the oxazolinone is reacted with an acid chloride (Scheme 33)J136 139] Due to the rapid epimer-ization of the oxazolinones, a diastereomeric mixture of product 99 is obtained. No detailed protocol has been published so far for the modified Dakin-West synthesis applied to (oxomethyleneamino) peptides, but the procedure is adapted from that already reported for (oxomethylene) peptides containing the tp[CO-CH2] link.1147 ... 

Exercise 17-23 Aldol additions also occur in the presence of acidic catalysts. For example, 2-propanone with dry hydrogen chloride slowly yields (CH3)2C=CHCOCH3 (mesityl oxide) and (CH3)2C=CHCOCH=C(CH3)2 (phorone). Write mechanisms for the formation of these products, giving particular attention to the way in which the new carbon-carbon bonds are formed. 

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