Acid chlorides aromatic

AROMATIC ACID CHLORIDES The chlorides of aromatic acids are prepared — 

By the action of phosphorus pentachlorido upon the aromatic acid, for example  

The liquid phosphorus oxychloride, b.p. 107 , is a by-product and is removed by fractional distillation under normal pressure. Unless the b.p. of the acid chloride differs very considerably (say, ] 100 ) from that of the phosphorus oxychloride, the acyl halide is liable to contain traces of the latter. In such ciicumstanccs it is preferable to use thionyl chloride for the preparation of the acid chloride. 

By the action of thionyl chloride upon the acid (see discussion preceding Section 111,86), for example  

It will be noted that the by-products are both gaseous. In practice, a slight excess over the theoretical quantity (20-75 per cent.) of thionyl chloride is used some of this is volatilised with the gaseous by-products and the remainder is easily removed by fractional distillation (thionyl chloride has b.p. 77°). 

The preparation of 3 5-dinitrobenzoyl chloride by both the PCI, and SOCl, methods is described in Section III,27J see also Section VII,22. 

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The choice of type of derivative should be based on whether the chloride or anhydride is aliphatic or aromatic, because this factoi largely determines the reactivity. Aliphatic acid chlorides are best converted into their anilides, as in 4 above aromatic acid chloride may be similarly converted into their anilides, or they may be converted into their amides by shaking with an excess of ammonia (p, 120). (M.ps., pp. 544-545.) Aliphatic acid anhydrides should be converted into their crystalline anilides, but aromatic acid anhydrides arc best hydrolysed to the acid, which can then be converted into one of the standard derivatives (p. 349). 

Almost insoluble in cold water. Higher alcohols (including benzyl alcohol), higher phenols (e.g., naphthols), metaformaldehyde, paraldehyde, aromatic aldehydes, higher ketones (including acetophenone), aromatic acids, most esters, ethers, oxamide and domatic amides, sulphonamides, aromatic imides, aromatic nitriles, aromatic acid anhydrides, aromatic acid chlorides, sulphonyl chlorides, starch, aromatic amines, anilides, tyrosine, cystine, nitrocompounds, uric acid, halogeno-hydrocarbons, hydrocarbons. 

Most aromatic acid chlorides impart a strongly acid reaction when shaken with water (compare Section 111,88). All are completely hydrolysed by boiling with solutions of caustic alkalis and yield no product volatile from the alkaline solution (compare Eaters, Sections 111,106 and IV, 183). They may be distinguished from acids by their facile reactions with alcohols (compare Section 111,27), phenols (compare Section IV,114), and amines (compare Sections 111,123 and IV.lOO). 

Tetrahydroharman, m.p. 179-80°, has been prepared by a number of workers by a modification of this reaction, viz., by the interaction of tryptamine (3-)5-aminoethylindole) with acetaldehyde or paraldehyde and Hahn et al. have obtained a series of derivatives of tetrahydronorharman by the use of other aldehydes and a-ketonic acids under biological conditions of pH and temperature, while Asahina and Osada, by the action of aromatic acid chlorides on the same amine, have prepared a series of amides from which the corresponding substituted dihydronorharmans have been made by effecting ring closure with phosphorus pentoxide in xylene solution. 

If a substituted aromatic hydrocarbon is used, the ketone gioLip then enteis the paia-position, or, if this is occupied, the oitho-position. Substituted aromatic acid chlorides may. also be used, and if the acid is dibasic and has two caiboxyl chloiide gioups, two molecules of the aromatic hydiocaibon may be. attached. If phosgene is used with two molecules of benzene, benzophenone is obtained. 

Acylation with aromatic acid chlorides was believed to occur on carbon 91). The dibenzoylation of the enamine (113) with benzoyl chloride in the presence of triethylamine has, however, been shown to give a mixture of three products (92). The major components are the cis and Irons isomers of the O-acylated enamino ketone (Ola and b) and the minor isomer is the 2,6-diacylated enamine (132). 

CoBr2 is a very efficient catalyst for acylation of organozinc compounds with aliphatic and aromatic acid chlorides,... 

Further investigation of model reactions revealed that the reaction of aromatic acid chlorides with diols such as butanediol or ethylene glycol was too slow to be useful for kinetically controlled p.vcMdo-high-dilution reactions carried out... 

The reaction of the phospholen (65) with aromatic acid chlorides in the presence of triethylamine, followed by addition of DaO, gives a ready route to aromatic [1-2H]-aldehydes with 100% incorporation of deuterium.55... 

Aromatic acid chlorides are converted into the corresponding anhydrides in high yields (>95%), when reacted with carbon monoxide under solid liquid basic catalysed conditions in the presence of a complexed cobalt or palladium salt [6]. In the absence of the quaternary ammonium salt, only hydrolysis to the carboxylic acid occurs. 

Aromatic acid chlorides and 2-(triphenylphosphoranylidenamino)cinna-mates (127) give rise to l,3-oxazol-5-ones (129), as shown in Scheme 51. After an intermolecular aza-Wittig reaction with 127, the ethoxy O attacks... 

Aromatic acid chlorides react with phosphine at 50 °C in absolute pyridine to form mono-, di- and triacylphosphines. For example, PH3 and benzoyl chloride give tribenzoylphosphine, a yellow crystalline compound which is resistent to water and dilute acids but is hydrolysed to PH3 and alkali benzoate by alkalis... 

The principal method for preparation of pyrazino[2,3- [l,3]oxazines, as reported in CHEC-II(1996) <1996CHEC-II(7)737> involves cyclization of a 2-aminopyrazine-3-carboxylic acid ester with an aromatic acid chloride. Further applications of this three-step approach have been reported <19948405, 2000BMC2803>, but a one-pot approach has also been developed (Equation 157). This cyclization has also been carried out using acetic anhydride in place of an acid chloride <2005JMT(741)67>. 

Figure 3.5 The synthesis of diazepam is initiated by the double acylation of an aromatic amine with an aromatic acid chloride. A second equivalent of the p-chloroaniline leads to a six-membered ring with two nitrogens. This is hydrolytically opened to expose a free amino group which reacts with an aminoester to yield a seven-member ring. The amide nitrogen is then methylated.

It seems safe to say that coordination will generally decrease the reactivity of donor atoms in the first row of the periodic table through steric effects. With some reactions the extent of this steric hindrance may be small. Ammonia can be transformed into chloramines when coordinated (34), and aromatic acid chlorides coordinated to A1C13 or TiCl4 may be esterified even when the functional group is a hindered one, as in mesitylene carbonyl chloride (47). These last reactions may proceed through a very reactive carbonium ion, whose existence is rendered possible by the polarization of the ligand which it suffers as a result of coordination. 

Chemistry similar to this was used in Ellman s paper to promote application of a silicon-based traceless linker.62 The full report on this work63 shows that both aliphatic and aromatic acid chlorides may be used in the coupling step. The same,approach is also shown to be successful with a germanium-based linker in place of the silicon. The couplings were typically performed for 1 h only, with equilibration time of a few minutes... 

Investigations into the mechanism of hydrolysis and alcoholysis of acyl halides have been largely concerned with acyl chlorides and in particular with benzoyl chloride and the related aromatic acid chlorides. This was a result of the relatively slow rate of hydrolysis of benzoyl chloride compared with acetyl chloride (although their alcoholysis rates are easily measurable) and it is only comparatively recently90 that stop-flow techniques have been used to measure the faster rate of hydrolysis. However, in spite of this limitation, considerable progress has been made towards elucidation of the mechanism or mechanisms of hydrolysis and alcoholysis of these halides. 

The method for the preparation of the chloride is the general method for preparing aromatic acid chlorides with thionyl chloride,10 which has been applied to the preparation of mesitoyl chloride.9... 

Perhaps the most industrially feasible approach has been developed by Rich and co-workers at General Electric, a palladium-catalyzed silylative decarbonylation reaction of aromatic acid chlorides with disilanes [Eq. (35)].97 One of the silicon centers from the disilane is transferred to the arene whereas the other acts as a chloride acceptor to produce the chlorosi-... 

Aromatic acid chlorides are decarbonylated to aryl chlorides when they are heated to 300-360 C with palladium on carbon. The reaction proceeds by way of an aroylpalladium chloride, then to an arylpalla-dium chloride and finally through a reductive elimination to the aryl chloride. If the reaction is conducted in the presence of a reactive alkene under mild conditions the aroylpalladium chloride intermediate will sometimes acylate the alkene, as noted in Section 4.3.5.3.I. More usually, however, decarboxylation is more rapid than acylation, especially at higher temperatures (>100 C), and decarbonylation occurs. The... 

Bis(triphenylphosphine)copper(i) tetrahydroborate [(Ph3P)2CuBH4] has found use as a reagent for the reduction of aliphatic and aromatic acid chlorides to the corresponding aldehyde, and is an alternative to the standard Rosenmund procedure. This is illustrated in Expt 6.120. The reagent may be prepared by either of the following two methods both preparations should be conducted in an efficient fume cupboard as hydrogen is evolved. 

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