Acyl derivatives acid chloride

Pyrazoles, isoxazoles and isothiazoles with a hydroxyl group in the 3-position (491 Z = NR, O, S) could isomerize to 3-azolinones (492). However, these compounds behave as true hydroxy derivatives and show phenolic properties. They give an intense violet color with iron(III) chloride and form a salt (493) with sodium hydroxide which can be O-alkylated by alkyl halides (to give 494 R = alkyl) and acylated by acid chlorides (to give 494 R = acyl). 

The enamino ketone 49 has also been found to react with o-nitrobenzene-sulfenyl chloride to give the derivative 156, having the o-nitrophenylthio group substituted in the 2 position (93), i.e., the same position at which normal acylation with acid chlorides takes place. 

Primary and secondary amines are acylated by acid chlorides and anhydrides, in particular also by the chloride of benzene sulphonic add (p. 192). The preparation of acetanilide has already been described (pp. 125, 128). The acetyl- and benzoyl-derivatives of all the simpler primary amines of the benzene and naphthalene series are known, so that these derivatives can always serve for purposes of identification. 

Cagniant and Cagniant have reported that succinoylation of benzo[6]thiophene under Friedel-Crafts conditions yields a separable mixture of the y-ketobutyric acids 42a and 43a in a ratio of 9 1 (combined yield 85%). Huang-Minlon reduction of 42a to the butyric acid (90%) followed by cyclization of the derived acid chloride (90%) was reported to yield 4-keto-l,2,3,4-tetrahydrodibenzothiophene (44a) (69% overall). Likewise, acylation of benzo[6]thiophene with the ester chloride of succinic acid in carbon disulfide-aluminum chloride gave a separable mixture (80%) of the 2- and 3-y-ketobutyric esters. Two alternative... 

Octahydrodibenzothiophene (73) has been prepared by the following sequence. Friedel-Crafts acylation of 4,5,6,7-tetra-hydrobenzo[6]thiophene with succinic anhydride (87%) or with the ester chloride of succinic acid followed by hydrolysis (80%), yields the keto acid (74). Huang-Minlon reduction of 74 followed by cyclization of the derived acid chloride with stannic chloride yields l-keto-1,2,3,4,6,7,-8,9-octahydrodibenzothiophene (53) (Section V,A). Reduction of 53 gives 73 as a solid (overall yield 32%). 

C-acylation with acid chloride has been used by Kishi in the synthesis of sporidesmin A (73JA6493). The carbanion from the appropriate pipera-zinedione (derived by treatment with butyl lithium) was reacted with the... 

The same process has been extended to trialkylphosphonoacetates. Acylation with acid chlorides of the magnesium enolates derived from trimethyl and triethyl phospho-noacetates using a MgCl2/Et3N system provides 2-acyl dialkylphosphonoacetates. Further decarboxylation of these latter compounds affords /3-ketophosphonates . 

Alkynes are readily acylated with acid chlorides under Friedel-Crafts conditions to form, in most cases, fram-p-chlorovinyl ketones through the corresponding vinyl cation intermediate [Eq. (8.16)]. The first study in 1935 reported low yields.11 Later in acylations with acyl triflates, p-keto vinyl triflates were obtained in satisfactory yields.123 When aroyl derivatives are used, the intermediate can undergo cyclization to form indenones. Chlorovinyl ketones formed from terminal alkynes may also react further losing hydrogen chloride to yield conjugated acetylenic ketones 11,13... 

From carboxylic acids or acyl derivatives Aluminum chloride, 15 1-Benzotriazolyl diethyl phosphate, 28 Bis(dichloroaluminum)phenylimide,... 

The hydroxy group of 3-hydroxy-3,4-dihydro-2//-pyrido[l,2-a]pyrimi-dine was acylated with acid chlorides in pyridine341 and exchanged for chlorine by treatment with thionyl chloride.190 The resulting chloro derivative (131 mp = 46.5-47 C) was transformed on standing to a compound containing ionic chlorine (mp = 193 C). The structure of the latter remained unclarified.190... 

In the Friedel-Crafts acylation, carboxylic acid chlorides and carboxylic acid anhydrides are activated with stoichiometric amounts of A1C13 (Section 5.2.7). However, this activation is only possible in the presence of very weak nucleophiles such as aromatic compounds. Stronger nucleophiles would react with the A1C13 instead of the carboxylic acid derivative. If one wants to acylate such stronger nucleophiles—for example, alcohols or amines—with car-... 

Reactions of Acid Chlorides Acid chlorides react quickly with water and other nucleophiles and are therefore not found in nature. Because they are the most reactive acid derivatives, acid chlorides are easily converted to other acid derivatives. Often, the best synthetic route to an ester, anhydride, or amide may involve using the acyl chloride as an intermediate. 

The first is the acylation of the magnesium derivative of diethyl malonate. The magnesium atom prevents 0-acylation with acid chlorides, and decarboxylation (p. 678) removes the redundant ester group. 

Camphor-10-sulfonic acid (1) is available in large quantities in both enantiomeric forms. In only 3 steps the cyclic sulfonamide 2 (sultam) can be synthesized, which can be acylated with acid chlorides after deprotonation with sodium hydride (Scheme 1) [1, 2]. The resulting amides 3 are considerable more reactive towards nucleophiles than the corresponding carboxylic esters and the a,/ -unsaturated derivatives undergo, with excellent selectivities, Diels-Alder reactions or Michael additions under mild conditions. Al-... 

Among the most important reactions of carboxylic acids are those that convert the carboxyl group into an acid derivative by a nucleophilic acyl substitution. Acid chlorides, anhydrides, esters, and amides can all be prepared from carboxylic acids (Figure 21.4). 

These methods of acylation are devices to solve the problem that acid chlorides and organo-lithium or magnesium derivatives are not good partners. To get good acylation with acid chlorides, as well as good alkylation with alkyl halides, we need to turn to other metals which provide softer carbanion complexes, less basic compounds with metals showing a lower affinity for oxygen. The most important is copper. 

Whilst bismuth (III) chloride is an efficient catalyst for the aromatic ether acylation by acid chlorides or anhydrides, it is not strong enough to carry out the acylation of non activated aromatics. However, the potential of using a wide range of Bi (III) salts as catalysts (ref. 41), in particular the oxide, the oxychloride and the carboxylates, all non hygroscopic compounds, offers advantages, and is indicative of the great versatility of Bi (III) derivatives. Moreover, the Bi salts obtained after hydrolytic workup are directly reusable. 

N-(l-Alkoxyalkyl)-aniides or -carbamates (2 X = OR), most frequently used as stable precursors for A -acyliminium ions, are usually prepared by one of the following routes (equations 7-13). For five- or six-membered cyclic cases a simple acid-catalyzed solvolysis of the hydroxy compound provides the alk-oxy derivative (equation 7). A silicon-assisted approach involves the TMSOTf-catalyzed reaction of bis(trimethylsilyl)formamide with aldehydes (equation 8). /V-(l-Trimethylsilyloxyalkyl)formamides are thus formed in good yields, which on TMSOTf-catalyzed solvolysis lead to the /V-( 1-alkoxyalkyl)form-amides. A third method is based on the NaBH4 reduction of imidates (equation 9), and has proved useful for a total synthesis of the insect poison pederine. Addition of reactive acid derivatives to imines constitutes another method (equations 10 and 11). Acylation with acid chlorides followed by treatment with ethanol in the presence of base leads to N-(l-alkoxyalkyl)amides. A one-step protocol using diethyl dicarbonate provides the corresponding carbamates. 2... 

Ketones are formed from pyridylzinc halides on acylation with acid chlorides or anhydrides in reactions with benzoyl chloride or benzoic anhydride, pyridyl ketones (307) are formed in moderate yields. Reactions with 3-iodoquinoline gave the 3-benzoyl derivative 308. Organostannanes may be a better choice for ketone formation (see above). 

Both the Reimer-Tiemann and the Vilsmeier reactions lead to formylation in the 5-position in pyrimidines with at least two strongly releasing substituents. Thus 6-amino-1,3-dimethyluracils are readily formylated by DMF/POCI3 <84S589,92AHC(55)129), acylated by acid chlorides or converted into thiocarbamoyl derivatives by isothiocyanates (100) (Scheme 12) <79H(12)503>. 

Propene derivatives produce pyrylium salts 28 (Balaban synthesis) by a double acylation with acid chlorides or anhydrides in the presence of Lewis acids, e.g. AICI3 ... 

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