Chlorides, acyl preparation

VI-Halo acyl chlorides (3,35). a-Bromo acyl chlorides can be prepared In about 70-80% yield by reaetion of acyl chlorides, prepared in situ by reac-llon of carboxylic acids with thionyl chloride, which can also be employed as solvent for the bromination reaction. NBS is considerably more efficient than liromine in this reaction. Use of NCS under similar conditions gives a-chloro acyl chlorides in comparable yields. Benzyhc protons are not replaced by either leiigcnt. a-Iodo acyl chlorides can be obtained in 70-80% yield by iodination of acyl chlorides with molecular iodine in this case thionyl chloride must be iiNi d as solvent rather than CCI4 and a higher temperature (140°) is required. 

Acyl chlorides, prepared by the reaction of carboxyhc acids with thionyl chloride, react readily with alcohols to give ester. Pyridine is used as a base to neutralize the HCl that forms in the reaction. 

This preparation illustrates the use of phosphorus pentachloride for the preparation of acyl chlorides in this case no difficulty is experienced in separating the 3,5-dinitrobenzoyl chloride from the phosphorus oxychloride formed simultaneously (c/. p. 240), because the former is readily isolated as a crystalline... 

TTie true ketones, in which the >CO group is in the side chain, the most common examples being acetophenone or methyl phenyl ketone, C HjCOCH, and benzophenone or diphenyl ketone, C HjCOC(Hj. These ketones are usually prepared by a modification of the Friedel-Crafts reaction, an aromatic hydrocarbon being treated with an acyl chloride (either aliphatic or aromatic) in the presence of aluminium chloride. Thus benzene reacts with acetyl chloride... 

In these cases the acyl azides formed have been used to prepare amines via Curtius rearrangement. The acyl chloride or azide intermediates can. however, also be reacted with amines or alcohols to form amides or esters. 

The o -diketone 865 can be prepared by the coupling of the acylstannane 864 with acyl chlorides[738,739]. The a-keto ester 868 is prepared by the coupling of (a-methoxyvinyl)tributylstannane (866) with acyl chloride, followed by ozo-nization of the coupled product 867[740,741],... 

The acylstannanes 874 and 875 are prepared by the reaction of acyl chlorides with (MciSnl - The symmetrical 1,2-diketones 877 can be prepared by the reaction of an excess of benzoyl chloride with (EtjSn) . Half of the benzoyl chloride is converted into the benzoyltin reagent 876, which is then coupled with the remaining benzoyl chloride under a CO atmosphere to afford the a-diketone 877[748], Triethyl phosphite is used as a ligand. 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

These compounds are easily prepared from the appropriate 2-aminothiazole and acyl chloride (see Section III.2.D) or by general heterocydization methods. Acyl chlorides may be replaced by the corresponding anhydrides (471). Acids themselves may be used as acylating agents provided that the imidazole-triphenyl phosphine mixture is used as a catalyst (472). The Curtius degradation of 247 yields 2-acetamido-4-phenylthiazole (248) (Scheme 149) (473). 

Since the exocyclic sulfur is more reactive in the ambident anion than in A-4-thiazoIine-2-thione. greater nucleophilic reactivity is to be expected. Thus a large variety of thioethers were prepared in good yields starting from alkylhalides (e.g.. Scheme 38 (54, 91, 111, 166-179). lactones (54, 160), aryl halides (54, 152. 180, 181), acyl chlorides (54. 149, 182-184). halothiazoles (54, 185-190), a-haloesters (149. 152. 177. 191-194), cyanuric chloride (151). fV.N-dimethylthiocarbamoyl chloride (151, 152. 195. 196), /3-chloroethyl ester of acrylic acid (197), (3-dimethylaminoethyl chloride (152). l,4-dichloro-2-butyne (152), 1,4-dichloro-2-butene (152), and 2-chloro-propionitrile (152). A general... 

Acyl chlorides are readily available They are prepared from carboxylic acids by reaction with thionyl chloride... 

Acyl chlorides react with carboxylic acids to yield acid anhydrides When this reaction is used for preparative purposes a weak organic base such as pyridine is normally added Pyridine is a catalyst for the reaction and also acts as a base to neutralize the hydrogen chloride that is formed... 

Hydrolysis (Section 20 4) Acyl chlorides react with water to yield carboxylic acids In base the acid is converted to its carbox ylate salt The reaction has little prepara tive value because the acyl chloride is nearly always prepared from the carboxyl ic acid rather than vice versa... 

Amides are readily prepared by acylation of ammonia and amines with acyl chlorides acid anhydrides or esters... 

These thermal methods for preparing amides are limited m their generality Most often amides are prepared m the laboratory from acyl chlorides acid anhydrides or esters and these are the methods that you should apply to solving synthetic problems... 

This chapter concerns the preparation and reactions of acyl chlorides acid anhydrides thioesters esters amides and nitriles These com pounds are generally classified as carboxylic acid derivatives and their nomenclature is based on that of carboxylic acids... 

Section 20 5 Acid anhydrides may be prepared from acyl chlorides m the laboratory but the most commonly encountered ones (acetic anhydride phthahc anhydride and maleic anhydride) are industrial chemicals prepared by specialized methods... 

Section 20 6 Acid anhydrides are less reactive toward nucleophilic acyl substitution than acyl chlorides but are useful reagents for preparing esters and amides... 

Section 20 7 Esters occur naturally or are prepared from alcohols by Fischer estenfi cation or by acylation with acyl chlorides or acid anhydrides (see Table 20 3)... 

As a dibasic acid, malic acid forms the usual salts, esters, amides, and acyl chlorides. Monoesters can be prepared easily by refluxing malic acid, an alcohol, and boron trifluoride as a catalyst (9). With polyhydric alcohols and polycarboxyUc aromatic acids, malic acid yields alkyd polyester resins (10) (see Alcohols, polyhydric Alkyd resins). Complete esterification results from the reaction of the diester of maUc acid with an acid chloride, eg, acetyl or stearoyl chloride (11). 

Synthesis. Symmetrical diacyl peroxides (20, R = R = alkyl or aryl) are prepared by the reaction of an acyl chloride or anhydride with sodium peroxide or hydrogen peroxide and a base ... 

Potassium salts of the peroxides (27—29) are prepared from the reaction of Caro s acid [7722-86-3] H2SO, with acyl chlorides, chloroformates, or organosulfonyl chlorides in the presence of potassium hydroxide (44). 

Mixed chloiide alkoxides aie prepared by reaction with acyl chlorides, metal chlorides, hydrogen chloride, or chlorine (64). 

Cellulose esters of unsaturated acids, such as the acetate methacrylate, acetate maleate (34), and propionate crotonate (35), have been prepared. They are made by treating the hydrolyzed acetate or propionate with the corresponding acyl chloride in a pyridine solvent. Cellulose esters of unsaturated acids are cross-linkable by heat or uv light solvent-resistant films and coatings can be prepared from such esters. 

When nitration of pyridazine iV-oxides is carried out with acyl nitrates (prepared in situ from acyl chlorides and silver nitrate) the reaction takes place at the /3-position relative to the iV-oxide group. Under these circumstances only mononitro derivatives are formed. For example, nitration of pyridazine 1-oxide with acetyl nitrate yields 3-nitropyridazine 1-oxide (17%) and 5-nitropyridazine 1-oxide (0.8%), whereas with benzoyl nitrate a better yield of 5-nitropyridazine 1-oxide is obtained. 

Benzyl chloromethyl ketone has been prepared by the reaction of diazomethane with phenylacetyl chloride. The method of Clibbens and Nierenstein, in which one equivalent of diazomethane is added to the acyl chloride and the chloromethyl ketone obtained directly, could not be duplicated by Bradley and Schwarzenbach or by the submitters. 

The acyl derivatives of A-hydroxypyridine-2-thione are a synthetically versatile source of free radicals. These eompounds are readily prepared from reactive acylating agents, sueh as acyl chlorides, and a salt of A-hydroxypyridine-2-thione ... 

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