Acid halide preparation

Many salt-like halides can be prepared by the action of the hydro-halic acid. HX, on the metal or its oxide, hydroxide or carbonate. The halides prepared by this method are often hydrated, particularly when a less electropositive metal is involved, for example zinc, iron. 

Strictly speaking the alkyl halides are esters of the halogen acids, but since they enter into many reactions (t.g., formation of Grignard reagents, reaction with potassium cyanide to yield nitriles, etc.) which cannot be brought about by the other eaters, the alkyl halides are usually distinguished from the esters of the other inorganic acids. The preparation of a number of these is described below. 

Thiazolecarboxylic acid hydrazides are prepared by the same general methods used to prepare amides, that is, by treating acids, esters, amides, anhydrides, or acid halides with hydrazine or substitued hydrazines. For example, see Scheme 21 (92). The dihydrazides are obtained in the same way (88). With diethyl 2-chloro-4,5-thiazoledicarboxylate this reaction gives the mono hydr azide monoester of 2-hydrazine-4,5-... 

Conversion of Acid Halides into Anhydrides Nucleophilic acyl substitution reaction of an acid chloride with a carboxylate anion gives an acid anhydride. Both symmetrical and unsymmetrical acid anhydrides can be prepared in this way. 

Conversion of Acid Halides into Esters Alcoholysis Acid chlorides react with alcohols to yield esters in a process analogous to their reaction with water to yield acids. In fact, this reaction is probably the most common method for preparing esters in the laboratory. As with hydrolysis, alcoholysis reactions are usually carried out in the presence of pyridine or NaOH to react with the HC1 formed. 

Conversion of Acid Halides into Amides Aminolysis Acid chlorides react rapidly with ammonia and amines to give amides. As with the acid chloride plus alcohol method for preparing esters, this reaction of acid chlorides with amines is the most commonly used laboratory method for preparing amides. Both monosubstituted and disubstituted amines can be used, but not trisubstituted amines (R3N). 

In the alkyl chain hydroxy groups or side chains may be present. The reaction is somewhat different when acyl halides are used. Hydroxymethanediphosphonic acid is prepared by reacting phosgene with an alkali metal, dialkyl phosphite. The reaction is rapid and exothermic. The temperature is controlled between 10 and 20°C. After hydrolysis with HC1, hydroxymethanediphosphonic acid is recovered [91,92]. 

The above transformations show a few of the many inorganic esters that can be prepared by attack of an inorganic acid or, better, its acid halide or anhydride, on an alcohol. Although for convenience all these similar reactions are grouped together, these are not all nucleophilic substitutions at R. The other possible pathway is nucleophilic substitution at the inorganic central atom ... 

These reactions are most important for the preparation of acyl fluorides. " Acyl chlorides and anhydrides can be converted to acyl fluorides by treatment with polyhydrogen fluoride-pyridine solution" or with liquid HF at — 10°C. Formyl fluoride, which is a stable compound, was prepared by the latter procedure from the mixed anhydride of formic and acetic acids. Acyl fluorides can also be obtained by reaction of acyl chlorides with KF in acetic acid or with DAST. Carboxylic esters and anhydrides can be converted to acyl halides other than fluorides by the inorganic acid halides mentioned in 10-77, as well as with PhsPXa (X = Cl or but this is seldom done. Halide exchange can be carried out in a... 

Even though sulfuryl chloride and sulfuryl fluoride can be considered as the disubstituted acid halides of sulfuric acid, the monosubstituted derivatives are also useful compounds that undergo many reactions a result of the reactive -OH group. The monosubstituted compounds can be prepared by the following reactions ... 

Esters of 4, which are used as substrates for the preparation of D-glucofuranosylurono-6,3-lactone halides (see Section 1,1) or aryl D-glucofuranosidurono-6,3-lactones (see Section 1,2), are prepared by reaction of 4 with acid halides or anhydrides in the presence of a basic or an acidic catalyst. 

A useful approach for the preparation of chiral (3-aminophospho-nic acids from the naturally occurring a-amino acids has been reported.139 The overall scheme (Equation 3.4) involves formation of the phthalimide-acid halide from the starting a-amino acid followed by a Michaelis-Arbuzov reaction with triethyl phosphite to give the acylphosphonate. Complete reduction of the carbonyl group in three steps followed by hydrolysis of the ester and amide linkages provides the target material in very high yield without racemization (>99% ee). 

The 7-hydroxy-a,/3-( )-alkenoic esters were prepared readily from acid halides and silver acetylenides followed by NaBH4 reduction (Table 7).515... 

Like simple aryl halides, furyl halides take part in Suzuki couplings as electrophiles [41, 42]. Young and Martin coupled 2-bromofuran with 5-indolylboronic acid to prepare 5-substituted indole 37 [43]. Terashima s group cross-coupled 3-bromofuran with diethyl-(4-isoquinolyl)borane 38 to make 4-substituted isoquinoline 39 [44]. Similarly, 2- and 3-substituted isoquinolines were also synthesized in the same fashion [45]. 

This procedure has been used to prepare a variety of substituted a-bromohydrocinnamic acids 2 p-acetyl-a-bromohydro-cinnamic acid was prepared for the first time by this method. The method illustrates a typical application of the Meerwein reaction for the arylation of unsaturated substrates.3 In this reaction a catalytic amount of a copper(I) salt is used to reduce an aryl diazonium salt forming an aryl radical and a copper(II) halide. Addition of the aryl radical to an unsaturated substrate forms an alkyl radical that is reoxidized by the copper(II) halide present forming an alkyl halide and regenerating the copper(I) salt catalyst. In this preparation, the product, an a-bromo acid, is formed in an acidic reaction mixture and dehydro-halogenation does not occur. However, dehydrohalogenation... 

The most frequently used method for the preparation of isoquinoline Reissert compounds is treatment of an isoquinoline with acyl chloride and potassium cyanide in water or in a dichloromethane-water solvent system. Though this method could be successfully applied in a great number of syntheses, it has also some disadvantages. First, the starting isoquinoline and the Reissert compound formed in the reaction are usually insoluble in water. Second, in the case of reactive acyl halides the hydrolysis of this reaction partner may became dominant. Third, the hydroxide ion present could compete with the cyanide ion as a nucleophile to produce a pseudobase instead of Reissert compound. To decrease the pseudobase formation phase-transfer catalysts have been used successfully in the case of the dichloromethane-water solvent system, resulting in considerably increased yields of the Reissert compound. To avoid the hydrolysis of reactive acid halides in some cases nonaqueous media have been applied, e.g., acetonitrile, acetone, dioxane, benzene, while utilizing hydrogen cyanide or trimethylsilyl cyanide as reactants instead of potassium cyanide. 

KCl, dissolution process, 39 416 Ketab, synthesis, 30 263 Ketenimine complexes with iron, 12 245 KetiminoberyIlium halides, preparation and properties of, 14 307-308 a-Keto acid, formation, 43 427-428... 

Carbazole can be more easily converted fully and irreversibly to its N-anion by bases stronger than potassium or sodium hydroxide amide and hydride bases under anhydrous conditions have been employed. Thus, sodium amide in liquid ammonia was utilized with the appropriate halide for the preparation of 9-(prop-l-yn-3-yl)carbazole (29 R = CH2C=CH) ° and 9-methylcarbazol-l-ylcarboxylic acid the preparation of 3-dimethylamino-9-(2-hydroxyethyl)carbazole from ethylene oxide utilized sodium amide in... 

The most convenient synthesis of halogenopyrazines and -quinoxalines is by halogenation of pyrazinones and quinoxalinones with phosphoryl or other acid halides for example, 5-hydroxy-2-pyrazinecarboxylic acid, rather than 5(477)-pyrazinone-2-carboxylic acid, is chlorinated with phosphorus pentachloride/phosphoryl chloride to afford a 63% yield of 5-chloro-2-pyrazinecarbonyl chloride <1994SL814>. Sato and Narita provided an improved synthesis of various halogenopyrazines in which 2(l//)-pyrazinones were activated with chlorotrimethylsilane to give silyl ethers (Section 8.03.7.3). This procedure is most effective for synthesis of bromopyrazines whose overall yields are 62-81% <1999JHC783>. Bromopyrazine is directly prepared by treatment of 2-(l//)-pyrazinone with phosphoryl... 

Smith and co-workers adapted Sheehan and Izzo s original synthesis of 2-aryl-4(57/)-oxazolones and developed a general synthesis of 2-aIkylA(57/)-oxazo-lones. Teatment of an acid halide with AgNCO followed by diazomethane produced 344 that were immediately converted to the 2-alkylA-oxazole triflates 345. The authors noted that ethanol-free diazomethane was required to prepare 344. The oxazole triflates 345 were, in turn, key intermediates leading to a variety of 2,4-disubstituted oxazoles required for natural products (Scheme 6.73). 

The two bridgehead hydrogens Ha and Hb in the anisaldehyde dithioace-tal (130) have a large difference in their acidities, as indicated by the NMR chemical-shift difference (4.88 and 5.03 ppm). Preparation of the monocarbanion (1 BuLi in THF at -78°C) and quenching with DC1 removed only the higher field hydrogen. The carbanion can be reacted with electrophiles such as primary halides, acid halides, or aldehydes to produce (135). Carbanion generation and alkylation can be repeated on (135) to yield the disubstituted derivative (136) as shown in Scheme 44. 

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