Aluminum chloride-phosphorus oxychloride

Aluminum chloride-phosphorus oxychloride complex, 31, 88 Amberlite IR-4B resin, 32, 13 Amidation, of isocyanic acid with bromo-aniline and other aromatic amines, 31,8... 

Chloro-(/7-cyanophenyl)phenylphosphine 349 Dichloro(phenyl)phosphine (60 g) is added to a slurry of i -cyanobenzenediazonium tetrafluoroborate (72 g) and copper(i) bromide (2.4 g) in dry isopropyl acetate (300 ml). After about 20 min a violent reaction sets in which is moderated by external cooling so that the temperature remains between 20° and 40°. When gas evolution ceases, aluminum turnings (8 g) are added and the mixture is stirred for 2 h at 40-50°. Then the liquid is decanted from unused aluminum, and phosphorus oxychloride (51 g) is added to decompose the aluminum chloride complex. Distillation then affords a forerun (5 g), followed by the main fraction (39 g, 47%) between 15870.7 mm and 195°/ 3.1 mm (owing to unavoidable decomposition the pressure does not remain constant during the distillation). Further distillation gives a product boiling at 16270.2 mm. 

The title compounds also undergo the Claisen rarrangement (5-allyloxypyrazoles 4-allyl-5-pyrazolones) and are readily transformed into 5-chloropyrazoles by means of phosphorus oxychloride (8OCHE1). In the presence of aluminum chloride 5-acyloxypyrazoles (481) undergo the Fries rearrangement affording 4-acyl-5-hydroxypyrazoles (482). 

For the preparation of aryl esters from phosphorus oxychloride, a Lewis acid is generally added as a catalyst. Commonly, aluminum chloride with an excess of phosphorus oxychloride added to the phenol provides excellent yields (Equation 4.2).4... 

Controlled alkylation of phosphorus oxychloride may also be accomplished using a modification of this approach. Reaction of alkyl-aluminum dichloride with phosphorus oxychloride generates the aluminum chloride complex of the alkylphosphonodichlori-date,54 which may be isolated as the simple compound or directly used in reaction to generate other derivatives of the alkylphospho-nic acid. 

An indolone comprises a prominent moiety in the dopamine D2 selective antipsychotic agent ziprasidone (32-8). Reduction of the ketonoid carbonyl group on the indoxyl (32-1) under Wolff-Kischner conditions affords the indolone (32-2). Acylation of the product with chloroacetyl chloride in the presence of aluminum chloride then affords the reactive chloroacetyl derivative (32-3). In a convergent sequence, reaction of isothiazolone (32-4) with phosphorus oxychloride leads to... 

Much the same activity is retained when the nitrogen atoms in the heterocyclic nucleus are shifted around. The convergent scheme to this related compound starts with the acylation of alanine (35-1) with butyryl chloride (35-2). The thus-produced amide (35-3) is then again acylated, this time with the half-acid chloride from ethyl oxalate in the presence of DMAP and pyridine to afford the intermediate (35-4). In the second arm of the scheme, the benzonitrile (35-5) is reacted with the aluminate (35-6), itself prepared from trimethyl aluminum and ammonium chloride, to form the imidate (35-7). Treatment of this intermediate with hydrazine leads to the replacement of one of the imidate nitrogen atoms by the reagent by an addition-elimination sequence to form (35-8). Condensation of this product with (35-4) leads to the formation of the triazine (35-9). Phosphorus oxychloride then closes the second ring... 

Phosphorus oxychloride reacts with ethylene oxide in the presence of aluminum chloride to give tris-2-chloroethyl phosphate, a valuable plasticizer (75). Phosgene reacts with ethylene oxide and other alkylene oxides to form esters of chlorocarbonic acid (76) (see Carbonic and carbonochloridic esters). 

There is some indication that the phosphorus oxychloride formed in the preparation of the acid chloride interferes with the cyclization when aluminum chloride is used. Thus, the cyclization of a/y-diphenylbutyrio acid was effected in 94% yield only after the volatile phosphorus compounds had been removed from the reaction mixture -otherwise the yield was only 77%.114 By removing the phosphorus oxychloride under reduced pressure before introduction of the aluminum chloride,114 115 114 seven acids have been cyclized in yields of 85% or better. No single set of directions can be given which is entirely general. The following description of the cyclization of a/y-diphenylbutyric acid is a typical example of the form of procedure. The critical phase of the reaction is during the aluminum chloride treatment the optimum time and temperature may vary for each add. 

The reaction between phosphorus oxychloride and aluminum chloride is exothermic. 

Aromatic nitriles are also prepared by heating amides with phosphorus pentoxide, phosphorus oxychloride, phosphorus pentachloride, thionyl chloride, and ammonium sulfamate. In addition, the action of a double salt of aluminum and sodium chlorides, NaCl- AlClj, gives excellent yields of nitriles from both aliphatic and aromatic amides. Heating an amide with phthalic anhydride causes dehydration. A novel synthesis consists in treating a mixture of an aromatic acid and p-toluene-sulfonamide with phosphorus pentachloride the yields of nitriles range from 63% to 79%. ... 

These compounds have been prepared in two ways from 3-amino-l,2,4-triazines. In the first case, the aminotriazine is converted into the amidine (359) with iV,iV-dimethylfor-mamide or -acetamide acetal. Reaction of the amidine with hydroxylamine produces the amidoxime (360) and cyclization with phosphorus oxychloride forms the desired bicyclic product (361) (77JOC1018). Also, the desired ring system can be synthesized by treating 3-amino-l,2,4-triazines with acetonitrile in the presence of aluminum chloride to afford the acetamidines (362) which, in one case (R = = Me), can be transformed into... 

Thiophenealdehyde has been prepared by the decarboxylation of 2-thienylglyoxalic acid, by the action of 2-thienylmagne-sium iodide on ethyl orthoformate followed by hydrolysis of tbe acetal, in small yields by the Rosenmund reduction of 2-thio-phenecarboxylic acid chloride, in small yields by the action of hydrogen cyanide, hydrogen chloride, and aluminum chloride on thiophene using benzene as a solvent, by a series of reactions from l-chloro-2,3-diketocyclopentane, by the hydrolysis of 2-thienylmethylhexamethylenetetrammonium chloride in neutral solution, and by the action of N-mcthylformanilidc on thiophene in the presence of phosphorus oxychloride. ... 

The yields of the pyrimidines 147 and the pyridines 151 are not high and vary greatly, depending on the structure of the starting materials. The latter can also determine the nature of the product. Thus, a mixture of 2,4-dimethyl-6-phenylpyrimidine, 2,4-dimethyl-4,6-diphenyl-4//-l,3-oxazine and 1-chloro-l-phenylethene was obtained by refluxing a 1 3 3 ratio of the acetophenone-benzonitrile-phosphorus oxychloride mixture, followed by treatment of the crude product with sodium carbonate solution .It has been shown that addition of an additional ketone molecule to the iminium intermediate is an alternative to the formation of the A -acylenamines and this route is catalyzed by aluminum chloride. Auricchio and coworkers believe also that the reaction of ketones with nitriles catalyzed with both protic and Lewis acids must be considered as a Ritter reaction (see, however, Section V.C). The cationic intermediate 152 thus formed can undergo either a proton shift giving enamide 153 or addition of another ketone molecule... 

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