Oxalyl chloride-Dimethylformamide

N-Vinylpyrroles were also formylated by dimethylformamide-oxalyl chloride (CH2CI2, rt, 40 min) to give the corresponding N-vinylpyrrole-2-carbaldehydes 157 in yields up to 97% (09S587). 

A. N,N-Dimethylchloromethylenammonium chloride. A 500-mL, three-necked, round-bottomed flask is equipped with a magnetic stirring bar, thermometer (Note 1), and a three way stopcock fitted with a drying tube containing anhydrous calcium chloride and a rubber septum. The flask is charged with 50 mL of dichloromethane (Note 2) and 3.07 g (0.042 mol) of N,N-dimethylformamide (Note 3) added throu i the septum from a syringe, and cooled in an ice bath. To the cooled mixture is slowly added 5.23 mL (0.06 mol) of oxalyl chloride (Note 4) by means of a syringe. The addition 1s accompanied by gas evolution and formation of a white precipitate. The reaction mixture is stirred for an... 

A 1.00 g (1.9 mmoles) of (y-N-Tfa-L-Glu-a-OMe)-L-Glu-L-Glu-tetra-OMe was dissolved under argon in dry dimethoxyethane (30 ml) with warming and magnetic stirring, and triethylamine (0.55 ml, 3.97 mmoles) was added. The reaction mixture was cooled to -30°C (dry ice isopropyl alcohol), and oxalyl chloride (0.35 ml, 3.97 mmoles) was added followed by dimethylformamide (2... 

As an example we describe here the synthesis of the l//-l,2,4-diazaphosphole 22 that, on account of its easy accessibility and as parent compound of the class, is of general interest. The synthesis proceeds through condensation of the cation 21. The reaction of 21 with hydrazine involves cleavage of an ammonium salt to furnish the phosphole 23.46 The cation 21 is obtained via a methanaminium chloride—generated as an intermediate from N, A-dimethylformamide and oxalyl chloride—by condensation with tris(trimethylsilyl)phosphine. 

To this Schlenk tube (500 mL), add dimethylformamide (7.74 mL, 7.31 g, 100 mmol) and diethyl ether (150 mL) at room temperature, stirrer and cool the solution in an ice bath. Transfer oxalyl chloride (8.73 mL, 12.70 g, 100 mmol) in the pressure-equalizing funnel. 

Preparation of acid chlorides. The thionyl chloride method of preparing acid chlorides fails with some carboxylic acids (e.g., p-NOjCsHaCOzH) and with all sulfonic acids. Bosshard and co-workers" found that dimethylformamide catalyzes both reactions, either when used as solvent or when employed in catalytic amount in an inert solvent. The reactive, hygroscopic intermediate dimethylformirainium chloride was isolated from one equivalent each of dimethylformamide and thionyl chloride, and also obtained by reaction of dimethylformamide with phosgene, oxalyl chloride, or phosphorus pentachloride. It reacts with an acid with regeneration of dimethylformamide, the catalyst. In one example, 0.3 mole of p-nitrobenzoic acid was heated briefly at 90-95° with 0.315 mole of thionyl chloride and 0.03 mole... 

Bhongle, N.N., Notter, R.H., and Turcotte, J.G., Expedient and high-yield synthesis of alkylphosphonyl dichlorides under mild, neutral conditions. Reaction of f>w(trimethylsilyl)alkyl phosphonates with oxalyl chloride/dimethylformamide, Synth. Commun., 17, 1071, 1987. 

Briefly, carboxylic acid 14 which must be an essentially pure enantiomer (ratio 98 2) is converted to acid chloride 15 which is an oil that needs to be directly reacted with Meldrum s acid 16 in the presence of 2 moles of pyridine to yield 17 as a stable solid however, a slurry of 17 is treated with glacial acetic acid to provide 18 directly and 17 is not isolated. The process is telescoped in practice, and all the reactions are carried out in dichloromethane, which is recovered and recycled. Thus, 14 is converted into 15 using only a 10% molar excess of oxalyl chloride using 10 mole% of dimethylformamide as catalyst. The reaction is complete after 3 h reaction at room temperature (20 to 25°C) concentration and removal of the dichloromethane yields 15 as a crude oil that is suitable for direct reaction with Meldrum s acid and pyridine at 0 to 5°C in the relative molar ratio 1 2 in fresh dichloromethane. Workup with dilute hydrochloric acid and layer separation followed by water washes results in a solution of 17 in dichloromethane. The solution is concentrated to a slurry, which is treated with acetic acid at about 70 to 80°C to form 18. The reaction mixture is worked up by adding dichloromethane and washing with aqueous sodium carbonate followed by water washes. Concentration of the washed dichloromethane layer yields enantiomer 18 that is equal in optical purity to that of the starting carboxylic acid 14. The concentrate is vacuum distilled to provide a chemically stable and chemically pure ketone 18. This material has been shown to have a shelf life of 5 years at room temperature (Scheme 11.4). 

Reaction of phthalimidine with an equimolar ratio of oxalyl chloride-dimethylformamide generates tris(l-oxoisoindolin-2-yl)methane (32).52... 

It is formed on treatment of dimethylformamide with SOCl2, PC15, PC13, oxalyl chloride, or phosgene and affords the acid chlorides from carboxylic or suflonic acids [reaction (g)]. 

Acylation and alkylation reactions are illustrated in the following examples. Two modes of cyclisation of 2-(3,4-dimethoxybenzyl)-3-phenylpropionic acid in dichloromethane, after conversion to the acid chloride, have been described by reaction with oxalyl chloride in dimethylformamide during 12 hours (ref.81). After cooling of the starting solution to -15°C, aluminium bromide (in 100mole% proportion) in dichloromethane for 24 hours gave... 

Pettit and Nelson (1986) have designed an apparatus for diazo ketone preparation in which the carboxylic acid is first treated with oxalyl chloride dissolved in ether in one compartment. The acid chloride is formed after addition of triethylamine and a catalytic amount of dimethylformamide. Then the solution is filtered and added to ethereal diazomethane at -78°C in the second compartment. 

Similarly, monoalkyl methylphosphonochloridates (eq 8) can be made from dialkyl esters thionate acid chlorides could not be made by this method. Thionyl chloride and PCI5 were also used to make this type of compound (see also Oxalyl Chloride— Dimethylformamide). 

Physical Data see entries for Oxalyl Chloride and N,N-Dimethylformamide. 

Form Supplied in generated in situ under anhydrous conditions from oxalyl chloride and either catalytic or stoichiometric dimethylformamide, typically in halogenated solvents such as dichloromethane acetonitrile, or hexane. The intermediate dimethylforminium chloride (DMFCl) can be isolated as a hygroscopic solid, mp 140 °C (see also Thionyl Chloride, Phosphorus Oxychloride). 

Formylation. Vilsmeier formylation reactions have been reviewed. Oxalyl chloride-dimethylformamide has found occasional use one application has been preparation of a piperidine substituted dialdehyde (eq 10). ... 

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