Formation, heats Paraformaldehyde

The heat of the desired reaction between paraformaldehyde and glycols was estimated from the difference between the heats of formation of the reactants and products. As the heat of formation of paraformaldehyde is not available, the reaction between formaldehyde and propylene glycol was used — that is ... 

Gorski 8t Makarov (Ref 4) consists of treating Nitromethane with paraformaldehyde in tbe presence of K carbonate. Yields are 43—45%-Pure compd can be prepd by treating an ethereal soln of CHgl-CHgOH with Ag nitrate (See also Ref 5). Its heats of cocibstn formation are given by Medard Thomas (Ref 9). 

In one route, tidopidine (1) was assembled via Sn2 displacement of 2-chlorobenzyl chloride (9) with 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine (8). " The nucleophile 8 was synthesized by heating 2-thiophen-2-yl-ethylamine (6) with 1,3-dioxolane in the presence of concentrated hydrochloric acid. 1,3-Dioxolone gave better yields than with formaldehyde, paraformaldehyde and 1,3,5-ttioxane. The interesting transformation 6 —> 8 first involved the formation of the corresponding Mannich base 7, which then underwent a Pictet-Spengler type reaction to afford the ring-closure product 8. It was of interest to note that a possible intramolecular aminomethylation did not take place. 

The formaldiminium ion formed from the reaction of 4-hexynylamine (90 R = R = Me) with paraformaldehyde and camphorsulfonic acid is reported not to cyclize when heated for 1 h at 1(X) C in the weakly nucleophilic solvent acetonitrile. However, when nucleophilic salts are added the 3-alkylidene-piperidines (91) are formed in good yields (Scheme 32). Attempted cyclizations of (90) in the presence of weaker nucleophiles such as benzenethiol or methanol were less effective, the former yielding <15% of the expected alkylidenepiperidine product, while the latter provided no products of cyclization. If the strong nucleophile iodide is employed, even a weakly nucleophilic terminal alkyne can be successfully cyclized. In all of these cyclizations of 4-alkynylamines only formation of a six-membered ring product was observed. The (2)-stereochemistry of the alkylidene side chain evolves from antarafacial addition of the internal iminium cation and the external nucleophile to the alkyne. 

The first example of an addition reaction of an C(sp -B based organoboronic add to an iminium ion was reported by Petasis and Akritopoulou in 1993 [24]. They demonstrated the addition of ( )-alkenylboronic acids to preformed iminium ions derived from secondary amines and formaldehyde, to generate allylic amines 1 (Scheme 7.1). Typically, a two-stage process was employed for the formation of 1. Initially, a secondary amine (including, dialkyl, acyclic and cydic examples) was heated with paraformaldehyde in dioxane or toluene solvent at 90 °C for 10 min. An ( )-alkenyl-boronic acid was then added, and the solution either stirred at 90 °C for 10 min, or at room temperature for 3 h. The allylic amine product 1 was then isolated through a standard aqueous work-up (sequential treatment with aqueous HCl and NaOH). The synthetic utility of this chemistry was demonstrated in this first report by a synthesis of the oral antifungal agent naftifine (2). 

A suspension of powdered 91 %-paraformaldehyde in glacial acetic acid and coned. H2SO4 heated at 50 until dissolved, cooled to ca. 35 , acetonitrile added dropwise at 35-45 , stirring continued until the spontaneous reaction is completed, jn-xylene added, heated slowly to 65-75 whereupon a self-sustaining reaction occurs with formation of a homogeneous mixture, finally heated 5 hrs. at 85-90 crude N,N -diacetyl-4,6-dimethyl-l,3-di(aminomethyl)benzene. Y 75%. F. e. s. G.L. Parris and R. M. Ghristenson, J. Org. Ghem. 25, 1888 (1960). 

Meth) i formate is also reported among the products obtained on heating formaldehyde polymers, such as paraformaldehyde, aloneand in the presence of sulfuric acid . 

Iodine is stated not to act upon paraformaldehyde even in the presence of sunlight at ordinary temperatures. However, on heating in a sealed tube at 120-125°C for 7 to 8 hours, reaction takes place with formation of methyl iodide, acetaldehyde, diiodomethyl ethei (ICH2OCH2I), carbon monoxide, and hydrogen iodide . In the presence of alkali, solutions of iodine in potassium iodide oxidize formaldehyde quantitatively to formic acid,... 

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