DMFDEA

Fig. 27 Synthesis of heterocycies via propenoates. Reagents and conditions a Hippuric acid, CsCOs, DMF, 200 °C, 10 min, closed vessel b DMFDEA in DMF, 180 °C, 10 min, closed vessel c HOAc, 180 °C, 10 min, closed vessel...

Various other examples in this chapter have already highlighted how N,N-dimeth-ylformamide dimethyl acetal can be efficiently utilized as a synthon for the construction of heterocydic rings (see Schemes 6.189, 6.194, 6.195, 6.229, and 6.230). West-man and coworkers have described a two-step method for the generation of a wide variety of heterocydic scaffolds, based on the initial formation of alkylaminoprope-nones and alkylaminopropenoates from N,N-dimethylformamide diethyl acetal (DMFDEA) and the corresponding CH-acidic carbonyl compounds (Scheme 6.256)... 

In a more recent study, Westman and Lundin have described solid-phase syntheses of aminopropenones and aminopropenoates en route to heterocycles [32], Two different three-step methods for the preparation of these heterocycles were developed. The first method involved the formation of the respective ester from N-pro-tected glycine derivatives and Merrifield resin (Scheme 7.12 a), while the second method involved the use of aqueous methylamine solution for functionalization of the solid support (Scheme 7.12 b). The desired heterocycles were obtained by treatment of the generated polymer-bound benzylamine with the requisite acetophenones under similar conditions to those shown in Scheme 7.12 a, utilizing 5 equivalents of N,N-dimethylformamide diethyl acetal (DMFDEA) as reagent. The final... 

In a recent study, another method for microwave-assisted heterocycle synthesis leading to a small set of imidazole derivatives has been reported [54], These pharmaceutically important scaffolds were synthesized utilizing polymer-bound 3-N,N-(dimethylamino)isocyanoacrylate. This polymer support was easily prepared by treatment of [4-(bromomethyl)phenoxy]methyl polystyrene with a twofold excess of the appropriate isocyanoacrylate potassium salt in N,N-dimethylformamide (Scheme 7.37). The obtained intermediate was subsequently treated with N,N-di-methylformamide diethyl acetal (DMFDEA) in a mixture of tetrahydrofuran and ethanol to generate the desired polymer-bound substrate. 

N, N-Dimethylformamide diethyl acetal (DMFDEA) is a interesting reagent, since it can be used to form alkylaminopropenones or alkylaminopropenoates when reacted with compounds having activated methylene groups such as (3-ketoesters, acetophenone and N-acylglycine. These alkylaminopropenones or alkylaminopropenoates can subsequently be reacted with dinucleophiles to form a variety of heterocycles. Westman and co-workers32 have used DMFDEA for the synthesis of propenoates and propenones, which were used directly without intermediate purification for the formation of a number of heterocycles in a combinatorial fashion. Some examples are outlined in Scheme 5.16. The reactions were performed in a two-step one-pot procedure, which in this case were more suitable for combinatorial synthesis. 

The above described methodology was found to be very useful in a solid-supported synthesis of pyrazoles and pyrimidines via propenones developed by Westman and co-workers35 (Scheme 5.19). Merrifield resin was reacted with methylamine in water at 150°C for 10 min to form the solid-supported benzylmethylamine (3) in high yield (86% yield, 1.08 mmol/g based on elemental analysis). After washing, the resin was treated with 5 equiv. DMFDEA and 5 equiv of 4-phenoxyacetophenone at 180°C for 10 min in DMF to form the solid supported benzyl methyl aminopropenones (4). 

Treatment of L-biopterin with DMFDMA (or DMFDEA), then acetic anhydride in pyridine, gives l 2 -di-0-acety]-/V -(/V,ALdimethylaminoethylene)-L-biopterin (87). This can be converted by the Mitsunobu reaction into 3-methyl and 3-p-nitrophenethyl derivatives. The protective groups on the side chain diols and N1 of these compounds can be selectively cleaved to give biopterin. These reactions indicate their potential for biopterin modification [95MI31. 

A 2-amidinobenzoate (prepared from the amino ester and either a nitrilium salt or DMFDEA) is cyclized on heating with t-butoxide-t-butanol or a primary amine. Both methods yield a 3-substituted product. The internal amidinium salt... 

Many reagents may be used to cyclize an aminocarboxamide into a fused pyrimidinone (see pp. 211-216) the following may be added to the list triformamidomethane, DMFDEA and thiourea. Another example is shown in Section III.2. 

The reaction of a side-chain carboxamide with DMFDEA joins the NH to a neighbouring ring-NH and a fused pyrimidinone ring is formed. The same type of reaction may operate in acetic acid when carboxamide and ring-nitrogen are in different rings. 

Aminolysis of benzopyran 301 with ammonium acetate afforded the quinoline 302, which upon reaction with DMF diethyl acetal (DMFDEA) produced a mixture of the respective N- and O-alkylated derivatives 303 and 304. The latter compound was also prepared by chlorination of 302 with PCI5 followed by reaction with sodium ethoxide. Further treatment of 303 and 304 with DMFDEA in toluene at 180-200 °C resulted in C-alkylation to give 305 and 307, respectively. Column chromatography on silica gel resulted in the formation of 306 and 308, respectively with the recovery of the starting material 303 (91KGS86) (Scheme 57). 

Double condensation of dimethylformamide diethyl acetal (DMFDEA) with a suitable dinitro-xylene, followed by catalytic reduction of the resulting bis-enamine, directly afforded the benzo-... 

Adamsite 1 is the most difficult of the organoarsenicals to analyze. It has very high thermal stability and does not hydrolyze readily in the environment. Like most arsenicals, attempts to assess Adamsite by gas chromatography (GC) lead to rapid column deterioration and Adamsite carmot be derivatized with thiol derivatives <2003JCH(1000)253>. Schoene etal. developed two derivatization reactions for Adamsite. In the first, it was reacted with bromine in AcOH to give 2,2, 4,4, 6,6 -hexabromodiphenylamine 37. The alternative derivatization involved pyrolytic ethylation with dimethylformamide diethyl acetal (DMFDEA) and pyridine to yield 10-ethyl-5,10-dihydrophenarsazinine 38. The reaction mixture, which is Adamsite, EtOH, pyridine, and DMFDEA 39, was stored for 3 days in a closed vial at 90 °C. On column injection of 1 pi from this solution, no ethyl derivative could be detected, whereas splitless injection at 290°C injector temperature afforded EtPA 38 in the expected amount (Scheme 14) <1996JCH(719)401>. 

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