Hiinig s base

A theoretical study based on PM3 frontier molecular orbital (FMO) and potential energy surface (PES) analysis at the RHF/6-31-I-G level was performed to examine the reaction of l-amino-2-ethoxycarbonylpyridinium mesitylenesulfonate and acrylonitrile in the presence of Hiinig s base leading to the formation of 3-cyano-4-hydroxy-l,2-dihydropyrido[l,2-ft]pyridazi-nium inner salt (54) (99JOC9001). The calculations indicated that both the... 

A small library of thiazolidinones 138 has been prepared mixing directly a primary amine (as the HCl salt), an aldehyde and mercaptoacetic acid in EtOH in the presence of Hiinig s base and molecular sieves (120 °C for 30 min) [88]. Working with a chiral amine, a 1 2 mixture of diastereoisomers was obtained (Scheme 49). 

The reaction of bromide 17 with thiophenol 7 was instantaneous in the presence of Hiinig s base. The adduct 37 was isolated by crystallization in 88% overall yield... 

Reduction of 3-benzyl-8-chloro-4-oxo-4//-pyrido[l,2- ]pyrimidine-2-carboxylate <2004W004/064741> and 2-methyl-4-oxo-4//-pyrido[l,2-tf]pyrimidine-3-carboxylate <2003T4123> with DIBAL-H afforded 2- and 3-formyl derivatives, respectively. Reduction of /V-(4-fluorobenzyl)-3-hydroxy-8-[methoxy(methyl)amino]-4-oxo-6,7,8,9-tetra-hydro-4//-pyrido[l,2- ]pyrimidine-2-carboxamide with Zn-dust in aqueous AcOH afforded the 8-methylamino derivative, which was acylated with AcOH in the presence of Hiinig s base, HOBt, and l-(3-dimethylaminopro-pyl)-3-ethylcarbodiimide-HCl <2004W004/058756>. 3-(Perhydropyrido[l,2- ]pyrimidin-2-yl)propylamine was obtained by catalytic hydrogenation of 2-(perhydropyrido[l,2- ]pyrimidin-2-yl)propionitrile over a Pt02 catalyst <2003FRP1275647>. 

Rees and co-workers have carried out extensive studies of the highly sulfurated bis[l,2]-dithiolo[l,4]thiazine ring system 469, formed by reaction of Hiinig s base 468 with S2C12 and l,4-diazabicyclo[2.2.2]octane (DABCO) (Equation 128) <1997AGE281>. 

With these solid supports in hand, we turned our attention to a new route to the synthesis of our target molecule 23 (Scheme 8). The tricky reductive amination should be replaced by an N-alkylation. To that end, bromoacetic acid is attached to 24c using DIC and Hiinig s base followed by the nucleophilic substitution with the corresponding benzy-lamine in DMSO/toluene (1 1), which can be easily monitored by the Beilstein test, followed by sulfonamide formation in DCM using N-methylmorpholine as base. For the final cleavage, 2% TFA in DCM is used and the resulting solution is filtered in a saturated NaHCC>3 solution to neutralise the acid before evaporation of the solvent. The crude product was then crystallised from ethyl acetate/heptane to yield the desired product in 27% yield overall and 99A% HPLC purity (see Table 4). 

Stereoselective Clycosylations of Glycosyl Iodides General methods for a-selective glycosylation of glycosyl iodides via in situ anomerization have been established [197]. Armed glycosyl iodides undergo the reaction in the presence of tetrabutylam-monium iodide (TBAI) and Hiinig s base (diisopropyl ethylamine DIPEA) with... 

Stock solutions of the anthranilic acids 1 to 5 (note 5) in CH2C12 were prepared by dissolving 2.4 mmol of each anthranilic acid in 10 mL CH2C12 and 1 mL Hiinig s base. A total of 2.00 mL of the appropriate anthranilic acid solution was added to each reactor (0.4 mmol). The resins were mixed at ambient temperature for 2h drained and washed with CH2C12 (5 x 2mL), MeOH (5 x 2mL), and DMA (10 x 2mL) (note 6). A few resin beads were sampled for each anthranilic acid used and analyzed by diffuse reflectance FT-IR to confirm complete reaction. 

Stock solutions of amines 6-10 in DMA were prepared by dissolving 4.14 mmol of each amine in 11 mL DMA and 1 mL Hiinig s base (10 mL DMA/2mL Hiinig s base were used for the hydrochloride salt 10). Aliquots, 1.00 mL (0.345 mmol), of the appropriate amine solution were added to each reactor followed by 1.00 mL 0.345 M PyBOP in DMA (0.345 mmol). The resins were mixed for 2h and drained then equal amounts of amine and PyBOP solutions were added and the resins were mixed for another 1 h (note 7). The reactions were drained and washed with DMA (5 x 2mL), MeOH (5 x 2mL), and DMF (10 x 2mL). 

The anthracenesulfonamide linkage was cleaved under mild, solid support compatible conditions such as thiophenol or 1,3-propanedithiol and Hiinig s base. 

Other bis[l,2]dithiolo[l,4]thiazines 75 and 76 can be also selectively obtained by the reaction of Hiinig s base with sulfur monochloride through the addition of oxygen donors such as cyclopentadienylacetic or formic acid (1998JOC2189 Scheme 38). 

When the reaction of Hiinig s base with sulfur monochloride was performed in boiling chlorobenzene, the corresponding bis[l,2]dithiolopyrroles 77-79 were formed by sulfur extrusion from intermediates 74-76 (Scheme 39). 

The reaction of Hiinig s base, sulfur monochloride and toluene-p-sulfonhydrazide under the same conditions is more complex and gives monohydrazone 91 in low yield (2001JCS(P1)2409 Scheme 43). 

Cyclopentenylacetic acid when treated with sulfur monochloride, Hiinig s base and N-chlorosuccinimide in tetrahydrofuran gave trichlorocyclopenta[l,2]-dithiole ester 104, a product of heterocyclic ring formation, chlorination and dehydrochlorination and, unexpectedly, the conversion of the acid in THF into its 4-chlorobutyl ester (1999JCS(P1)1023 Scheme 52). 

This reaction was extended further to cyclopentenone and cyclopentanone oximes (Scheme 68). The greatest improvement in the syntheses was the use of M-ethyldizsopropylamine (Hiinig s base) that led to the highest yields of... 

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