Paraformaldehyde hydrolysis

These amines are also synthesized by refluxing 2-aminothiazole with paraformaldehyde and acetophenone in ethanol (Scheme 6) (39) or by alkaline alkylation of 2-acetamidothiazole followed by hydrolysis (40-44). 

An enzyme-catalyzed appHcation has been used to prepare the enantiomers of hydroxy-substituted tetrahydroisoquinolines (160). The synthesis of ( V)-reticuline [485-19-8] (30) has been reported using similar methodology (161). The substitution of formic acid and paraformaldehyde in this method leads to lower reaction temperatures, freedom from hydrolysis of protective groups, and improved yields (162). 

Paraformaldehyde/DMSO dissolves cellulose rapidly, with neghgible degradation, and forms the hydoxymethyl (methylol) derivative at Ce [ 140-142]. Therefore, cellulose derivatives at the secondary carbon atoms are easily obtained after (ready) hydrolysis of the methylol residue. Additionally, fresh formaldehyde may add to the methylol group, resulting in longer methylene oxide chains, that can be functionahzed at the terminal OH group, akin to non-ionic, ethylene oxide-based surfactants [143,144]. 

Pindur et al. reported the synthesis of carazostatin (247) starting from the 2-vinylindole 958, which previously served as the key building block in the total synthesis of carbazoquinocin C (274) (see Scheme 5.130). The 2-vinylindole (958), readily available in four steps starting from Af-(phenylsulfonyl)indole (956), was transformed to the indolylacetic acid (1568) by treatment with KCN and paraformaldehyde followed by alkaline hydrolysis. Subsequent acid-catalyzed polar cyclization of 1568 led to carazostatin (247) (648) (Scheme 6.1). 

Treatment of pentasubstituted benzene 1169 with an excess of paraformaldehyde in the presence of ZnCl2 under acidic conditions successfully installs a chloromethyl group ortho- to the acetic acid substituent, furnishing a mixture of 1170 and the cyclized isochroman-3-one 1171. As these acidic conditions are not themselves enough to totally finish the cyclization, basic hydrolysis is conducted to complete the cyclization to the isochroman-3-one 1171, a key intermediate during a synthesis of mimosamycin (Scheme 288) <2000JOC635>. 

Ligands 56 and 46 were made by the same procedure except that in 56 iV-(2-chloroethanoyl)-2-phenylethylamine was replaced by a combination of paraformaldehyde and MeP(OEt)2 and the resulting triphosphi-nate ester was subjected to base hydrolysis. 

Substituted oxazolidin-5-one derivatives, which are prepared from N -protected a-annino dicarboxyhc acids and paraformaldehyde, are employed for dual protection of the a-annino and a-carboxy groups in the synthesis of P-aspartyl and y-glutamyl esters (Scheme 4).Py For this purpose the oxazolidinone derivatives are synthesized by treatment of the Z amino acids with paraformaldehyde in a nnixture of acetic anhydride, acetic acid, and traces of thionyl chloride or by azeotropic distillation of the Z amino acids with paraformaldehyde and 4-toluenesulfonic acid in benzene. The resulting heterocychc compounds are readily converted into the tert-butyl esters with isobutene under acid catalysis. Esterification is achieved with tert-butyl bromidet or with Boc-F.P l Finally, the oxazolidinone ring is opened by alkaline hydrolysis or catalytic hydrogenolysis to yield the tert-butyl esters. 

Reaction of 9 with paraformaldehyde afforded the 1,3-dioxane 10, which was subjected to oxidative hydrolysis of dithioacetal group with mercuric perchlorate to form 11, the AB ring moiety of sesbanimides 1 and 3, in 35% overall yield from 4. 

Five different crystalline products were separated and characterized from the reaction mixture obtained from the condensation of L-rhamnose with paraformaldehyde. None of the products isolated corresponded to the acetal isolated earlier by Lobry de Bruyn and Alberda van Ekenstein. The expected 1,2 3,5-di-0-methylene-a-L-rhamnofuranose was identified on graded hydrolysis, this gave the 3,5-0-methylene acetal. However, the possibility of the 3,4-0-methylene-L-rhamnopyranose structure was not eliminated. The main product was 3,4-0-(oxidodimethylene)-L-rhamnose a smaller yield of 2,3-0-(oxidodimethylene)-a-L-rhamnose was obtained. 

Suh et al.65 have reported a formal total synthesis of Mansonone F and this is described in Scheme 12. 5-Methoxy-a-tetralone (127) was converted to 1-methyl-5-hydroxy-naphthalene (128) by the standard organic reactions. Treatment of (128) with phenyl boronic acid, paraformaldehyde and propionic acid followed by catalytic hydrogenation yielded compound (129). This on alkylation gave the compound (130) which on alkaline hydrolysis was converted to acid. The acid halide underwent intramolecular Friedal-Crafts acylation affording an intermediate (131) whose transformation to Mansonone F has been accomplished by Best and Wege.59... 

A highly enantioselective enzymatic acylation was observed on N-hydroxymethylated P-lactam 50, which was prepared from ( )-14 with paraformaldehyde by sonication in tetrahydrofuran [88]. Lipase AK-catalysed butyrylation with vinyl butyrate gave the readily separable azetidinones 51 and 52. Hydrolysis of 51 and 52 resulted in the 2-ACPC hydrochlorides 53 and 54, respectively (Scheme 8) [88]. 

General experimental details are as follows.697b It is usual first to mix the carbonyl component with the amine, which is presented as, e.g., hydrochloride or acetate. An appropriate hydrogen ion concentration must be maintained. For the preparation of aminoalkyl compounds that are liable to hydrolysis it is recommended that the water produced be removed by a drying agent or by azeotropic distillation. Dioxan is a suitable solvent, but it is often recommended that acetic acid be added to it. Ketones react better in alcohol with paraformaldehyde. Copper chloride or iron chloride is said to be a useful addition in reactions of acetylenes. Reactions of amines, phenols, and furans, even under mild conditions, may be accompanied by multiple condensation or resinification. 4-Hydroxybenzylamine is reported706 to be obtained in 92% yield when ammonia is led into a mixture of phenol and formaldehyde. 

Allylamines. Alkeneboronic acids are converted to allylamines of defined configuration on treatment with conventional Mannich reaction components (R2NH, paraformaldehyde). The required vinylboronic acids are available from 1-alkynes by reaction with catecholborane followed by hydrolysis. 

As a source of HCHO, formalin, a 37 percent aqueous solution of HCHO stabilized with 12 to 15 percent of methanol, is the most popular. Besides formalin, paraformaldehyde [(HCHO) ] and trioxane [(HCHO)3] are also used. When methanol is added in the feed or when methylal [CH2(OCH3)2] or hemiformal [CH3OCH2 OH] is used as the source of HCHO, a mixture of carboxylic acids and esters is obtained because both the esterification of carboxylic acid and the hydrolysis of ester are much more rapid than the condensation reaction. The reaction is usually performed in the presence of an excess of carboxylic acid with respect to the amount of HCHO the carboxylic acid/HCHO molar ratio is 1.3 to 20 because HCHO is generally more susceptible to degradation than carboxylic acids. The reaction temperature is in the range of 250 to 400 °C. 

As the sources of HCHO, formalin, trioxane [(HCHO)3], paraformaldehyde [(HCHO)J, methylal [CH2(OCH3)2], and hemiformal [CH3OCH2OH] are used. The reaction is usually accompanied with the hydrolysis of esters, which are fed and/or produced by the condensation reaction, and the esterification of acids which are fed and/or produced by the condensation reaction. 

Reagents i, MeOH-EtjN, RT ii, aq. HCl-MejCO iii, CrOj-aq. H SO -Me CO iv, MeOH-HCl v, 3MeONa-MeOH-heat vi, hydrolysis (and -COj) vii, 2 o-aminobenzaldehyde-SNaOH-HaO, heat viii, mono-esterify ix, 240 °C, 0.3 CuO X, Etl-NaH, RT, DME xi, paraformaldehyde-dioxan-trace cone. H2SO4, 100 °C, xii, 1 aq. HjOj-Bu OK-Bu OH-DMSO... 

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