Patent GB-688023-A (GB)
Title: Improvements in and relating to the production of ketonic amino alcohol compounds
IPC: C07C233/00
Filed: 1949-02-15
Abstract: Compounds of formula <FORM:0688023/IV (b)/1> are made by condensing a compound of formula <FORM:0688023/IV (b)/2> with formaldehyde in the presence of an alkaline condensation catalyst.  R1 and R2 are the same or different and are hydrogen, halogen, lower alkyl or lower alkoxy radicles, the term acyl including lower aliphatic acyl, halogen-substituted lower aliphatic acyl, benzoyl, substituted benzoyl and araliphatic acyl radicles.  Formaldehyde may be supplied as gas, as an aqueous or alcoholic solution, or as paraformaldehyde or other formaldehyde yielding polymer.  Preferably an excess of formaldehyde is used, about 3 to 5 mols. per mol. of nitro compound being indicated.  A solvent may be used and water, aqueous or anhydrous lower aliphatic alcohols, moist dialkyl ethers and dioxane-water mixtures are specified.  Condensation catalysts may be organic or inorganic bases or inorganic salts of acidic or pseudo-acidic organic compounds and many are specified, illustrative being hydroxides and amides or alkali and alkaline earth metals, alkali metal alkoxides, phenolates and salts of lower aliphatic carboxylic acids, tertiary amines and quat.-ammonium hydroxides. Weak alkaline catalysts, e.g. sodium and potassium bicarbonate, calcium hydroxide, pyridine, triethylamine, N-ethyl morpholine and N,N1-dimethylaniline are preferred since when strong alkalies are used the catalyst must be removed or inactivated immediately reaction ceases to prevent conversion of the product to the corresponding methylene bis compound.  In general 0.05 mol. or less of catalyst is used.  Temperatures specified are from 0-75 DEG  C. with reaction times of a few minutes to several hours.  The products are useful in the synthesis of and as antibiotics.  In examples: (1) p-nitro-o -bromoacetophenone is converted to its complex with hexamethylene tetramine by treatment with the latter in chloroform solution; the complex on treatment with ethanolic HCl yields p-nitro-o -aminoacetophenone hydrochloride which after isolation is acylated with acetic anhydride and sodium acetate to p-nitro-o -acetaminoacetophenone which with formaldehyde, methanol and sodium bicarbonate yields the corresponding b -hydroxypropiophenone, and substituted b -hydroxypropiophenones are also made by warming (2) p-nitro-o -benzamidoacetophenone with paraformaldehyde, methanol and sodium bicarbonate, potassium carbonate or sodium, (3) o - methyl - p - nitro - o  - acetamidoacetophenone, methanol, paraformaldehyde and sodium bicarbonate, (4) m-methoxy-p-nitrophenyl - o  - p1 - toluylaminoacetophenone, paraformaldehyde, ethanol and pyridine, (5) 2-nitro - 4,5 - dimethyl - o  - phenacetamido - acetophenone with paraformaldehyde, ethanol and calcium hydroxide; (6) 3-nitro-5-chlorophenyl - o  - (a  - chloropropionamido) - acetophenone, paraformaldehyde, aqueous methanol and sodium carbonate, and (7) p-nitro-o -dichloroacetamido-acetophenone, aqueous formaldehyde, methanol and sodium bicarbonate.  Specifications 652,273, 652,280 and 660,381 are referred to  The Specification as open to inspection under Sect. 91 also comprises the subject-matter of Specifications 688,107, 688,108 and 688,109.  This subject-matter does not appear in the Specification as accepted.