Patent GB-814359-A (GB)
Title: Novel pyridine derivatives and a process for the manufacture thereof
Filed: 1957-11-15
Abstract: The invention comprises compounds and tautomeric forms of the formula <FORM:0814359/IV (b)/1> wherein the broken line denotes that a double bond may be present in the 5:6-position and wherein R1 and R2 are identical or different aliphatic hydrocarbon radicals containing a total of 2-10 C. and are saturated when there is a single bond in said 5:6-position but may be saturated or unsaturated when there is a double bond in the said 5:6-position, and acid addition salts thereof.  The compounds are prepared by cyclizing a 1-R1-1-R2-1-cyano-2-oxo-4-amino-butene-(3), wherein R1 and R2 are identical or different saturated aliphatic hydrocarbon radicals containing a total of 2-10 C, in the presence of an alkaline cyclization agent (e.g. an alkali metal alcoholate) and, where the tetrahydro derivative is required, catalytically hydrogenating the so-obtained 3-R1-3-R2-2-amino-4-oxo-3:4-dihydro-pyridine.  Salts may be formed with acetic, tartaric, salicylic, hydrohalic, sulphuric and phosphoric acids.  R1 and R2 may be methyl, ethyl, propyl, butyl, isopropyl, isobutyl, allyl or isobutenyl.  The examples describe the preparation of 3-R1-3-R2-2 - amino - 4 - oxo - 3:4 - dihydropyridines, in which R1 and R2 are diethyl, di-n-propyl, diallyl, diisobutyl, diisobutenyl, allyl and isopropyl, n-propyl and isopropyl, methyl and ethyl, methyl and n-propyl, methyl and isopropyl, and methyl and allyl; 3-R1-3-R2-2-amino - 4 - oxo - 3:4:5:6 - tetrahydropyridines in which R1 and R2 are diethyl, di-n-propyl, diisobutyl, methyl and ethyl, methyl and n-propyl, methyl and isopropyl, and n-propyl and isopropyl; and hydrochlorides of such compounds.  1 - R1 - 1 - R2 - 1 - cyano - 2 - oxo - 4 - aminobutenes-(3) are prepared by reacting the corresponding 1 - R1 - 1 - R2 - 1 - cyano - 2 - oxo - 4 - hydroxybutenes - (3) with ammonia. Compounds are prepared in which R1 and R2 are diethyl, di-n-propyl, diallyl, diisobutyl, diisobutenyl, methyl and ethyl, methyl and n-propyl, methyl and isopropyl, methyl and allyl, and allyl and isopropyl.  1 - R1 - 1 - R2 - 1 - cyano - 2 - oxo - 4 - hydroxybutenes-(3) are prepared by condensing the corresponding a -R1-a -R2-acetoacetonitrile with a formic acid ester (e.g. methyl formate) in the presence of an alkaline condensation agent (e.g. sodium methylate).  The sodium salts of compounds in which R1 and R2 are diethyl and allyl and isopropyl are prepared.  a  - R1 - a  - R2 - acetoacetonitriles are prepared by alkylating or alkenylating (e.g. using R1 or R2 halide) an appropriate a -monoalkyl- or a -monoalkenyl-acetoacetonitrile, or by dehydrating an appropriate a -R1-a -R2-acetoacetamide with thionyl chloride or phosphorus oxychloride.  Compounds in which R1 and R2 are diethyl, di-n - propyl, diallyl, diisobutyl, diisobutenyl, methyl and ethyl, methyl and n-propyl, methyl and isopropyl, methyl and allyl, allyl and isopropyl, and n-propyl and isopropyl are prepared. Isopropyl-acetoacetonitrile is prepared by dehydrating isopropyl-acetoacetamide with phosphorus oxychloride.  The compound CH3.CO.C(Na)(CN).CH(CH3)2 is prepared by treating boiling diethyl carbonate with sodium methylate and isopropyl-acetoacetonitrile. Treatment with allyl bromide replaces the sodium by allyl.