Patent GB-808849-A (GB)
Title: Process for the manufacture of pimelic acid
Inventor: KAMLET JONAS
IPC: C07C51/31
Filed: 1956-02-14
Abstract: Pimelic acid is prepared by reacting a compound of the general formula: <FORM:0808849/IV (b)/1> where R1 is chosen from -CH2OH, -CHO, -COOR11, -CONH2 and -CN, R11 being hydrogen, an alkali metal or an alkyl or aryl radical, with an alkali metal hydroxide in the presence of a hydrogen acceptor, in an amount at least equivalent to reacting proportions, chosen from elemental sulphur, alkali metal polysulphides and the inorganic sulphurous compounds containing sulphur atoms at a valence level above minus two and below plus six, at a temperature between 200 DEG  and 400 DEG  C., preferably between 300 DEG  and 350 DEG  C., and acidifying the resultant alkali metal pimelate.  The reaction with alkali metal hydroxide may be effected in an aqueous medium at super-atmospheric pressure or by fusion in a caustic alkali melt.  It is desirable to use at least two mols., preferably four mols., of alkali metal hydroxide for each mol. of starting material.  Potassium hydroxide is the preferred alkali, but sodium hydroxide may also be used.  The hydrogen acceptors which may be used, in addition to sulphur and polysulphides, are alkali metal hydrosulphites, tetrathionates, thiosulphates, sulphites and hyposulphites.  It is preferred to use a small excess (about 20 per cent) of hydrogen acceptor over the theoretical amount.  The starting materials may be prepared: (a) by hydrogenation in aqueous and/or alcoholic solution of salicyclic acid or a salt or ester thereof, salicylaldehyde, salicylamide, o-hydroxybenzonitrile, or o-hydroxybenzyl alcohol, with Raney nickel, Raney cobalt, Adams platinum catalyst, copper chromite or reduced nickel, at atmospheric or superatmospheric pressure.  Thus salicyclic acid and its derivatives are hydrogenated to hexahydrosalicyclic acid and its derivatives (for example, sodium hexahydrosalicylate) which are dehydrated by the alkali treatment to the corresponding delta-1-tetra-hydrobenzoate derivatives which then undergo scission to pimelic acid. Salicylaldehyde, salicylamide, o-hydroxybenzonitrile and o-hydroxybenzyl alcohol similarly converted to hexahydro derivatives, delta-1-derivatives and finally to pimelic acid; (b) by Diels-Alder reaction of butadiene with allyl alcohol to form delta-1-tetrahydrobenzyl alcohol or with acrolein, acrylic acid, or salts or esters, acrylamide or acrylonitrile to form the corresponding delta - 3 - tetrahydrobenzoic acid derivative, e.g. aldehyde, acid, salt or ether, amide or nitrile.  These delta-3 adducts may be isomerized to delta-1 adducts by use of alkali metal hydroxides at temperatures up to 270 DEG  C. in solution under pressure or in caustic fusion.  This isomerization may be effected as a separate step prior to ring scission or may be effected in the same reaction as the ring scission to pimelic acid.  In examples: (1) methyl salicylate in methanol is hydrogenated under a hydrogen pressure of 3000-3500 p.s.i. at 140-145 DEG  C. in the presence of Raney nickel, the methyl hexahydrosalicylate formed is added to caustic soda solution and sulphur and heated in an autoclave at 300-320 DEG  C. for 10 hours, and the product is acidified with sulphuric acid to give pimelic acid; (2) butadiene, acrylonitrile and hydroquinone are heated in a copper-lined autoclave at 140-150 DEG C. for 8 hours, the product is mixed with caustic soda, sulphur and water and heated in an autoclave at 320-330 DEG  C. and then acidified to yield pimelic acid; (3) acrylic acid, butadiene and hydroquinone are heated in a copper-lined autoclave at 160-170 DEG C. for 3 hours, the product is mixed with caustic potash and sodium sulphide and the reaction mixture is fixed at 360-370 DEG  C., then dissolved in water and acidified to yield pimelic acid.