KUNA MAMMA WAMATATU US 20180244613A1 HAWA MO MATT ( 19) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2018 / 0244613 A1 RÜDENAUER et al. (43 ) Pub. Date : Aug . 30 , 2018 ( 54 ) PROCESS FOR PREPARING Publication Classification ALPHA - DAMASCONE (51 ) Int. Cl. (71 ) Applicant: BASF SE , Ludwigshafen am Rhein C07C 403 / 16 (2006 .01 ) (DE ) C07C 45 / 39 (2006 .01 ) C07C 49 / 203 (2006 .01 ) (72 ) Inventors: Stefan RÜDENAUER , Weinheim ( 52) U . S . CI. (DE ) ; Thomas FENLON , Mannheim CPC . .. C07C 403 / 16 (2013 . 01 ) ; C07C 2601 / 16 (DE ) ; Shriang HINDALEKAR , ( 2017 . 05 ) ; C07C 49 / 203 ( 2013 .01 ) ; C07C Mumbai ( IN ); Nisha PANSARE , Navi 45 / 39 ( 2013 . 01) Mumbai ( IN ) ; Abhijeet Deb ROY , Thane ( IN ) ; Vijay Narayanan SWAMINATHAN , Ludwigshafen (DE ) (57 ) ABSTRACT (21 ) Appl. No. : 15 /753 , 244 The present invention relates to a process for preparing ( 22 ) PCT Filed : Aug . 17 , 2016 1 - ( 2 , 6 , 6 - trimethylcyclohex - 2 - en - 1 - yl) but - 2 - en - 1 - one, which comprises a ) providing 6 , 10 - dimethylundeca - 1 , 5 , 9 ( 86 ) PCT No .: PCT/ EP2016 / 069489 trien - 4 -ol , b ) oxidizing 6 , 10 -dimethylundeca - 1, 5 , 9 - trien - 4 ol provided in step a ) with an oxidizing agent in the presence $ 371 ( c ) ( 1 ) , of at least one organic nitroxyl radical, at least one nitrate ( 2 ) Date : Feb . 16 , 2018 compound and an inorganic solid to yield 6 , 10 -dimethylun ( 30 ) Foreign Application Priority Data deca - 1 , 5 , 9 -trien - 4 - one, c ) reacting the 6 , 10 - dimethylun deca - 1 , 5 , 9 - trien - 4 -one obtained in step b ) with an acid to Aug . 18 , 2015 (EP ) .. .. .. .. .. 15181406 . 8 yield 1 - ( 2 ,6 , 6 - trimethylcyclohex - 2 - en - 1 -yl )but - 2 - en - 1 - one . US 2018 /0244613 A1 Aug . 30 , 2018 PROCESS FOR PREPARING damascone is finally cyclized to a - damascone using a min ALPHA - DAMASCONE eral acid , in particular phosphoric acid , or a lewis acid , in particular tin tetrachloride . [ 0001 ] The present invention relates to a process for [0008 ] The iron catalyzed aerobic oxidation of allylic producing 1 - ( 2 , 6 , 6 - trimethylcyclohex - 2 - en - 1 -yl ) but - 2 - en - 1 alcohols is also described in the art. one ( a - damascone ), which comprises providing 6 , 10 - dim [ 0009 ] Liu et al. , Org . Lett. , 2013 , Vol. 15 , pp . 5150 -5153 , ethylundeca - 1 , 5 , 9 - trien - 4 - ol, oxidizing 6 , 10 -dimethylun describe the oxidation of several allylic alcohols , such as deca - 1 , 5 , 9 - trien - 4 - ol with an oxidizing agent to 6 , 10 geraniol or ( E ) - 4 -methylhept - 4 - ene - 3 - ol, with molecular dimethylundeca - 1 , 5 , 9 - trien - 4 - one and reacting the 6 , 10 oxygen in the presence of catalytic amounts of Fe( NO3 ) 3 , dimethylundeca - 1 , 5 , 9 - trien - 4 - one with an acid . ( 2 , 2 ,6 , 6 - Tetramethylpiperidin - 1 - yl ) oxyl ( TEMPO ) and NaCl. BACKGROUND OF THE INVENTION [0010 ] The vast majority of the known synthetic pro cesses , which aim for the synthesis of a - damascone from [ 0002 ] 1 - ( 2 ,6 , 6 - trimethylcyclohex - 2 - en - 1 -yl )but - 2 - en - 1 citral, proceed via the formation of allylic alcohol interme one ( a -damascone ) is a aroma substance that is found in a diates , which are oxidized to the corresponding ketones . The variety of essential oils . Due to its characteristic organolep oxidation of these allylic alcohol intermediates typically tic properties , a - damascone is of great commercial interest suffer from low yiels , due to the formation of side products , as fragrance or as flavor . In particular , a - damascone is when strong oxidants , such as chromium trioxide or potas widely used as fragrance chemical in deodorants and per sium permanganate , are used and / or suffer from long reac fumes . tion times, in particular if mild oxidants , such as manganese [ 0003 ] Today, the vast majority of the demanded a - or dioxide or molecular oxygen , are applied . Furthermore , B -damascone , respectively , is produced synthetically from these processes often require an additional isomerization unsaturated aldehydes or ketones, e . g . from citral, cycloci step in order to arrive at the desired a - damascone , which tral or cyclogeranic acid , which are available in large further lowers the overall yield . amounts from natural and /or petrochemical sources. [0011 ] Due to the unsatisfactory overall yields , these pro [0004 ] There is a demand for novel processes that allow cesses are unsuitable for the effective production of the efficient production of 1 - ( 2 , 6 ,6 - trimethylcyclohex - 2 - en a -damascone from citral , in particular for technical scale 1 - yl) but - 2 - en - 1 -one ( a -damascone ) , e . g . by making use of production . mild reaction conditions to improve the yield and reduce the formation of unwanted by -products . SUMMARY OF THE INVENTION [0005 ] The synthesis of a -damascone was frequently [0012 ] It is therefore an object of the present invention to described in the art . provide an improved process for the production of 1 - ( 2 ,6 , [ 0006 ] DE1807568 for instance describes, besides the 6 - trimethylcyclohex - 2 - en - 1 - yl) but- 2 - en - 1 -one ( a - damas synthesis of other compounds, a process for the synthesis of cone ) , e . g . from the readily available precursor 3 , 7 -Dimeth 1 - ( 2 , 6 , 6 - trimethylcyclohex - 2 - en - 1 - yl) but - 2 - en - 1 - one ylocta - 2 , 6 - dienal (citral ) , in high overall yields. The process ( a - damascone ) starting from 3 , 7 - Dimethylocta - 2 , 6 - dienal should be simple and efficient and should use mild reaction ( citral) mainly through two different routes . Route 1 com conditions to allow an economic production of a - damascone prises the reaction of a - cyclocitral ( 2 ,6 , 6 - trimethylcaclo on technical scales. Furthermore , expensive and / or hazard hex - 2 - ene - 1 -carbaldehyde ), obtained via the cyclization of ous reagents should be avoided . citral , with 1 -propenylmagnesiumbromide to the alcohol [0013 ] It was surprisingly found that 1 - ( 2 ,6 ,6 - trimethyl ( E ) - 1 - ( 2 ,6 , 6 -trimethylcyclohex - 2 - en - 1 -yl ) but - 2 -en - 1 -ol , cyclohex - 2 - en - 1 - yl) but - 2 - en - 1 - one ( a - damascone ) can be which is then oxidized to a -damascone using chromium prepared in high yields via the oxidation of 6 ,10 -dimethy trioxide or manganese dioxide . Route 2 comprises the reac lundeca - 1 , 5 , 9 - trien - 4 - ol, with an oxidizing agent in the tion of citral with 1 -propenylmagnesiumbromide to 6 , 10 presence of at least one organic nitroxyl radical, at least one dimethyl- 2 , 5 , 9 - trien - 4 - ol, which is oxidized with manga nitrate compound and an inorganic solid , followed by the nese dioxide to the corresponding ketone 6 , 10 -dimethyl - 2 , cyclization and in situ izomerization of the thus obtained 5 , 9 - trien - 4 - one (pseudo damascone ) . The pseudo 6 , 10 -dimethylundeca - 1 , 5 , 9 - trien - 4 -one using an acid . damascone is then cyclized to a - damascone using boron [0014 ]. Therefore , the present invention relates to a process trifluoride diethyl etherate . For the oxidation of the alcohol for preparing 1 - ( 2 , 6 , 6 - trimethylcyclohex - 2 - en - 1 - yl) but- 2 intermediates to the corresponding ketones , silver acetate , en - 1 -one , which comprises oxygen containing derivatives of transition metal elements , [ 0015 ] a ) providing 6 ,10 - dimethylundeca - 1 , 5 , 9 - trien - 4 - ol, in particular chromium trioxide, manganese dioxide or per [0016 ] b ) oxidizing 6 , 10 - dimethylundeca - 1 , 5 , 9 - trien - 4 - ol mangenate , and gaseous molecular oxygen are mentioned as provided in step a ) with an oxidizing agent in the presence suitable oxidizing agents . of at least one organic nitroxyl radical, at least one nitrate [ 0007 ] Nakatani et al ., Agr . Biol. Chem . , 1974 , Vol. 38 ( 7 ) , compound and an inorganic solid to yield 6 , 10 -dimethy pp . 1351 - 1354 , describe a process for the synthesis of lundeca - 1 , 5 , 9 - trien - 4 - one , a -damascone starting from citral, which first comprises the [ 0017 ] c ) reacting the 6 , 10 - dimethylundeca - 1 , 5 , 9 -trien - 4 reaction of citral with allylmagnesium bromide to the alco one obtained in step b ) with an acid to yield 1 - ( 2 , 6 ,6 hol 6 , 10 - dimethyl- 2 , 5 , 10 - trien - 4 -ol , which is oxidized with trimethylcyclohex - 2 - en - 1 - yl) but - 2 - en - 1 - one . chromium trioxide in the presence of pyridine or 3 , 5 [ 0018 ] The process is efficient and allows the production dimethyl pyrazole to the corresponding ketone 6 , 10 -dim of 1 - ( 2 ,6 , 6 - trimethylcyclohex - 2 - en - 1 - yl) but - 2 - en - 1 - one ethyl- 2 , 5 , 10 - trien - 4 - one . This ketone is then isomerized ( a - damascone ) in high space - time yields in only three steps with potassium tert- butanolate to 6 , 10 - dimethyl- 2 , 5 , 9 - trien starting from a cheap and readily available precursor. The 4 -one (pseudo damascone ) . The thus obtained pseudo present process uses mild reaction conditions , which reduces US 2018 /0244613 A1 Aug . 30 , 2018 the amount of by - products . The use of expensive and /or may have ( E ) - or ( Z ) -configuration . Hence , 6 , 10 -dimethyl hazardous reagents is avoided . The technical applicability of undeca - 1 , 5 , 9 - trien - 4 -one can be present in the form either of the process is simple and inexpensive . By using the process (5E ) - 6 , 10 - dimethylundeca - 1 , 5 , 9 - trien - 4 -one or (5Z ) - 6 , 10 according to the present invention , a - damascone can be dimethylundeca - 1 , 5 , 9 - trien - 4 -one or in the form of mixtures provided without difficulty on industrial scales . of these isomers. [ 0027 ] The term “ 6 , 10 - dimethylundeca - 1 , 5 , 9 - trien - 4 - one” DETAILED DESCRIPTION thus encompasses both the pure (5E ) - isomer and pure (5Z ) [ 0019 ] 1 - ( 2 , 6 , 6 - trimethylcyclohex - 2 - en - 1 - yl) but- 2 - en - 1 isomer , as well as mixtures , where these two isomers are one ( a -damascone ) is a compound of the following formula present in equal amounts or wherein one of these isomers is ( I ) : present in excess .