(19) & (11) EP 2 518 043 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 31.10.2012 Bulletin 2012/44 C07C 51/58 (2006.01) C07C 67/14 (2006.01) C07C 231/02 (2006.01) C07C 59/21 (2006.01) (2006.01) (21) Application number: 11003510.2 C07C 69/63 (22) Date of filing: 29.04.2011 (84) Designated Contracting States: (71) Applicant: Lonza Ltd AL AT BE BG CH CY CZ DE DK EE ES FI FR GB 4052 Basel (CH) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR (72) Inventor: The designation of the inventor has not Designated Extension States: yet been filed BA ME (54) Process for the production of 4- chloroacetyl chloride, 4-chloroacetic acid esters, amides and imides (57) The invention relates to process for the contin- acetoacetyl chloride. uous production of 4-chloroacetoacetyl chloride, com- prising the steps of The invention also relates to a process for the production (a) feeding diketene and chlorine into a thin film reactor of 4-chloroacetic acid ester, 4-chloroacetic acid amide or and 4-chloroacetic acid imide from 4- chloroacetoacetyl chlo- (b) reacting the diketene and chlorine to obtain 4- chloro- ride obtained according to the inventive process. EP 2 518 043 A1 Printed by Jouve, 75001 PARIS (FR) 1 EP 2 518 043 A1 2 Description reactors and equipment and more energy for cooling. When increasing the volume of the reactor, the yield [0001] The invention relates to processes for the pro- dropped "drastically" andthe selectivity was relatively low duction of 4-chloroacetoacetyl chloride, 4-chloroacetic (US 4,473,508, example 7). Thus it would be desirable acid esters, amides and imides. 5 to provide a more efficient process, which requires less solvent, is more selective and efficient on a large scale. Background of the invention [0007] A laboratory process in order to produce ethyl- 4-chloroacetoacetate from diketene and chlorine is dis- [0002] Methods for the production of chloroace-4- closed by Pan et al., Shandong Huagong 2007, 36 (10) toacetyl chloride (4-chloro-3-oxobutanoyl chloride) and 10 4-6. In this process, it is suggested to use a relatively esters obtained from 4-chloroacetoacetyl chloride are high concentration of diketene of about 24 to 28 weight- known in the art. In a specific process, the 4-chloroace- %. However, the yield of the ester is only about 80% and toacetyl chloride is obtained by reacting chlorine gas with the reaction is carried out in a reaction flask on small diketene (4-methylideneoxetan-2-one). scale, without any suggestion how to resolve the heat [0003] The reaction takes place exothermally and15 transfer problem on increased scale. therefore requires cooling. The reaction products are rel- [0008] The processes known in the art are also prob- atively sensitive to heat and the formation of undesired lematic with respect to process safety. Especially when side products and decomposition is observed if temper- carried out in an industrial scale, the reaction requires ature deviates locally or globally from a given range. For high amounts of chlorine and diketene. These substanc- example, undesired reaction products may be regioi-20 es are highly reactive and hazardous when inhaled. somers, such 2- chloroacetoacetyl chloride, or over- chlo- When the reactor is damaged or when the process is rinated products, such as di- or trihalogenated com- disturbed and gets out of control, the reactants could pounds, such as 2,4-dichloroacetoacetyl chloride or harm the people in the environment and explode. Thus 2,2,4-trichloroacetoacetyl chloride. Thus, it is difficult to an industrial upscale, if at all, would only be possible un- determine efficient production conditions by which a high 25 der severe safety precautions. yield is achieved. [0004] JP 113 824 suggests a process in which diket- Problem underlying the invention ene is dissolved in a solvent and reacted in a column reaction vessel with chlorine under cooling. The chlorine [0009] The problem underlying the invention is to pro- gas is fed into the column in a continuous current or coun- 30 vide a process for the production of 4- chloroacetoacetyl ter-current manner. However, selectivities of less than chloride and reaction products obtainable therefrom, 90% are achieved. which overcomes the above-mentioned problems. The [0005] A solvent-free process is disclosed by US process shall provide the reaction products at high yield 4,468,356, according to which a diketene spray is con- and selectivity. The process shall be applicable on large- tinuously contacted with chlorine gas in a reaction zone 35 industrial scale use and as a continuous process. Spe- at a temperature between 80°C and 210°C. Subsequent- cifically, the reaction efficiency shall be high and the con- ly, the intermediate product is subjected to an esterifica- sumption of solvents shall be low. tion reaction with ethanol. However, the overall yield is [0010] It is another problem underlying the invention below 80% and thus relatively low, which is probably due to provide an industrial scale process, which is relatively to the exposure of the intermediate product to relatively 40 safe and reduces the potential dangers associated with high temperatures. Further, the reaction is carried out the handling of high amounts of chlorine and diketene. only with small amounts of starting compounds at a lab- oratory scale. Disclosure of the invention [0006] Reactions for the production of haloacetoacetic acids from diketene and chlorine on laboratory scale are 45 [0011] Surprisingly, the problem underlying the inven- disclosed in US 3,950,412 and US 3,701,803. In US tion is solved by processes according to the claims. Fur- 4,473,508, the process of US 3,701,803 is discussed. ther inventive embodiments are disclosed throughout the The inventors conclude that an upscale would not be description. possible becauseof problems associated withheat trans- [0012] Subject of the invention is a process for the pro- fer. In order to provide an efficient reaction on increased 50 duction of 4-chloroacetoacetyl chloride, comprising the scale, it is suggested to react a solution of diketene in an steps of inert solvent with a solution of chlorine dissolved in an inert solvent in a tube reactor. According to Example 6, (a) feeding diketene and chlorine into a thin film re- the acid chloride intermediate can be produced at a yield actor and of 98%. However, the process is relatively inefficient, be- 55 cause both starting compounds are diluted in relatively (b) reacting the diketene and chlorine to obtain 4- large amounts of solvents. Thus, the overall reaction re- chloroacetoacetyl chloride. quires large amounts of solvent and consequently large 2 3 EP 2 518 043 A1 4 [0013] According to the invention, it was found that a further, the heat removal is more efficient if the volume highly efficient reaction between diketene and chlorine is low and if thus the film thickness is also small. Thus can be carried out in a thin film reactor. After feeding the process is efficient regarding energy and costs, es- diketene and chlorine into the thin film reactor, they react pecially when carried out on industrial scale. in the thin film reactor. 4-chloroacetoacetyl chloride is 5 [0018] According to the invention, it is preferred that in formed as the reaction product and can be removed from step (a) the chlorine is fed into the reactor in the form of the reactor. gaseous chlorine. When using gaseous chlorine, the total [0014] In a preferred embodiment of the invention, in consumption of solvents is decreased even further. Thus, step (a) the diketene is fed into the reactor in the form of when using diketene at a relatively high concentration a mixture with an organic solvent. The mixture is prefer- 10 dissolved in an organic solvent, preferably dichlorometh- ably a solution of diketene in the organic solvent. ane, and using gaseous chlorine, the reaction is highly [0015] In principle, any organic solvent may be used, efficient for the reasons outlined above regarding high in which diketene is readily dissolved and which does not diketene concentrations. The reaction volume in the thin react with diketene or interfere with the reaction. Thus film reactor is relatively low and the time-space yield is the solvent should be an inert solvent. In this respect, 15 increased, whereas heat transfer is facilitated. Further, alcohols are not applicable, because they would react in the useof chlorine in gaseous form avoids apredissolving an esterification reaction in the thin film reactor by ace- step. This is advantageous, because chlorine is aggres- toacetate formation. Preferred inert solvents are halo- sive and complicated to handle on large-scale industrial genated hydrocarbons, preferably halogenated alkanes, process. e.g. chloromethane, dichloromethane, trichloromethane 20 [0019] The inventive reaction in step (a) is carried out (chloroform), tetrachloromethane, chloroethane, 1,2- in a thin film reactor. In such a thin film reactor, the reac- dichlorethane, trichloroethane, tetrachloroethane, tion takes place on at least one reactor surface. Usually, dichloropropane, 1-chloro-2-fluoroethane, 1,1-dichlo- thin film reactors allow a continuous renewal of the reac- roethane, 1,2-dichloroethane, methylchloroform, 1-chlo- tion surfaces. The thin films are created on the reaction robutane, 2-chlorobutane, 1-bromobutane, ethyl bro- 25 surfaces by rotating the surfaces. The reactor is thus dis- mide, bromo-1- 2-chloroethane, 1-bromo-2-fluor- tinct from reactors, such as tube reactors, in which the oethane, 1-iodobutane, bromochloromethane, dibro- reaction is carried out in a spatial liquid volume. The re- momethane, 1,1-dibromomethane, difluoroiodometh- actor comprises means for distributing the liquid reac- ane, 1-bromopropane, bromochlorofluoromethane, 2- tants to the reaction surfaces.