Acetone reductive amination

REDUCTIVE AMINATION OF ACETONE DN TIN MODIFIED SKELETAL NICKEL CATALYSTS... 

In this work results obtained in a case study, i.e. the reductive amination of acetone on a skeletal nickel catalyst to isopropylamine and diisopropylamine will be given and discussed. Reactions involved in the reductive amination of acetone are given in ... 

It is known that upon distillation of the reaction mixture of the reductive amination of acetone diisopropylamine and isopropanol forms a binary azeotrope making the separation extremely difficult. Therefore, the goal of this work was to find the modes and ways for the suppression of the formation of isopropanol via selec tive poisoning the skeletal nickel catalyst by a second metal such as tin. 

A stainless steel flow reactor charged with 2D g catalyst was used to study the reductive amination of acetone [AC). Further details on experimental conditions can be found in Table 2. Reaction products were analysed by gas chromatography using a glass column filled with 18 wt% Carbowax 2000 + 5 wt% KDH on Chromosorb P... 

In the reductive amination of acetone carried out in the temperature range of 169-210°C the focus was laid on the selectivity changes at high conversion level. Experimental conditions, characteristic features of catalysts and corresponding activity and selectivity data obtained in the reductive amination of acetone are given in Table 2. It is noteworthy that in order to decrease the formation of isopropylalcohol by-product a relatively low hydrogen/ /ammonia molar ratio (H2/NH3 = D.5) has to be chosen. As seen in... 

Fig. 1. Relationship between selectivities and H2/NH3 molar ratio in the reductive amination of acetone on uninuUified skeletal nickel catalyst (T = i ilV., P = 0.0 MPa, WHSV = 0.0 h 1, NH3/AC = 2).

Data given in Table 2. indicated that upon increasing the reaction temperature in the reductive amination of acetone the selectivity towards DIPA especially on tin modified catalysts significantly increased, whereas selectivitiss towards other prodocts decreased in different extent. Such an increase in the selectivity of formation of DIPA upon increasing the reaction temperature can not be explained by thermodynamics LlA], and it has not been observed n conventional skeletal nickel catalysts [2, 14 ]. Therefore, it is suggested that the enhanced selectivity towards OIPA obtained at 19D-20G°C can be attributed to the high A10(0H) content of the catalyst l2]. However, the mechanism of the formation of the secondary amine requires further elucidation. 

Reductive amination of acetone on skeletal nickel catalysts3... 

The synthesis of the derivatives (339)-(346) was carried out as shown in Scheme 28. Metalation of the acetal (336), followed by thiolation and alkylation, gave the ester derivative (337). Acetal deprotection to form (338) and subsequent treatment under Knoevenagel conditions with piper-idinium acetate in benzene afforded the desired ester (339). Reduction of compound (339) gave alcohol (340), which was converted to aldehyde (341) and protected as its acetal (342) under standard conditions. Deprotonation was effected by Bu"Li in THF at — 78 °C and subsequent conversion to the sulfonyl chloride was carried out by sequential treatment with sulfur dioxide and A-chloro-succinimide. Treatment of the sulfonyl chloride (343) with concentrated NH4OH in acetone provided the sulfonamide (344), which was deprotected (345) and subjected to reductive amination to provide compounds in the aminomethyl sulfonamide series (346). 

Gobolos et al. studied reductive amination of acetone with ammonia in a flow system at 169-210°C and 0.8 MPa H2 (H2/NH3 = 0.5) on Raney Ni that had been modified by organic tin compounds with general formula of SnR l (R = Et, Bu, or benzyl) in order to suppress the formation of isopropyl alcohol.16 By introducing tin from tetraalkyl tin, the selectivity to the formation of secondary amine significantly increased at the expense of the primary amine (isopropylamine/diisopropylamine ratio = 68.2/24.1 at 192°C, compared to 83.6/8.6 at 190°C with unmodified catalyst). By modifying the catalyst with SnBzl2Cl2, the lowest selectivity (<1%) for the formation of isopropyl alcohol was obtained at temperatures of 171-202°C. The isopropy-lamine/diisopropylamine ratio was close to the values obtained on the unmodified catalyst (7.3% selectivity to isopropyl alcohol at 190°C). 

Reasonable conversions of NPBA were observed when using ketones as solvents however, product analysis showed increased byproducts formation with the use of ketones. When acetone is used as solvent, GC/MS analysis identified 2-methylindoline and N-phenylisopropylamine as the two major byproducts, which are produced via a secondary reaction between aniline (product), acetone and hydrogen (reductive amination). Similar byproducts were observed when using methyl ethyl ketone (MEK) as a solvent. In a parallel experiment, about 13% of aniline reacted with acetone under the same reaction conditions except in the absence of a catalyst. Most of the reaction product, about 11%, is non-hydrogenated product 2-methylindoline (C9H11N). These results clearly demonstrate that ketones are the least preferred solvents for N-debenzylation due to the secondary reaction between the desired product and the ketones. 

As these alkaloids are not only used in chemistry as chiral auxiliaries, starting materials, and catalysts, but also in medicine, so technical syntheses have been developed and all of these compounds are commercially available. The standard materials ( )-(l/ ,2,S )-ephedrine [(-)-3) and ( —)-(lff,25,)-norephedrine [(-)- ] are produced in a technical process on multikilogram scale by reductive amination (with methylamine or ammonia, respectively) of (—)-(f )-l -hydroxy- Tphenyl-2-acetone with a platinum catalyst1. The ketone is in turn obtained by a biotechnological procedure from cultures of selected yeast strains (Saccharomyces sp.)2. 

The homologues of 2,4-DMA that were iodinated (or occasionally fluor-inated) were mono- or di-alkylated on the nitrogen, and the precursor that was common to all was the corresponding acetone. The above nitrostyrene, 1-(2,4-dimethoxyphenyl)-2-nitropropene, was reduced in acetic acid with elemental iron, and the base-washed extracts stripped of solvent and distilled (125-145 deg C at 0.5 mm/Hg) to give 2,4-dimethoxyphenylacetone as a water-white oil. The principal reductive amination product of this, the one that was most thoroughly explored with various halogenation schemes, was obtained by the reaction of 2,4-dimethoxyphenylacetone with dimethylamine and sodium cyanoborohydride. This product,... 

Compounds of the general structure K-241 are prepared from the appropriate ketone (IX-240) and amines (R4RSNH) by reductive amination thus l-(5-methyl-2-pyridyl)-2-aminopropane (IX-243) is obtained by autoclaving (5-methyl-2-pyridyl)acetone (IX-242) in the presence of ammonia, hydrogen, and Raney Nickel. ... 

The other significant aliphatic diisocyanate, IPDI, is based on isophorone chemistry. Trimerization of acetone gives isophorone (15), which on reaction with HCN affords the /3-cyanoketone (16). Reductive amination of (16) to the diamine (17), followed by phosgenation, gives IPDI (18). 

DERA (deoxyribose-S-phosphate aldolase) has been used to catalyse the condensation of 3-azido-3-deoxy-D-glyceraldehyde 35 with acetone or fluoroacetone to give 6-azides 34, and with propanal to give the branched-chain sugar azides 36 and 37 which adopt furanosyl and pyranosyl ring forms, respectively (Scheme 6). Reductive amination of 36 and 37 gave novel 1,5-imino-additols (see Chapter IS). ... 

Palladium containing alumina supported catalysts were designed for hydrodechlorination of chlorobenezne and for conversion of 4-chloro-2-nitroaniline, in which both hydrodechlorination and reduction steps are involved. Best results were obtained on catalysts containing palladium in ionic form. For reductive amination of acetone a skeletal nickel catalyst and its tin modified version was designed. On these catalysts the ratio of primary to secondary amines could be controlled and the fonuation of isopropyl alcohol was strongly suppressed. 

In this work results obtained in two case studies will be given and discussed design of catalysts [i) for hydrodechlorination of chlorcbenzene and conversion of 4-chloro - 2-nitroani1ine (CNA) to orthophenylendiamine CDPDA) and for (ii) reductive amination of acetone. 

Reactions involved in reductive amination of acetone are given in Scheme 1. 

For reductive amination of acetone with ammonia two types of catalysts were designed (i) skeletal Ni catalyst prepared form a Ni-Al alloy and Ci) its tin modified versions. Both types of catalysts were used in a continuous flow gas phase reactor. The requirements for these catalysts were as follows high thermal and mechanical stability, high rates for the formation of both primary and secondary amines and suppression of the formation of isopropyl alcohol from acetone. 

The hydrodechlorination of chlorobenzene, and conversion 4-chlo-ro-2-nitrQ-aniline to orthophenylenediamine was carried out under different reaction conditions using stirred tank and trickle bed reactors in the pressure range of 1-70 bar. The reductive amination of acetone was studied in a continuous flow gas phase reactor at 20-50 bar and 1B0-2DQ°C. Both in the hydrodehalogenation and reductive amination the reaction products were analysed by gas chromatography. ... 

---