JP5555917B2 - Process for monomethylation of aliphatic primary amines - Google Patents
Process for monomethylation of aliphatic primary amines Download PDFInfo
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- JP5555917B2 JP5555917B2 JP2010036630A JP2010036630A JP5555917B2 JP 5555917 B2 JP5555917 B2 JP 5555917B2 JP 2010036630 A JP2010036630 A JP 2010036630A JP 2010036630 A JP2010036630 A JP 2010036630A JP 5555917 B2 JP5555917 B2 JP 5555917B2
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- -1 aliphatic primary amines Chemical class 0.000 title claims description 77
- 238000000034 method Methods 0.000 title claims description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 66
- 239000010948 rhodium Substances 0.000 claims description 47
- 238000006243 chemical reaction Methods 0.000 claims description 43
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical group [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 35
- 239000003054 catalyst Substances 0.000 claims description 30
- 229910052703 rhodium Inorganic materials 0.000 claims description 27
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 229930040373 Paraformaldehyde Natural products 0.000 claims description 21
- 229920002866 paraformaldehyde Polymers 0.000 claims description 21
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 claims description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 12
- 125000000962 organic group Chemical group 0.000 claims description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 claims description 9
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical group NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 8
- 239000012298 atmosphere Substances 0.000 claims description 8
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 claims description 8
- 239000007810 chemical reaction solvent Substances 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 150000003141 primary amines Chemical class 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- PWGJDPKCLMLPJW-UHFFFAOYSA-N 1,8-diaminooctane Chemical compound NCCCCCCCCN PWGJDPKCLMLPJW-UHFFFAOYSA-N 0.000 claims description 4
- 239000005700 Putrescine Substances 0.000 claims description 4
- 125000005263 alkylenediamine group Chemical group 0.000 claims description 4
- YQLZOAVZWJBZSY-UHFFFAOYSA-N decane-1,10-diamine Chemical compound NCCCCCCCCCCN YQLZOAVZWJBZSY-UHFFFAOYSA-N 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000001931 aliphatic group Chemical group 0.000 claims 1
- 239000000126 substance Substances 0.000 description 43
- 239000000047 product Substances 0.000 description 38
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- 150000002430 hydrocarbons Chemical group 0.000 description 18
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 239000000758 substrate Substances 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 10
- OYFWLCJAPSAGCG-UHFFFAOYSA-N n'-methylhexane-1,6-diamine Chemical compound CNCCCCCCN OYFWLCJAPSAGCG-UHFFFAOYSA-N 0.000 description 10
- 239000012265 solid product Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 9
- 238000007069 methylation reaction Methods 0.000 description 9
- 239000002994 raw material Substances 0.000 description 8
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 7
- 230000011987 methylation Effects 0.000 description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000012022 methylating agents Substances 0.000 description 4
- 125000001302 tertiary amino group Chemical group 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 238000013329 compounding Methods 0.000 description 3
- KFIGICHILYTCJF-UHFFFAOYSA-N n'-methylethane-1,2-diamine Chemical compound CNCCN KFIGICHILYTCJF-UHFFFAOYSA-N 0.000 description 3
- LCRVIUZAMYNZOC-UHFFFAOYSA-N n'-methylethane-1,2-diamine;hydrochloride Chemical compound Cl.CNCCN LCRVIUZAMYNZOC-UHFFFAOYSA-N 0.000 description 3
- 229920000768 polyamine Chemical group 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 3
- 150000003512 tertiary amines Chemical class 0.000 description 3
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- RMIVMBYMDISYFZ-UHFFFAOYSA-N N-methylputrescine Chemical compound CNCCCCN RMIVMBYMDISYFZ-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 125000002723 alicyclic group Chemical group 0.000 description 2
- 230000002152 alkylating effect Effects 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- MDKQJOKKKZNQDG-UHFFFAOYSA-N n,n'-dimethylhexane-1,6-diamine Chemical compound CNCCCCCCNC MDKQJOKKKZNQDG-UHFFFAOYSA-N 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- FJLUATLTXUNBOT-UHFFFAOYSA-N 1-Hexadecylamine Chemical compound CCCCCCCCCCCCCCCCN FJLUATLTXUNBOT-UHFFFAOYSA-N 0.000 description 1
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 1
- VILCJCGEZXAXTO-UHFFFAOYSA-N 2,2,2-tetramine Chemical compound NCCNCCNCCN VILCJCGEZXAXTO-UHFFFAOYSA-N 0.000 description 1
- RNLHGQLZWXBQNY-UHFFFAOYSA-N 3-(aminomethyl)-3,5,5-trimethylcyclohexan-1-amine Chemical compound CC1(C)CC(N)CC(C)(CN)C1 RNLHGQLZWXBQNY-UHFFFAOYSA-N 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 1
- RPNUMPOLZDHAAY-UHFFFAOYSA-N Diethylenetriamine Chemical compound NCCNCCN RPNUMPOLZDHAAY-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- PLZVEHJLHYMBBY-UHFFFAOYSA-N Tetradecylamine Chemical compound CCCCCCCCCCCCCCN PLZVEHJLHYMBBY-UHFFFAOYSA-N 0.000 description 1
- GKXVJHDEWHKBFH-UHFFFAOYSA-N [2-(aminomethyl)phenyl]methanamine Chemical compound NCC1=CC=CC=C1CN GKXVJHDEWHKBFH-UHFFFAOYSA-N 0.000 description 1
- FDLQZKYLHJJBHD-UHFFFAOYSA-N [3-(aminomethyl)phenyl]methanamine Chemical compound NCC1=CC=CC(CN)=C1 FDLQZKYLHJJBHD-UHFFFAOYSA-N 0.000 description 1
- ISKQADXMHQSTHK-UHFFFAOYSA-N [4-(aminomethyl)phenyl]methanamine Chemical compound NCC1=CC=C(CN)C=C1 ISKQADXMHQSTHK-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 229910045601 alloy Inorganic materials 0.000 description 1
- 239000000956 alloy Substances 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- IMUDHTPIFIBORV-UHFFFAOYSA-N aminoethylpiperazine Chemical compound NCCN1CCNCC1 IMUDHTPIFIBORV-UHFFFAOYSA-N 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- OTBHHUPVCYLGQO-UHFFFAOYSA-N bis(3-aminopropyl)amine Chemical compound NCCCNCCCN OTBHHUPVCYLGQO-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
- QFTYSVGGYOXFRQ-UHFFFAOYSA-N dodecane-1,12-diamine Chemical compound NCCCCCCCCCCCCN QFTYSVGGYOXFRQ-UHFFFAOYSA-N 0.000 description 1
- JRBPAEWTRLWTQC-UHFFFAOYSA-N dodecylamine Chemical compound CCCCCCCCCCCCN JRBPAEWTRLWTQC-UHFFFAOYSA-N 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- AWZYJAFKVGBFEU-UHFFFAOYSA-N heptane-1,6-diamine Chemical compound CC(N)CCCCCN AWZYJAFKVGBFEU-UHFFFAOYSA-N 0.000 description 1
- ATJCASULPHYKHT-UHFFFAOYSA-N hexadecane-1,16-diamine Chemical compound NCCCCCCCCCCCCCCCCN ATJCASULPHYKHT-UHFFFAOYSA-N 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 230000001035 methylating effect Effects 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- QOHMWDJIBGVPIF-UHFFFAOYSA-N n',n'-diethylpropane-1,3-diamine Chemical compound CCN(CC)CCCN QOHMWDJIBGVPIF-UHFFFAOYSA-N 0.000 description 1
- ZETYUTMSJWMKNQ-UHFFFAOYSA-N n,n',n'-trimethylhexane-1,6-diamine Chemical compound CNCCCCCCN(C)C ZETYUTMSJWMKNQ-UHFFFAOYSA-N 0.000 description 1
- CJYCVQJRVSAFKB-UHFFFAOYSA-N octadecane-1,18-diamine Chemical compound NCCCCCCCCCCCCCCCCCCN CJYCVQJRVSAFKB-UHFFFAOYSA-N 0.000 description 1
- IOQPZZOEVPZRBK-UHFFFAOYSA-N octan-1-amine Chemical compound CCCCCCCCN IOQPZZOEVPZRBK-UHFFFAOYSA-N 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- MSVPBWBOFXVAJF-UHFFFAOYSA-N tetradecane-1,14-diamine Chemical compound NCCCCCCCCCCCCCCN MSVPBWBOFXVAJF-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
本発明は脂肪族第一級アミンのモノメチル化方法に関する。本発明を用いることにより、目的とする脂肪族第二級アミンを選択的に高収率で製造することができる。 The present invention relates to a process for monomethylation of aliphatic primary amines. By using the present invention, the desired aliphatic secondary amine can be selectively produced in high yield.
脂肪族第二級アミンは、医薬品の合成中間体等、多くの化学工業製品に用いられる、極めて重要な化学物質である。
アミンのメチル化方法としては、例えば、第一級アミンをハロゲン化メチル化合物によってメチル化する方法が知られている。しかしながら、この方法では、第一級アミンがメチル化された第二級アミンだけでなく、ジメチル化反応やトリメチル化反応が進行して、第三級アミンやアンモニウム塩も生成する場合がある。このため、目的とする脂肪族アミンを高選択的に製造することは困難である。また、副生成物として、無機塩類がハロゲン化アルキル化合物の当量分だけ生成するため、その無機塩類を分離し、処分をしなければならないという問題もある。
Aliphatic secondary amines are extremely important chemical substances used in many chemical industrial products such as pharmaceutical synthetic intermediates.
As a method for methylating amines, for example, a method in which a primary amine is methylated with a halogenated methyl compound is known. However, in this method, not only a secondary amine in which a primary amine is methylated, but also a dimethylation reaction or a trimethylation reaction proceeds to produce a tertiary amine or an ammonium salt. For this reason, it is difficult to produce the target aliphatic amine with high selectivity. In addition, as a by-product, inorganic salts are produced in an amount equivalent to the alkyl halide compound, so that there is a problem that the inorganic salts must be separated and disposed of.
また、アミン化合物のメチル化方法として、例えば、特許文献１には、水素雰囲気下で、ラネーニッケル触媒を用いるメチル化方法が開示されている。しかしながら、この方法では、選択的にメチル化させるように制御する場合には、ホルムアルデヒドに対し数倍モル以上のアミンが必要であり、効率が悪い。
また、脂肪族アミンのアルキル化方法として、例えば、特許文献２及び非特許文献１には、ニトリル化合物を用いて還元的にアルキル化する方法が開示されている。しかしながら、この方法によって、脂肪族アミンをメチル化させるには、毒性の高い青酸を使用しなければならない問題がある。
脂肪族アミンを選択的に得るためのその他の方法としては、例えば、保護基を利用した合成法の手法が一般的に公知である。すなわち、第一級アミンをベンゾイル化し、次にベンゾイル化された第一級アミンをハロゲン化メチルでモノメチル化し、最後にベンゾイル基を脱離させる方法である。この方法によれば、第三級アミンを副生させることなく第二級アミンを選択的に合成することができる。しかしながら、この方法は保護基の導入及び保護基の脱離のために工程数が多くなり、製造コストの高騰化を招くこととなる。
Moreover, as a methylation method of an amine compound, for example, Patent Document 1 discloses a methylation method using a Raney nickel catalyst in a hydrogen atmosphere. However, in this method, when controlling to selectively methylate, an amine several times mol or more with respect to formaldehyde is required, and efficiency is bad.
Moreover, as a method for alkylating an aliphatic amine, for example, Patent Document 2 and Non-Patent Document 1 disclose a method of reductively alkylating using a nitrile compound. However, in order to methylate an aliphatic amine by this method, there is a problem that highly toxic hydrocyanic acid must be used.
As another method for selectively obtaining an aliphatic amine, for example, a synthesis method utilizing a protecting group is generally known. That is, the primary amine is benzoylated, then the benzoylated primary amine is monomethylated with methyl halide, and finally the benzoyl group is eliminated. According to this method, a secondary amine can be selectively synthesized without by-producting a tertiary amine. However, in this method, the number of steps increases due to the introduction of the protecting group and the elimination of the protecting group, leading to an increase in production cost.
本発明は、上記した背景技術に鑑みてなされたものであり、その目的は、脂肪族アミンを収率よくモノメチル化し、高い選択率で脂肪族アミンのモノメチル化体を製造することができる、脂肪族アミンのモノメチル化方法を提供することである。 The present invention has been made in view of the above-described background art, and an object of the present invention is to produce a monomethylated aliphatic amine with high selectivity by monomethylating an aliphatic amine with a high yield. It is to provide a method for monomethylation of a group amine.
本発明者らは、脂肪族第一級アミンのメチル化方法について鋭意研究を重ねた結果、本発明を完成するに至った。
即ち、本発明は、以下に示すとおりの脂肪族第一級アミンのメチル化方法である。
［１］白金族触媒の存在下、水素雰囲気下で、パラホルムアルデヒドを用いて、脂肪族第一級アミンをモノメチル化させ、
前記白金族触媒における白金族元素が、ロジウムであることを特徴とする脂肪族第一級アミンのモノメチル化方法。
［２］前記白金族触媒が、前記白金族元素を担体に担持した触媒である上記［１］に記載の脂肪族第一級アミンのモノメチル化方法。
［３］前記担体が、炭素である上記［２］記載の脂肪族第一級アミンのモノメチル化方法。
［４］前記脂肪族第一級アミンが、下記一般式（１）で表されるアルキレンジアミンであり、得られるモノメチル化体が、下記一般式（２）で表される上記［１］乃至［３］のいずれかに記載の脂肪族第一級アミンのモノメチル化方法。
Ｈ２Ｎ−Ｒ２−ＮＨ２ （１）
Ｈ２Ｎ−Ｒ２−ＮＨ−ＣＨ３ （２）
〔上記一般式（１）及び（２）において、Ｒ２は炭素数２〜１６の２価の有機基を表す。〕
［５］前記アルキレンジアミンが、１，２−ジアミノエタン、１，３−ジアミノプロパン、１，４−ジアミノブタン、１，６−ジアミノヘキサン、１，８−ジアミノオクタン、又は１，１０−ジアミノデカンである上記［４］に記載の脂肪族第一級アミンのモノメチル化方法。
［６］反応溶媒として、メタノール、ヘキサン及びテトラヒドロフランから選ばれる少なくとも１種を用いて反応させる上記［１］乃至［５］のいずれかに記載の脂肪族第一級アミンのモノメチル化方法。
［７］水素加圧下で反応を行う上記［１］乃至［６］のいずれかに記載の脂肪族第一級アミンのモノメチル化方法。
As a result of intensive studies on the methylation method of aliphatic primary amines, the present inventors have completed the present invention.
That is, this invention is the methylation method of an aliphatic primary amine as shown below.
[1] Monomethylation of an aliphatic primary amine using paraformaldehyde in the presence of a platinum group catalyst in a hydrogen atmosphere ;
Platinum group elements in the platinum group catalyst, monomethyl method aliphatic primary amine, wherein rhodium der Rukoto.
[2] The platinum group catalyst, monomethyl method aliphatic primary amine according to the platinum group element in the above [1] is a catalyst supported on a carrier.
[3] The monomethylation method of an aliphatic primary amine according to the above [2], wherein the carrier is carbon.
[ 4 ] The aliphatic primary amine is an alkylenediamine represented by the following general formula (1), and the resulting monomethylated product is represented by the above general formula (2). 3 ] The monomethylation method of the aliphatic primary amine in any one of 3 .
H 2 N-R 2 -NH 2 (1)
H 2 N-R 2 -NH- CH 3 (2)
[In the above general formulas (1) and (2), R 2 represents a divalent organic group having 2 to 16 carbon atoms. ]
[ 5 ] The alkylene diamine is 1,2-diaminoethane, 1,3-diaminopropane, 1,4-diaminobutane, 1,6-diaminohexane, 1,8-diaminooctane, or 1,10-diaminodecane. The method for monomethylation of an aliphatic primary amine according to the above [ 4 ].
[ 6 ] The monomethylation method of an aliphatic primary amine according to any one of the above [1] to [ 5 ], wherein the reaction is performed using at least one selected from methanol, hexane and tetrahydrofuran as a reaction solvent.
[ 7 ] The method for monomethylating an aliphatic primary amine according to any one of [1] to [ 6 ] above, wherein the reaction is carried out under hydrogen pressure.
本発明によれば、従来困難であった脂肪族第一級アミン化合物のモノメチル化反応を、簡便かつ低コストに実施することが可能となる。
また、本発明により、脂肪族第一級アミンのモノメチル化反応を行って、脂肪族第二級アミンを合成した後、別のアルキル化反応によってさらに異なるアルキル基を脂肪族第二級アミンに導入することで、三つの異なるアルキル基を有する非対称第三級アミンを僅か２段階で合成することができる。
このように、本発明は、目的とする脂肪族アミンを収率よく、選択的に製造することができるものであり、工業的に極めて有用である。
According to the present invention, the monomethylation reaction of an aliphatic primary amine compound, which has been difficult in the past, can be carried out simply and at low cost.
In addition, according to the present invention, an aliphatic secondary amine is monomethylated to synthesize an aliphatic secondary amine, and then another alkylation reaction introduces a different alkyl group to the aliphatic secondary amine. Thus, an asymmetric tertiary amine having three different alkyl groups can be synthesized in only two steps.
Thus, the present invention is capable of selectively producing the target aliphatic amine with good yield, and is extremely useful industrially.
以下、本発明を詳細に説明する。
本発明の脂肪族第一級アミンのモノメチル化方法（以下、単に「メチル化方法」ともいう）は、白金族触媒の存在下、水素雰囲気下で、パラホルムアルデヒドを用いて、脂肪族第一級アミンをモノメチル化させ、前記白金族触媒における白金族元素が、ロジウムであることを特徴とする。
Hereinafter, the present invention will be described in detail.
The method for monomethylation of an aliphatic primary amine of the present invention (hereinafter, also simply referred to as “methylation method”) uses an aliphatic primary amine using paraformaldehyde in a hydrogen atmosphere in the presence of a platinum group catalyst. amine is mono- to, platinum group elements in the platinum group catalyst, wherein the rhodium der Rukoto.
本発明のメチル化方法は、少なくとも「−ＣＨ２−ＮＨ２」を含む化合物である脂肪族第一級アミンを基質として用いて、高い選択率で脂肪族第一級アミンのモノメチル化体を得る方法である。具体的には、下記一般式（３）及び（４）で表される原料の脂肪族第一級アミンから、それぞれ下記一般式（５）及び（６）で表されるモノメチル化体を効率良く得ることができる。
Ｒ１−ＮＨ２ （３）
（ＮＨ２）ｎＲｎ （４）
Ｒ１−ＮＨ−ＣＨ３ （５）
（ＮＨ２）ｎ−１Ｒｎ−ＮＨ−ＣＨ３ （６）
上記一般式（３）及び（５）におけるＲ１は１価の有機基であり、この有機基は、炭化水素基又は窒素原子（Ｎ）を含む炭化水素基であり、この炭化水素基における窒素原子の結合状態は第二級アミノ基又は第三級アミノ基である。
また、上記一般式（４）及び（６）におけるＲｎはｎ価の有機基であり、この有機基は
、炭化水素基又は窒素原子を含む炭化水素基であり、この炭化水素基における窒素原子の結合状態は第二級アミノ基又は第三級アミノ基である。ｎは、通常、２〜１０の整数である。
The methylation method of the present invention obtains a monomethylated product of an aliphatic primary amine with high selectivity using an aliphatic primary amine, which is a compound containing at least “—CH 2 —NH 2 ”, as a substrate. Is the method. Specifically, monomethylated products represented by the following general formulas (5) and (6) are efficiently obtained from the aliphatic primary amines represented by the following general formulas (3) and (4), respectively. Can be obtained.
R 1 —NH 2 (3)
(NH 2 ) n R n (4)
R 1 —NH—CH 3 (5)
(NH 2) n-1 R n -NH-CH 3 (6)
R 1 in the above general formulas (3) and (5) is a monovalent organic group, and this organic group is a hydrocarbon group or a hydrocarbon group containing a nitrogen atom (N), and nitrogen in this hydrocarbon group The bonding state of the atoms is a secondary amino group or a tertiary amino group.
Further, R n in the general formulas (4) and (6) is an n-valent organic group, and this organic group is a hydrocarbon group or a hydrocarbon group containing a nitrogen atom, and the nitrogen atom in the hydrocarbon group The bonding state is a secondary amino group or a tertiary amino group. n is usually an integer of 2 to 10.
また、上記一般式（４）で表される原料の脂肪族第一級アミンが、下記一般式（１）で表されるアルキレンジアミン化合物である場合、下記一般式（２）で表されるモノメチル化体を得ることができる。
Ｈ２Ｎ−Ｒ２−ＮＨ２ （１）
Ｈ２Ｎ−Ｒ２−ＮＨ−ＣＨ３ （２）
但し、上記一般式（１）及び（２）におけるＲ２は２価の有機基であり、この有機基は
、炭化水素基又は窒素原子を含む炭化水素基であり、この炭化水素基における窒素原子の結合状態は第二級アミノ基又は第三級アミノ基である。
Moreover, when the aliphatic primary amine of the raw material represented by the general formula (4) is an alkylenediamine compound represented by the following general formula (1), monomethyl represented by the following general formula (2) Can be obtained.
H 2 N-R 2 -NH 2 (1)
H 2 N-R 2 -NH- CH 3 (2)
However, R 2 in the above general formulas (1) and (2) is a divalent organic group, and this organic group is a hydrocarbon group or a hydrocarbon group containing a nitrogen atom, and the nitrogen atom in this hydrocarbon group The bonding state is a secondary amino group or a tertiary amino group.
また、アミノ基を３以上有する脂肪族第一級アミンを原料とする場合にも、上記と同様にモノメチル化体が得られる。
本発明においては、１つ以上のアミノ基を有する脂肪族第一級アミンから、高い選択率で、効率良くモノメチル化体を得ることができる。特に、原料として上記一般式（１）で表されるアルキレンジアミン化合物から、上記一般式（２）で表されるモノメチル化体を高い選択率で、効率的に得ることができることから、アルキレンジアミン化合物のモノメチル化体の製造に好適に用いることができる。
Further, when an aliphatic primary amine having 3 or more amino groups is used as a raw material, a monomethylated product can be obtained in the same manner as described above.
In the present invention, a monomethylated product can be efficiently obtained from an aliphatic primary amine having one or more amino groups with high selectivity. In particular, from the alkylenediamine compound represented by the general formula (1) as a raw material, the monomethylated product represented by the general formula (2) can be efficiently obtained with high selectivity. It can use suitably for manufacture of the monomethylated body of this.
本発明において、脂肪族第一級アミンとしては、特に限定するものではないが、上記一般式（３）及び（４）で表される、少なくとも１つの第一級アミノ基を有する脂肪族第一級アミンを使用することができる。このような脂肪族第一級アミンとしては、具体的には、直鎖状若しくは分岐状のアルキル基、又はアリール基等の１価の炭化水素基を持つモノアミン化合物、直鎖状若しくは分岐状アルキレン基、又はアリール基等の２価の炭化水素基を持つジアミン化合物、直鎖状若しくは分岐状の炭化水素基をもつポリアミン化合物等が挙げられる。これらのうち、好ましくは、下記式（１）で示されるジアミン化合物である。
Ｈ２Ｎ−Ｒ２−ＮＨ２ （１）
但し、上記一般式（１）における、Ｒ２は２価の有機基であり、この有機基は、炭化水素基又は窒素原子を含む炭化水素基であり、Ｒ２の炭素数は、好ましくは２〜１６（より好ましくは１０以下、更に好ましくは８以下）である。
In the present invention, the aliphatic primary amine is not particularly limited, but the aliphatic primary amine represented by the above general formulas (3) and (4) has at least one primary amino group. Secondary amines can be used. Specific examples of such aliphatic primary amines include monoamine compounds having a monovalent hydrocarbon group such as a linear or branched alkyl group or an aryl group, and linear or branched alkylene. And a diamine compound having a divalent hydrocarbon group such as an aryl group or a polyamine compound having a linear or branched hydrocarbon group. Among these, Preferably, it is a diamine compound shown by following formula (1).
H 2 N-R 2 -NH 2 (1)
However, in the above general formula (1), R 2 is a divalent organic group, and this organic group is a hydrocarbon group or a hydrocarbon group containing a nitrogen atom, and the carbon number of R 2 is preferably 2. To 16 (more preferably 10 or less, still more preferably 8 or less).
上記一般式（１）における有機基（Ｒ２）としては、少なくとも２つのアミノ基にそれぞれメチレン基が結合して含まれる基である。具体的には、直鎖状又は分岐状の鎖状炭化水素基、又は、窒素原子を含む直鎖状又は分岐状の鎖状炭化水素基であり、これらの鎖状炭化水素基は、その他、芳香族基、脂環族基等を含んでいてもよい。これらの芳香族基及び脂環族基は、炭化水素基の主鎖に含まれてもよく、側鎖に含まれてもよい。好ましくは、２価のアルキレン基（「−ＣｎＨ２ｎ−」、但し、ｎは２以上の整数）である。 The organic group (R 2 ) in the general formula (1) is a group in which a methylene group is bonded to at least two amino groups. Specifically, it is a linear or branched chain hydrocarbon group, or a linear or branched chain hydrocarbon group containing a nitrogen atom, and these chain hydrocarbon groups include: An aromatic group, an alicyclic group, etc. may be included. These aromatic group and alicyclic group may be contained in the main chain of the hydrocarbon group or in the side chain. Preferably, it is a divalent alkylene group (“—C n H 2n —”, where n is an integer of 2 or more).
即ち、原料として用いられる脂肪族第一級アミンとしては、例えば、上記一般式（３）、及び（４）並びに（１）で示されるモノアミン化合物、ジアミン化合物、ポリアミン化合物、及びその他のアミン化合物等が挙げられる。
上記モノアミン化合物としては、具体的には、エチルアミン、ｎ−プロピルアミン、イソプロピルアミン、ｎ−ブチルアミン、イソブチルアミン、ｎ−ヘキシルアミン、オクチルアミン、デシルアミン、ドデシルアミン、テトラデシルアミン、ヘキサデシルアミン、オクタデシルアミン、及びベンジルアミン等が挙げられる。
また、上記ジアミン化合物としては、具体的には、１，２−ジアミノエタン、１，３−ジアミノプロパン、１，４−ジアミブタン、１，６−ジアミノヘキサン、１，８−ジアミノオクタン、１，１０−ジアミノデカン、１，１２−ジアミノドデカン、１，１４−ジアミノテトラデカン、１，１６−ジアミノヘキサデカン、１，１８−ジアミノオクタデカン、ｏ−キシリレンジアミン、ｍ−キシリレンジアミン、ｐ−キシリレンジアミン、及びイソホロンジアミン等が挙げられる。
また、上記ポリアミン化合物としては、具体的には、ジエチレントリアミン、Ｎ−アミノエチルピペラジン、トリエチレンテトラミン、ジメチルアミノプロピルアミン、ジエチルアミノプロピルアミン、ビスー（３−アミノプロピル）アミン等が挙げられる。
また、その他のアミン化合物としては、トリス（３−アミノプロピルアミン）、及びトリス（２−アミノエチルアミン）等の第三級アミノ基を有するアミン化合物が挙げられる。
これらのうち、好ましくは、１，２−ジアミノエタン、１，３−ジアミノプロパン、１，４−ジアミノブタン、１，６−ジアミノヘキサン、１，８−ジアミノオクタン、及び１，１０−ジアミノデカン等のアルキレンジアミンである。
That is, examples of the aliphatic primary amine used as a raw material include monoamine compounds, diamine compounds, polyamine compounds, and other amine compounds represented by the general formulas (3), (4), and (1). Is mentioned.
Specific examples of the monoamine compound include ethylamine, n-propylamine, isopropylamine, n-butylamine, isobutylamine, n-hexylamine, octylamine, decylamine, dodecylamine, tetradecylamine, hexadecylamine, and octadecyl. Examples include amines and benzylamine.
Specific examples of the diamine compound include 1,2-diaminoethane, 1,3-diaminopropane, 1,4-diamibutane, 1,6-diaminohexane, 1,8-diaminooctane, 1,10. -Diaminodecane, 1,12-diaminododecane, 1,14-diaminotetradecane, 1,16-diaminohexadecane, 1,18-diaminooctadecane, o-xylylenediamine, m-xylylenediamine, p-xylylenediamine, And isophoronediamine.
Specific examples of the polyamine compound include diethylenetriamine, N-aminoethylpiperazine, triethylenetetramine, dimethylaminopropylamine, diethylaminopropylamine, and bis (3-aminopropyl) amine.
Examples of other amine compounds include amine compounds having a tertiary amino group such as tris (3-aminopropylamine) and tris (2-aminoethylamine).
Of these, 1,2-diaminoethane, 1,3-diaminopropane, 1,4-diaminobutane, 1,6-diaminohexane, 1,8-diaminooctane, 1,10-diaminodecane, and the like are preferable. Of alkylenediamine.
本発明に用いられる上記白金族触媒としては、単体をそのまま用いることもできるが、白金族元素を、炭素、シリカ及びアルミナ等の担体に担持させたものを用いることもできる。これらのうち、担体に担持させることにより、白金族元素が細かく分散し、触媒としての機能が高められることから、白金族元素を担体に担持させた触媒が好ましい。また、白金族元素を担体に担持させた触媒を用いることにより、反応後の触媒の回収も容易となる。
また、上記担体としては、特に限定するものではないが、炭素を使用することが好ましい。炭素を担体とすることにより、目的とする脂肪族第二級アミン（モノメチル化体）を極めて効率よく、選択的に高収率で合成できる。
Examples of the platinum group catalyst employed in the present invention, can be used single body as it is, the platinum group element may be used that is supported on a carrier such as carbon, silica and alumina. Among these, the catalyst in which the platinum group element is supported on the support is preferable because the platinum group element is finely dispersed and supported as a catalyst by being supported on the support. Further, by using a catalyst in which a platinum group element is supported on a carrier, recovery of the catalyst after the reaction is facilitated.
Further, the carrier is not particularly limited, but carbon is preferably used. By using carbon as a carrier, the desired aliphatic secondary amine (monomethylated product) can be synthesized very efficiently and selectively in a high yield.
また、上記白金族元素としては、ルテニウム、ロジウム、パラジウム、オスミウム、イリジウム及び白金、並びにこれらの合金等が挙げられるが、本発明ではロジウムが用いられる。ロジウムを白金族元素として用いることにより、脂肪族第一級アミンのモノメチル化反応が円滑に進行するため、脂肪族第二級アミン（モノメチル化体）を選択的に合成することができる。 Moreover, as the platinum group elements, Le ruthenium, rhodium, palladium, osmium, iridium and platinum, as well as such alloys thereof, rhodium is used in the present invention. By using rhodium as the platinum group element, the monomethylation reaction of the aliphatic primary amine proceeds smoothly, so that the aliphatic secondary amine (monomethylated product) can be selectively synthesized.
本発明において、添加する白金族触媒の配合量は、特に限定されず、脂肪族第一級アミン（反応基質）の種類、及び反応温度等の反応条件により適宜選択される。白金族触媒の配合量（白金族元素の量）としては、通常、原料の脂肪族第一級アミン１ｍｏｌに対して
、０．０００１〜０．２ｍｏｌが好ましく、０．００１ｍｏｌ以上がより好ましく、０．００５ｍｏｌ以上が更に好ましい。添加する触媒の配合量が、上記範囲内にある場合、効率的に、モノメチル化体の脂肪族第二級アミンを製造することができる。また、添加する触媒の配合量を増やすことで、反応速度をさらに向上させることができるが、必要以上に増量すると経済性に乏しくなる。
In the present invention, the blending amount of the platinum group catalyst to be added is not particularly limited, and is appropriately selected according to the reaction conditions such as the kind of the aliphatic primary amine (reaction substrate) and the reaction temperature. The compounding amount of the platinum group catalyst (amount of platinum group element) is usually preferably 0.0001 to 0.2 mol, more preferably 0.001 mol or more, with respect to 1 mol of the aliphatic primary amine of the raw material. More preferably 0.005 mol or more. When the blending amount of the catalyst to be added is within the above range, a monomethylated aliphatic secondary amine can be efficiently produced. Further, the reaction rate can be further improved by increasing the amount of the catalyst to be added. However, if the amount is increased more than necessary, the economy becomes poor.
パラホルムアルデヒドは、本発明において、メチル化剤として作用する化合物である。このパラホルムアルデヒドは、通常、下記一般式（７）で表されるホルムアルデヒドの重合体である。
ＨＯ（ＣＨ２Ｏ）ｎＨ （７）
但し、上記一般式（７）において、ｎは１以上の整数である。
また、パラホルムアルデヒドとしては、市販品を用いることができる。
Paraformaldehyde is a compound that acts as a methylating agent in the present invention. This paraformaldehyde is usually a formaldehyde polymer represented by the following general formula (7).
HO (CH 2 O) n H (7)
However, in the said General formula (7), n is an integer greater than or equal to 1.
Moreover, as a paraformaldehyde, a commercial item can be used.
本発明において、パラホルムアルデヒドの配合量は、脂肪族第一級アミン１ｍｏｌに対して、０．１〜１０ｍｏｌが好ましく、０．５〜５ｍｏｌが更に好ましい。添加するパラホルムアルデヒドの配合量が、上記範囲内にある場合、効率的にモノメチル化体の脂肪族第二級アミンを製造することができる。尚、上記パラホルムアルデヒドの配合量は、パラホルムアルデヒドが、ホルムアルデヒドを構成単位とするポリマーであることから、モノマー（ホルムアルデヒド）で換算して、ｍｏｌ量を計算した。即ち、パラホルムアルデヒドは、一般式（ＣＨ２Ｏ）ｎで示されることから、上記のパラホルムアルデヒドの配合量（ｍｏｌ量）は、ＣＨ２Ｏ＝３０．０２６を１ｍｏｌの分子量として計算した。 In this invention, 0.1-10 mol is preferable with respect to 1 mol of aliphatic primary amines, and, as for the compounding quantity of paraformaldehyde, 0.5-5 mol is still more preferable. When the amount of paraformaldehyde to be added is within the above range, a monomethylated aliphatic secondary amine can be efficiently produced. In addition, since the paraformaldehyde is a polymer having formaldehyde as a structural unit, the amount of paraformaldehyde was calculated in terms of a monomer (formaldehyde) and calculated as a mol amount. That is, since paraformaldehyde is represented by the general formula (CH 2 O) n , the compounding amount (mol amount) of the above paraformaldehyde was calculated with CH 2 O = 30.026 as a molecular weight of 1 mol.
本発明において、反応溶媒を用いることができる。反応溶媒としては、プロトン性溶媒及び非プロトン性溶媒、並びにそれらの混合溶媒が挙げられる。この反応溶媒としては、具体的には、メタノール、ヘキサン及びテトラヒドロフラン等が挙げられる。これらのうち、パラホルムアルデヒドがほぼ定量的にメチル化剤として働くため、メタノールが特に好ましい。
本発明においては、反応は懸濁床による回分、半回分、連続式でも、また固定床流通式でも実施できる。
In the present invention, a reaction solvent can be used. Examples of the reaction solvent include protic solvents and aprotic solvents, and mixed solvents thereof. Specific examples of the reaction solvent include methanol, hexane, and tetrahydrofuran. Of these, methanol is particularly preferred because paraformaldehyde acts almost quantitatively as a methylating agent.
In the present invention, the reaction can be carried out in a batch, semi-batch, continuous, or fixed bed flow system using a suspended bed.
反応温度は、反応溶媒の沸点等により選択されるが、通常、０〜１５０℃、好ましくは１５〜６０℃の範囲である。１５０℃以下とすることで、原料及び生成物の分解が抑制され、０℃以上とすることで十分な反応速度が得られる。更に、本発明では、１５〜２５℃の常温又は常温付近でも好適にモノメチル化体を得ることができ、常温又は常温付近であれば、製造条件を簡略化できる点で好ましい。 The reaction temperature is selected depending on the boiling point of the reaction solvent and the like, but is usually in the range of 0 to 150 ° C, preferably 15 to 60 ° C. By making it 150 degrees C or less, decomposition | disassembly of a raw material and a product is suppressed, and sufficient reaction rate is obtained by making it 0 degrees C or more. Furthermore, in the present invention, a monomethylated product can be suitably obtained even at or near room temperature of 15 to 25 ° C., and if it is at or near room temperature, it is preferable in that the production conditions can be simplified.
本発明は、水素雰囲気下で実施される。水素雰囲気下とは、通常、水素ガスを含有する雰囲気であり、水素ガスが１００％でもよいし、水素ガスと、窒素、ヘリウム、アルゴン等の不活性ガスとを含むものであってもよい。水素ガス濃度は７０容量％以上が好ましく、８０容量％以上がより好ましい。水素ガスの量は、通常、上記脂肪族第一級アミンの当量以上とすることができる。
また、反応時における水素圧は、大気圧（通常、０．０９〜０．１１ＭＰａ範囲）〜５ＭＰａ、好ましくは大気圧〜０．５ＭＰａの範囲である。加圧とすることにより、反応を促進することができる。一方、０．０９〜０．１１ＭＰａの範囲である、常圧又は常圧付近であれば、製造条件を簡略化できる点で好ましい。
また、本発明においては、反応は懸濁床による回分、半回分、連続式のいずれでもよい。また、固定床流通式でもよい。
The present invention is carried out under a hydrogen atmosphere. The hydrogen atmosphere is usually an atmosphere containing hydrogen gas. The hydrogen gas may be 100%, or may contain hydrogen gas and an inert gas such as nitrogen, helium, or argon. The hydrogen gas concentration is preferably 70% by volume or more, and more preferably 80% by volume or more. The amount of hydrogen gas can usually be greater than or equal to the equivalent of the aliphatic primary amine.
The hydrogen pressure during the reaction is atmospheric pressure (usually in the range of 0.09 to 0.11 MPa) to 5 MPa, preferably in the range of atmospheric pressure to 0.5 MPa. By applying pressure, the reaction can be promoted. On the other hand, if it is a normal pressure or the vicinity of a normal pressure which is the range of 0.09-0.11 MPa, it is preferable at the point which can simplify manufacturing conditions.
In the present invention, the reaction may be any of batch, semi-batch, and continuous with a suspended bed. Moreover, a fixed bed flow type may be used.
本発明における反応時間は、特に限定されない。原料である脂肪族第一級アミンの種類、反応溶媒の種類及び反応温度等のその他の反応条件により適宜選択される。反応時間は、通常、３０分〜７２時間であり、上記のように加熱や加圧することにより反応時間を短縮することができる。 The reaction time in the present invention is not particularly limited. It is appropriately selected depending on other reaction conditions such as the type of aliphatic primary amine as a raw material, the type of reaction solvent, and the reaction temperature. The reaction time is usually 30 minutes to 72 hours, and the reaction time can be shortened by heating or pressurizing as described above.
本発明のモノメチル化方法では、目的とするモノメチル化体である脂肪族第二級アミンへの反応を効率よく進めることができ、高い収率でモノメチル化体である脂肪族第二級アミンを得ることができる。本発明のモノメチル化方法により得られるモノメチル化体である脂肪族第二級アミンの収率は、好ましくは４０％以上、より好ましくは６０％以上、更に好ましくは８０％以上、特に好ましくは１００である。特に収率が１００％である場合には、目的とする脂肪族第二級アミン以外の化合物が副生等することがなく、脂肪族第二級アミンの精製及び回収を極めて効率よく進めることができる。
本発明の脂肪族第一級アミンのモノメチル化方法により、脂肪族第一級アミンから、脂肪族第二級アミンを製造することができる。
In the monomethylation method of the present invention, the reaction to an aliphatic secondary amine, which is the target monomethylated product, can proceed efficiently, and an aliphatic secondary amine that is a monomethylated product is obtained in a high yield. be able to. The yield of the aliphatic secondary amine that is a monomethylated product obtained by the monomethylation method of the present invention is preferably 40% or more, more preferably 60% or more, still more preferably 80% or more, and particularly preferably 100. is there. In particular, when the yield is 100%, compounds other than the desired aliphatic secondary amine are not by-produced, and the purification and recovery of the aliphatic secondary amine can proceed extremely efficiently. it can.
An aliphatic secondary amine can be produced from an aliphatic primary amine by the monomethylation method of an aliphatic primary amine of the present invention.
本発明のモノメチル化方法による反応後の反応液に含まれる、原料脂肪族第一級アミンに由来する成分は、通常、目的とするモノメチル化体である脂肪族第二級アミン、及び、未反応の脂肪族第一級アミンである。また、副生物として、微量のジメチル化体が含まれる場合もある。 The component derived from the raw material aliphatic primary amine contained in the reaction solution after the reaction by the monomethylation method of the present invention is usually an aliphatic secondary amine that is the target monomethylated product, and unreacted Is an aliphatic primary amine. Moreover, a trace amount dimethylated body may be contained as a by-product.
本発明を以下に詳細に説明するが、本発明はこれらに限定して解釈されるものではない。
実施例１〜７では、脂肪族第一級アミンをロジウム触媒の存在下において水素雰囲気下で反応させ、メチル化を行った。なお、脂肪族第一級アミン及びパラホルムアルデヒドは、市販品をそのまま用いた。
また、比較例１〜３では、メチル化剤を変えて検討を行った。各メチル化剤は市販品をそのまま用いた。
実施例及び比較例において、得られた生成物は塩酸と反応させて、塩酸塩とした後、重水（Ｄ２Ｏ）に溶解し、核磁気共鳴装置（日本電子ＪＥＯＬ−ＥＸ４００ Ｓｐｅｃｔｒｏｍｅｔｅｒ）を用いて分析（核磁気共鳴分析（１Ｈ−ＮＭＲ））をした。生成物（塩酸塩）の化学シフト値は溶媒中に存在するプロトンによる吸収（４．６５ｐｐｍ）を内部標準としてｐｐｍ単位で表示した。
The present invention will be described in detail below, but the present invention should not be construed as being limited thereto.
In Examples 1 to 7, methylation was performed by reacting an aliphatic primary amine in the presence of a rhodium catalyst in a hydrogen atmosphere. Commercially available aliphatic primary amines and paraformaldehyde were used as they were.
Moreover, in Comparative Examples 1-3, it examined by changing a methylating agent. Each methylating agent was a commercially available product.
In Examples and Comparative Examples, the obtained products were reacted with hydrochloric acid to form hydrochlorides, then dissolved in heavy water (D 2 O), and using a nuclear magnetic resonance apparatus (JEOL JEOL-EX400 Spectrometer). was analyzed (nuclear magnetic resonance analysis (1 H-NMR)) and. The chemical shift value of the product (hydrochloride) was expressed in ppm with absorption (4.65 ppm) by protons present in the solvent as an internal standard.
（実施例１）
１，６−ジアミノヘキサン〔Ｈ２Ｎ（ＣＨ２）６ＮＨ２〕（和光純薬工業社製）１１６ｍｇ（１ｍｍｏｌ）及びパラホルムアルデヒド（和光純薬工業社製）３６．０ｍｇ（１．２ｍｍｏｌ）を５ｍｌのメタノールに溶解した。さらに、白金族触媒として、炭素担体に対して１０質量％のロジウムが担持されているＲｈ／Ｃ（Ｎ．Ｅ．Ｃｈｅｍｃａｔ社製、ｋ−ｔｙｐｅ、ｄｒｙ）を３１ｍｇ（基質に対してロジウムが３ｍｏｌ％となる）を加え、有機合成装置（製品名：Ｃｈｅｍｉｓｔ Ｐｌａｚａ、柴田科学社製）に据え付けた。大気圧の水素ガス（約１５００ｍｌ）を封入し、２５℃で３６時間撹拌し反応を行った。その後、反応液をセライト（和光純薬工業社製）ろ過してＲｈ／Ｃを除去し、メタノール（４０ｍｌ）で洗浄した。こうして得られたろ液に３５％塩酸（和光純薬工業社製）１ｍｌを加えた後、溶媒を減圧留去し、白色固体の生成物１６０ｍｇを得た。
そして、核磁気共鳴分析（１Ｈ−ＮＭＲ）によって、この生成物を解析した結果、Ｎ−メチル−１，６−ジアミノヘキサン〔Ｈ２Ｎ（ＣＨ２）６ＮＨＣＨ３〕の塩酸塩の１Ｈ−ＮＭＲデータ（Ｄ２Ｏ）：δ１．２８（ｍ、４Ｈ）、１．５６（ｍ、４Ｈ）、２．５７（ｓ、３Ｈ）、２．９０（ｍ、４Ｈ）が得られた。
以上から、Ｎ−メチル−１，６−ジアミノヘキサンが収率１００％で得られたことがわかった。
Example 1
116 mg (1 mmol) of 1,6-diaminohexane [H 2 N (CH 2 ) 6 NH 2 ] (manufactured by Wako Pure Chemical Industries, Ltd.) and 36.0 mg (1.2 mmol) of paraformaldehyde (manufactured by Wako Pure Chemical Industries, Ltd.) Dissolved in 5 ml of methanol. Further, as a platinum group catalyst, 31 mg of Rh / C (manufactured by NE Chemcat, k-type, dry) on which 10% by mass of rhodium is supported with respect to the carbon support (3 mol of rhodium with respect to the substrate). %) And was installed in an organic synthesizer (product name: Chemist Plaza, manufactured by Shibata Kagaku Co., Ltd.). Atmospheric hydrogen gas (about 1500 ml) was sealed, and the reaction was carried out by stirring at 25 ° C. for 36 hours. Thereafter, the reaction solution was filtered through Celite (manufactured by Wako Pure Chemical Industries, Ltd.) to remove Rh / C, and washed with methanol (40 ml). 1 ml of 35% hydrochloric acid (manufactured by Wako Pure Chemical Industries, Ltd.) was added to the filtrate thus obtained, and then the solvent was distilled off under reduced pressure to obtain 160 mg of a white solid product.
As a result of analyzing this product by nuclear magnetic resonance analysis ( 1 H-NMR), 1 H of hydrochloride of N-methyl-1,6-diaminohexane [H 2 N (CH 2 ) 6 NHCH 3 ] was obtained. -NMR data (D 2 O): δ1.28 ( m, 4H), 1.56 (m, 4H), 2.57 (s, 3H), 2.90 (m, 4H) was obtained.
From the above, it was found that N-methyl-1,6-diaminohexane was obtained in a yield of 100%.
（実施例２）
１，６−ジアミノヘキサン〔Ｈ２Ｎ（ＣＨ２）６ＮＨ２〕（和光純薬工業社製）１１６ｍｇ（１ｍｍｏｌ）及びパラホルムアルデヒド（和光純薬工業社製）３３．０ｍｇ（１．１ｍｍｏｌ）を５ｍｌのメタノールに溶解した。さらに、白金族触媒として、炭素担体に対して１０質量％のロジウムが担持されているＲｈ／Ｃ（Ｎ．Ｅ．Ｃｈｅｍｃａｔ社製、ｋ−ｔｙｐｅ、ｄｒｙ）を３１ｍｇ（基質に対してロジウムが３ｍｏｌ％となる）を加え、有機合成装置（製品名：Ｃｈｅｍｉｓｔ Ｐｌａｚａ、柴田科学社製）に据え付けた。大気圧の水素ガス（約１５００ｍｌ）を封入し、２５℃で４２時間撹拌し反応を行った。その後、反応液をセライト（和光純薬工業社製）ろ過してＲｈ／Ｃを除去し、メタノール（４０ｍｌ）で洗浄した。こうして得られたろ液に３５％塩酸（和光純薬工業社製）１ｍｌを加えた後、溶媒を減圧留去し、白色固体の生成物２１９ｍｇを得た。
そして、核磁気共鳴分析（１Ｈ−ＮＭＲ）によって、この生成物を解析した結果、Ｎ−メチル−１，６−ジアミノヘキサンの塩酸塩のデータが得られた。そして、そのデータより、Ｎ−メチル−１，６−ジアミノヘキサンが収率９２％で得られたことがわかった。
(Example 2)
116 mg (1 mmol) of 1,6-diaminohexane [H 2 N (CH 2 ) 6 NH 2 ] (manufactured by Wako Pure Chemical Industries, Ltd.) and 33.0 mg (1.1 mmol) of paraformaldehyde (manufactured by Wako Pure Chemical Industries, Ltd.) Dissolved in 5 ml of methanol. Further, as a platinum group catalyst, 31 mg of Rh / C (manufactured by NE Chemcat, k-type, dry) on which 10% by mass of rhodium is supported with respect to the carbon support (3 mol of rhodium with respect to the substrate). %) And was installed in an organic synthesizer (product name: Chemist Plaza, manufactured by Shibata Kagaku Co., Ltd.). Atmospheric hydrogen gas (about 1500 ml) was sealed, and the reaction was carried out by stirring at 25 ° C. for 42 hours. Thereafter, the reaction solution was filtered through Celite (manufactured by Wako Pure Chemical Industries, Ltd.) to remove Rh / C, and washed with methanol (40 ml). 1 ml of 35% hydrochloric acid (manufactured by Wako Pure Chemical Industries, Ltd.) was added to the filtrate thus obtained, and then the solvent was distilled off under reduced pressure to obtain 219 mg of a white solid product.
As a result of analyzing this product by nuclear magnetic resonance analysis ( 1 H-NMR), data on the hydrochloride of N-methyl-1,6-diaminohexane was obtained. From the data, it was found that N-methyl-1,6-diaminohexane was obtained in a yield of 92%.
（実施例３）
１，６−ジアミノヘキサン〔Ｈ２Ｎ（ＣＨ２）６ＮＨ２〕（和光純薬工業社製）１１６ｍｇ（１ｍｍｏｌ）及びパラホルムアルデヒド（和光純薬工業社製）３０．０ｍｇ（１．０ｍｍｏｌ）を５ｍｌのメタノールに溶解した。さらに、白金族触媒として、炭素担体に対して１０質量％のロジウムが担持されているＲｈ／Ｃ（Ｎ．Ｅ．Ｃｈｅｍｃａｔ社製、ｋ−ｔｙｐｅ、ｄｒｙ）を３１ｍｇ（基質に対してロジウムが３ｍｏｌ％となる）を加え、有機合成装置（製品名：Ｃｈｅｍｉｓｔ Ｐｌａｚａ、柴田科学社製）に据え付けた。大気圧の水素ガス（約１５００ｍｌ）を封入し、２５℃で２４時間撹拌し反応を行った。その後、反応液をセライト（和光純薬工業社製）ろ過してＲｈ／Ｃを除去し、メタノール（４０ｍｌ）で洗浄した。こうして得られたろ液に３５％塩酸（和光純薬工業社製）１ｍｌを加えた後、溶媒を減圧留去し、白色固体の生成物１９３ｍｇを得た。
そして、核磁気共鳴分析（１Ｈ−ＮＭＲ）によって、この生成物を解析した結果、Ｎ−メチル−１，６−ジアミノヘキサンの塩酸塩のデータが得られた。そして、そのデータより、Ｎ−メチル−１，６−ジアミノヘキサンが収率７３％で得られたことがわかった。
(Example 3)
116 mg (1 mmol) of 1,6-diaminohexane [H 2 N (CH 2 ) 6 NH 2 ] (manufactured by Wako Pure Chemical Industries, Ltd.) and 30.0 mg (1.0 mmol) of paraformaldehyde (manufactured by Wako Pure Chemical Industries, Ltd.) Dissolved in 5 ml of methanol. Further, as a platinum group catalyst, 31 mg of Rh / C (manufactured by NE Chemcat, k-type, dry) on which 10% by mass of rhodium is supported with respect to the carbon support (3 mol of rhodium with respect to the substrate). %) And was installed in an organic synthesizer (product name: Chemist Plaza, manufactured by Shibata Kagaku Co., Ltd.). Atmospheric hydrogen gas (about 1500 ml) was sealed, and the reaction was carried out by stirring at 25 ° C. for 24 hours. Thereafter, the reaction solution was filtered through Celite (manufactured by Wako Pure Chemical Industries, Ltd.) to remove Rh / C, and washed with methanol (40 ml). After adding 1 ml of 35% hydrochloric acid (manufactured by Wako Pure Chemical Industries, Ltd.) to the filtrate thus obtained, the solvent was distilled off under reduced pressure to obtain 193 mg of a white solid product.
As a result of analyzing this product by nuclear magnetic resonance analysis ( 1 H-NMR), data on the hydrochloride of N-methyl-1,6-diaminohexane was obtained. From the data, it was found that N-methyl-1,6-diaminohexane was obtained in a yield of 73%.
（実施例４）
１，４−ジアミノブタン〔Ｈ２Ｎ（ＣＨ２）４ＮＨ２〕（和光純薬工業社製）８８．２ｍｇ（１ｍｍｏｌ）及びパラホルムアルデヒド（和光純薬工業社製）３６．０ｍｇ（１．２ｍｍｏｌ）を５ｍｌのメタノールに溶解した。さらに、白金族触媒として炭素担体に対して１０質量％のロジウムが担持されているＲｈ／Ｃ（Ｎ．Ｅ．Ｃｈｅｍｃａｔ社製、ｋ−ｔｙｐｅ、ｄｒｙ）を８．８ｍｇ（基質に対してロジウムが０．８６ｍｏｌ％となる）を加え、有機合成装置（製品名：Ｃｈｅｍｉｓｔ Ｐｌａｚａ、柴田科学社製）に据え付けた。大気圧の水素ガス（約１５００ｍｌ）を封入し、２５℃で２４時間撹拌し反応を行った。その後、反応液をセライト（和光純薬工業社製）ろ過してＲｈ／Ｃを除去し、メタノール（４０ｍｌ）で洗浄した。こうして得られたろ液に３５％塩酸（和光純薬工業社製）１ｍｌを加えた後、溶媒を減圧留去し、白色固体の生成物１３２ｍｇを得た。
そして、核磁気共鳴分析によって、この生成物を解析した結果、Ｎ−メチル−１，４−ジアミノブタン〔Ｈ２Ｎ（ＣＨ２）４ＮＨＣＨ３〕の塩酸塩の１Ｈ−ＮＭＲデータ（Ｄ２Ｏ）：δ１．６８（ｍ、４Ｈ）、２．６３（ｓ、３Ｈ）、２．９８（ｍ、４Ｈ）が得られた。
以上から、Ｎ−メチル−１，４−ジアミノブタンが収率１００％で得られたことがわかった。
(Example 4)
1,4-diaminobutane [H 2 N (CH 2 ) 4 NH 2 ] (manufactured by Wako Pure Chemical Industries, Ltd.) 88.2 mg (1 mmol) and paraformaldehyde (manufactured by Wako Pure Chemical Industries, Ltd.) 36.0 mg (1.2 mmol) ) Was dissolved in 5 ml of methanol. Further, 8.8 mg of Rh / C (manufactured by NE Chemcat, k-type, dry) on which 10% by mass of rhodium is supported as a platinum group catalyst with respect to the carbon support (rhodium is present relative to the substrate). 0.86 mol%) was added and installed in an organic synthesizer (product name: Chemist Plaza, manufactured by Shibata Kagaku). Atmospheric hydrogen gas (about 1500 ml) was sealed, and the reaction was carried out by stirring at 25 ° C. for 24 hours. Thereafter, the reaction solution was filtered through Celite (manufactured by Wako Pure Chemical Industries, Ltd.) to remove Rh / C, and washed with methanol (40 ml). 1 ml of 35% hydrochloric acid (manufactured by Wako Pure Chemical Industries, Ltd.) was added to the filtrate thus obtained, and then the solvent was distilled off under reduced pressure to obtain 132 mg of a white solid product.
As a result of analyzing this product by nuclear magnetic resonance analysis, 1 H-NMR data (D 2 ) of hydrochloride of N-methyl-1,4-diaminobutane [H 2 N (CH 2 ) 4 NHCH 3 ] was obtained. O): δ 1.68 (m, 4H), 2.63 (s, 3H), 2.98 (m, 4H) were obtained.
From the above, it was found that N-methyl-1,4-diaminobutane was obtained with a yield of 100%.
（実施例５）
１，２−ジアミノエタン〔Ｈ２Ｎ（ＣＨ２）２ＮＨ２〕（和光純薬工業社製）６０．１ｍｇ（１ｍｍｏｌ）及びパラホルムアルデヒド（和光純薬工業社製）３６．０ｍｇ（１．２ｍｍｏｌ）を５ｍｌのメタノールに溶解した。さらに、白金族触媒として炭素担体に対して１０質量％のロジウムが担持されているＲｈ／Ｃ（Ｎ．Ｅ．Ｃｈｅｍｃａｔ社製、ｋ−ｔｙｐｅ、ｄｒｙ）を２０．６ｍｇ（基質に対してロジウムが２ｍｏｌ％となる）を加え、有機合成装置（製品名：Ｃｈｅｍｉｓｔ Ｐｌａｚａ、柴田科学社製）に据え付けた。０．３ＭＰａの水素ガス（約２００ｍｌ）を封入し、４０℃で２４時間撹拌し反応を行った。その後、反応液をセライト（和光純薬工業社製）ろ過してＲｈ／Ｃを除去し、メタノール（４０ｍｌ）で洗浄した。こうして得られたろ液に３５％塩酸（和光純薬工業社社製）１ｍｌを加えた後、溶媒を減圧留去し、白色固体の生成物１６６ｍｇを得た。
そして、核磁気共鳴分析（１Ｈ−ＮＭＲ）によって、この生成物を解析した結果、Ｎ−メチル−１，２−ジアミノエタンの塩酸塩のデータが得られた。そして、そのデータより、Ｎ−メチル−１，２−ジアミノエタンが収率６３％で得られたことがわかった。
(Example 5)
1,2-Diaminoethane [H 2 N (CH 2 ) 2 NH 2 ] (Wako Pure Chemical Industries, Ltd.) 60.1 mg (1 mmol) and paraformaldehyde (Wako Pure Chemical Industries, Ltd.) 36.0 mg (1.2 mmol) ) Was dissolved in 5 ml of methanol. Furthermore, 20.6 mg of Rh / C (manufactured by NE Chemcat, k-type, dry) on which 10% by mass of rhodium is supported as a platinum group catalyst with respect to the carbon support (rhodium is present relative to the substrate). 2 mol%) and added to an organic synthesizer (product name: Chemist Plaza, manufactured by Shibata Kagaku). 0.3 MPa of hydrogen gas (about 200 ml) was sealed, and the reaction was carried out by stirring at 40 ° C. for 24 hours. Thereafter, the reaction solution was filtered through Celite (manufactured by Wako Pure Chemical Industries, Ltd.) to remove Rh / C, and washed with methanol (40 ml). 1 ml of 35% hydrochloric acid (manufactured by Wako Pure Chemical Industries, Ltd.) was added to the filtrate thus obtained, and then the solvent was distilled off under reduced pressure to obtain 166 mg of a white solid product.
As a result of analyzing this product by nuclear magnetic resonance analysis ( 1 H-NMR), N-methyl-1,2-diaminoethane hydrochloride data was obtained. From the data, it was found that N-methyl-1,2-diaminoethane was obtained with a yield of 63%.
（実施例６）
１，２−ジアミノエタン〔Ｈ２Ｎ（ＣＨ２）２ＮＨ２〕（和光純薬工業社製）６０．１ｍｇ（１ｍｍｏｌ）及びパラホルムアルデヒド（和光純薬工業社製）３６．０ｍｇ（１．２ｍｍｏｌ）を５ｍｌのテトラヒドロフラン（ＴＨＦ）に溶解した。さらに、白金族触媒として炭素担体に対して１０質量％のロジウムが担持されているＲｈ／Ｃ（Ｎ．Ｅ．Ｃｈｅｍｃａｔ社製、ｋ−ｔｙｐｅ、ｄｒｙ）を１７．９ｍｇ（基質に対してロジウムが１．７４ｍｏｌ％となる）を加え、有機合成装置（製品名：Ｃｈｅｍｉｓｔ Ｐｌａｚａ、柴田科学社製）に据え付けた。０．５ＭＰａの水素ガス（約２００ｍｌ）を封入し、６０℃で２４時間撹拌し反応を行った。その後、反応液をセライト（和光純薬工業社製）ろ過してＲｈ／Ｃを除去し、メタノール（４０ｍｌ）で洗浄した。こうして得られたろ液に３５％塩酸（和光純薬工業社製）１ｍｌを加えた後、溶媒を減圧留去し、白色固体の生成物１６０ｍｇを得た。
そして、核磁気共鳴分析（１Ｈ−ＮＭＲ）によって、この生成物を解析した結果、Ｎ−メチル−１，２−ジアミノエタンの塩酸塩のデータが得られた。そして、そのデータより、Ｎ−メチル−１，２−ジアミノエタンが収率６５％で得られたことがわかった。
(Example 6)
1,2-Diaminoethane [H 2 N (CH 2 ) 2 NH 2 ] (Wako Pure Chemical Industries, Ltd.) 60.1 mg (1 mmol) and paraformaldehyde (Wako Pure Chemical Industries, Ltd.) 36.0 mg (1.2 mmol) ) Was dissolved in 5 ml of tetrahydrofuran (THF). Further, 17.9 mg of Rh / C (manufactured by NE Chemcat, k-type, dry) on which 10% by mass of rhodium is supported as a platinum group catalyst with respect to the carbon support (rhodium with respect to the substrate). 1.74 mol%) was added and installed in an organic synthesizer (product name: Chemist Plaza, manufactured by Shibata Kagaku). 0.5 MPa of hydrogen gas (about 200 ml) was sealed, and the reaction was carried out by stirring at 60 ° C. for 24 hours. Thereafter, the reaction solution was filtered through Celite (manufactured by Wako Pure Chemical Industries, Ltd.) to remove Rh / C, and washed with methanol (40 ml). 1 ml of 35% hydrochloric acid (manufactured by Wako Pure Chemical Industries, Ltd.) was added to the filtrate thus obtained, and then the solvent was distilled off under reduced pressure to obtain 160 mg of a white solid product.
As a result of analyzing this product by nuclear magnetic resonance analysis ( 1 H-NMR), N-methyl-1,2-diaminoethane hydrochloride data was obtained. From the data, it was found that N-methyl-1,2-diaminoethane was obtained with a yield of 65%.
（実施例７）
１，２−ジアミノエタン〔Ｈ２Ｎ（ＣＨ２）２ＮＨ２〕（和光純薬工業社製）６０．１ｍｇ（１ｍｍｏｌ）及びパラホルムアルデヒド（和光純薬工業社製）３６．０ｍｇ（１．２ｍｍｏｌ）を５ｍｌのヘキサンに溶解した。さらに、白金族触媒として炭素担体に対して１０質量％のロジウムが担持されているＲｈ／Ｃ（Ｎ．Ｅ．Ｃｈｅｍｃａｔ社製、ｋ−ｔｙｐｅ、ｄｒｙ）を２０．６ｍｇ（基質に対してロジウムが２ｍｏｌ％となる）を加え、有機合成装置（製品名：Ｃｈｅｍｉｓｔ Ｐｌａｚａ、柴田科学社製）に据え付けた。０．５ＭＰａの水素ガス（約２００ｍｌ）を封入し、６０℃で２４時間撹拌し反応を行った。その後、反応液をセライト（和光純薬工業社製）ろ過してＲｈ／Ｃを除去し、メタノール（４０ｍｌ）で洗浄した。こうして得られたろ液に３５％塩酸（和光純薬工業社製）１ｍｌを加えた後、溶媒を減圧留去し、白色固体の生成物１０９ｍｇを得た。
そして、核磁気共鳴分析（１Ｈ−ＮＭＲ）によって、この生成物を解析した結果、Ｎ−メチル−１，２−ジアミノエタンの塩酸塩のデータが得られた。そして、そのデータより、Ｎ−メチル−１，２−ジアミノエタンが収率６３％で得られたことがわかった。
(Example 7)
1,2-Diaminoethane [H 2 N (CH 2 ) 2 NH 2 ] (Wako Pure Chemical Industries, Ltd.) 60.1 mg (1 mmol) and paraformaldehyde (Wako Pure Chemical Industries, Ltd.) 36.0 mg (1.2 mmol) ) Was dissolved in 5 ml of hexane. Furthermore, 20.6 mg of Rh / C (manufactured by NE Chemcat, k-type, dry) on which 10% by mass of rhodium is supported as a platinum group catalyst with respect to the carbon support (rhodium is present relative to the substrate). 2 mol%) and added to an organic synthesizer (product name: Chemist Plaza, manufactured by Shibata Kagaku). 0.5 MPa of hydrogen gas (about 200 ml) was sealed, and the reaction was carried out by stirring at 60 ° C. for 24 hours. Thereafter, the reaction solution was filtered through Celite (manufactured by Wako Pure Chemical Industries, Ltd.) to remove Rh / C, and washed with methanol (40 ml). 1 ml of 35% hydrochloric acid (manufactured by Wako Pure Chemical Industries, Ltd.) was added to the filtrate thus obtained, and then the solvent was distilled off under reduced pressure to obtain 109 mg of a white solid product.
As a result of analyzing this product by nuclear magnetic resonance analysis ( 1 H-NMR), N-methyl-1,2-diaminoethane hydrochloride data was obtained. From the data, it was found that N-methyl-1,2-diaminoethane was obtained with a yield of 63%.
（比較例１）
１，６−ジアミノヘキサン〔Ｈ２Ｎ（ＣＨ２）６ＮＨ２〕（和光純薬工業社製）１１６ｍｇ（１ｍｍｏｌ）及び３５％ホルマリン（和光純薬工業社製）８５．８ｍｇ（１．０ｍｍｏｌ）を５ｍｌのメタノールに溶解した。さらに、白金族触媒として炭素担体に対して１０質量％のロジウムが担持されているＲｈ／Ｃ（Ｎ．Ｅ．Ｃｈｅｍｃａｔ社製、ｋ−ｔｙｐｅ、ｄｒｙ）を３１ｍｇ（基質に対してロジウムが３ｍｏｌ％となる）を加え、有機合成装置（製品名：Ｃｈｅｍｉｓｔ Ｐｌａｚａ、柴田科学社製）に据え付けた。大気圧の水素ガス（約１５００ｍｌ）を封入し、２５℃で２６時間撹拌し反応を行った。その後、反応液をセライト（和光純薬工業社製）ろ過してＲｈ／Ｃを除去し、メタノール（４０ｍｌ）で洗浄した。こうして得られたろ液に３５％塩酸（和光純薬工業社製）１ｍｌを加えた後、溶媒を減圧留去し、白色固体の生成物１１０ｍｇを得た。
そして、核磁気共鳴分析（１Ｈ−ＮＭＲ）によって、この生成物を解析した結果、生成物は未反応の１，６−ジアミノヘキサン、Ｎ−メチル−１，６−ジアミノヘキサン、Ｎ，Ｎ−ジメチル−１，６−ジアミノヘキサン、Ｎ，Ｎ‘−ジメチル−１，６−ジアミノヘキサン、Ｎ，Ｎ，Ｎ‘−トリメチル−１，６−ジアミノヘキサン、Ｎ，Ｎ，Ｎ‘，Ｎ‘−テトラメチル−１，６−ジアミノヘキサンの塩酸塩の混合物であることがわかった。そして、そのデータより、Ｎ−メチル−１，６−ジアミノヘキサンが１１％の収率で得られたことがわかった。
(Comparative Example 1)
1,6-diaminohexane [H 2 N (CH 2) 6 NH 2 ] (manufactured by Wako Pure Chemical Industries, Ltd.) 116 mg (1 mmol) and 35% formalin (Wako Pure Chemical Industries, Ltd.) 85.8mg (1.0mmol) Was dissolved in 5 ml of methanol. Further, 31 mg of Rh / C (manufactured by NE Chemcat, k-type, dry) on which 10% by mass of rhodium is supported as a platinum group catalyst with respect to the carbon support (3 mol% of rhodium with respect to the substrate). And was installed in an organic synthesizer (product name: Chemist Plaza, manufactured by Shibata Kagaku Co., Ltd.). Atmospheric hydrogen gas (about 1500 ml) was sealed, and the reaction was carried out by stirring at 25 ° C. for 26 hours. Thereafter, the reaction solution was filtered through Celite (manufactured by Wako Pure Chemical Industries, Ltd.) to remove Rh / C, and washed with methanol (40 ml). After adding 1 ml of 35% hydrochloric acid (manufactured by Wako Pure Chemical Industries, Ltd.) to the filtrate thus obtained, the solvent was distilled off under reduced pressure to obtain 110 mg of a white solid product.
And as a result of analyzing this product by nuclear magnetic resonance analysis ( 1 H-NMR), the product was unreacted 1,6-diaminohexane, N-methyl-1,6-diaminohexane, N, N- Dimethyl-1,6-diaminohexane, N, N′-dimethyl-1,6-diaminohexane, N, N, N′-trimethyl-1,6-diaminohexane, N, N, N ′, N′-tetra It was found to be a mixture of hydrochlorides of methyl-1,6-diaminohexane. From the data, it was found that N-methyl-1,6-diaminohexane was obtained in a yield of 11%.
（比較例２）
１，６−ジアミノヘキサン〔Ｈ２Ｎ（ＣＨ２）６ＮＨ２〕（和光純薬工業社製）１１６ｍｇ（１．０ｍｍｏｌ）及びトリメチルシリルシアニド（和光純薬工業社製）４９６ｍｇ（５．０ｍｍｏｌ）を５ｍｌのメタノールに溶解した。さらに、白金族触媒として炭素担体に対して１０質量％のロジウムが担持されているＲｈ／Ｃ（Ｎ．Ｅ．Ｃｈｅｍｃａｔ社製、ｋ−ｔｙｐｅ、ｄｒｙ）を３１ｍｇ（基質に対してロジウムが３ｍｏｌ％となる）を加え、有機合成装置（Ｃｈｅｍｉｓｔ Ｐｌａｚａ、柴田科学社製）に据え付けた。大気圧の水素ガス（約１５００ｍｌ）を封入し、２５ ℃で２４時間撹拌し反応を行った。その後、反応液をセライト（和光純薬工業社製）ろ過してＲｈ／Ｃを除去し、メタノール（４０ｍｌ）で洗浄した。こうして得られたろ液に３５％塩酸（和光純薬工業社製）１ｍｌを加えた後、溶媒を減圧留去し、白色固体の生成物１０５ｍｇを得た。
そして、核磁気共鳴分析（１Ｈ−ＮＭＲ）によって、この生成物を解析した結果、メチル化反応は進行せず、１，６−ジアミノヘキサンが未反応のままであることがわかった。Ｎ−メチル−１，６−ジアミノヘキサンの収率は０％であった
(Comparative Example 2)
116 mg (1.0 mmol) of 1,6-diaminohexane [H 2 N (CH 2 ) 6 NH 2 ] (manufactured by Wako Pure Chemical Industries, Ltd.) and 496 mg (5.0 mmol) of trimethylsilyl cyanide (manufactured by Wako Pure Chemical Industries, Ltd.) Was dissolved in 5 ml of methanol. Further, 31 mg of Rh / C (manufactured by NE Chemcat, k-type, dry) on which 10% by mass of rhodium is supported as a platinum group catalyst with respect to the carbon support (3 mol% of rhodium with respect to the substrate). And was installed in an organic synthesizer (Chemist Plaza, manufactured by Shibata Kagaku). Atmospheric hydrogen gas (about 1500 ml) was sealed, and the reaction was carried out by stirring at 25 ° C. for 24 hours. Thereafter, the reaction solution was filtered through Celite (manufactured by Wako Pure Chemical Industries, Ltd.) to remove Rh / C, and washed with methanol (40 ml). 1 ml of 35% hydrochloric acid (manufactured by Wako Pure Chemical Industries, Ltd.) was added to the filtrate thus obtained, and then the solvent was distilled off under reduced pressure to obtain 105 mg of a white solid product.
As a result of analyzing this product by nuclear magnetic resonance analysis ( 1 H-NMR), it was found that the methylation reaction did not proceed and 1,6-diaminohexane remained unreacted. The yield of N-methyl-1,6-diaminohexane was 0%.
（比較例３）
１，６−ジアミノヘキサン〔Ｈ２Ｎ（ＣＨ２）６ＮＨ２〕（和光純薬工業社製）１１６ｍｇ（１．０ｍｍｏｌ）及びシアノアミン（和光純薬工業社製）２１０ｍｇ（５．０ｍｍｏｌ）を５ｍｌのメタノールに溶解した。さらに、白金族触媒として炭素担体に対して１０質量％のロジウムが担持されているＲｈ／Ｃ（Ｎ．Ｅ．Ｃｈｅｍｃａｔ社製、ｋ−ｔｙｐｅ、ｄｒｙ）を３１ｍｇ（基質に対してロジウムが３ｍｏｌ％となる）を加え、有機合成装置（製品名：Ｃｈｅｍｉｓｔ Ｐｌａｚａ、柴田科学社製）に据え付けた。大気圧の水素ガス（約１５００ｍｌ）を封入し、２５℃で２４時間撹拌し反応を行った。その後、反応液をセライト（和光純薬工業社製）ろ過してＲｈ／Ｃを除去し、メタノール（４０ｍｌ）で洗浄した。こうして得られたろ液に３５％塩酸（和光純薬工業社製）１ｍｌを加えた後、溶媒を減圧留去し、白色固体の生成物１０８ｍｇを得た。
そして、核磁気共鳴分析（１Ｈ−ＮＭＲ）によって、この生成物を解析した結果、メチル化反応は進行せず、１，６−ジアミノヘキサンが未反応のままであることがわかった。Ｎ−メチル−１，６−ジアミノヘキサンの収率は０％であった。
以上の結果を表１に併せて示す。
(Comparative Example 3)
116 ml (1.0 mmol) of 1,6-diaminohexane [H 2 N (CH 2 ) 6 NH 2 ] (manufactured by Wako Pure Chemical Industries, Ltd.) and 5 ml of 210 mg (5.0 mmol) of cyanoamine (manufactured by Wako Pure Chemical Industries, Ltd.) In methanol. Further, 31 mg of Rh / C (manufactured by NE Chemcat, k-type, dry) on which 10% by mass of rhodium is supported as a platinum group catalyst with respect to the carbon support (3 mol% of rhodium with respect to the substrate). And was installed in an organic synthesizer (product name: Chemist Plaza, manufactured by Shibata Kagaku Co., Ltd.). Atmospheric hydrogen gas (about 1500 ml) was sealed, and the reaction was carried out by stirring at 25 ° C. for 24 hours. Thereafter, the reaction solution was filtered through Celite (manufactured by Wako Pure Chemical Industries, Ltd.) to remove Rh / C, and washed with methanol (40 ml). After adding 1 ml of 35% hydrochloric acid (manufactured by Wako Pure Chemical Industries, Ltd.) to the filtrate thus obtained, the solvent was distilled off under reduced pressure to obtain 108 mg of a white solid product.
As a result of analyzing this product by nuclear magnetic resonance analysis ( 1 H-NMR), it was found that the methylation reaction did not proceed and 1,6-diaminohexane remained unreacted. The yield of N-methyl-1,6-diaminohexane was 0%.
The above results are also shown in Table 1.
Claims (7)
前記白金族触媒における白金族元素が、ロジウムであることを特徴とする脂肪族第一級アミンのモノメチル化方法。 Monomethylation of an aliphatic primary amine using paraformaldehyde in the presence of a platinum group catalyst in a hydrogen atmosphere ,
Platinum group elements in the platinum group catalyst, monomethyl method aliphatic primary amine, wherein rhodium der Rukoto.
Ｈ２Ｎ−Ｒ２−ＮＨ２ （１）
Ｈ２Ｎ−Ｒ２−ＮＨ−ＣＨ３ （２）
〔上記一般式（１）及び（２）において、Ｒ２は炭素数２〜１６の２価の有機基を表す。〕 The aliphatic primary amine is a alkylene amine represented by the following general formula (1), the resulting monomethyl embodying found in any of claims 1 to 3 represented by the following general formula (2) The monomethylation method of the aliphatic primary amine as described.
H 2 N-R 2 -NH 2 (1)
H 2 N-R 2 -NH- CH 3 (2)
[In the above general formulas (1) and (2), R 2 represents a divalent organic group having 2 to 16 carbon atoms. ]
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