IE42786B1 - Improvements in and relating to a process for the preparation of 2-(2-thienyl)-ethylamine and deivatives thereof - Google Patents
Improvements in and relating to a process for the preparation of 2-(2-thienyl)-ethylamine and deivatives thereofInfo
- Publication number
- IE42786B1 IE42786B1 IE53776A IE53776A IE42786B1 IE 42786 B1 IE42786 B1 IE 42786B1 IE 53776 A IE53776 A IE 53776A IE 53776 A IE53776 A IE 53776A IE 42786 B1 IE42786 B1 IE 42786B1
- Authority
- IE
- Ireland
- Prior art keywords
- formula
- derivative
- thienyl
- reaction
- preparation
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 21
- 238000002360 preparation method Methods 0.000 title claims description 7
- HVLUYXIJZLDNIS-UHFFFAOYSA-N 2-thiophen-2-ylethanamine Chemical compound NCCC1=CC=CS1 HVLUYXIJZLDNIS-UHFFFAOYSA-N 0.000 title description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 7
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 6
- -1 alkaline-earth metal carbonate Chemical class 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 6
- RPNUMPOLZDHAAY-UHFFFAOYSA-N Diethylenetriamine Chemical compound NCCNCCN RPNUMPOLZDHAAY-UHFFFAOYSA-N 0.000 claims description 5
- 150000001340 alkali metals Chemical class 0.000 claims description 4
- 238000005576 amination reaction Methods 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 150000004678 hydrides Chemical class 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 239000002585 base Substances 0.000 claims 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims 1
- 150000004703 alkoxides Chemical class 0.000 claims 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- NYVQQTOGYLBBDQ-UHFFFAOYSA-N 1-thiophen-2-ylpropan-2-amine Chemical compound CC(N)CC1=CC=CS1 NYVQQTOGYLBBDQ-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GSVJCILCEOKEIJ-UHFFFAOYSA-N 1-thiophen-2-ylpropan-2-yl 4-methylbenzenesulfonate Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)OC(C)CC1=CC=CS1 GSVJCILCEOKEIJ-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- CLSHQIDDCJTHAJ-UHFFFAOYSA-N 2-thienylacetonitrile Chemical compound N#CCC1=CC=CS1 CLSHQIDDCJTHAJ-UHFFFAOYSA-N 0.000 description 1
- HLPRKWVEMYDPAU-UHFFFAOYSA-N 2-thiophen-2-ylethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCCC1=CC=CS1 HLPRKWVEMYDPAU-UHFFFAOYSA-N 0.000 description 1
- FWRBHKLKOBUBEQ-UHFFFAOYSA-N 2-thiophen-2-ylpropan-1-amine Chemical compound NCC(C)C1=CC=CS1 FWRBHKLKOBUBEQ-UHFFFAOYSA-N 0.000 description 1
- BLFRQYKZFKYQLO-UHFFFAOYSA-N 4-aminobutan-1-ol Chemical compound NCCCCO BLFRQYKZFKYQLO-UHFFFAOYSA-N 0.000 description 1
- 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- HFACYLZERDEVSX-UHFFFAOYSA-N benzidine Chemical compound C1=CC(N)=CC=C1C1=CC=C(N)C=C1 HFACYLZERDEVSX-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 150000002148 esters Chemical group 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N mono-n-propyl amine Natural products CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- ZMRUPTIKESYGQW-UHFFFAOYSA-N propranolol hydrochloride Chemical compound [H+].[Cl-].C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 ZMRUPTIKESYGQW-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- AGGKEGLBGGJEBZ-UHFFFAOYSA-N tetramethylenedisulfotetramine Chemical compound C1N(S2(=O)=O)CN3S(=O)(=O)N1CN2C3 AGGKEGLBGGJEBZ-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
Description
This invention' relates to a new process for the preparation of 2-(2- thienyl) - ethylamine and derivatives thereof, which are known compounds used as intermediates in the synthesis of a large number of derivatives used in both the chemical and pharmaceutical industries.
The compounds prepared according to the process of this invention have the following general formula:
S ./
I! i|
2 in which R und R each represent hydrogen or a C^_4 alkyl or an optionally substituted phenyl radical. They have already been pre pared according to a variety of methods. Thus, their synthesis was effected by reduction of 2 - 0 - nitrovinyl - thiophene with lithium aluminium hydride (S. Gronovitz & F, Sandberg, Arkiv. ffir Kemi, 1970, 32, 217; M. L. Dressier, M. Soullii, J. Het. Chem.,
CO
1970, 7, 1257).
They have also been prepared from 2-(2- thienyl) - propylamide, by means of a Hoffman degradation reaction (G. Barger, A. Easson, J. Chem. Soc., 1938, 2100).
Other authors have also operated by reduction of 2-cyanomethyl thiophene with lithium aluminium hydride (B. F. Crowe, F. F. Nord. J. Org. Chem., 1950, 15, 81; J. ty. MacFarland, H. L. Howes,
J. Med. Chem., 1969, 12, 1079),
However, such prior methods are, all three, difficulty applicable industrially and do not provide compounds of the formula (I) in good yields.
Consequently, the object of the present invention is to provide an inexpensive industrial synthesis process which will produce 2-(2- thienyl) - ethylamine and derivatives thereof of the aforementioned formula (I) in good yields.
The process according to this invention comprises aminating a derivative of the formula:
in which R^ and R2 are as defined for formula (Τ), and in which r3 is an optionally substituted alkyl, aryl or aralkyl group, such as CH3, CC13, CF3, and p. CH3—CgHj.
According to an embodiment of the process of this invention, the amination is carried out directly by reacting the derivative of the formula (II) with ammonia.
The reaction is generally conducted at elevated temperatures, in an autoclave, during a period of time of 10—20 hours.
According to another embodiment of the process of this invention, the derivative of the formula (XI) is reacted with phthalimide, to give a compound having the formula;
which is subsequently transaminated with an amine or hydrazine 5 hydrate.
As amine, use is made of a markedly basic mono- or polyfunctional amine of high boiling point. Typically useful amines have the formula RNH2 in which R may be a Cg—Cg,. straight or branched chain alkyl radical, an aralkyl radical, (typically benzyl10 amine and its substituted derivatives), an aryl radical such as an optionally substituted phenyl or naphthyl radical, particularly the halogenoanilines, the alkyloxyanilines and benzidine. The radical R itself may carry other NH or NH2 functions, as in bis(2 - aminoethyl) amine (diethylenetriamine), ethylenediamine, triethylene15 tetramine, or even other functional groups such as hydroxy, ester, and alkoxy. Thus, the amine may be 4 - hydroxy - butylamine, 2pentoxy - propylamine, or ethanolamine.
The reaction is preferably effected at elevated temperature, and diethylene triamine, benzylamine or ethanolamine are advan20 tageously used.
The reaction of the derivative of the formula (II) with phthalimide is usually carried out in the presence of an inorganic or organic base, such as an alkali metal (Na, K) or alkaline-earth metal (.Ca) carbonate or hydroxide, an alkali metal tNa, K) amide, an alkali metal (Jia) hydride, or an alkali metal alkoxide.
The starting compounds of general formula II, some of which are novel, can all be prepared by known chemical methods.
The following non limiting examples are given to illustrate the invention.
EXAMPLE 1
Preparation of 2 - amino - 1 - (2 - thienyl) propane, via direct amination
Into a 1000 ml autoclave, are added 1-(2- thienyl) - 2propanol p-toluenesulfonate (75 g) and ammonia (600 ml). The whole is heated to 80°C during 15 hours. After cooling, the autoclave is opened and the ammonia is allowed to evaporate. After adding water (100 ml) and a IN sodium hydroxide solution (175 ml), the resulting material is extracted with ether. The ether phase is separated and then mixed with IN hydrochloric acid (75 ml). The aqueous phase is made alkaline and is then extracted with ether.
The ether extract is washed with a 5% sodium bicarbonate solution, and then with a saturated sodium chloride solution, after which it is dried over sodium sulfate. After evaporation, the residue is distilled in vacuo, to give 19 g 2 - amino - 1 - (2 - thienyl)propane (Yield: 53%) boiling at 84—86°C under 12 mm Hg.
EXAMPLE 2
Preparation of 2 - (2 - thienyl) - ethylamine, via indirect amination
a) Preparation of N - 2 - (2 - thienyl) - ethyl phthalimide To a solution maintained at 80°C and comprising 294 g (2 moles) phthalimide dissolved in 800 ml dimethylformamide, are added 120 g anhydrous sodium carbonate followed, within 1.25 hour, by a solution of 564 g (2 moles) 2-(2- thienyl) - ethyl paratoluenesulfonate in 20 ml dimethylformamide. The reaction medium is maintained at 80°C during 2 hours and 20 minutes and is then cooled and poured over 1 litre water.
The resulting precipitate is collected by filtration; it is then washed, dried and recrystallized from ethanol, to give 396 g
- 5 42786
N-2 - (.2 - thienyl} - ethylphthalimide (Yield; 44%) which has a melting point (Koefler Block} of 129—130°C.
b) Preparation of 2 - (2 - thienyl) - ethylamine
51.4 g CO.2 mole ) of the N-2 - C2 - thienyl) - ethyl 5 phthalimide are mixed with 10.3 g. diethylenetriamine (0.1 mole) and heated at 120°C during 4 hours. The pressure is then gradually decreased to 19 Torr, and distillation gives 19.7 g 2 - (2 thienyl) - ethylamine (Yield; 77%) which has a boiling point of 98°C/19 Torr.
Claims (11)
1. Process for the preparation of compounds having the formula; CH—CH—NH n R 2 R 1 (I) in which and R 2 each represent hydrogen or a C^_ 4 alkyl or an optionally substituted phenyl radical, comprising aminating a derivative having the formula; R 2 R 1 \ I 1 x __CH PH S —CH—CH—SO 3 R 3 (II) in which radicals R p and R 2 have the above-mentioned meanings and 10 R 3 is an optionally substituted alkyl, aryl or aralkyl group.
2. Process as claimed in claim 1, wherein the amination is carried out by reacting the derivative of the formula (II) with ammonia.
3. Process as claimed in claim 2, wherein the reaction is 15 carried out at elevated temperature in an autoclave.
4. Process as claimed in claim 1, wherein the derivative of the formula (II) is reacted with phthalimide, to give a compound (III) - 7 43786 which, is subsequently transaminated with, an amine or with hydrazine hydrate.
5. Process as claimed in claim 4, wherein the reaction of the derivative of the formula Cll) with phthalimide is effected 5 in the presence of a base.
6. A process as claimed in claim 5 wherein the base comprises an alkali metal or alkaline-earth metal carbonate or hydroxide or an alkali metal amide, hydride or alkoxide.
7. Process as claimed in claim 4, wherein the amine is 10 diethylenetriamine, benzylamine or ethanolamine.
8. A process as claimed in any one of claims 4 to 7 wherein the reaction is effected at elevated temperature.
9. A process as claimed in claim 1 substantially as herein disclosed. 15
10. A process as claimed in claim 1 substantially as herein disclosed in either of Examples 1 or 2.
11. Compounds of general formula I whenever prepared by a process as claimed in any of claims 1 to 8.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE53776A IE42786B1 (en) | 1976-03-15 | 1976-03-15 | Improvements in and relating to a process for the preparation of 2-(2-thienyl)-ethylamine and deivatives thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE53776A IE42786B1 (en) | 1976-03-15 | 1976-03-15 | Improvements in and relating to a process for the preparation of 2-(2-thienyl)-ethylamine and deivatives thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IE42786B1 true IE42786B1 (en) | 1980-10-22 |
Family
ID=11014280
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE53776A IE42786B1 (en) | 1976-03-15 | 1976-03-15 | Improvements in and relating to a process for the preparation of 2-(2-thienyl)-ethylamine and deivatives thereof |
Country Status (1)
| Country | Link |
|---|---|
| IE (1) | IE42786B1 (en) |
-
1976
- 1976-03-15 IE IE53776A patent/IE42786B1/en unknown
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