CA1267156A - Process for synthesis of n-acetylamino acids from olefins, acetamide and synthesis gas - Google Patents
Process for synthesis of n-acetylamino acids from olefins, acetamide and synthesis gasInfo
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Abstract
PROCESS FOR SYNTHESIS OF N-ACETYLBMIMO
ACIDS FROM OLEFINS, ACETAMIDE AND SYNGAS
(D#80,424-FB) ABSTRACT
A solid or liquid N-acetylamino derivative is synthesized by reacting an olefin, acetamide and synthesis gas with a bimetallic catalyst comprising a rhodium-containing compound and a cobalt-containing compound, optionally in the presence of a solvent at a pressure of at least 500 psi and a temperature of at least 50°C. The derivatives produced may be used for example as surfactants, chelating agents or gas treating agents.
ACIDS FROM OLEFINS, ACETAMIDE AND SYNGAS
(D#80,424-FB) ABSTRACT
A solid or liquid N-acetylamino derivative is synthesized by reacting an olefin, acetamide and synthesis gas with a bimetallic catalyst comprising a rhodium-containing compound and a cobalt-containing compound, optionally in the presence of a solvent at a pressure of at least 500 psi and a temperature of at least 50°C. The derivatives produced may be used for example as surfactants, chelating agents or gas treating agents.
Description
~ ,4~-r This invention relates to the synthesis of ~-acyl-amino acids from olefinically unsaturated hydrocarbons, amides and syngas.
More particularly this invention uses a bimetallic rhodium-cobalt catalyst to synthesize N-acylamino acids from various types of olefinically unsaturated hydrocarbon, amides and synthesis gas, with very high yield using mod-erate pressures and temperatures.
~arly attempts were unsuccessfully made to syn-thesize alpha-amino acids, or derivatives thereof, by reacting a Schiff's base or a nitrile with carbon monoxide and hydrogen. /Bull. Chem. Soc. Japan 33 (160) 787 US-A-3 766 266 discloses a cobalt-catalysed method of producing an N-acyl-alpha-amino acid from an aldehyde, a carboxylic acid amide and carbon monoxiae at a tempera-ture of 10 to 300C and a pressure of at least 500 atm.
(50~Mpa)~
In Chem. Comm. 1540 (1971), Wakamatsu, et al. dis-close a cobalt~catalysed reaction which gives ~arious N-acyl amino-acids from an aldehyde, an amide and carbon monoxide. When benzaldehyde was used as the starting aldehyde, no corresponding alpha-phenvl-substituted amino acid was obtained. Instead, an imine was obtained by a simple "amination" reaction.
An article by Parnaud, et al., in Journal_of Mol cular Catalysis, 6 (1379) 341-350, discusses the reac-tion wherein N-acyl-alpha-amino acids are produced by reacting an aldehyde, C0 and an amide in the presence of dicobalt octacarbonyl.
In amidocarbonylation, the aldehyde can be added as such, or generated in situ from allyl alcohol, alkyl ~
halides, oxiranes, alcohols or olefins, followe~ by the ~-reaction with an amide and carbon monoxi~e to produce an N-acyl-alpha-amino acid~ ~
, -:
More particularly this invention uses a bimetallic rhodium-cobalt catalyst to synthesize N-acylamino acids from various types of olefinically unsaturated hydrocarbon, amides and synthesis gas, with very high yield using mod-erate pressures and temperatures.
~arly attempts were unsuccessfully made to syn-thesize alpha-amino acids, or derivatives thereof, by reacting a Schiff's base or a nitrile with carbon monoxide and hydrogen. /Bull. Chem. Soc. Japan 33 (160) 787 US-A-3 766 266 discloses a cobalt-catalysed method of producing an N-acyl-alpha-amino acid from an aldehyde, a carboxylic acid amide and carbon monoxiae at a tempera-ture of 10 to 300C and a pressure of at least 500 atm.
(50~Mpa)~
In Chem. Comm. 1540 (1971), Wakamatsu, et al. dis-close a cobalt~catalysed reaction which gives ~arious N-acyl amino-acids from an aldehyde, an amide and carbon monoxide. When benzaldehyde was used as the starting aldehyde, no corresponding alpha-phenvl-substituted amino acid was obtained. Instead, an imine was obtained by a simple "amination" reaction.
An article by Parnaud, et al., in Journal_of Mol cular Catalysis, 6 (1379) 341-350, discusses the reac-tion wherein N-acyl-alpha-amino acids are produced by reacting an aldehyde, C0 and an amide in the presence of dicobalt octacarbonyl.
In amidocarbonylation, the aldehyde can be added as such, or generated in situ from allyl alcohol, alkyl ~
halides, oxiranes, alcohols or olefins, followe~ by the ~-reaction with an amide and carbon monoxi~e to produce an N-acyl-alpha-amino acid~ ~
, -:
-2-US-A-3 99~ 288 discloses that when an alcohol or certain of its ester deriva~ives is held at 50C to 200C
and 10 to 50 atm. (1 to 50 ~a) in the presence of hydro-gen, carbon monoxide, the amide of a carboxylic acid and S a carbonylation catalyst, an aldehyde having one or more carbon atom than the alcohol or ester is formed in good yleld. If the amide has at least one active hydrogen atom on its amiae nitrogen, it further reacts with the aldehyde and carbon monoxide to form an N-acylamino acid.
Hirai, et al. in Tetrahedron Letters, Vol. 23, No.
24, pp. 2491-2494, tl982) discuss a process for combining the transition metal-catalyzed isomerization of allyl alcohol to aldehyde with cobalt-catalyzed amidocarbonyla-tion, to provide a route to N-acyl-alpha-amino acids.
US-A-4 264 515 discloses a process for obtaining terminal N-acyl-alpha-amino acids by a reaction wherein the aldehyde is produced in situ from olefins and CO/H2 mixtures. An unsaturated vegetable oil or C8-C30 mono-olefinic compound is reacted with an amide, carbon monoxide and hydrogen in the presence of a cobalt catalyst.
The proeess is operated in one stage and provides for increased selecti~ity.
A recent review article by Ojima in Journal of Organometallic Che,mistry, 279 (1985~, 203-214, discussed _ the synthesis of N-acetyl-alpha-amino acids from (a) the isomerization-amidocarbonylation of allylic alcohols, (b) the isomerization-amidocarbonylation of oxiranes, and (c~
the hydroformylation-amidocarbonylation of trifluoropro-pene. The hydroformylation~amidocarbonylation of tri-fluoropropene demonstrated a surprising regioselectivityfor pro'ducts 1 and 2.
!CF CO~H COOH
Catalyst \3 CF3CH=CH2 + CO + H2 ~ H2NCQMe - ~ ~ + CF3 CH3 NHOOMe .~ .
and 10 to 50 atm. (1 to 50 ~a) in the presence of hydro-gen, carbon monoxide, the amide of a carboxylic acid and S a carbonylation catalyst, an aldehyde having one or more carbon atom than the alcohol or ester is formed in good yleld. If the amide has at least one active hydrogen atom on its amiae nitrogen, it further reacts with the aldehyde and carbon monoxide to form an N-acylamino acid.
Hirai, et al. in Tetrahedron Letters, Vol. 23, No.
24, pp. 2491-2494, tl982) discuss a process for combining the transition metal-catalyzed isomerization of allyl alcohol to aldehyde with cobalt-catalyzed amidocarbonyla-tion, to provide a route to N-acyl-alpha-amino acids.
US-A-4 264 515 discloses a process for obtaining terminal N-acyl-alpha-amino acids by a reaction wherein the aldehyde is produced in situ from olefins and CO/H2 mixtures. An unsaturated vegetable oil or C8-C30 mono-olefinic compound is reacted with an amide, carbon monoxide and hydrogen in the presence of a cobalt catalyst.
The proeess is operated in one stage and provides for increased selecti~ity.
A recent review article by Ojima in Journal of Organometallic Che,mistry, 279 (1985~, 203-214, discussed _ the synthesis of N-acetyl-alpha-amino acids from (a) the isomerization-amidocarbonylation of allylic alcohols, (b) the isomerization-amidocarbonylation of oxiranes, and (c~
the hydroformylation-amidocarbonylation of trifluoropro-pene. The hydroformylation~amidocarbonylation of tri-fluoropropene demonstrated a surprising regioselectivityfor pro'ducts 1 and 2.
!CF CO~H COOH
Catalyst \3 CF3CH=CH2 + CO + H2 ~ H2NCQMe - ~ ~ + CF3 CH3 NHOOMe .~ .
3 6~26-l~g N-acetyltrlfluorovaline (1) (94~) and N-acetyltri-fluoronorvaline (2) (96%) were ohtained in high yields by u~ing Co2(CO)B-Rh6(CO)16 and Co2(C0)8 as catalysts respactively. This shows a surprising difference in product when using Co2(C0)8 as opposecl to Co2(C0)8-Rh6(CO)16 catalysts, in the special case of the fluorole~in substrate.
The results of the present invention, using Co2(CO)8-HRh(CO) ~PPh3)3 for various olefinically-unsaturated hydrocarbons, are significantly different from those o$ the ~wo last-mentioned documents in the following respects:
(1~ The presence of HRh(CO) (PPh3~3 stabiliæes dicobalt octacarbonyl, and allows the reaction ~o proceed predic~ably at a low temperature in co~parison with dicobalt octacarbonyl alone.
(2) The combination of HRh(C0) (PPh3)3 and Co2(C0)8 constitutes a bi~etallic complex, as shown by the presence of new infrared absorption in the carbonyl region and by the catalyst behaviour attributable to the complex.
(3) The combined HRh(C0) (PPh3)3-Co2(CO~8 catals~st performs the reaction under milder reaction conditions, for example, as low as ~ 4) Various rhodium species in the Rh-Co complexes affect the reactivity and regioselectivity.
(5) In some cases, dicobalt octacarbonyl performs the same catalyst activity at higher temperatures but simultaneously produced the reduced hydrocarbon as by-product.
This disadvantage ~as overcome by uslng a suitable Rh-Co ~67~
3a 68626-169 catalyst.
The present invention provides a process for the production of solid linear alkyl-N~acetylamino acids or liquid branched alkyl-N-acylamino acids characterlzed in that an olefinically-unsaturated hydrocarbon~ an amide of the formula R ITNH~
where R1 and R2, which may be the same or different, are each substitu~ed or unæubstituted aryl, alkyl, arylalkyl, alkylaryl, or hydrogen, carbon monoxide and hydrogan are reacted in an inert or polar solvent at a temperature of at least 50C and a pressure of at least 3.5 MegaPascals in the presence of a catalyst comprising hydridotris-(triphenylphosphine) carbonyl rhodium HRh~CO) (PPh3)3, and dicobalt octacarbonyl Co2(CO)8.
In one embodiment o~ the invention~ solid or liquld N-acylamino acids are obtained from alpha olefins or internal olefins. Yields o~ the ~-acylamino acids are as ~7~
The results of the present invention, using Co2(CO)8-HRh(CO) ~PPh3)3 for various olefinically-unsaturated hydrocarbons, are significantly different from those o$ the ~wo last-mentioned documents in the following respects:
(1~ The presence of HRh(CO) (PPh3~3 stabiliæes dicobalt octacarbonyl, and allows the reaction ~o proceed predic~ably at a low temperature in co~parison with dicobalt octacarbonyl alone.
(2) The combination of HRh(C0) (PPh3)3 and Co2(C0)8 constitutes a bi~etallic complex, as shown by the presence of new infrared absorption in the carbonyl region and by the catalyst behaviour attributable to the complex.
(3) The combined HRh(C0) (PPh3)3-Co2(CO~8 catals~st performs the reaction under milder reaction conditions, for example, as low as ~ 4) Various rhodium species in the Rh-Co complexes affect the reactivity and regioselectivity.
(5) In some cases, dicobalt octacarbonyl performs the same catalyst activity at higher temperatures but simultaneously produced the reduced hydrocarbon as by-product.
This disadvantage ~as overcome by uslng a suitable Rh-Co ~67~
3a 68626-169 catalyst.
The present invention provides a process for the production of solid linear alkyl-N~acetylamino acids or liquid branched alkyl-N-acylamino acids characterlzed in that an olefinically-unsaturated hydrocarbon~ an amide of the formula R ITNH~
where R1 and R2, which may be the same or different, are each substitu~ed or unæubstituted aryl, alkyl, arylalkyl, alkylaryl, or hydrogen, carbon monoxide and hydrogan are reacted in an inert or polar solvent at a temperature of at least 50C and a pressure of at least 3.5 MegaPascals in the presence of a catalyst comprising hydridotris-(triphenylphosphine) carbonyl rhodium HRh~CO) (PPh3)3, and dicobalt octacarbonyl Co2(CO)8.
In one embodiment o~ the invention~ solid or liquld N-acylamino acids are obtained from alpha olefins or internal olefins. Yields o~ the ~-acylamino acids are as ~7~
-4 high as 80 to 9C%~ and a linearity of 95% is observed using very mild reaction. The products from internal olefins could be valuable as surfactants, chelating agents or gas treating agents. The N-acylamino acids obtained from the alpha olefins can be useful as surfactants.
In another embodiment the olefinically unsaturated hydrocarbon is a diene, and the products comprise novel amino acids with an ole-fin functionality, and regioisomer mixtures of novel bis-(N-acetylamino acids). These compounds may be intermediate for surfactants and chelating agents.
In another embodiment, the olefinically unsaturated hydrocarbon can be styrene or a substituted styrene.
The products may be solid or liquid at room temperature, depending on the type of olefin used as a reactant.
The N-acylamino acids from alpha olefins are generally solids at room temperature. In contrast the N-acylamino acids from C14 and C18 internal olefins are generally liquid at room temperature.
These latter derivatives are predominantly branched alkyl-N-acylamino acids, useful for surfactants, chelating agents and gas treating agents.
In general, the alpha-olefin or internal olefin can have the formula:
R.CH=CH2 or R.CH=CH.R
in which R is alkyl, or the two groups R can together represent the- carbon atoms necessary to complete an ali-cyclic ring.
The reaction for producing solid linear alkyl-N-acetylamino acids from alpha olefins can be represented by equation (1):
s~
COO~
2 ~ CH3CONH2 + CO/H2 - ~ R CH CH
R = C3 to C14 (solid) Th~ reaction for producing li~uid branched alkyl-N-acetylamino acids from int~rnal olefins can be representea by equation (2):
CH-COOH
¦ NHCOCH3 (2) R-CH=CH-R + CH3CNH2 ~ C/H2 ~> R-CH2-CH-R
R = C14 or C18 (li~uid) The reactions for producing solid amino acid deriva-tives from acyclic and cyclic in~ernal olefins can respec-tively be represented by equations (3) and (4):
CH-COOH
¦ NHCOCH3 (3) CH3-CH=CH~CH3 ~ CH3CONH2 + CO/H2 ~-~ CH -CH -CH-CH
(solid)mp 130-i36C
CH-COOH
(4) 0 ~ CH3CON~2 ~ C/H2 ~ NH-COCH3 (solid)mp 180-186C
When the olefinically unsaturated hydrocarbon is a diene, it may be unsymmetrical, or it may be symmetrical.
Amino acids bearing an olefin functionality are obtained from unsymmetrical dienes having two double bonds, each with different reactivity. Suitable dienes include 4-vinyl-1-cyclohexene, vinylnorbornene, bicyclopentadiene, 1,6-octadiene and limonene.
~, ' ' .
Preferred dienes are unsymmetrical dienes such as 4-vinylcyclohexene, limonene bicyclopentadiene or 1,6-octadiene.
The reaction can be demonstrated by the following equations:
,4~__ " ~ HOOC
+ CH3CNH2 + C/H2----~ CH
CH3lCINH (5) o ¢J~ + CH3CONH2 ~ CO/H2 ~ ~ &
. ,l.~ I
CH3CONH~ + CO/H2 --~ ~ / COOH
\ NHCOCH3 Regio-isomer mixtures of bis-(N-acetylamino acids) are synthesized from symmetrical dienes, in which the two double bonds have identical reactivities.
Suitable dienes include 1,3-butadiene, 1,7-octadiene, norbornadiene, 1,3-cyclohexadiene, a~d 1,5-cyclooctadiene.
Preferred dienes include 1,7-octadiene or 1,3-butadiene. Synthesis of the novel bis amino acids pro-ceeds, for example, according to the following reactions (8) and (9):
.HOOC COOH
+ CO/H2 ~ CH3CONH2 ~----~ . CH ~ CH (8) CH3coNH NHCOCH3 a ~- .
' ~, 7~f~
~]ooc coo}~
_ ~
. l l ~ CO/H2 ~ CH ~CONH2 3 ~ H f ~ Cli (9) 3~NH NHCCH3 O O
In another embo~iment, the olefinically unsaturated hydrocarbon is styrene or a substituted styrene having ~he formula ~ CH=CH
R ~ J 2 in which R is alkyl. --The reaction can best be represented by the following equation (10):
¦ COOH
/~2 ~ C~CNH2 - ~ ~ CHC~ (10) .
,, .
' , ~, ' , . -.' . ~ , .
~S7 ~
Recovery of the N acetylamino acids from the reac-tion product can be carried out ln any convenient or con-ventional manner such as by distillation, ex~raction, filtration, crystallization, etc. In the reactions illustrated above, the products were recovered by a simple extraction procedure, and identified by ~MR.
The catalyst system suitable for the practice of this invention comprises a bimetallic rhodium-cobalt catalyst, optionally in a substantially inert solvent.
In the catalyst system, the rhodium-compound and cobalt compound are believed to be in complex equilibrium during amidocarbonylation. The controlled experiments represented by the Examples show that the presence of both Rh and Co i5 essential for consistent prodl~ction of the desired results. This catalyst system provides the follow-ing important advantages over the use of cobalt alone:
(1) It gives higher yields and selectivities of the N-acetylamino acid products under milder conditions than can be obtained with a catalyst comprising only a cobalt compound dispersed in a solvent.
~2) It is possible to employ relatively mild operating conditions, especially in the embodiment using internal ole~ins to produce solid N-acetylamino acids~
~3) It was possible to obtain from alpha olefins a 95~ linear product. This degree of linear~
ity is specifically observed with the alpha i~
olefin l-tetradecene as a feedstock and is affected by certain species of rhodium com- .
pound.
(4) Mi~tures of HRh(CO)~PPh3)3 and Co2(C0)8 ~orm stable catalytically active complexes which are easily recovered from the reaction mixture. ~-~35 The rhodium compound may take many different forms. L -' ~or instance the rhodium could be added in the form of an .-~
oxide, a salt of a mineral aald, the salt of a suitable ' ~ .
organlc carboxylic acid, or a carbonyl, hydrocarbonyl or derivative thereof.
In the process of this invention the rhodium compound is hydridorhodium tris(triphenyl-phosphine)carbonyl, HRh(CO) (pPh3)3-It is worthwhile to note that some rhodium specieshave adverse ef~ects on catalyst activity as shown, in the comparative examples. It is assumed that these rhodium species might form an unactive species, or might deactivate cobal~ carbonyl, al~hough the mechanism for this effect is unclear.
The cobalt compound is dicobalt octacarbonyl.
The alpha olefins can have the following structure, R-CH-CH~
and the internal olefins can have the structure~
R-CH=CH-R
The R-group can he any alkyl~ such as methyl, e~hyl, hexyl or octyl, either the normal or branched isomers. The preferred alpha olefins include propylene, 1-octene, ' ~67~5~j - 10 - ~8626-169 l-decene, 1-dodecene and l-tetradecene. Particularly good results are obtained using l-tetradecene.
The olefin can also be an in-ternal olefin such as a C14 to Clg in-ternal olefin including, but not limited to 7-tetradecene, 9-octadecene or 2-butene and cycloalkenes, such as cyclohexene and cyclopentene.
The starting olefinically unsaturated hydrocarbon can be styrene or a substituted styrene having the structure:
R ~ CH=CH2 R can be any alkyl, such as methyl, ethyl, hexyl or octyl, at any of the ortho-, meta- or para-positions. The preferred compound is styrene.
The amides in the amidocarbonylation reaction have the general structure:
Rl (:~N~R2 where Rl and R2, which may be the same or different, are each substituted or unsubstituted aryl, alkyl, arylalkyl, alkylaryl, or hydrogen, e.y. methyl, ethyl, butyl, n-octyl, phenyl, benzyl or chlorophenyl. Examples of suitable amides include acetamide, benzamide, formamide, ~`
~, :
N-methylformamide, lauramide and N-methylbenzamide. The preferred amide is acetamide The carbon monoxide employed need ~ot satlsfy particular purity requirements, although catalyst contami-nants should be avoided if the reaction is intended tocontinue over an extended period. Particularly in contin-uous operations, but also in batch experiments, the carbon monoxide and hydrogen gas may also be use2 in conjunction with up to 10% by volume of one or more other gases. These other gases may-include one or more inert gases that are not inert but which may, or ma~ not, undergo reaction under carbon monoxide hydrogenation conditions, such as carbon dioxide, hydrocarbons, such as methane, ethane and propane, ethers, such as dimethyl ether, methyl ethyl ether and diethyl ether and alkanols, such as methanol.
As characterized above, ~his process is operated as a homogeneous li~uid phase mixture. The reaction is preferably operated in an inert solvent. Preferred inert solvents are those which permit at least partial solution of the cobalt and rhodium catalyst precursors, the amide and the olefinically unsaturated hydrocarbon. These are generally polar solvents, of the ester, ether, ketone, amide, sulfoxide or aromatic hydrocarbon type, for example.
Methyl and ethyl acetate are examples of suitable solvents. Other polar solvents are ethers, such as p-dioxan, methyl tertiary-butyl ether, methyl tertiary-amyl ether or tetrahydrofuran, tertiary amides, such as dimethyl formamide, dimethyl sulfoxide and ethylene carbonate. ~ b~
The preferred solvent is ethyl acetate.
The amino acid products are often insoiuble in the h solvent phase. Thi~ permits separation of the rhodium catalyst which may dissolve into the solvent phase, with or without prior acidification.
In all these syntheses, in order to achieve a high degree of selectivity, the amounts of carbon monoxide, olefin and amide present in the reaction mixture should be sufficient at least to sa~isfy the s~oichiometry of the f`~ ^
., desired reaction forming N-acetylamino acid as shown in Equations 1 to 10 above~ An exce~s of carbon monoxide over the stoichiometrlc amount ls desirable.
The quantity of rhodium compound and cobalt compound to be used in the catalyst may vary. The process is conduc-ted in the presence of cakalytically effective quantities of the active rhodium and cobalt compounds which give the desired products in reasonable yield. The reaction pro-ceeds when employing as little as 0.01 weight % of the rhodium compound or even less, along with as little as 0.1 weight ~ of the cobalt compound, based on the total w~ight of the reaction ~ixture. The upper concentra$ion is dic-tated by a variety of factors, including catalyst cost, partial pressures of carbon monoxi~e and hydrogen, opera-ting temperature, etc. Amounts of rhodium compound from 0.01 to 1.0 weight % in conjunction with from 0.1 to 10 weight ~ cobalt compound, based on the total weight of the reaction mixture, are generally desirable in ~he practice of this invention.
Particularly superior results are obtained when the rhodium to cobalt mol ratio is from 1.0:1~0 to 1.0:1000.
The operating conditions may vary over a wide range.
The reaction temperature is generally from 25 to 300C.
The preferred temperature is from 80 to 150C. The pres-sure may range from 3.5 to 20 MPa, but may be higher, depending on the olefinically unsaturated hydrocarbon. In the embodiment using internal olefins, it appears that higher selectivities are obtained when operating at moder-ate pressures, in the range from 7 to 25 MPa. In the embodiment using alpha olefins, very good yields are observed using very mild pressures and temperatures, in the range of 5.5 to 14 MPa and 100 to 120C respectively.
With dienes, preferred conditions are 7 to 25 MPa and 70 to 150C. With styrenes~ preferred conditions are 7 to 25 MPa and 80 to 150C.
The amldocarbonylation reaotion is best conducte~
' ' ~13-in a carbon monoxide-rich atmosphere, although some hydro-gen gas should also be present in order to achieve maximum cobalt catalyst activity. The hydrogen to carbon monoxide mol ratio in the reactor may be varied, for example, with-in the range from 20:1 to 1:20, but preferably it should be relatively rich in carbon monoxide and the H2:C0 ratio should be in the range 5:1 to 1:5.
The main products of the synthesis using alpha olefins are solid N-acylamino acids, for exa~ple N-acetyl-alpha-amino-isovaleric acid, alpha-(n-dodecyl~-N-acetyl-glycine, alpha-N-acetylamino-tetradecanoic acid, alpha-(n-tetradecyl)-N-acetyl-glycine, al~ha-(decyl)-N-acetvl-glyciner and alpha-~n-octyl~N-acetyl-glycine. Also formed are significant amounts of aldehyde. Each of these products, including by produc~s, can be recovered from the reaction mixture by conventional means, e.g. crystalliza-tion or-filtration.
The main products from internal ~lefins are, for example, alpha-(sec-butyl)-N-acetylglycine, alpha-tn-tetradecyl-7)-N-acetylglycine and alpha-(cyclohexyl)-N-acetylglycine.
The major products from uns~mmetrical dienes are amino acids with an olefin functionality. The main product from dicyclopentadiene and acetamide has the structure:
\CH
~ .
and may be formed in significant quantities of as much as 78~ yield.
The main products from symmetrical dienes/ i.e.
bis-(N-acetylamino) acids, are formed in significant quan-tities. TAey have the structure:
;
-:
\ coo~
CHCH (C 2 ) x Where x=l tc~ 10 ~H3CON l l \NHCOCH3 R, R'=methyl or H
R R' The main products f rom styrenes are phenyl substi-tuted amino acids. The main product from styrene itself, beta-phenyl-N-acetyl-alpha-amino acid, will be formed in significant quantities.
The process of the invention can be conducte~ in a batch, semi-continuous or continuous manner. The catalyst can be initially introduced into the reaction zone batchwise, or it may be continuously or intermittently introduced into such a zone during the course of the synthesis reaction. Operating conditions can be adjusted to optimize the formation of the desired amino acid Pro-duct, and said m~terial may be recoverea by methods kno~m to the art, such as filtration, recrystallization distilla-tion, extraction and the like. A ~raction rich in the catalyst components may then be recycled to the reaction zone, if desired, and additional products generated.
ThP products have been identified in this work by one or more of the following analytical procedures: gas- -liquid phase chromatograPhy tglc), gas chroma*ography/
23 infrared spectroscopy (GC/IR), nuclear magnetic resonance -~
(nmr) and elemental analysis~ or a combination of these techniques. Analyses have for the most part, been by molar weight; all temperatures are in degrees centigrade and all pressures in Megapascals (MPa).
The yield (mol %) of N acylamin~ a~d derivative ` in this synthesis using an olefin is estimated using the formula:
5S~
Mols of N~ac lamino acids obtained ~ols of olefinlcall~ unsaturated compound charged x 100 A glass-lined reactor equipped with rocking device was charged with dicobalt octacarbonyl (0.34g), hydrido-tris-(triphenylphosphino) carbonyl rhodium (0.046g), acetamide (5.9g, 0.1 mol), and ethyl acetate (lO~Og). The reactor was ~lushed with a 1:1 CO/E12 mixture. Propylene (lOg) was added to ~he reactor, and the ~ressure t~as brought up to 13.9 MPa with 1:1 CO/H2 and 18.0 MPa with pure CO.
The system was heated to ca. 120C. During the heating process the maximum pressure reached 21.8 MPaO After two hours reaction time, the reactor was cooled to room tem perature. The solid product (ll.Og) and liquid (22.0g) lS were recovered. H-nmr analysis showed that the solid was a mixture of the N-acetyl-amino acids N-acetyl-alpha-aminovaleric acid 3 and N-acetyl-alpha-amino-isovaleric acid 4 at 2:1 molar ratio. The combined yield of these two isomers was calculated to be 70~, based on acetamide charged. The liquid solution contained compounds of Structures 5 and 6:
COOH COOH
/
~,~,,CH ~ CH ~ CHO ~ CHO
Aldehydes 5 and 6 were present at 1.6 to 1.0 mol ratio. The isomer distribution, i.e. linear vs~ branched products, for 3:4 was the reverse of that ~or 6:5. Two possible explanations were proposed: (1) the reaction of linear aldehyde 6 with acetamide and CO is faster than the reaction of aldehyde 5; or (2) the aldehydes are not the intermediateS for amino acid formation. The actual mechanism for N-acetylamino acid formation ~rom olefins is unknown.
:.
.
' EXAMPLE 2 (Comparative) Example 1 was repeated, omltting the dicobalt octa-carbonyl, the reactor being pressurised to 13.0 MPa with CO/H2 (molar ratio .6:1). The maximum pressure reached 18.4 MPa and a significant consumption of gas was noted.
After 2 hours, the reactor was cooled to room temperature.
The product solution (25.4g) was analyzed. H-nmr showed that only aldehyde compounds were produced.
It was thereby demonstrated that the amidocarbonyl-ation of aldehydes into N-acetylamino acid requires the presence of cobalt catalyst.
E AMPLE 3 (Comparative) Example 2 was repeated, using dicobalt octacarbonyl (0.34g, 1 mmol) in place of the rhodium compound. The maximum pressure reached 22.8~ MPa~ Af~er two hours, the ~ reactor was allowed to cool to room temperature. The solid material (~.Og) and the liquid material (9.Og) were recovered. H nmr analyses indicated the solid was unreac-ted acetamide, and no N-acetylamino acid was obtained.
- 20 Dicobalt octacarbonyl is ineffective for propylene hydroformylation, although the recovered liquid solution showed 1.0% concentration of cobalt (ca. 80% based on cobalt charged.
A glass lined reactor equipped with a rocking device was charged with hydrido-tris(triphenylphosphino)carbonyl - rhodium (0.046g), dicobalt octacarbonyl (0.34g), l-dodecene (8.4g, O.O~ mmol), acetamide (3 0g, 0.05 mol~ and p-dioxane (lO.Og). The reactor was sealed and flushed with CO/H2 mixture (1:1 molar ratio). The system was pressurized with CO/H2 mixture (1:1) to 0.8 MPa and heated to 100C. The - pressure was raised to 15~25 MPa (with CO/H2=1:1). The conditions were held ~or four hours. During the process, a pressure drop of 2.75 MPa was noted. A~ter cooling to room temperature, the reactor was opened and solid and .
~ 7~
liyuid product mixtures were rec~vered. ~he mixtures ~ere filtered and 12.8g of solld materlal was obtained. The solid was analyzed by H-nmr to be alpha-(n-dodecyl)-N-acetyl-glycine (or alpha-N-acetylamino-tetradecanoic acid~.
COOH
CH3 (CH2) llCH
The yield was ca. 74%. There were no other issmeric N-acetylamino acids in the products or starting materials.
The linearity of the product was estimated to be ~95%
based on H-nmr analysis.
EXAMP~E_5 (Comparati~e) The same experimental proce~ures and reaction condi-tions as in Example 4 were used, except that no HRh(CO) ~PPh3)3 was added. The recovered mixtures contained only l-dodecene, acetamide and no N-acetyl-alpha-amino acid was observed.
The experiment was repeated, and the same results were reported. It was concluded that, at the conditions used, the presence of HRh(CO)(PPX3)3 is essential for hydro-ormylation/amidocarbonylation of alpha olefins.
The experimental procedures of Examples 1 to 5 were followed, employing: HRh(CO)(PPh3)3, (0.046g), Co2(CO)8 (0.34g), acetamide (3.0g), l-tetradecene (98g) and ethyl acetate (lO.Og) at 13.9 MPa, CO/H2=1:1 and 100C for 4 hours. The recovered materials (25.4g) containe~ some crystalline solid. After filtration, a white solid powder was obtained (13.8g). H-nmr analysis indicated the solid product had the structure 8; alpha (n-tetradecyl)-N-acetyl-glycine. Its branched isomer was no~ detected by H-nmr.
'' ' ' . ~ . ' , 7~s~
/ COOH
\ NHCOCH3 The yield of compound 8 was ca. 89~. The product con-tained 45.8 ppm of rhodium and 400 ppm of cobalt.
The typical procedures o~ the previous Examples were followed, employing HRh(CO)~PPh3)3 (0.023g), Co2(CO)8 (0.17g), acetamide (3.0g), 1 tetradecene (9.8g) and ethyl acetate (l5.Og), at 13.9 MPa, CO/H2=1:1 and 100C for 4 hours. The recovered materials contained liquid and crystalline solid. After filtration and washing twice with ethyl acetate, 13.0g of white powdered solid material was obtained. H-nmr and C13 nmr analyses indicated it was the pure form of alpha-(n-tetradecyl-N-acetyl)-glvcine, and no isomeric branched amino acids were observed.
lS The yield of this desired product was ca. 83%.
The solid product contained only ~5 ppm Rh and 170 ppm Co.
EXAMPLE ~
Typical experimental procedures were employed, except the rhodium species was in the form of rhodium (0.5~) on an alumina support.
The reactor was charged with Rh (0.5%) on Al (O.lOg), Co2(CO)8 (0.17g), l-tetradecene (9.8g), acetamide (3.0g) and ethyl acetate tl5.0g). The reaction conditions were 13.9 MPa, CO/Hz=l:l, 100C and 2 hours. The recovered pro-duct solution was anlyzed by H-nmr, showing that unreacted l-tetradecene and acetamide were the major components, and -no aldehyde was in the amino acid product.
The example demonstrates the importance of the rhodium species. --.
The same experimental procedures were used, except that Rh6(~0)16 was employed as the rhodium species.
Rh6(CO)1~ ~0.015g), Co2~CO)8 (0.17g), l-tetradecene 19.8g), acetamide (3.0g) and ethyl acetate ~15.0g) were reacted at 13.9 MPa, CO/H2=1:1 and 100C for 4 hours.
The reaction solution (12.3g) and solid product (ll.Og) were recovered. The solid product was analyzed by H-nmr showing two isomeric products represented by Struc-tures 8 and 9, in a ca. 75:25 ratio.
COOH COOH
~' /
CH3(CH2)13C \ 8 CH3~CH2)11 1 \ _ The use of rhodium carbonyl demonstrated that the linearityof the product was affected by different species of rhodium carbonyl in the reaction medium.
Typical experimental procedures were used, except that Rh(acac)3 was the rhodium source, and dicobalt octa-carbonyl was the cobal~ source.
Co2(COj8 (0.17g), Rh(acac)3 (O.OlOg, 0.025 mmol), l-tetradecene ~9.8g), acetamide (3.0g) and ethyl acetate (15.0g) were reacted at 100C and 13.9 MPa, CO/X2=1:1, for 4 hours. The recovered solution (23.0g) and solid (5.0g) were analyzed by H-nmr. There was no alkyl N-acetyl-glycine, the desired product. Instead, the bisamidal com-pound was the major component of the solid material.
This showed that the comb.ination of Rh(acac)3/Co2(CO)8 is not suitable for amino acid synthesis.
In another embodiment the olefinically unsaturated hydrocarbon is a diene, and the products comprise novel amino acids with an ole-fin functionality, and regioisomer mixtures of novel bis-(N-acetylamino acids). These compounds may be intermediate for surfactants and chelating agents.
In another embodiment, the olefinically unsaturated hydrocarbon can be styrene or a substituted styrene.
The products may be solid or liquid at room temperature, depending on the type of olefin used as a reactant.
The N-acylamino acids from alpha olefins are generally solids at room temperature. In contrast the N-acylamino acids from C14 and C18 internal olefins are generally liquid at room temperature.
These latter derivatives are predominantly branched alkyl-N-acylamino acids, useful for surfactants, chelating agents and gas treating agents.
In general, the alpha-olefin or internal olefin can have the formula:
R.CH=CH2 or R.CH=CH.R
in which R is alkyl, or the two groups R can together represent the- carbon atoms necessary to complete an ali-cyclic ring.
The reaction for producing solid linear alkyl-N-acetylamino acids from alpha olefins can be represented by equation (1):
s~
COO~
2 ~ CH3CONH2 + CO/H2 - ~ R CH CH
R = C3 to C14 (solid) Th~ reaction for producing li~uid branched alkyl-N-acetylamino acids from int~rnal olefins can be representea by equation (2):
CH-COOH
¦ NHCOCH3 (2) R-CH=CH-R + CH3CNH2 ~ C/H2 ~> R-CH2-CH-R
R = C14 or C18 (li~uid) The reactions for producing solid amino acid deriva-tives from acyclic and cyclic in~ernal olefins can respec-tively be represented by equations (3) and (4):
CH-COOH
¦ NHCOCH3 (3) CH3-CH=CH~CH3 ~ CH3CONH2 + CO/H2 ~-~ CH -CH -CH-CH
(solid)mp 130-i36C
CH-COOH
(4) 0 ~ CH3CON~2 ~ C/H2 ~ NH-COCH3 (solid)mp 180-186C
When the olefinically unsaturated hydrocarbon is a diene, it may be unsymmetrical, or it may be symmetrical.
Amino acids bearing an olefin functionality are obtained from unsymmetrical dienes having two double bonds, each with different reactivity. Suitable dienes include 4-vinyl-1-cyclohexene, vinylnorbornene, bicyclopentadiene, 1,6-octadiene and limonene.
~, ' ' .
Preferred dienes are unsymmetrical dienes such as 4-vinylcyclohexene, limonene bicyclopentadiene or 1,6-octadiene.
The reaction can be demonstrated by the following equations:
,4~__ " ~ HOOC
+ CH3CNH2 + C/H2----~ CH
CH3lCINH (5) o ¢J~ + CH3CONH2 ~ CO/H2 ~ ~ &
. ,l.~ I
CH3CONH~ + CO/H2 --~ ~ / COOH
\ NHCOCH3 Regio-isomer mixtures of bis-(N-acetylamino acids) are synthesized from symmetrical dienes, in which the two double bonds have identical reactivities.
Suitable dienes include 1,3-butadiene, 1,7-octadiene, norbornadiene, 1,3-cyclohexadiene, a~d 1,5-cyclooctadiene.
Preferred dienes include 1,7-octadiene or 1,3-butadiene. Synthesis of the novel bis amino acids pro-ceeds, for example, according to the following reactions (8) and (9):
.HOOC COOH
+ CO/H2 ~ CH3CONH2 ~----~ . CH ~ CH (8) CH3coNH NHCOCH3 a ~- .
' ~, 7~f~
~]ooc coo}~
_ ~
. l l ~ CO/H2 ~ CH ~CONH2 3 ~ H f ~ Cli (9) 3~NH NHCCH3 O O
In another embo~iment, the olefinically unsaturated hydrocarbon is styrene or a substituted styrene having ~he formula ~ CH=CH
R ~ J 2 in which R is alkyl. --The reaction can best be represented by the following equation (10):
¦ COOH
/~2 ~ C~CNH2 - ~ ~ CHC~ (10) .
,, .
' , ~, ' , . -.' . ~ , .
~S7 ~
Recovery of the N acetylamino acids from the reac-tion product can be carried out ln any convenient or con-ventional manner such as by distillation, ex~raction, filtration, crystallization, etc. In the reactions illustrated above, the products were recovered by a simple extraction procedure, and identified by ~MR.
The catalyst system suitable for the practice of this invention comprises a bimetallic rhodium-cobalt catalyst, optionally in a substantially inert solvent.
In the catalyst system, the rhodium-compound and cobalt compound are believed to be in complex equilibrium during amidocarbonylation. The controlled experiments represented by the Examples show that the presence of both Rh and Co i5 essential for consistent prodl~ction of the desired results. This catalyst system provides the follow-ing important advantages over the use of cobalt alone:
(1) It gives higher yields and selectivities of the N-acetylamino acid products under milder conditions than can be obtained with a catalyst comprising only a cobalt compound dispersed in a solvent.
~2) It is possible to employ relatively mild operating conditions, especially in the embodiment using internal ole~ins to produce solid N-acetylamino acids~
~3) It was possible to obtain from alpha olefins a 95~ linear product. This degree of linear~
ity is specifically observed with the alpha i~
olefin l-tetradecene as a feedstock and is affected by certain species of rhodium com- .
pound.
(4) Mi~tures of HRh(CO)~PPh3)3 and Co2(C0)8 ~orm stable catalytically active complexes which are easily recovered from the reaction mixture. ~-~35 The rhodium compound may take many different forms. L -' ~or instance the rhodium could be added in the form of an .-~
oxide, a salt of a mineral aald, the salt of a suitable ' ~ .
organlc carboxylic acid, or a carbonyl, hydrocarbonyl or derivative thereof.
In the process of this invention the rhodium compound is hydridorhodium tris(triphenyl-phosphine)carbonyl, HRh(CO) (pPh3)3-It is worthwhile to note that some rhodium specieshave adverse ef~ects on catalyst activity as shown, in the comparative examples. It is assumed that these rhodium species might form an unactive species, or might deactivate cobal~ carbonyl, al~hough the mechanism for this effect is unclear.
The cobalt compound is dicobalt octacarbonyl.
The alpha olefins can have the following structure, R-CH-CH~
and the internal olefins can have the structure~
R-CH=CH-R
The R-group can he any alkyl~ such as methyl, e~hyl, hexyl or octyl, either the normal or branched isomers. The preferred alpha olefins include propylene, 1-octene, ' ~67~5~j - 10 - ~8626-169 l-decene, 1-dodecene and l-tetradecene. Particularly good results are obtained using l-tetradecene.
The olefin can also be an in-ternal olefin such as a C14 to Clg in-ternal olefin including, but not limited to 7-tetradecene, 9-octadecene or 2-butene and cycloalkenes, such as cyclohexene and cyclopentene.
The starting olefinically unsaturated hydrocarbon can be styrene or a substituted styrene having the structure:
R ~ CH=CH2 R can be any alkyl, such as methyl, ethyl, hexyl or octyl, at any of the ortho-, meta- or para-positions. The preferred compound is styrene.
The amides in the amidocarbonylation reaction have the general structure:
Rl (:~N~R2 where Rl and R2, which may be the same or different, are each substituted or unsubstituted aryl, alkyl, arylalkyl, alkylaryl, or hydrogen, e.y. methyl, ethyl, butyl, n-octyl, phenyl, benzyl or chlorophenyl. Examples of suitable amides include acetamide, benzamide, formamide, ~`
~, :
N-methylformamide, lauramide and N-methylbenzamide. The preferred amide is acetamide The carbon monoxide employed need ~ot satlsfy particular purity requirements, although catalyst contami-nants should be avoided if the reaction is intended tocontinue over an extended period. Particularly in contin-uous operations, but also in batch experiments, the carbon monoxide and hydrogen gas may also be use2 in conjunction with up to 10% by volume of one or more other gases. These other gases may-include one or more inert gases that are not inert but which may, or ma~ not, undergo reaction under carbon monoxide hydrogenation conditions, such as carbon dioxide, hydrocarbons, such as methane, ethane and propane, ethers, such as dimethyl ether, methyl ethyl ether and diethyl ether and alkanols, such as methanol.
As characterized above, ~his process is operated as a homogeneous li~uid phase mixture. The reaction is preferably operated in an inert solvent. Preferred inert solvents are those which permit at least partial solution of the cobalt and rhodium catalyst precursors, the amide and the olefinically unsaturated hydrocarbon. These are generally polar solvents, of the ester, ether, ketone, amide, sulfoxide or aromatic hydrocarbon type, for example.
Methyl and ethyl acetate are examples of suitable solvents. Other polar solvents are ethers, such as p-dioxan, methyl tertiary-butyl ether, methyl tertiary-amyl ether or tetrahydrofuran, tertiary amides, such as dimethyl formamide, dimethyl sulfoxide and ethylene carbonate. ~ b~
The preferred solvent is ethyl acetate.
The amino acid products are often insoiuble in the h solvent phase. Thi~ permits separation of the rhodium catalyst which may dissolve into the solvent phase, with or without prior acidification.
In all these syntheses, in order to achieve a high degree of selectivity, the amounts of carbon monoxide, olefin and amide present in the reaction mixture should be sufficient at least to sa~isfy the s~oichiometry of the f`~ ^
., desired reaction forming N-acetylamino acid as shown in Equations 1 to 10 above~ An exce~s of carbon monoxide over the stoichiometrlc amount ls desirable.
The quantity of rhodium compound and cobalt compound to be used in the catalyst may vary. The process is conduc-ted in the presence of cakalytically effective quantities of the active rhodium and cobalt compounds which give the desired products in reasonable yield. The reaction pro-ceeds when employing as little as 0.01 weight % of the rhodium compound or even less, along with as little as 0.1 weight ~ of the cobalt compound, based on the total w~ight of the reaction ~ixture. The upper concentra$ion is dic-tated by a variety of factors, including catalyst cost, partial pressures of carbon monoxi~e and hydrogen, opera-ting temperature, etc. Amounts of rhodium compound from 0.01 to 1.0 weight % in conjunction with from 0.1 to 10 weight ~ cobalt compound, based on the total weight of the reaction mixture, are generally desirable in ~he practice of this invention.
Particularly superior results are obtained when the rhodium to cobalt mol ratio is from 1.0:1~0 to 1.0:1000.
The operating conditions may vary over a wide range.
The reaction temperature is generally from 25 to 300C.
The preferred temperature is from 80 to 150C. The pres-sure may range from 3.5 to 20 MPa, but may be higher, depending on the olefinically unsaturated hydrocarbon. In the embodiment using internal olefins, it appears that higher selectivities are obtained when operating at moder-ate pressures, in the range from 7 to 25 MPa. In the embodiment using alpha olefins, very good yields are observed using very mild pressures and temperatures, in the range of 5.5 to 14 MPa and 100 to 120C respectively.
With dienes, preferred conditions are 7 to 25 MPa and 70 to 150C. With styrenes~ preferred conditions are 7 to 25 MPa and 80 to 150C.
The amldocarbonylation reaotion is best conducte~
' ' ~13-in a carbon monoxide-rich atmosphere, although some hydro-gen gas should also be present in order to achieve maximum cobalt catalyst activity. The hydrogen to carbon monoxide mol ratio in the reactor may be varied, for example, with-in the range from 20:1 to 1:20, but preferably it should be relatively rich in carbon monoxide and the H2:C0 ratio should be in the range 5:1 to 1:5.
The main products of the synthesis using alpha olefins are solid N-acylamino acids, for exa~ple N-acetyl-alpha-amino-isovaleric acid, alpha-(n-dodecyl~-N-acetyl-glycine, alpha-N-acetylamino-tetradecanoic acid, alpha-(n-tetradecyl)-N-acetyl-glycine, al~ha-(decyl)-N-acetvl-glyciner and alpha-~n-octyl~N-acetyl-glycine. Also formed are significant amounts of aldehyde. Each of these products, including by produc~s, can be recovered from the reaction mixture by conventional means, e.g. crystalliza-tion or-filtration.
The main products from internal ~lefins are, for example, alpha-(sec-butyl)-N-acetylglycine, alpha-tn-tetradecyl-7)-N-acetylglycine and alpha-(cyclohexyl)-N-acetylglycine.
The major products from uns~mmetrical dienes are amino acids with an olefin functionality. The main product from dicyclopentadiene and acetamide has the structure:
\CH
~ .
and may be formed in significant quantities of as much as 78~ yield.
The main products from symmetrical dienes/ i.e.
bis-(N-acetylamino) acids, are formed in significant quan-tities. TAey have the structure:
;
-:
\ coo~
CHCH (C 2 ) x Where x=l tc~ 10 ~H3CON l l \NHCOCH3 R, R'=methyl or H
R R' The main products f rom styrenes are phenyl substi-tuted amino acids. The main product from styrene itself, beta-phenyl-N-acetyl-alpha-amino acid, will be formed in significant quantities.
The process of the invention can be conducte~ in a batch, semi-continuous or continuous manner. The catalyst can be initially introduced into the reaction zone batchwise, or it may be continuously or intermittently introduced into such a zone during the course of the synthesis reaction. Operating conditions can be adjusted to optimize the formation of the desired amino acid Pro-duct, and said m~terial may be recoverea by methods kno~m to the art, such as filtration, recrystallization distilla-tion, extraction and the like. A ~raction rich in the catalyst components may then be recycled to the reaction zone, if desired, and additional products generated.
ThP products have been identified in this work by one or more of the following analytical procedures: gas- -liquid phase chromatograPhy tglc), gas chroma*ography/
23 infrared spectroscopy (GC/IR), nuclear magnetic resonance -~
(nmr) and elemental analysis~ or a combination of these techniques. Analyses have for the most part, been by molar weight; all temperatures are in degrees centigrade and all pressures in Megapascals (MPa).
The yield (mol %) of N acylamin~ a~d derivative ` in this synthesis using an olefin is estimated using the formula:
5S~
Mols of N~ac lamino acids obtained ~ols of olefinlcall~ unsaturated compound charged x 100 A glass-lined reactor equipped with rocking device was charged with dicobalt octacarbonyl (0.34g), hydrido-tris-(triphenylphosphino) carbonyl rhodium (0.046g), acetamide (5.9g, 0.1 mol), and ethyl acetate (lO~Og). The reactor was ~lushed with a 1:1 CO/E12 mixture. Propylene (lOg) was added to ~he reactor, and the ~ressure t~as brought up to 13.9 MPa with 1:1 CO/H2 and 18.0 MPa with pure CO.
The system was heated to ca. 120C. During the heating process the maximum pressure reached 21.8 MPaO After two hours reaction time, the reactor was cooled to room tem perature. The solid product (ll.Og) and liquid (22.0g) lS were recovered. H-nmr analysis showed that the solid was a mixture of the N-acetyl-amino acids N-acetyl-alpha-aminovaleric acid 3 and N-acetyl-alpha-amino-isovaleric acid 4 at 2:1 molar ratio. The combined yield of these two isomers was calculated to be 70~, based on acetamide charged. The liquid solution contained compounds of Structures 5 and 6:
COOH COOH
/
~,~,,CH ~ CH ~ CHO ~ CHO
Aldehydes 5 and 6 were present at 1.6 to 1.0 mol ratio. The isomer distribution, i.e. linear vs~ branched products, for 3:4 was the reverse of that ~or 6:5. Two possible explanations were proposed: (1) the reaction of linear aldehyde 6 with acetamide and CO is faster than the reaction of aldehyde 5; or (2) the aldehydes are not the intermediateS for amino acid formation. The actual mechanism for N-acetylamino acid formation ~rom olefins is unknown.
:.
.
' EXAMPLE 2 (Comparative) Example 1 was repeated, omltting the dicobalt octa-carbonyl, the reactor being pressurised to 13.0 MPa with CO/H2 (molar ratio .6:1). The maximum pressure reached 18.4 MPa and a significant consumption of gas was noted.
After 2 hours, the reactor was cooled to room temperature.
The product solution (25.4g) was analyzed. H-nmr showed that only aldehyde compounds were produced.
It was thereby demonstrated that the amidocarbonyl-ation of aldehydes into N-acetylamino acid requires the presence of cobalt catalyst.
E AMPLE 3 (Comparative) Example 2 was repeated, using dicobalt octacarbonyl (0.34g, 1 mmol) in place of the rhodium compound. The maximum pressure reached 22.8~ MPa~ Af~er two hours, the ~ reactor was allowed to cool to room temperature. The solid material (~.Og) and the liquid material (9.Og) were recovered. H nmr analyses indicated the solid was unreac-ted acetamide, and no N-acetylamino acid was obtained.
- 20 Dicobalt octacarbonyl is ineffective for propylene hydroformylation, although the recovered liquid solution showed 1.0% concentration of cobalt (ca. 80% based on cobalt charged.
A glass lined reactor equipped with a rocking device was charged with hydrido-tris(triphenylphosphino)carbonyl - rhodium (0.046g), dicobalt octacarbonyl (0.34g), l-dodecene (8.4g, O.O~ mmol), acetamide (3 0g, 0.05 mol~ and p-dioxane (lO.Og). The reactor was sealed and flushed with CO/H2 mixture (1:1 molar ratio). The system was pressurized with CO/H2 mixture (1:1) to 0.8 MPa and heated to 100C. The - pressure was raised to 15~25 MPa (with CO/H2=1:1). The conditions were held ~or four hours. During the process, a pressure drop of 2.75 MPa was noted. A~ter cooling to room temperature, the reactor was opened and solid and .
~ 7~
liyuid product mixtures were rec~vered. ~he mixtures ~ere filtered and 12.8g of solld materlal was obtained. The solid was analyzed by H-nmr to be alpha-(n-dodecyl)-N-acetyl-glycine (or alpha-N-acetylamino-tetradecanoic acid~.
COOH
CH3 (CH2) llCH
The yield was ca. 74%. There were no other issmeric N-acetylamino acids in the products or starting materials.
The linearity of the product was estimated to be ~95%
based on H-nmr analysis.
EXAMP~E_5 (Comparati~e) The same experimental proce~ures and reaction condi-tions as in Example 4 were used, except that no HRh(CO) ~PPh3)3 was added. The recovered mixtures contained only l-dodecene, acetamide and no N-acetyl-alpha-amino acid was observed.
The experiment was repeated, and the same results were reported. It was concluded that, at the conditions used, the presence of HRh(CO)(PPX3)3 is essential for hydro-ormylation/amidocarbonylation of alpha olefins.
The experimental procedures of Examples 1 to 5 were followed, employing: HRh(CO)(PPh3)3, (0.046g), Co2(CO)8 (0.34g), acetamide (3.0g), l-tetradecene (98g) and ethyl acetate (lO.Og) at 13.9 MPa, CO/H2=1:1 and 100C for 4 hours. The recovered materials (25.4g) containe~ some crystalline solid. After filtration, a white solid powder was obtained (13.8g). H-nmr analysis indicated the solid product had the structure 8; alpha (n-tetradecyl)-N-acetyl-glycine. Its branched isomer was no~ detected by H-nmr.
'' ' ' . ~ . ' , 7~s~
/ COOH
\ NHCOCH3 The yield of compound 8 was ca. 89~. The product con-tained 45.8 ppm of rhodium and 400 ppm of cobalt.
The typical procedures o~ the previous Examples were followed, employing HRh(CO)~PPh3)3 (0.023g), Co2(CO)8 (0.17g), acetamide (3.0g), 1 tetradecene (9.8g) and ethyl acetate (l5.Og), at 13.9 MPa, CO/H2=1:1 and 100C for 4 hours. The recovered materials contained liquid and crystalline solid. After filtration and washing twice with ethyl acetate, 13.0g of white powdered solid material was obtained. H-nmr and C13 nmr analyses indicated it was the pure form of alpha-(n-tetradecyl-N-acetyl)-glvcine, and no isomeric branched amino acids were observed.
lS The yield of this desired product was ca. 83%.
The solid product contained only ~5 ppm Rh and 170 ppm Co.
EXAMPLE ~
Typical experimental procedures were employed, except the rhodium species was in the form of rhodium (0.5~) on an alumina support.
The reactor was charged with Rh (0.5%) on Al (O.lOg), Co2(CO)8 (0.17g), l-tetradecene (9.8g), acetamide (3.0g) and ethyl acetate tl5.0g). The reaction conditions were 13.9 MPa, CO/Hz=l:l, 100C and 2 hours. The recovered pro-duct solution was anlyzed by H-nmr, showing that unreacted l-tetradecene and acetamide were the major components, and -no aldehyde was in the amino acid product.
The example demonstrates the importance of the rhodium species. --.
The same experimental procedures were used, except that Rh6(~0)16 was employed as the rhodium species.
Rh6(CO)1~ ~0.015g), Co2~CO)8 (0.17g), l-tetradecene 19.8g), acetamide (3.0g) and ethyl acetate ~15.0g) were reacted at 13.9 MPa, CO/H2=1:1 and 100C for 4 hours.
The reaction solution (12.3g) and solid product (ll.Og) were recovered. The solid product was analyzed by H-nmr showing two isomeric products represented by Struc-tures 8 and 9, in a ca. 75:25 ratio.
COOH COOH
~' /
CH3(CH2)13C \ 8 CH3~CH2)11 1 \ _ The use of rhodium carbonyl demonstrated that the linearityof the product was affected by different species of rhodium carbonyl in the reaction medium.
Typical experimental procedures were used, except that Rh(acac)3 was the rhodium source, and dicobalt octa-carbonyl was the cobal~ source.
Co2(COj8 (0.17g), Rh(acac)3 (O.OlOg, 0.025 mmol), l-tetradecene ~9.8g), acetamide (3.0g) and ethyl acetate (15.0g) were reacted at 100C and 13.9 MPa, CO/X2=1:1, for 4 hours. The recovered solution (23.0g) and solid (5.0g) were analyzed by H-nmr. There was no alkyl N-acetyl-glycine, the desired product. Instead, the bisamidal com-pound was the major component of the solid material.
This showed that the comb.ination of Rh(acac)3/Co2(CO)8 is not suitable for amino acid synthesis.
5 ~ j !
Typlcal experimental procedures were used, except that dicobalt octacaxbonyl was the catalyst, p-dioxane was the solvent, and no rhodium was in~olved.
A glass-lined autoclave was charged with dicobalt octacarbonyl (0.125g, 0.37 mmol), l-tetradecene (9.~g, 0.05 mol), acetamide ~3.0g, 0.05 mmol), and p-dioxane (15.0g). The reactor was flushed with syngas and pressur-ized ~o 10.1 MPa with C0/H2=1:1 mixture. The system was heated to 110C and held at 12.2 MPa for two hours, then cooled to room temperature, and the excess gas was vented off. The two-layered li~uid materials were recovered, 18~0g and 6.8g. The top layer contained l-tetradecene and p-dioxane and the bottom layer contained acetamide and p-dioxa~e. Therefore, it was concluded dicobalt octa-carbonyl was not a good catalyst for the l-tetradecene/
acetamide reaction under such conditions.
A glass lined autocla~e was charged with HRhtC~)(PPh3)3 (0.023g), Co2(C0)8 (0~34g), l-decene (10.5g), acetamide (3.0g) and p-dioxane (15.0g). The reaction con-ditions were 100C, 14~6 MPa, CQ/H2=1:1 for four hours.
A homogeneous product solution ~Jas obtained (30.3g).
The solid product appeared while setting at room tempera-ture. The solid material (9.Og) was washed twice by ca.
lOg of cold ethyl acetate, resulting in a light grey solid ~8.1g). H-nmr analysis indicated a structure of alpha-(decyl)-N-acetyl glycine. The yield was ca. 63~.
Analysis of the solid product by atomic absorption showed it contained only 4.5 ppm of rhodium and 4.5 ppm of cobalt.
-The typical experimental procedures of previous examples were used, employing hydrido-tris(triphenylphos-phino)carbonyl rhodium (0.046g), dicobalt octacarbonyl -(0.34g), acetamide (5.9g, 0.1 mol), 1-octene (~.96g, 0.08 mole) and ethyl acetate (lO.Og~. A pressure of 13.9 MPa, (CO/H2-1:1 mol ratio) was added to the reactor and a temperature of 120C was maintained. At these conditions the pressure was maintained at 18.0 MPa with CO and kept for two hours~ A deep red homogeneous solution (28.3g) was obtained, which was analyzed by H-nmr. The conversion of l-octene was 100% and the only product detected was alpha-(n~octyl)-N-acetyl glycine.
EXAMPLE _ Typical experimental procedures were used, except a 300 ml stirring autoclave was charged with HRh(CO)(PPh3)3 50.06g), Co2(CO)~ (0.68g), l-tetradecene (9.8g), acetamide (3.0g) and ethyl acetate (20.0g). The reaction condi~ions were 5.6 MPa t CO/H2=1:1 and 109-112C for 4 hours. Alkyl-N-acetyl glycine (8.5g) was obtained. The yiPld- was estimated to be ca. 55~.
This example showed the catalyst was active under the low pressure conditions although the isolated yield was relatively lower.
Examples ~5 to 21 demonstrate the use of internal olefins to produce novel liquid amino acid derivatives.
A glass-lined reactor was charged with HRh(CO)(PPh3)3 (0.046g, 0.05 mmol), Co2(CO)8 (0.34g, 1 mmol)~
acetamide (3.0g, 51 mmols), 7-tetradecene (9.8g, 50 mmols), and e~hyl acetate (lO.Og). The system was purged of air and pressurized with CO/H2 mixture (1:1 molar ratio) to 0.8 MPa, then heated to 100C. The pressure was raised to 13.9 MPa and held for four hours at these conditions. -The reac~or was cooled to room temperature and the excess gas vented. The resulting homogeneous liquid (25.0g~ was recovered. The metal analyses indicated ~04 ppm rhodium (ca. 99% of theoretical) and 0.417% cobalt (ca. 91% of q j 7 ~ 5 ~ A~
theoretical). A portion of the product ~olution (2.00g) was subjected to hi~h vacuum ko remo~e ethyl acetate sol-vent. The viscous liquid product (1.15y) was analyzed by H-nmr (90 M~z) in various solvents and shown to be the N-acetyl-alkyl-amino acid compound (structure 10~. The yield of the product, based on 7-tetradecene, was ca. 85%.
CH3(CH2)5 ~COOH
CH3(C~2)6 NHcocH3 The experimental procedure of Example 15 was repeated, except for using HRh(CO)(PPh3)3 (0.023g~, Co2(CO)8 (0.17g), 9-octadecene (12.7g), acetamide (3.0g) a~d ethyl acetate (8.0g)~ The operating conditions were 120C, 13.9 MPa of CO/H2=1:1, for 4 hours. The resulting homogeneous solution (25.4 g) was analyzed by H-nmr and showed structure 11.
CH3(CH2)8 ~
CH3(CH2)7 NHCCH3 O
.
The experimental procedure of Example 15 was repeated, using HRh(CO)(PPh3)3 (0.023g), Co2(CO)~ (0.34g), acetamide (2.9g~, 9-octadecene (12.7g) and ~thyl acetate (lO.Og), with 13.9 MPa of CO/H2=1:1 mol ratio at 100C for 4 hours. The resulting liquid (28.9g) was analyzed by atomic absorption and contained 3500 ppm of cobalt and 109 ppm of rhodium. A liquid product was recovered a~ter jt;)~L~fj ~23-removing the ethyl acetate solvent. The H-nmr showed ca.
80~ yleld of N-acetyl-alkyl-amino acld. The glc analysis showed that the conversion of 9-octadecene was ~95~ and the by product was formed with ~14~ selectivit~.
EXAMPLE 18 (Comparative) The experimental procedure o~ Example 15 was repeated, except for omitting the rhodium compound. The resulting material contained 40.4 ppm of cobalt. The glc analysis showed the recovered 9-octadec~ne (~90~) in the solution. The presence of HRh(CO)(PPh3)3 was important a~ these operating conditions.
EXAMPLE 19 (Comparative) Experimental procedures similar to those in Example 18 were employed, using Co2(C0)8 (0.68g), 9-octadecene (12.6g)l acetamide (3.0g) and ethyl acet~te (20g). The operating conditions were 5.6 MPa, 130C, and CO~H2=1:2 for four hoursO The recovered liquid was analyzed by H-nmr, showing c~. 52% yield of N-acetylamino acid and ca.
48% yield of reduced hydrocarbons. It is noted that dicobalt oc~acarbonyl alone re~uired a higher reaction temperature than 100C and resulted in a lower yield of the desired product.
The reactor was charged with HRh(CO)(PPh3)3 (0.023g), Co2(C0)8 (0.17g)~ acetamide (3.0g), 2-butene (~ 14.0g) and ethyl acetate (lO.Og). The conditions were 13.9 MPa, C0/H2-1:1 and 120C for 4 hours. The resulting -product mixtures were filtered to obtain 3.5g solid and 12.5g filtrate. The H-nmr showed the solid was the iso-meric N~acetyl-amino acid 12, (m.p. 130-136C~
t ~ -/ COOH
~C 2 3 The yield was estimated at ca. 34~, based on charged acetamide.
E ~PLE 21 Experimental procedures identical to Example 2Q
were used, except for using HRhiCO)tPPh3~3 (0.046g), Co2(Co)8 (0.34g), acetamide (3.0g), cyclohexene (4.1g, 50 mmol) and ethyl aceta~e (lO.Og) with reaction conditions of CO/H2=1:1 and 1~0C for 4 hours.
The resulting product mixture ~19.2g) was filtered and the solid material (8.5g) was analyzed by H-nmr, show-ing structure 13.
COOH
~ CHNHCOCH3 13 The melting.point of compound 13 was 180-186C and the.
yield was 85~.
A glass-lined reactor was chargea with hydridocar-bonyl-(tris triphenylphosphine) rhodium(I), ~Rh(CO)(PPh3)3 . (0.0~6g, 0.05 mmol), dicobalt octacarbonyl (0.34g, 1 mmol), ~ 20 dicyclopentadiene (3.3g, 25 mmols), acetamide (3.0g, 51 mmols) ana p-dioxane ~15.0g). The reactor was sealed and purged-of air with a mixture o~ CO/H2. Then the pressure was raised to 13~9 MPa with CO/H2 mixture ~1:1 molar ratio) and heated to 100C. .A maximum pressure o* 15~6 MPa was recorde~.. After two hours the system was cooled to room temperature and excess gas was vente~. The ':. `
" . ~ ' ' 7~
-25~
resulting product solution ~brown llguld, 23.1g) was analyzed by atomic absorption, and contained 4260 ppm of cobalt (~85~ of theoretical) and 136 ppm of rhodium (B3~
of theoretical). H-nmr analysis identified structure 14 as the major product in ca. 78% yield based on charged dicyclopentadiene.
HOOC
/ CH- ~ l4 The experimental procedures of Example 22 were employed, using HRh(CO)(PPh3)3 (0,046g), Co2tc0)8 (0-34g), acetamide (3.0g), 4-vinyl-l-cyclohexene (5.4g, 0.50 mmols) and ethyl acetate (lO.Og) at 13.9 MPa, CO/H~ l:l molar ratio and 100C for 4 hours. The product solution (22.3g) was recovered. H-nmr analysis showed the presence of com-pound.l~.
COOH
\
O
. The experimental procedures of Example 23 were employed, except that the pressure was 7.0 MPa. The pro~
duct solution (20.6g) contained only compound 16 and no compound 15.
lrj~
~6-tJ NHCOCH3 Presumably, compound 16 is the inkermediate to compound 1 and required addi~ional carbonylation.
EXA~LE 25 The experimental procedures of Example 22 were employed, using H~h(CO)(PPh3)3 (0.046g), Co2(CO)8 (0.34g3, 4-vinyl-1-cvclohexene (65g), acetamlde (3.0g) and ethyl acetate (lO.Og), at 13.9 MPa, CO/H2=1:1 and 100C for 4 hours. The resulting product mixture (22.2g) was analyzed by H-nmr, The presence of compound 15 and th~ aldehyde by product was detected.
The experimental procedures of Example 22 were employed~ using HRh(CO)(PPh3)3 (0.046g), Co2(CO)8 t0.34g), acetamide (2.9g), limonene (6.8g) and e~hyl acetate (lOg) at 13.9 MPa, CO/~i2=1:1 and 100C for 4 hours. The result-ing product solution ~21.3g) was analyzed by H-nmr. The conversion o~ limonene was 100%. Two products were detec-ted at ca. 1:1 molar ratio.
COOH ~ NHCOCH3 NHCCH3 \ NHCOCH3 O
' ., , .
~r . ....................... .
~_ Jr _.
EX~RLE ~7 (Comparative) Procedures similar to those used in Examples ~2 to 26 were employed, using Co2(CO)8 (o.3ag)l acetamide (3.0g), dicyclopentadiene (3.3g) and p~dioxane at 13.9 MPa o:E
5 CO/H2=1:1, and 100C for 2 hours. The resulting light brown solution (21.9g) co~tained mostly recovered dicyclo-pen~adiene (~80~ recovery).
EXAMPLE 2~
. A glass-lined autoclave was charged with hydrido-carbonyl(tris-triphenylphosphino)rho~ium(I}, HRh~CO) (PPh3) 3 (0.046g, 0~05 mmol), Co2(CO)~ ~0.34g, 1 mmo~), acetamide . . (3.0g, 51 mmol), 1,7~octadiene (2.8g, 25 mmols) and ethyl acetate (15.0g)u The autoclave was purged of air wi~h a mixture of CO/H2 a~ 1:1 ratio and pressurized to-0~8 MPa with CO/H2. Then the reactor was heated to 100C and the pressure was increased to 13.9 MPa. After 2 hours the system was cooled to room temperature, excess gas was -; ~ented and the reaction mixture t23.4g) was filtered to - - obtain 7.5g of solid product. H-nmr analysis of the solia -20 product showed the presence of isomer mixtures:
.
\ I L n ~OOH HOOC \
C~ CH CH
C~3llU~ U~oC~3 C~3CU / ~ ~ / COO~
19 20 N~ICCH3 O
HOOC / COOH
CR ~H
CH3CNH ~ ~ ~ \ NHCCH3 O O
~ -28-The product distribution for linear to branched (i.e. 19:21) was estimated to be 2:1, based on the H-nmr integration.
The isolated yield of bis-amino ac~d was 30%.
The exper~nental procedures of Example 22 were employed, using HRh(CO)(PPh3)3 (0.046g, 0.05 mmol), Co2(C0)8 (0.34g, 1 mmol), acetamide (3.0g, 51 mmols), 1,7-octadiene (5.6g, 50 mmols) and p-dioxane (15.0g) at: 13.9 MPa of C0/H2 ~1:1) and 100C for 2 hours. The homogeneous product solution (28.lg) was analyzed by H-nmr. The pro-duct distribution, based on 1,7-octadiene charged, was 44%
for N-acetylamino acid and 34~ for aldehyde intermet~iates.
The experimental procedures of Example 29 were employed, using HRh(CO)lPPh3)3 (0.046g~ 0.05 mmol), Co2(C0)8 ~0.34g, 1 mmol), acetamide (3.0g, 51 mmols), p-dioxane (15.0g) and 1,3-butadiene (6g, 110 mmols) at 13.9 MPa of C0/H2 (1:1 molar ratio) and 100C for 4 hours.
A homogeneous product solution was recovered t22.1g). The H-nmr showed the mixture of bis-amino acid derivatives in 45% yield, based on acetamide reactant.
HOOC COOH
\ ~ / , , CH ~ CH
CH CNEI . NHC CH
311 . Il 3 O , O ' ;
The reactor was charged with HRh(CO)(PPh3~3 (0.046g), Co2(C0)8 (0.34g),-acetamide (3.0g), 1,7~octa~
die~e (2.8g) and ethyl acetate (15.0g).
The system was pressurized with C0/H2 at a 1:2 mix-ture to 8.4 MPa then with C0 to 13.9 MPa (totally). It , ~ .
~-29-was heated at 100C for 2 hours. The resI~ltlng product ~24.9g~ was analyzed by H-nmr, showing the presence o~ bis-amidal compound and no N-acetylamlno acid.
A glass-lined reactor was charged with HRh(CO)(PPh3)3 (0.092g, 0.10 mmol), aicobal~ octacarbonyl (0.34g, 1.0 mmol), styrene (5,2g, 0.05 mol), ace~amide (3.0g, 0.05 mmol) and p-dioxane (lOg). The reactor was purged of air with CO/H2 mixture, then pressurized to 3.5 MPa w~th CO/H2 ~1:2 molar ratio). The system was heated to 100C and the pressure was raised to 13.9 MPa with CO/H~ mixtuxe (1:2).
Aft r 4 hours the reactor was cooled to room temperature.
A deep dark homogeneous solution (l9.Bg) was obtained.
~1.3g wt gain based on material charged). A solid material (2.35g) appeared in the bottom of the product solution after standing overnight. The solid product was analyzed by H-nmr to be: bis(acetylamino)propyl benzene ~A ~ B) at approximately 21% yield. The liquid product contained two aldehyde products.
CH
~ CHCH(CHCOcH3)2 ~ CH2CH2CH(NHCOCH3)2 ~A) (B) The experimental procedures of Example 32 were used, except that the solvent was ethyl acetate and the molar ratio of CO/H2 was 1:1.
The reactor was charged with HRh(CO(PPh3)3 (0.46g, 0.050 mmol), dicobalt octacarbonyl (0.34g, 1.0 mmol), styrene (5.2g, 0.05 mol), acetamide (3.0g, 0.05 mol) and ethyl acetate (15.0g). The reactor was purged of air and pressurized to 0.8 MPa with CO/H2 mixture (1:1 molar ratio). The system was heated to 100C and the pressure was raised to 13.g MPa. After 4 hours the reactor was cooled to room temperature. The excess gas was vented.
A dark ~lack solution ~25.5g) was recovPred with approxim-ately 2.0g weight gain, based on starting material charged.
After standing at room temperature, a precipi~ate appeared.
The mixture was filtered. 8.2g of light bxown solid was obtained. The H-nmr showed the solid product was beta-phenyl-~-acetyl-alpha-amino acid (C). The yield was ca.
75%, based on styrene charged. The product was further identified by its silyl derivative (D) using BSTFA, ~N,O-bis-(trime*hylsilyl)-trifluoroacetamide) reagent.
f OOH / COOSi(CH3)3 CH CH
¦\NHCOCH3 ¦\ NHCOCH3 ~C) ~ tD) EXAMPLE 34 (Comparative) The procedures of Examples 32 and 33 were used, except no rhodium catalyst was employed.
The reactor was charged with dicobalt octacarbonyl ~0.34g, 1 mmol), styrene (5.2g, 0.05 mol), acetamide (3.0g, 0.05 mol) and ethyl acetate (15.0g). The reaction condi-tions were 13.9 MPa of CO/H2=1:1 molar ratio and 100C for 4 hours. The reaction product contained only ethyl benzene and aldehyde product. No N-acetyl amino acid was obtained.
This Ex~mple shows that the rhodium catalyst enhances the reaction to achieve the amino acid product. Otherwise, the reaction product (ethyl benzene) will be formed.
-A 300 ml stirred reactor was charged with HRh(CO~(PPh3)3 (0.046g, 0~05 mmol), dicobalt octacarbonyl (0.68g, 2.0 mmol), styrene (5.2g, 0.05 mol), acetamide (3~0g, ca. 0.05 mmol~ and ethyl acetate (20g). The reactor .
. ' , was purged of air and pressurized to 0.8 MPa. After heating to 100C~ the system was pressurized with C0/H2 mixture) to 5.6 MPa. During 4 hours reaction time, 0.97 MPa of syngas pressure uptake was recorded. The final product mixture contained 6.0g solid and 23.39 liquid. The solid was analyzed by H-nmr, shown to be N-acetyl-beta-phenyl-am;no acid.
The yield was 55%, based on styrene charged.
This Example showed the Rh/Co bimetallic catalyst was active even at 5.6 MPa.
EXAMPLE 36 (Comparative) 1~
Example 35 was repeated, except that no rhodium catalyst was present.
The reactor was charged with Co2(C0)8 (0.689), styrene (5.29), acetamide (3.09) and ethyl acetate (209).
The conditions were 100C, 5.6 MPa and 4 hours. The recovered liquid product contained no N-acetyl-beta-phenyl-amino acid.
-.
' ' ' ~
.
Typlcal experimental procedures were used, except that dicobalt octacaxbonyl was the catalyst, p-dioxane was the solvent, and no rhodium was in~olved.
A glass-lined autoclave was charged with dicobalt octacarbonyl (0.125g, 0.37 mmol), l-tetradecene (9.~g, 0.05 mol), acetamide ~3.0g, 0.05 mmol), and p-dioxane (15.0g). The reactor was flushed with syngas and pressur-ized ~o 10.1 MPa with C0/H2=1:1 mixture. The system was heated to 110C and held at 12.2 MPa for two hours, then cooled to room temperature, and the excess gas was vented off. The two-layered li~uid materials were recovered, 18~0g and 6.8g. The top layer contained l-tetradecene and p-dioxane and the bottom layer contained acetamide and p-dioxa~e. Therefore, it was concluded dicobalt octa-carbonyl was not a good catalyst for the l-tetradecene/
acetamide reaction under such conditions.
A glass lined autocla~e was charged with HRhtC~)(PPh3)3 (0.023g), Co2(C0)8 (0~34g), l-decene (10.5g), acetamide (3.0g) and p-dioxane (15.0g). The reaction con-ditions were 100C, 14~6 MPa, CQ/H2=1:1 for four hours.
A homogeneous product solution ~Jas obtained (30.3g).
The solid product appeared while setting at room tempera-ture. The solid material (9.Og) was washed twice by ca.
lOg of cold ethyl acetate, resulting in a light grey solid ~8.1g). H-nmr analysis indicated a structure of alpha-(decyl)-N-acetyl glycine. The yield was ca. 63~.
Analysis of the solid product by atomic absorption showed it contained only 4.5 ppm of rhodium and 4.5 ppm of cobalt.
-The typical experimental procedures of previous examples were used, employing hydrido-tris(triphenylphos-phino)carbonyl rhodium (0.046g), dicobalt octacarbonyl -(0.34g), acetamide (5.9g, 0.1 mol), 1-octene (~.96g, 0.08 mole) and ethyl acetate (lO.Og~. A pressure of 13.9 MPa, (CO/H2-1:1 mol ratio) was added to the reactor and a temperature of 120C was maintained. At these conditions the pressure was maintained at 18.0 MPa with CO and kept for two hours~ A deep red homogeneous solution (28.3g) was obtained, which was analyzed by H-nmr. The conversion of l-octene was 100% and the only product detected was alpha-(n~octyl)-N-acetyl glycine.
EXAMPLE _ Typical experimental procedures were used, except a 300 ml stirring autoclave was charged with HRh(CO)(PPh3)3 50.06g), Co2(CO)~ (0.68g), l-tetradecene (9.8g), acetamide (3.0g) and ethyl acetate (20.0g). The reaction condi~ions were 5.6 MPa t CO/H2=1:1 and 109-112C for 4 hours. Alkyl-N-acetyl glycine (8.5g) was obtained. The yiPld- was estimated to be ca. 55~.
This example showed the catalyst was active under the low pressure conditions although the isolated yield was relatively lower.
Examples ~5 to 21 demonstrate the use of internal olefins to produce novel liquid amino acid derivatives.
A glass-lined reactor was charged with HRh(CO)(PPh3)3 (0.046g, 0.05 mmol), Co2(CO)8 (0.34g, 1 mmol)~
acetamide (3.0g, 51 mmols), 7-tetradecene (9.8g, 50 mmols), and e~hyl acetate (lO.Og). The system was purged of air and pressurized with CO/H2 mixture (1:1 molar ratio) to 0.8 MPa, then heated to 100C. The pressure was raised to 13.9 MPa and held for four hours at these conditions. -The reac~or was cooled to room temperature and the excess gas vented. The resulting homogeneous liquid (25.0g~ was recovered. The metal analyses indicated ~04 ppm rhodium (ca. 99% of theoretical) and 0.417% cobalt (ca. 91% of q j 7 ~ 5 ~ A~
theoretical). A portion of the product ~olution (2.00g) was subjected to hi~h vacuum ko remo~e ethyl acetate sol-vent. The viscous liquid product (1.15y) was analyzed by H-nmr (90 M~z) in various solvents and shown to be the N-acetyl-alkyl-amino acid compound (structure 10~. The yield of the product, based on 7-tetradecene, was ca. 85%.
CH3(CH2)5 ~COOH
CH3(C~2)6 NHcocH3 The experimental procedure of Example 15 was repeated, except for using HRh(CO)(PPh3)3 (0.023g~, Co2(CO)8 (0.17g), 9-octadecene (12.7g), acetamide (3.0g) a~d ethyl acetate (8.0g)~ The operating conditions were 120C, 13.9 MPa of CO/H2=1:1, for 4 hours. The resulting homogeneous solution (25.4 g) was analyzed by H-nmr and showed structure 11.
CH3(CH2)8 ~
CH3(CH2)7 NHCCH3 O
.
The experimental procedure of Example 15 was repeated, using HRh(CO)(PPh3)3 (0.023g), Co2(CO)~ (0.34g), acetamide (2.9g~, 9-octadecene (12.7g) and ~thyl acetate (lO.Og), with 13.9 MPa of CO/H2=1:1 mol ratio at 100C for 4 hours. The resulting liquid (28.9g) was analyzed by atomic absorption and contained 3500 ppm of cobalt and 109 ppm of rhodium. A liquid product was recovered a~ter jt;)~L~fj ~23-removing the ethyl acetate solvent. The H-nmr showed ca.
80~ yleld of N-acetyl-alkyl-amino acld. The glc analysis showed that the conversion of 9-octadecene was ~95~ and the by product was formed with ~14~ selectivit~.
EXAMPLE 18 (Comparative) The experimental procedure o~ Example 15 was repeated, except for omitting the rhodium compound. The resulting material contained 40.4 ppm of cobalt. The glc analysis showed the recovered 9-octadec~ne (~90~) in the solution. The presence of HRh(CO)(PPh3)3 was important a~ these operating conditions.
EXAMPLE 19 (Comparative) Experimental procedures similar to those in Example 18 were employed, using Co2(C0)8 (0.68g), 9-octadecene (12.6g)l acetamide (3.0g) and ethyl acet~te (20g). The operating conditions were 5.6 MPa, 130C, and CO~H2=1:2 for four hoursO The recovered liquid was analyzed by H-nmr, showing c~. 52% yield of N-acetylamino acid and ca.
48% yield of reduced hydrocarbons. It is noted that dicobalt oc~acarbonyl alone re~uired a higher reaction temperature than 100C and resulted in a lower yield of the desired product.
The reactor was charged with HRh(CO)(PPh3)3 (0.023g), Co2(C0)8 (0.17g)~ acetamide (3.0g), 2-butene (~ 14.0g) and ethyl acetate (lO.Og). The conditions were 13.9 MPa, C0/H2-1:1 and 120C for 4 hours. The resulting -product mixtures were filtered to obtain 3.5g solid and 12.5g filtrate. The H-nmr showed the solid was the iso-meric N~acetyl-amino acid 12, (m.p. 130-136C~
t ~ -/ COOH
~C 2 3 The yield was estimated at ca. 34~, based on charged acetamide.
E ~PLE 21 Experimental procedures identical to Example 2Q
were used, except for using HRhiCO)tPPh3~3 (0.046g), Co2(Co)8 (0.34g), acetamide (3.0g), cyclohexene (4.1g, 50 mmol) and ethyl aceta~e (lO.Og) with reaction conditions of CO/H2=1:1 and 1~0C for 4 hours.
The resulting product mixture ~19.2g) was filtered and the solid material (8.5g) was analyzed by H-nmr, show-ing structure 13.
COOH
~ CHNHCOCH3 13 The melting.point of compound 13 was 180-186C and the.
yield was 85~.
A glass-lined reactor was chargea with hydridocar-bonyl-(tris triphenylphosphine) rhodium(I), ~Rh(CO)(PPh3)3 . (0.0~6g, 0.05 mmol), dicobalt octacarbonyl (0.34g, 1 mmol), ~ 20 dicyclopentadiene (3.3g, 25 mmols), acetamide (3.0g, 51 mmols) ana p-dioxane ~15.0g). The reactor was sealed and purged-of air with a mixture o~ CO/H2. Then the pressure was raised to 13~9 MPa with CO/H2 mixture ~1:1 molar ratio) and heated to 100C. .A maximum pressure o* 15~6 MPa was recorde~.. After two hours the system was cooled to room temperature and excess gas was vente~. The ':. `
" . ~ ' ' 7~
-25~
resulting product solution ~brown llguld, 23.1g) was analyzed by atomic absorption, and contained 4260 ppm of cobalt (~85~ of theoretical) and 136 ppm of rhodium (B3~
of theoretical). H-nmr analysis identified structure 14 as the major product in ca. 78% yield based on charged dicyclopentadiene.
HOOC
/ CH- ~ l4 The experimental procedures of Example 22 were employed, using HRh(CO)(PPh3)3 (0,046g), Co2tc0)8 (0-34g), acetamide (3.0g), 4-vinyl-l-cyclohexene (5.4g, 0.50 mmols) and ethyl acetate (lO.Og) at 13.9 MPa, CO/H~ l:l molar ratio and 100C for 4 hours. The product solution (22.3g) was recovered. H-nmr analysis showed the presence of com-pound.l~.
COOH
\
O
. The experimental procedures of Example 23 were employed, except that the pressure was 7.0 MPa. The pro~
duct solution (20.6g) contained only compound 16 and no compound 15.
lrj~
~6-tJ NHCOCH3 Presumably, compound 16 is the inkermediate to compound 1 and required addi~ional carbonylation.
EXA~LE 25 The experimental procedures of Example 22 were employed, using H~h(CO)(PPh3)3 (0.046g), Co2(CO)8 (0.34g3, 4-vinyl-1-cvclohexene (65g), acetamlde (3.0g) and ethyl acetate (lO.Og), at 13.9 MPa, CO/H2=1:1 and 100C for 4 hours. The resulting product mixture (22.2g) was analyzed by H-nmr, The presence of compound 15 and th~ aldehyde by product was detected.
The experimental procedures of Example 22 were employed~ using HRh(CO)(PPh3)3 (0.046g), Co2(CO)8 t0.34g), acetamide (2.9g), limonene (6.8g) and e~hyl acetate (lOg) at 13.9 MPa, CO/~i2=1:1 and 100C for 4 hours. The result-ing product solution ~21.3g) was analyzed by H-nmr. The conversion o~ limonene was 100%. Two products were detec-ted at ca. 1:1 molar ratio.
COOH ~ NHCOCH3 NHCCH3 \ NHCOCH3 O
' ., , .
~r . ....................... .
~_ Jr _.
EX~RLE ~7 (Comparative) Procedures similar to those used in Examples ~2 to 26 were employed, using Co2(CO)8 (o.3ag)l acetamide (3.0g), dicyclopentadiene (3.3g) and p~dioxane at 13.9 MPa o:E
5 CO/H2=1:1, and 100C for 2 hours. The resulting light brown solution (21.9g) co~tained mostly recovered dicyclo-pen~adiene (~80~ recovery).
EXAMPLE 2~
. A glass-lined autoclave was charged with hydrido-carbonyl(tris-triphenylphosphino)rho~ium(I}, HRh~CO) (PPh3) 3 (0.046g, 0~05 mmol), Co2(CO)~ ~0.34g, 1 mmo~), acetamide . . (3.0g, 51 mmol), 1,7~octadiene (2.8g, 25 mmols) and ethyl acetate (15.0g)u The autoclave was purged of air wi~h a mixture of CO/H2 a~ 1:1 ratio and pressurized to-0~8 MPa with CO/H2. Then the reactor was heated to 100C and the pressure was increased to 13.9 MPa. After 2 hours the system was cooled to room temperature, excess gas was -; ~ented and the reaction mixture t23.4g) was filtered to - - obtain 7.5g of solid product. H-nmr analysis of the solia -20 product showed the presence of isomer mixtures:
.
\ I L n ~OOH HOOC \
C~ CH CH
C~3llU~ U~oC~3 C~3CU / ~ ~ / COO~
19 20 N~ICCH3 O
HOOC / COOH
CR ~H
CH3CNH ~ ~ ~ \ NHCCH3 O O
~ -28-The product distribution for linear to branched (i.e. 19:21) was estimated to be 2:1, based on the H-nmr integration.
The isolated yield of bis-amino ac~d was 30%.
The exper~nental procedures of Example 22 were employed, using HRh(CO)(PPh3)3 (0.046g, 0.05 mmol), Co2(C0)8 (0.34g, 1 mmol), acetamide (3.0g, 51 mmols), 1,7-octadiene (5.6g, 50 mmols) and p-dioxane (15.0g) at: 13.9 MPa of C0/H2 ~1:1) and 100C for 2 hours. The homogeneous product solution (28.lg) was analyzed by H-nmr. The pro-duct distribution, based on 1,7-octadiene charged, was 44%
for N-acetylamino acid and 34~ for aldehyde intermet~iates.
The experimental procedures of Example 29 were employed, using HRh(CO)lPPh3)3 (0.046g~ 0.05 mmol), Co2(C0)8 ~0.34g, 1 mmol), acetamide (3.0g, 51 mmols), p-dioxane (15.0g) and 1,3-butadiene (6g, 110 mmols) at 13.9 MPa of C0/H2 (1:1 molar ratio) and 100C for 4 hours.
A homogeneous product solution was recovered t22.1g). The H-nmr showed the mixture of bis-amino acid derivatives in 45% yield, based on acetamide reactant.
HOOC COOH
\ ~ / , , CH ~ CH
CH CNEI . NHC CH
311 . Il 3 O , O ' ;
The reactor was charged with HRh(CO)(PPh3~3 (0.046g), Co2(C0)8 (0.34g),-acetamide (3.0g), 1,7~octa~
die~e (2.8g) and ethyl acetate (15.0g).
The system was pressurized with C0/H2 at a 1:2 mix-ture to 8.4 MPa then with C0 to 13.9 MPa (totally). It , ~ .
~-29-was heated at 100C for 2 hours. The resI~ltlng product ~24.9g~ was analyzed by H-nmr, showing the presence o~ bis-amidal compound and no N-acetylamlno acid.
A glass-lined reactor was charged with HRh(CO)(PPh3)3 (0.092g, 0.10 mmol), aicobal~ octacarbonyl (0.34g, 1.0 mmol), styrene (5,2g, 0.05 mol), ace~amide (3.0g, 0.05 mmol) and p-dioxane (lOg). The reactor was purged of air with CO/H2 mixture, then pressurized to 3.5 MPa w~th CO/H2 ~1:2 molar ratio). The system was heated to 100C and the pressure was raised to 13.9 MPa with CO/H~ mixtuxe (1:2).
Aft r 4 hours the reactor was cooled to room temperature.
A deep dark homogeneous solution (l9.Bg) was obtained.
~1.3g wt gain based on material charged). A solid material (2.35g) appeared in the bottom of the product solution after standing overnight. The solid product was analyzed by H-nmr to be: bis(acetylamino)propyl benzene ~A ~ B) at approximately 21% yield. The liquid product contained two aldehyde products.
CH
~ CHCH(CHCOcH3)2 ~ CH2CH2CH(NHCOCH3)2 ~A) (B) The experimental procedures of Example 32 were used, except that the solvent was ethyl acetate and the molar ratio of CO/H2 was 1:1.
The reactor was charged with HRh(CO(PPh3)3 (0.46g, 0.050 mmol), dicobalt octacarbonyl (0.34g, 1.0 mmol), styrene (5.2g, 0.05 mol), acetamide (3.0g, 0.05 mol) and ethyl acetate (15.0g). The reactor was purged of air and pressurized to 0.8 MPa with CO/H2 mixture (1:1 molar ratio). The system was heated to 100C and the pressure was raised to 13.g MPa. After 4 hours the reactor was cooled to room temperature. The excess gas was vented.
A dark ~lack solution ~25.5g) was recovPred with approxim-ately 2.0g weight gain, based on starting material charged.
After standing at room temperature, a precipi~ate appeared.
The mixture was filtered. 8.2g of light bxown solid was obtained. The H-nmr showed the solid product was beta-phenyl-~-acetyl-alpha-amino acid (C). The yield was ca.
75%, based on styrene charged. The product was further identified by its silyl derivative (D) using BSTFA, ~N,O-bis-(trime*hylsilyl)-trifluoroacetamide) reagent.
f OOH / COOSi(CH3)3 CH CH
¦\NHCOCH3 ¦\ NHCOCH3 ~C) ~ tD) EXAMPLE 34 (Comparative) The procedures of Examples 32 and 33 were used, except no rhodium catalyst was employed.
The reactor was charged with dicobalt octacarbonyl ~0.34g, 1 mmol), styrene (5.2g, 0.05 mol), acetamide (3.0g, 0.05 mol) and ethyl acetate (15.0g). The reaction condi-tions were 13.9 MPa of CO/H2=1:1 molar ratio and 100C for 4 hours. The reaction product contained only ethyl benzene and aldehyde product. No N-acetyl amino acid was obtained.
This Ex~mple shows that the rhodium catalyst enhances the reaction to achieve the amino acid product. Otherwise, the reaction product (ethyl benzene) will be formed.
-A 300 ml stirred reactor was charged with HRh(CO~(PPh3)3 (0.046g, 0~05 mmol), dicobalt octacarbonyl (0.68g, 2.0 mmol), styrene (5.2g, 0.05 mol), acetamide (3~0g, ca. 0.05 mmol~ and ethyl acetate (20g). The reactor .
. ' , was purged of air and pressurized to 0.8 MPa. After heating to 100C~ the system was pressurized with C0/H2 mixture) to 5.6 MPa. During 4 hours reaction time, 0.97 MPa of syngas pressure uptake was recorded. The final product mixture contained 6.0g solid and 23.39 liquid. The solid was analyzed by H-nmr, shown to be N-acetyl-beta-phenyl-am;no acid.
The yield was 55%, based on styrene charged.
This Example showed the Rh/Co bimetallic catalyst was active even at 5.6 MPa.
EXAMPLE 36 (Comparative) 1~
Example 35 was repeated, except that no rhodium catalyst was present.
The reactor was charged with Co2(C0)8 (0.689), styrene (5.29), acetamide (3.09) and ethyl acetate (209).
The conditions were 100C, 5.6 MPa and 4 hours. The recovered liquid product contained no N-acetyl-beta-phenyl-amino acid.
-.
' ' ' ~
.
Claims (10)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the production of solid linear alkyl-N-acetylamino acids or liquid branched alkyl-N-acylamino acids characterized in that an olefinically-unsaturated hydrocarbon, an amide of the formula where R1 and R2, which may be the same or different, are each substituted or unsubstituted aryl, alkyl, arylalkyl, alkylaryl, or hydrogen, carbon monoxide and hydrogen are reacted in an inert or polar solvent at a temperature of at least 50°C and a pressure of at least 3.5 MegaPascals in the presence of a catalyst comprising hydridotris-(triphenylphosphine) carbonyl rhodium HRh(Co) (PPh3)3, and dicobalt octacarbonyl Co2(CO)8.
2. A process according to Claim 1 characterized in that the olefinically unsaturated hydrocarbon is an alpha-olefin or internal olefin having the formula:
R.CH=CH2 or R.CH=CH.R
in which R is alkyl, or the two groups R can together represent the carbon atoms necessary to complete an alicyclic ring.
R.CH=CH2 or R.CH=CH.R
in which R is alkyl, or the two groups R can together represent the carbon atoms necessary to complete an alicyclic ring.
3. A process according to Claim 2 characterized in that the olefinically unsaturated hydrocarbon is propylene, 1-octene, 1-decene, 1-dodecene or 1-tetradecene.
4. A process according to Claim 2 characterized in that the olefinically unsaturated hydrocarbon is 7-tetradecene or 9-octadecene.
5. A process according to Claim 2 characterized in that the olefinically unsaturated hydrocarbon is cyclohexene or cyclopentene.
6. A process according to Claim 1 characterized in that the olefinically unsaturated hydrocarbon is styrene or a substituted styrene having the formula in which R is alkyl.
7. A process according to Claim 1 characterized in that the olefinically unsaturated hydrocarbon is an unsymmetrical diene having two olefin functions of different reactivity.
8. A process according to Claim 7 characterized in that the diene is 4-vinylcyclohexene, limonene, bicyclopentadiene, 1,6-octadiene or vinyl norbornene.
9. A process according to Claim 1 characterized in that the olefinically unsaturated hydrocarbon is a symmetrical conjugated or non-conjugated diene.
10. A process according to Claim 9 characterized in that the diene is 1,3-butadiene, 1,7-octadiene, norbornadiene, 1,3-cyclohexadiene or 1,5-cyclooctadiene.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US72024885A | 1985-04-05 | 1985-04-05 | |
| US06/720,248 | 1985-04-05 |
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| Publication Number | Publication Date |
|---|---|
| CA1267156A true CA1267156A (en) | 1990-03-27 |
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ID=24893258
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000505116A Expired - Fee Related CA1267156A (en) | 1985-04-05 | 1986-03-26 | Process for synthesis of n-acetylamino acids from olefins, acetamide and synthesis gas |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113373466B (en) * | 2021-06-19 | 2023-07-21 | 安徽科技学院 | Electrochemical synthesis method of beta-acetaminocarbonyl compound |
-
1986
- 1986-03-26 CA CA000505116A patent/CA1267156A/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113373466B (en) * | 2021-06-19 | 2023-07-21 | 安徽科技学院 | Electrochemical synthesis method of beta-acetaminocarbonyl compound |
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