CA2006270A1 - Process for the preparation of n-phosphonomethylglycine - Google Patents
Process for the preparation of n-phosphonomethylglycineInfo
- Publication number
- CA2006270A1 CA2006270A1 CA002006270A CA2006270A CA2006270A1 CA 2006270 A1 CA2006270 A1 CA 2006270A1 CA 002006270 A CA002006270 A CA 002006270A CA 2006270 A CA2006270 A CA 2006270A CA 2006270 A1 CA2006270 A1 CA 2006270A1
- Authority
- CA
- Canada
- Prior art keywords
- acid
- alkyl
- phosphonomethylglycine
- hydrogen
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 12
- XDDAORKBJWWYJS-UHFFFAOYSA-N glyphosate Chemical compound OC(=O)CNCP(O)(O)=O XDDAORKBJWWYJS-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 239000002253 acid Substances 0.000 claims abstract description 21
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 8
- 239000001257 hydrogen Substances 0.000 claims abstract description 8
- 150000002148 esters Chemical class 0.000 claims abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 150000007524 organic acids Chemical class 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract 4
- 150000002431 hydrogen Chemical class 0.000 claims abstract 2
- 238000006467 substitution reaction Methods 0.000 claims abstract 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 11
- 239000004471 Glycine Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
- 150000003973 alkyl amines Chemical class 0.000 claims 1
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- 238000010931 ester hydrolysis Methods 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 claims 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims 1
- -1 benzyl halide Chemical class 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 238000001816 cooling Methods 0.000 description 3
- 230000020335 dealkylation Effects 0.000 description 3
- 238000006900 dealkylation reaction Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- OGNVQLDIPUXYDH-ZPKKHLQPSA-N (2R,3R,4S)-3-(2-methylpropanoylamino)-4-(4-phenyltriazol-1-yl)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid Chemical compound CC(C)C(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)OC(C(O)=O)=C[C@@H]1N1N=NC(C=2C=CC=CC=2)=C1 OGNVQLDIPUXYDH-ZPKKHLQPSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- 239000005562 Glyphosate Substances 0.000 description 1
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical class COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000193803 Therea Species 0.000 description 1
- 241000736772 Uria Species 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000005587 carbonate group Chemical group 0.000 description 1
- 229940089960 chloroacetate Drugs 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-M chloroacetate Chemical compound [O-]C(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-M 0.000 description 1
- 229960001701 chloroform Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 150000002332 glycine derivatives Chemical class 0.000 description 1
- 229940097068 glyphosate Drugs 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- AMEKQAFGQBKLKX-UHFFFAOYSA-N oxycarboxin Chemical compound O=S1(=O)CCOC(C)=C1C(=O)NC1=CC=CC=C1 AMEKQAFGQBKLKX-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 241000894007 species Species 0.000 description 1
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Substances CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
- C07F9/3813—N-Phosphonomethylglycine; Salts or complexes thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
ABSTRACT
A process for the preparation of N-phosphonomethylglycine isdisclosed which comprises:
preparing an N-alkyl-N-phosphonomethylglyaine or its ester reprinted by the formula wherein R is an alkyl group represented by the formula
A process for the preparation of N-phosphonomethylglycine isdisclosed which comprises:
preparing an N-alkyl-N-phosphonomethylglyaine or its ester reprinted by the formula wherein R is an alkyl group represented by the formula
Description
2C)06270 - 1 - 09-21(2945)A
~ .
This in~ention relate~ to a p~oc-o~ for th~ prep~ration of N-phosphonomethylglycine or it~ ~te~, and morQ
particularly to th~ pr-paration of N-phosphonomethylgly~ine ~r~m N-substituted glyc~ne derivatives N-Phosphono~ethylglycine, known by it~ common name o~
glyphosate, i9 widely used around the world a~ a broa~-spe¢trum herbicid~ to control th- gxowth o~ m~ny plant specie8 Generally, it ~g u~ed in an aqueou~ solution ns one of it~ salts for application to plant~ to control the growth of woody plants, aquatic ~peci-~, qra~e~, ~nd the like It i~ kno~n to be gen~rally non-toxio to ~umsn~ and other mammals, and environment~lly ~- Millions of llter~ -of the formulated product ar~ ~old each yea~ for such purposes It i~ kno~n that N-benzyl-N-phosphono~ethylglya$ne (or --itR esters) unde~go~# hydrohal~c acid d-benzyl~tion to yield benzyl halide and N-phosphono~ethylglyaine or it~ ester~
(see ~or example Briti~h Patent No 1 436 843) A large -excess o~ very ~onc~ntrated (eg 48~) hydro~alic acid is required, however, amounting to ~any mol-~ o~ ac~d ~or eacA ~-mole o~ ~tarting co~pound Thls rendor~ ~h- proc-~ing ~nd i~olation o~ the deslred glycin~ deriv~tive di~lcUlt, mainly becau~e of th~ problem of r-moving thi~ large ~mount o~ hydro~alia ac~d a~ter the reaction.
Attempts to lmprove the proce~- by the use o~ ~tarting COmpOUnd# hav~ng other ~ubstitu~nts than b~n~yl on the nitrogen atom, eg ts u~e N-alkyl-N-pho~phonomethylglya~ne~, ~0 have bccn ~tt~nded ~ith the sa~ proc~ing disAdvantag~
(se~ ~or exa~lQ US Patent ~o 3 g27 080) The lit~rature contain~ no ~ugge~tiona as to the use o~ ~c~fl~ other than th~ hydrohalla acldn to re~ove the ~lkyl group ~rom N-alkyl-2~ 270 - - 2 - 09-21~2945)A
N-phosphonomethylglyainn ~o produc~ tho d~irad nd ~roduct Now, t~e~e is provided nn ~A~y procQdure to dealkylato a wide variety o~ N-alkyl-N-pho~phono~ethylglycine~ to provid~
N-phosphonomethylglycine in hi~h yield~ at an ~¢onomical ~o~
The~e and other advantage~ aro achiev-d by ~ proaes~
for the pr~p~ration of N-phosphonomQthylgly~ine which compr~ S-8:
prepa~ing An N-alkyl-N-pho~phonomethylglycln- or it~
ester represented by the ~ormul~
R ~ oR2 RlOOC - CHz -- I -- CH2 P\
oR3 :: 15 wh~rein R i~ an alkyl group repr~ented by th~ formula R~
R~ - C -and Rl, RZ and R3 ar~ independently select0d from the group consisting of hydrog~n and alkyl hav~ng on~ ~o about four carbon ato~s, and R4, ks and R6 ~re independ~ntly ~elected from ~ubstit~ted and un~u~titut~a ~lk~l ~ruu~
having ~rom one to about ~ix c~bon atom~ wh~rein any sub~ti~u~ion on th~ alkyl group ha~ atron wlthdrawing prope~es, and hydrogen, provided that R~, R5 and R6 cannot ~11 be hydrogen; and therea~ter treating the N-Alkyl-N-pho~phonom~thylglycine with an acid, oth~r than a hydrohalic aoid, having a pR~ value ~-low a~out ~3 in the ~re~enc- o~ an o~ganic acid to proviao N-pho~phono~ thylgl~clne ~0~2~o _ 3 _ 09~ 2945)A
.,' _ ~_ We have found that, apart from known proces~e~ u~ing hydrohalic ac~ds, cort~in ~-~lkyl-N-phos~honom~hylglycine~, : and t~eir ester~, in which the N-~lkyl aub-tituent ~
suitably chosen, can bo dealkylat-d by treatment not only with a hydrohalic aoid ~ut with any ~aid whose ~K. value i6 below ~3. Pref~rably, the acid u~ed is solected ~rom th~
group that con~i~ts o~ sulfurio ~aid, ~-toluene ~ul~onic acid, methylsul~onic acid (subgroup ~) and trichl~r~a~tic acid, phosphori~ acid and phosphorou~ acid (subgroup B).
The acids of ~ubgroup A are p~eferred, and sulfuria acid i~
e~pecially pre~erred.
In the case of sulfuric Aaid, an adoquate molar proportion is le~ than about 10%, ba~ed on the ~OlQ~ 0~ -alkyl substituted glycine derivati~e used in the p~oC~
OE th~ other ~c~d~ n~ed, molar proportion~ o~ ~bout 5% t~ ~
about 50% can be used, the ~refexred range being 10% to 20~, -based on the moles o~ alXyl ~ub~titut-d glycin~ ~erivativ~
used.
Any nu~ber of organic acids known to those ~illed in - the ~rt c~n be used in the tr~atm~nt of the N-alkyl-N- ---pho~phonomethylglycine with th~ ~c~d having a pK, value of le~ than about ~3. It ~ 8 only nece~ary that the o~anlc acid i~ water 301uble, and low~r molecular w~ight orqAnic acids are pre~err~d. Suitablo organic ac~ds inolude formic acid, acetic acid, propionic acid, butanol~ a~id, and th~
lik~, for u~e in the rea¢tion medium. Aa~tlc ~cid i~
pre~erred.
m Q temperatures to be u~ed in the pXe~ant proces~ aan vary w~th~n wid~ rango~ Temperaturo~ be~ween a~out 20~C
an~ about 100C pro~ide nati~actory ~esult~. Lower ~QmpQrn~ur~s can be u#ed, but tho reactlon ~- ~omewhat ~low.
TQmp~aturQ~ above 100C can b~ u~ed, but a~ ~7ill ocour to , ~~iZ7() ,:
- 4 - 09-21~2g45)h ~hose s~illed in the art, the reaat~on v~8~1 may h~v~ to ~e pres~urized at such higher tem~erature~. Temp~ratur-~
between about 40C and 100C ar- pre~err~d. When sulfuria a¢$d i~ used, d~alkylation bQgin~ at a temper~ture of about 50C, and become~ rapid ~t about 80C, with aopious evolution o~ the relevant alkene.
In a preferred ombod~m-nt o~ the proan~ of the invention the dealkylation i~ carried out in the pre-enc- of acetic acid a~ a ~olvent. This h~ b~en ~hown to impart economie~ to the proc-ss, ~nae the target aompound crystallizes directly from the Acetic acid in th- cour~ of the dealkylat~on reaction.
In another pre~erred e~bodi~ent, which can bo co~bined with any of the ombodimentoe de~aribed above, the proce~ of the invention compri~e~ pr~paring th- alkyl d~rivative in a ~anner Xnown E~E_~ and thereafter dealkylating it according to the invention a~ ~ot out above, without previous i~olation, in a one-pot procedure. More ~pecifically, in the preferred embodiment, the N-alkyl-N-phosphonomethylglycine or e~t-r u~-d i~ synthe~izQd f~om ethyl chloroa¢etate and an appropriat~ alkylamin~, ~ollowed ;- by Q~te~ hydroly3~s, ~ollow~d by pho~phonomethylation of the re~ulting N-alkyl glycine or ester, and that ent~re proce~s ~ performed without i~olation or purifi~ation of any intermediat-. ~n the pre~erred e~bodiment N-t-butyl-N-phosphonomethylglyaine may be pr~par~d by pho~phonomethyla~ion of N-~-butylglycin~ whiah in turn may be th- produc~ o~ the coupling o~ ~-butylnmin~ ana ~thyl chloroac~tat~, ~ollow~d by e~ter hydroly~
Wh~n thQ mo#t pr~erred glycin~ d~rivativ-, namQly N-~-bUtyl-N-pho~phono~ethylgly~in~ dealkylated in accordance with th~ invQntion~ eB~ccially wh~n ac~tic acid ~ used as a ~olven~ utylene iB e~olved. If, how~v~r, th~r- l- a _ g _ 09-21(294S)A
~igni~icant amount of water pre~ent ln the reac~ion ~ixturo, then in addition t~ ~Q-butylon~, ~-butanol i~ obtained a~ a by-product, As will occur to tho~- ~killed in the art, corre~ponding produats are ob~a~ned when o~her glycine derivat~ve are u~ed As previou~ly ~tat-d, thQ dealkylation of N-~-butyl-N-phosphonometh~lglyoine proceed~ moro rapidly in ~cetic ncid than it does ~n water; however, it is the b¦5~L~ 1l of N-phosphonomethyl~lya~ne from tho AC~tiC nc~d m-diu~, with minimal processing, that provid-~ ~ m~or technical advantage in the proc~ss of the invention A final product of ~urity exceeding 90% by w-ight is obtainablQ by the proces~ of th~ invention in a routinely reproduaible ~anner Typical reaction times ar~ 2 to 4 hours With cooling and filtration over g0% yield~ ar-obtainable The following example~ s~rve ~urth~r to illu~trate tha invention Exa~pl~
N-t-Butyl-N-phosphonomethylglycino (100 g, 96~ ~ure, 0 426 mol) wa~ m~xed with ac~tic ~¢id (500 ml) and 97~
sul~uria acid (4 0 g, 0 04 mol) On h-ating the mixture to 50C in a round-bottomed fla~k fitted wi~h a Liebig condense~ Q-butylen- was det~t~d down~tream o~ th~
conden~er At 80C large guant~ti~s o~ ~Q-butylene were ev~lved and tho rate o~ evolution of this off-ga~ in~rea~ed with te~perature. After 3 hour~ ~t 100C th~re w~ no N-~-butyl-N-phosphonomethylglycine detectable by ~PLC in the reac~ion v~sel, and l~rge quantitie~ of ary~talline N-pho~phon~methylyglycine wer~ pre~nt. Cooling to ambi~nt, f~ ring ~n~ drying g~e N-pho~phono~ethylglycine (6g 0 g, g5~ pure, 91 2~ yield) Analy~i~ o~ th- mother l~quor ~00~i270 - 6 - 09-21t2g~5)A
showed a further 3.7 g of N-pho~phonomethylglycin-, giving a total c~emical yield for this dQal~ylation of 96.3~.
E~amplç I~
~-t-Butyl-N-pho~phonom~thylylyc~no (100 ~, 96~ ~ur~, 0.42 mol) was ~ixed with acetic ac~d ~500 m~s) ~nd ~-toluen~
~ulfoni¢ acid (14.6 g, 0.085 mol). HQating at 100C for 4 hour.~ co~pleted the react~on and tha che~ical yield of the dealkylation was 94~.
~e~
Ethyl chloroacetate ~1~2.5 g 1.0 mole) wa~ reAotQd with exces~ t-butylamin~ in trichloromethane and the ethyl gly~inate ~eparated ~rom the t-butyla~in~ hydrochlorid~.
The ethyl ~lycinate was hydrolyz~d with hyd~o~hloric acid and the N-~-butyl-N-pho~phono~e~hylqlycine (167.6 g a~
deter~ined by HP~C) was reacted with suluric ac~d (3.8 mle, 0.07 mol) a~ ambient temperatur- and the ~ixture wa~ th~n ; heated at 100C for 4 hour~. Cooling to 20C, filto~ng and drying gave N-pho~phonomethylyglycine (118.5 g, 95.8 purity, gO.3% y~eld). The overall yi~ld ~rom ~thyl chloroacetate was ~7.2%.
The invention i~ not li~ited by or to tho de~ail~ ~f ~ -the speci.~ic embadiments describ~d, ~any o which c~n undergo wide variation without departing ~or fro~ the ~ope of the invention.
~ .
This in~ention relate~ to a p~oc-o~ for th~ prep~ration of N-phosphonomethylglycine or it~ ~te~, and morQ
particularly to th~ pr-paration of N-phosphonomethylgly~ine ~r~m N-substituted glyc~ne derivatives N-Phosphono~ethylglycine, known by it~ common name o~
glyphosate, i9 widely used around the world a~ a broa~-spe¢trum herbicid~ to control th- gxowth o~ m~ny plant specie8 Generally, it ~g u~ed in an aqueou~ solution ns one of it~ salts for application to plant~ to control the growth of woody plants, aquatic ~peci-~, qra~e~, ~nd the like It i~ kno~n to be gen~rally non-toxio to ~umsn~ and other mammals, and environment~lly ~- Millions of llter~ -of the formulated product ar~ ~old each yea~ for such purposes It i~ kno~n that N-benzyl-N-phosphono~ethylglya$ne (or --itR esters) unde~go~# hydrohal~c acid d-benzyl~tion to yield benzyl halide and N-phosphono~ethylglyaine or it~ ester~
(see ~or example Briti~h Patent No 1 436 843) A large -excess o~ very ~onc~ntrated (eg 48~) hydro~alic acid is required, however, amounting to ~any mol-~ o~ ac~d ~or eacA ~-mole o~ ~tarting co~pound Thls rendor~ ~h- proc-~ing ~nd i~olation o~ the deslred glycin~ deriv~tive di~lcUlt, mainly becau~e of th~ problem of r-moving thi~ large ~mount o~ hydro~alia ac~d a~ter the reaction.
Attempts to lmprove the proce~- by the use o~ ~tarting COmpOUnd# hav~ng other ~ubstitu~nts than b~n~yl on the nitrogen atom, eg ts u~e N-alkyl-N-pho~phonomethylglya~ne~, ~0 have bccn ~tt~nded ~ith the sa~ proc~ing disAdvantag~
(se~ ~or exa~lQ US Patent ~o 3 g27 080) The lit~rature contain~ no ~ugge~tiona as to the use o~ ~c~fl~ other than th~ hydrohalla acldn to re~ove the ~lkyl group ~rom N-alkyl-2~ 270 - - 2 - 09-21~2945)A
N-phosphonomethylglyainn ~o produc~ tho d~irad nd ~roduct Now, t~e~e is provided nn ~A~y procQdure to dealkylato a wide variety o~ N-alkyl-N-pho~phono~ethylglycine~ to provid~
N-phosphonomethylglycine in hi~h yield~ at an ~¢onomical ~o~
The~e and other advantage~ aro achiev-d by ~ proaes~
for the pr~p~ration of N-phosphonomQthylgly~ine which compr~ S-8:
prepa~ing An N-alkyl-N-pho~phonomethylglycln- or it~
ester represented by the ~ormul~
R ~ oR2 RlOOC - CHz -- I -- CH2 P\
oR3 :: 15 wh~rein R i~ an alkyl group repr~ented by th~ formula R~
R~ - C -and Rl, RZ and R3 ar~ independently select0d from the group consisting of hydrog~n and alkyl hav~ng on~ ~o about four carbon ato~s, and R4, ks and R6 ~re independ~ntly ~elected from ~ubstit~ted and un~u~titut~a ~lk~l ~ruu~
having ~rom one to about ~ix c~bon atom~ wh~rein any sub~ti~u~ion on th~ alkyl group ha~ atron wlthdrawing prope~es, and hydrogen, provided that R~, R5 and R6 cannot ~11 be hydrogen; and therea~ter treating the N-Alkyl-N-pho~phonom~thylglycine with an acid, oth~r than a hydrohalic aoid, having a pR~ value ~-low a~out ~3 in the ~re~enc- o~ an o~ganic acid to proviao N-pho~phono~ thylgl~clne ~0~2~o _ 3 _ 09~ 2945)A
.,' _ ~_ We have found that, apart from known proces~e~ u~ing hydrohalic ac~ds, cort~in ~-~lkyl-N-phos~honom~hylglycine~, : and t~eir ester~, in which the N-~lkyl aub-tituent ~
suitably chosen, can bo dealkylat-d by treatment not only with a hydrohalic aoid ~ut with any ~aid whose ~K. value i6 below ~3. Pref~rably, the acid u~ed is solected ~rom th~
group that con~i~ts o~ sulfurio ~aid, ~-toluene ~ul~onic acid, methylsul~onic acid (subgroup ~) and trichl~r~a~tic acid, phosphori~ acid and phosphorou~ acid (subgroup B).
The acids of ~ubgroup A are p~eferred, and sulfuria acid i~
e~pecially pre~erred.
In the case of sulfuric Aaid, an adoquate molar proportion is le~ than about 10%, ba~ed on the ~OlQ~ 0~ -alkyl substituted glycine derivati~e used in the p~oC~
OE th~ other ~c~d~ n~ed, molar proportion~ o~ ~bout 5% t~ ~
about 50% can be used, the ~refexred range being 10% to 20~, -based on the moles o~ alXyl ~ub~titut-d glycin~ ~erivativ~
used.
Any nu~ber of organic acids known to those ~illed in - the ~rt c~n be used in the tr~atm~nt of the N-alkyl-N- ---pho~phonomethylglycine with th~ ~c~d having a pK, value of le~ than about ~3. It ~ 8 only nece~ary that the o~anlc acid i~ water 301uble, and low~r molecular w~ight orqAnic acids are pre~err~d. Suitablo organic ac~ds inolude formic acid, acetic acid, propionic acid, butanol~ a~id, and th~
lik~, for u~e in the rea¢tion medium. Aa~tlc ~cid i~
pre~erred.
m Q temperatures to be u~ed in the pXe~ant proces~ aan vary w~th~n wid~ rango~ Temperaturo~ be~ween a~out 20~C
an~ about 100C pro~ide nati~actory ~esult~. Lower ~QmpQrn~ur~s can be u#ed, but tho reactlon ~- ~omewhat ~low.
TQmp~aturQ~ above 100C can b~ u~ed, but a~ ~7ill ocour to , ~~iZ7() ,:
- 4 - 09-21~2g45)h ~hose s~illed in the art, the reaat~on v~8~1 may h~v~ to ~e pres~urized at such higher tem~erature~. Temp~ratur-~
between about 40C and 100C ar- pre~err~d. When sulfuria a¢$d i~ used, d~alkylation bQgin~ at a temper~ture of about 50C, and become~ rapid ~t about 80C, with aopious evolution o~ the relevant alkene.
In a preferred ombod~m-nt o~ the proan~ of the invention the dealkylation i~ carried out in the pre-enc- of acetic acid a~ a ~olvent. This h~ b~en ~hown to impart economie~ to the proc-ss, ~nae the target aompound crystallizes directly from the Acetic acid in th- cour~ of the dealkylat~on reaction.
In another pre~erred e~bodi~ent, which can bo co~bined with any of the ombodimentoe de~aribed above, the proce~ of the invention compri~e~ pr~paring th- alkyl d~rivative in a ~anner Xnown E~E_~ and thereafter dealkylating it according to the invention a~ ~ot out above, without previous i~olation, in a one-pot procedure. More ~pecifically, in the preferred embodiment, the N-alkyl-N-phosphonomethylglycine or e~t-r u~-d i~ synthe~izQd f~om ethyl chloroa¢etate and an appropriat~ alkylamin~, ~ollowed ;- by Q~te~ hydroly3~s, ~ollow~d by pho~phonomethylation of the re~ulting N-alkyl glycine or ester, and that ent~re proce~s ~ performed without i~olation or purifi~ation of any intermediat-. ~n the pre~erred e~bodiment N-t-butyl-N-phosphonomethylglyaine may be pr~par~d by pho~phonomethyla~ion of N-~-butylglycin~ whiah in turn may be th- produc~ o~ the coupling o~ ~-butylnmin~ ana ~thyl chloroac~tat~, ~ollow~d by e~ter hydroly~
Wh~n thQ mo#t pr~erred glycin~ d~rivativ-, namQly N-~-bUtyl-N-pho~phono~ethylgly~in~ dealkylated in accordance with th~ invQntion~ eB~ccially wh~n ac~tic acid ~ used as a ~olven~ utylene iB e~olved. If, how~v~r, th~r- l- a _ g _ 09-21(294S)A
~igni~icant amount of water pre~ent ln the reac~ion ~ixturo, then in addition t~ ~Q-butylon~, ~-butanol i~ obtained a~ a by-product, As will occur to tho~- ~killed in the art, corre~ponding produats are ob~a~ned when o~her glycine derivat~ve are u~ed As previou~ly ~tat-d, thQ dealkylation of N-~-butyl-N-phosphonometh~lglyoine proceed~ moro rapidly in ~cetic ncid than it does ~n water; however, it is the b¦5~L~ 1l of N-phosphonomethyl~lya~ne from tho AC~tiC nc~d m-diu~, with minimal processing, that provid-~ ~ m~or technical advantage in the proc~ss of the invention A final product of ~urity exceeding 90% by w-ight is obtainablQ by the proces~ of th~ invention in a routinely reproduaible ~anner Typical reaction times ar~ 2 to 4 hours With cooling and filtration over g0% yield~ ar-obtainable The following example~ s~rve ~urth~r to illu~trate tha invention Exa~pl~
N-t-Butyl-N-phosphonomethylglycino (100 g, 96~ ~ure, 0 426 mol) wa~ m~xed with ac~tic ~¢id (500 ml) and 97~
sul~uria acid (4 0 g, 0 04 mol) On h-ating the mixture to 50C in a round-bottomed fla~k fitted wi~h a Liebig condense~ Q-butylen- was det~t~d down~tream o~ th~
conden~er At 80C large guant~ti~s o~ ~Q-butylene were ev~lved and tho rate o~ evolution of this off-ga~ in~rea~ed with te~perature. After 3 hour~ ~t 100C th~re w~ no N-~-butyl-N-phosphonomethylglycine detectable by ~PLC in the reac~ion v~sel, and l~rge quantitie~ of ary~talline N-pho~phon~methylyglycine wer~ pre~nt. Cooling to ambi~nt, f~ ring ~n~ drying g~e N-pho~phono~ethylglycine (6g 0 g, g5~ pure, 91 2~ yield) Analy~i~ o~ th- mother l~quor ~00~i270 - 6 - 09-21t2g~5)A
showed a further 3.7 g of N-pho~phonomethylglycin-, giving a total c~emical yield for this dQal~ylation of 96.3~.
E~amplç I~
~-t-Butyl-N-pho~phonom~thylylyc~no (100 ~, 96~ ~ur~, 0.42 mol) was ~ixed with acetic ac~d ~500 m~s) ~nd ~-toluen~
~ulfoni¢ acid (14.6 g, 0.085 mol). HQating at 100C for 4 hour.~ co~pleted the react~on and tha che~ical yield of the dealkylation was 94~.
~e~
Ethyl chloroacetate ~1~2.5 g 1.0 mole) wa~ reAotQd with exces~ t-butylamin~ in trichloromethane and the ethyl gly~inate ~eparated ~rom the t-butyla~in~ hydrochlorid~.
The ethyl ~lycinate was hydrolyz~d with hyd~o~hloric acid and the N-~-butyl-N-pho~phono~e~hylqlycine (167.6 g a~
deter~ined by HP~C) was reacted with suluric ac~d (3.8 mle, 0.07 mol) a~ ambient temperatur- and the ~ixture wa~ th~n ; heated at 100C for 4 hour~. Cooling to 20C, filto~ng and drying gave N-pho~phonomethylyglycine (118.5 g, 95.8 purity, gO.3% y~eld). The overall yi~ld ~rom ~thyl chloroacetate was ~7.2%.
The invention i~ not li~ited by or to tho de~ail~ ~f ~ -the speci.~ic embadiments describ~d, ~any o which c~n undergo wide variation without departing ~or fro~ the ~ope of the invention.
Claims (9)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the preparation of N-phosphonomethylglycine which comprises:
preparing an N-alkyl-N-phosphonomethylglycine or its ester represented by the formula wherein R is an alkyl group represented by tho formula and R1, R2 and R3 are independently selected from the group consisting of hydrogen and alkyl having one to about four carbon atoms, and R4, R5 and R6 are independently selected from substituted and unsubstituted alkyl groups having from one to about six carbon atoms wherein any substitution on the alkyl group has electron withdrawing properties, and hydrogen, provided that R4, R5 and R6 cannot all be hydrogen; and thereafter treating ths N-alkyl-N-phosphonomethylglycino with an acid, other than a hydrohalic acid, having a pK, value below about +3 in the presence of an organic acid to provide N-phosphonomethylglycine.
preparing an N-alkyl-N-phosphonomethylglycine or its ester represented by the formula wherein R is an alkyl group represented by tho formula and R1, R2 and R3 are independently selected from the group consisting of hydrogen and alkyl having one to about four carbon atoms, and R4, R5 and R6 are independently selected from substituted and unsubstituted alkyl groups having from one to about six carbon atoms wherein any substitution on the alkyl group has electron withdrawing properties, and hydrogen, provided that R4, R5 and R6 cannot all be hydrogen; and thereafter treating ths N-alkyl-N-phosphonomethylglycino with an acid, other than a hydrohalic acid, having a pK, value below about +3 in the presence of an organic acid to provide N-phosphonomethylglycine.
2. The process of claim 1 wherein R is isopropyl or t-butyl.
3. The process of Claim 1 wherein R is t-butyl.
4. The process of Claim 1 wherein the acid having a pK, value below about +3 is selected from the group consisting of p-toluene sulfonic acid, methyl sulfonic acid, sulfuric acid, trichloroacetic acid, phosphoric acid and phosphorous acid.
5. The process of Claim 4 wherein the acid in sulfuric acid.
6. The process of Claim 1 wherein the organic acid in acetic acid.
7. The process of Claim 1 wherein in the N-alkyl-phosphonomethylglycine is synthesized by reacting ethyl chloroacetatic with an alkylamino, followed by ester hydrolysis, followed by phosphonomethylation of the resulting N-alkyl glycine.
8. The process of Claim 7 wherein the alkylamine in t-butylamine.
9. N-Phosphonomethylglycine produced by any of the processes in claims 1-8.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE3838/88 | 1988-12-22 | ||
| IE883838A IE883838L (en) | 1988-12-22 | 1988-12-22 | N-phosphonomethylglycine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2006270A1 true CA2006270A1 (en) | 1990-06-22 |
Family
ID=11039131
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002006270A Abandoned CA2006270A1 (en) | 1988-12-22 | 1989-12-21 | Process for the preparation of n-phosphonomethylglycine |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0449987A1 (en) |
| KR (1) | KR910700255A (en) |
| AU (1) | AU620489B2 (en) |
| CA (1) | CA2006270A1 (en) |
| IE (1) | IE883838L (en) |
| WO (1) | WO1990006929A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6054608A (en) * | 1997-05-05 | 2000-04-25 | Monsanto Company | Method for preparing formylphosphonic acid |
| JP2002510305A (en) * | 1998-02-12 | 2002-04-02 | モンサント カンパニー | Method for producing glyphosate by oxidation of N-substituted glyphosate |
| EP1520857A1 (en) * | 1998-08-12 | 2005-04-06 | Monsanto Technology LLC | Process for the preparation of N-(phosphonomethyl) glycine by oxidizing N-substituted N-(phosphonomethyl) glycine |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3927080A (en) * | 1974-09-03 | 1975-12-16 | Monsanto Co | Process for producing N-phosphonomethyl glycine |
| US4650613A (en) * | 1984-12-28 | 1987-03-17 | Monsanto Company | Process for preparing N-phosphonomethylglycine and derivatives |
| US4851159A (en) * | 1988-05-02 | 1989-07-25 | Monsanto Company | Process for the preparation of N- phosphonomethylglycine |
-
1988
- 1988-12-22 IE IE883838A patent/IE883838L/en unknown
-
1989
- 1989-12-20 AU AU48418/90A patent/AU620489B2/en not_active Ceased
- 1989-12-20 KR KR1019900701832A patent/KR910700255A/en not_active Application Discontinuation
- 1989-12-20 EP EP19900902002 patent/EP0449987A1/en not_active Withdrawn
- 1989-12-20 WO PCT/US1989/005711 patent/WO1990006929A1/en not_active Application Discontinuation
- 1989-12-21 CA CA002006270A patent/CA2006270A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| KR910700255A (en) | 1991-03-14 |
| WO1990006929A1 (en) | 1990-06-28 |
| AU620489B2 (en) | 1992-02-20 |
| IE883838L (en) | 1990-06-22 |
| AU4841890A (en) | 1990-07-10 |
| EP0449987A1 (en) | 1991-10-09 |
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Legal Events
| Date | Code | Title | Description |
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| FZDE | Discontinued | ||
| FZDE | Discontinued |
Effective date: 19930621 |