DE1443335A1 - Process for producing mercaptopropionylglycine and mercaptopropionylglycine amide - Google Patents

Description

SANTiSH? HARUAOEUTIOAL 00., LTD. 2, Shiaoehinjo-Cho, Hlgaehi Yodogawa-ku, Osaka, Japan

Process sau manufacturing τοη Meroaptopropionylglyoin and Meroap-

toproi> ionylglyoina "ld.

The invention relates to a method of dividing up meroaptoproyionylglycine and meroaptopropionylglyoinamide. Crflnduogegeaap "earth in a special o- and ß-uroaptopropionyl-lyoin e as well as α- and ß-mefoaptopropionylglyoinaaid represent the novel abbreviations of uroaptopropionic acid". Dieee Tereindenea rarely therapeutleohe Wlrkeaakelt for the therapy τοη poison * gen »die duroÄ da« administer tob drugs TerureaoAt wravk · In the au combating poisoning aereolielntage ea eioh, among other things, illnesses, which are due to the Tereohiedene types το ηall de Sohweraet for the treatment Kretaea eier eel eier Irradiation of medium radioactive agents (β · Β · Leakopeaie) rerabreioht «Furthermore, the connections established are« Irksan as the most likely in case of treatment tos Sohlan-Ceable »,« le deaohlangenglfie »of the rivinerla 8angglfestani Viper"

IrflBdungegeaMp aan dergeetalt that Or Mereaftoreet Aar «- or t-meroaptoprcaloic acid suitable for a saiietlient "Ir", or later leloht is removed, aan eedann aeter An "en4e"

209817/1484 bad original ^

harltUOBlieher Bslogealeraiigvaltt ·! The Carboxy! group of the connection In the Stturehalog © nid 'du sr leads, GXy an on tor manufacture dt «α- or ß-Herofeptoproplonylglyoin-Aäicäai & linga unsetst» and then in a suitable manner * the © oMittend® 3ufe®tituant of the mercapto group Obtaining the et- or ß-mero & ptöpropionylglyoinö is removed · According to the formula, the method according to the invention can be represented as follows

3-R

oi% -OH-OOX
8-H

OH-COM-OH ₈ -0001 * 3-Ä

001% - ^ 0i% -OH-OOIH-O ^,

a-Meroaptoproplonyiglyoinsaid

tattr 5 let a bed su Teretelien, which can be easily presented oh Waaaer- • toff ercetsen, as sB «ii« Beste 0, H ₁ OH, -, 0, ^ 00-, 0 _e V-3.H ₄ -CH ₈ -, O ₁ 1-C _e 3S ₄ ^ CO-J uew «^ iad 1 * iet« in AUtylreet, and X a IalogtnatOB. Ia slialieJier W9i @ ® will
laid Bach ier following Av »tita« «i ··
BS-CH ₁ -OHj-OOOH} HS-Oi ^

Cn «atepreeiiieader Welae lets see p-Meroaftopropioaylglyain aaek Is the following * Irkelt ewe ie e manufacturers

ES-OB ₁ -02V-0001 ---- ^ M-OB ₁ -Oa ₁ -OOIII-OH ₁ -OOOH

BAD ORiGSNAL

209817/1484

Dae β- and ß-uronptoproplonylelyain and dl · corresponding Aside »Peculiarly low toxicity, beelteen excellent effect aXa Antidote »as against poisoning caused by queuilber and macaw deaths to be respected Therapeutically, the JTU is extremely suitable for strengthening the liver function.

Table 1 Acute ^; Toxicity given in LD, _e for the intreyenöeen insectlon

with little ones

a-MeroaptopropioayigXjdn α-Meroaptopropionylelyoinamide 0 ~ MeroaptoproplonyIglyoin ß- * eroaptopropionylglyoinaaid Thioetic acid

2170 g / kg

1970 «g / kg

3000 ag / kg

1790 g / kg

197 «c / kg

31S «g / kg

209817 / U84

- 4th

BATH ORIGINAL

Table II

St ·· des
wet, de «
Tertbrelshen

(stated Io Ansajal the dead SÜere, checked at ftitisen)

40 mice, 20 mice, 20 mice, 40 mice, 20 mice, 30 mice,

will the 20 BgAg the 20 BgAg will the 20 tog / ke the 20 ogAg

20 BgAg Subliaat ♦ Subllnat + 20 BgAg Subliaat + Sublimate +

SaslLtat 100 BgAg i-Her- 100 BgAg 0-Her-SubliBat 500 ^ gAg a-Mer- 500 BgAg l-Mer-

▼ administered oaptoproploeyl- captopropionyl- administered oaptopropionyl- captopropionyl-

glyein rerab- glycine Terab- glyclnamid rer- glyclnaold τβΓ-

1
3
5

24

camouflaged

17th
8th

35/40

1
1

4/20

20 *

1 1

'20

40 *

Todeeftll · 87 »5 *

(specified in AnsaJbl of geetorMoei » Startes 20 IlMen 10 Behind are 10 Waeen «eriMeli des, become «den 30» «Ag den 30 OgAg

Veras- 30 BgAg. Qxypheo- Oxyphesmrein

Oxypbjsserein arsine + 300 sg / kg · «· 300 qgAg administered« -Meroaptopropio- p-Mercapto-

nylglyoln propioeylglycine

i t

40/40
100 *

3/20

15 *

Mice 20 mice

would be the 40 s ^ g / kg

Bg / lEg oxyphenarsine Phsnarsln 4- 500 Bg / k ^

▼ eras—

enough nylglyoinaaid

0 1 0

5/30 17 *

Become mice ag / kg arein + 500 ^ ß-mercaptoproll

ygy tsra hands

24
% gee «st
^ foe falls

10
15/20

65 *

0/10

0 *

0 0 0 0 0/10

O*

100 *

0
0
0
0
0

0 0 0 2 2

Ca)

on

Invention "according to" shares "with α- or ß-Meraaptopropioaylglycln and Aald-e as well as üeterabköealinge the same eo that α- or ß-Halogenpropionylglyoin or amide- and BeterabkSualinge the same hasten a sulfur compound, which in the aioh • eta-dissolving easily Thiolreat bildat, uageaatst is how above! Ehiobensoat, Xhloaoetat, Alkylxanthogenat, AlkalidieUlfid or 'fhioeulfat represents, whereby one obtains a J? Roplonylglycinabklira »linß, which has a sulphurous Thai tender» Bubatituenten at «a division or ß-3. The connection is then established or reduced in an entapreahender manner without separating it, resulting in the desired end product being obtained using the following equations) OH ₁ -CH (X) -OOIH-CH ₁ -COa (or X-CH ₁ -OH ₁ -COHH-CH ₁ -COa) + 2Ϊ -

OH ₁ -CH (If) -COHH-CH ₁ -COA (or Y-OH ₁ -CH ₁ -COIIH-OH ₈ -OOA) ■ '^ OBa-OH (SU) -COIH-OH ₁ -COA (or HB-OH ₁ -OH ₁ -COIH-OlIj-0OA) _f

In the compounds, X is a halogen atom and A let is selected from a group consisting of HydroxyIreet (OH), Atoinoreet (, 9H ₁ ), and Alkyloxyreet (OB) , 'I let au "a group consisting of" O ₉ H ₁ OOS, OH ₉ COS, BOOS ₁ , and ΰ-ϋ excluded "and Z" divides "into alkali" et a U.

SI "Krflndmg is 1" the following eeiepieleweiee under Besugnah "· on dl · floodplain guide «b ο iep ie Ie explained.

At Example 1

Maa lä | t 100 g α-Benayleeroaptopropioneäure »it one ·" mp 76-78 m * 0, dl "dureh ^r Jia 's tsen a-ittiroaptoproploncäure" it Boumylohlorid erikeltea will "iet," and "a", "s" with 80 g of Tnionylohlorid Uter! «. Sim ft "erechü""lie Thlonylohlorid is removed and linked under Terrlneerte" ImMk 4ee. Here, “an 70 g” -Benaylneroaptopriil · “-“ • “!” “IOAVid“ it receives an “8” - 158 · 139 · Ο / 7-8 m lg · q ^ 0RlGt ^ 4AL. 4 ·

209817/1484

Then warden 25 ölyotn g, daa in 165 ml of a 2 η '.tfn dissolved lüoung iai, 70 g of a-JtfrjayluerottiJ Sopropionaäuroojilorid UNAE 100 al 2 η 2fatriuahydro: grdlUttung equilateral b "i" iiidx tenses goal' - 5 ^{0 <>} a dripped. Ivan stirs the solution at home temperature for 3 to 4 hours until the heating is complete. Jh e Un is accustomed to rait ether, the wa-aarigu Üühicnt ui i; ü acidified and the ariialfcenon crystals wordexi aurcn filter separated. J £ an crystallized from a mixture of methanol and AeXhyl acetate over. Hiorbui fooled 60 g flc-BßnKyXinerc ^ iro ^ JOpionylglyr-in old a yp a Γ33 -ΐ; 4 ° ΰ fulfilled

The 90 ernaltenen 60 "-Benaylnercaptopropionyl ^ Lyoln nerdfn aodoxia dissolved in 400 al Flue ei β sweet A.amoniRlc and maintained at a I'eaperatur from about -50 ^e C. 3cdoJ) n are 12 g iaetallieciiee ifstrluß; allaiäli "Iioh" ugeeetirfc. ITaoh <ler llf ^ etsuui ^ wii * d UberaahüGöigar AiUiaDrfiak removed "the Hüoltatüca ia Waaaer dissolved, ait ether" ewaachen, the remaining aqueous oohioiit old 3al3 * aur "set to a p _{} i} ~ v / ert τοη 1, and sodium under reduced »ftruck in a bchvfefelwaeaer-» toffetros constricted. The crystalline Bokatand is dried and lutcrietallized with ethyl acetate. This gives 25 g of a-meroaptopropionylglyoin old 93-97 * 0.

Aalalyte value is used for ι O ₈ H, 0, JfBi 0 * 36,80f>, H » 5 * 56 /» »

found t 0 «37» 07 ⁽ > _t H «5»

40 g of thioyl chloride are added to 50 g of fl-flenaylaeroaptopropionic acid, which is obtained by aetnening of β-mero-ptopropione * urold benzyl chloride. About laughs "loh eelbet Uberlaeeen and then the 9B""tsUBgaproduct detailed under reduced pressure. Here "46 g jl-Jeiiyl *" ra *? Topropionylahlorid old "lnea 3p - 150 - 52 * 0/7 mi Hf are obtained.

209817 / U84

BAD ORIGINAL _e - _e

Ea are 16 & lly a la 200 ml gin er 1 η Natriunüi ;;.}? ^: Cy <llU'vana Ä ⁰ ** dissolves, at about 50 ° ö genaltan and oodauo 46 & ß-Bousylworoaptopropionylchlorid and 5, 0 al 1 η ammonium hydroxide solution dripped in giuiciisoitig egg then Tile is im. Example 1 stated, T.eitu Hon receives 00 40 g p - Benaylnerci'.ptoi'i * opionylglycine :. \ 1τ 115-117 ° C. Kö 40g p-Benaj'laoroaptopropioJayi ^ liroin in 260 g ammonia al flüaeigem "löat and golialter at a Seaperatur of -50 ⁰ C. Then Wiv; dtm t · llküiiiich 8 g ßiätallieciaee fiatriua" ugegoben. Naoii conclusion d <-; r U: .Ui «t; r <nn; · becomes llberuciiüysi ^ or .-«. Nraonifik isnt> t * tvn%, the Btiokotand in Wa «esa ^ & nUoHt ₉ dl® ^ üsarige uokioht with Viuueer gewaeohen and doroii a column Xonienauathabenherharnee st.irfc GSiaruJctere gafUlirfc · do «o dae Satrittahydro ^ 'd tu remover». The rige solution is concentrated under Terriugertea pressure, whereby ium one

nd. receives. This residue is nird /.ctii^ t. Ma »orr.älx 30 16 g ß-Merof.ptorrorionylelycin a? p »ίου, 5-102 ° ΰ.

Analy »« JT »is calculated for C» H, ü _? H3i G «36.8OjC, H» 5 »56'Λ,

found! 0 * 37 "12 £ ι Η" 5 * 48 ^.

Example 3

To 21 c a-Bensoyl & ercaptopropiontäur · old a · «J ^ p« 66.3-67.5 ° G, the ummen of o-meroaptopropionic acid with benzoylochloride have been obtained, herds are given 14 g of thionyl chloride and the mixture is used about Hucht «ich · elbet Uberlaeeen. Aneohliepend ub «r« eatt «« lg * 8 thionyl chloride under reduced · «Drude« bd «« tllli «rt and the KuoJeetand in 100 tal Aother. This HU.ok «tand is uit Waeeer g * wa »ohen, old sodium sulfate dried one in a solution yc 7.5 g of olyoin and Λ g of sodium hydroxide in 100 al Waeeer at «iner T ·» - peratmr τοη 0 * C xunüimen Kit of a solution of 4 g of sodium hydroxide In 9 · al Va «« «r cing · drips. Since «Uiu» «tsaimeg« aie «h becomes aiek« «!» «T about laughs ub «rla« «« n, aodana Satriaabicarbouat sugegeöen, die

2 0 9 8 1 7 / U 8 4 _{BAD οηιΘ1ΝΑ} ξΟΡΥ -β-

rleone Sohloht in Waeeer geweeohen and dae WajwhwRSGBr ait der istteorigun Laiiicht aut * »afiica] g« geu «& · Aü * Oüliö £ e & ici is αΐΐ r-aJajfeur« unleavened, cooled »the received Üiedereonlag uitgeii'tam» _r Oe mi eck, consisting of a in Aethylaoetax and A β than oil ua-

Here »8 g of α-Bewaoylaerep.ptogXycin Bdt a

Ee become 8 ga ~ lH »iiKo / ltterc ..-. Ptaglycin ßtt« i2 »er Lt'jung το» 9 »5 β Sariuehyoiroxyd: L & SO ml <a ^ cer, ie ^ .ab ·«, * uf de » Water bath built for 4 hours "scduxiu ^ oh.;. 'O £ cl: .iiurc sug & give and oiiv ^ ojiwoi'tiwiiiieeritofX geeättiijt" Your calibrated Hiodoreohl ^ g yflrd oldfXl triert "and doe Piltrat untiir verriüeierter ,. Tinr VVok \ <* niu \ becomes {• trooknet and aue i ^ thi'laoetat uakrietnllieicrt. iimi erhilx uo> g "-CercaptoproirpJßnylelycin" it an "fp" * 94-97 ° C.

if ^ pi ^ A

fi «in example; an ^ o ^ ebon * will be ot-p-FitxOtoeneo / inHrc i »urt, the durcii Uioueujbe» yen a-MeroaptopropioneMiare mis p- »entoyloJtllorid uruilxoti has been let, nit IhicnylUthloriU) ee eo it will oiletatlyoloria und -p-Iitrobecsoylneroaytopropionyl ^ ilyoin With a »Pp * 152-153» 5 * C (is never given in the example 'h / drolyeiert · Hxerdaroh er) iält m lae a-Meroaptopropionylglyoin *

ie is a-wercaptopropiooic acid old p-Witrobenaylbrraid under er ep-IitrobeneylaerceptopropioiieMiire with an "Fp * 91 * 9" 5 * 0 ageetet. Aneohlleßend becomes like 1 "leleplel 'nnge ^ ebea," it nlorld aiageeetEt, woduroh. due 3tturediloria g ^ vronnon is that> in ~ ohließend a üaeetiung old aiyei «is subjected · Uan gewiMit ο dae ep-IitrobeneyleeroHptopropioaylelyoin old a JPp« 14 · τΟ49 ^# 0

2098 17/1484 BAD ORIGINAL

Connection is given "i" followed by netsllltnhe.n tfptrluA In flttneigea AnBOnIaJi ₁ "ie la Beiapiel 1, redutfierfc, βύ that in da""receives -elerceptopropionylgtyoln.

Balanlal 6

Mm will be a-Ben "yltturc * i>xoyropioB" äuxe, dl "duroh lauuattten from a - ^" reaptoproploneaure old B * naylohlorid let, old fhlonjB.-ohlarld under Quwlxuicn from aB “nayla * rciap toi / i'opioneäur «Six of an 8t · l33-39 * C / 7-ö na Ug uageeetat. * e "earth 51 β Glyoinuaulchydro- • olorld in 150 al Waeeor goluet, with a 'Üdtepexutar of 2 Wie ^ ⁵ O feiudten," ad eodann "earth 560 as a 1 η latriuahydroxyulöeung Aaechlieptn." troyft nan glelahMltl ^ VJ & dr, «<t erl -..-» ltenen

and 270 «1« ltt «r <i a. a «D * e UiaeetstMeegeaieoh wlrl at l

3 bie 4 8bunJen lang ble sur full «ülndigen Uueetttuu-g gerliluv, dlu eraaltenen Hriatalle geeaauelt uad so« Aothylttu ^ Utt, a ^ crletclll alert · aaa gewiaat eo 35 Λ e-Beneylaercwptoproplonylglyclaamlt The connection is in ISO til / lttnal ^ eu A ^ acnlrOc gd «18 ·« »« it is gthelten at about -30 * 0 »and iodtnii allM2xUoL 7 <aetallieohee Ittrium sun SureniBhrea of the editors ^ eebau · Xaeh of the tfaeetsaeadak« ird en ti »rat, the Mtoketiind in Uethaaol, aetaaaelieohe 8 as« ft «re ble stia lent anaeros given» 4er eo erbalteae Ilederaolilag separated uad dit. Mother liquor under Tevringertea tr «ak la eiaea 8efti« erel «« ee «retoffetron elngeesgt · Ue t« gweaaaaia KrIatulle are aua eiaea OemieoA iue letly laeet «t and iataanel eaaxrl4talllelert a β foy a-Mer eo 12 134 · Ο ·

Aaaljreeawerte bereohaet XUr 0.1 ^ 0.1 ₁ 81 0 - 57, O2>, H - e »

I- 17.27 * gefaadea ι 0 · 3 », 84 *, H -

20981 7 / U84

- ίο -

Example 7

As stated in Example 6, starting from ß-mercapfcopropionic acid, ß-bensylmeroaptopropionyl chloride is produced. 5 g of Glyoinäthyleaterhydroohlorid are stirred with 50 ml of aaaer and 100% of ether. It is then cooled to a temperature of 0 ^e U and 5 5 g of ß-Benayliaercaptopropionylohlorid and 250 ml of 2 η sodium hydroxyc solution are added dropwise on the same side. The reaction mixture is stirred at room temperature for 3 hours. After completion of the urning, the ethereal layer is separated and washed with aqueous galaaic acid, sodium carbonate solution and V / asaer. It is then dried and the ether is removed. The ß-Benssyla eruptopropionyiglyoin ether remains as a residue. Here are 150 al aethanoliacher namonlak. given, left to calibrate for 7 ', and then the precipitate from methanol uakristallioiert. This gives 5 g of ß-Benayliaeroaptopropionylglyoinaßdd a with a Pp * ^{140.5-141.5 0} O. The Abapalteu of the Beas ^ l group is given as in Example 6, using netalliaohee Hatriun in liquid analonia. The asuaonia is removed and alcohol is added to the residue. Alcoholic salestture is then added until a Congo red reaction occurs. The 31uat is cooled and the separated crystals are combined with the crystals obtained by concentrating the mother liquor. The combined crystals are recrystallized from alcohol, giving 13 g of ß-meroaptopropionylglyoinamide ait a 9p - 142-143 * 0.

ÄMlyaen values calculated for 0.1 ^, 0, *, Ss 0 * 37.02 *, H - 6.15Ji,

H - 17.27 *

found C - 36.70 *, H - 6.50 *

V. 17.04 *.

BAD ORIGINAL -U-

209817 / U84, _r ™

CO- i

Example 8

iva 10.5 g of a-bromopropionyl ^ iyoin are dissolved in 30 ml of water and neutralized by adding sodium bicarbonate. A solution of 7.5 β thiobenaoic acid and 4 »8 g of potassium carbonate is added to 50 ml of iVuseer and left to stand overnight. The next day, the solution is filtered so that small amounts of insoluble matter are removed. The piltrate is then macerated by adding hydrochloric acid, and the precipitate obtained in this way is separated off and washed with water. After drying, 12.8 g of a-Beneoylaeroaptopropionylglyoin with a J? P «158 to 161 ⁰ G.

The 8.9 g of a-bensoyl & aroaptoproplonylglyoin thus obtained are in Suspended 18 ml of water and neutralized with sodium bicarbonate dissolved, 9 μl of concentrated ammonia are added to the solution, left to seibat over Nuoht and then filtered. Lbs of the benzoic acid amide that is then separated off becomes old in a small amount of water Hiengc washed and the Waochwaeser with the previously obtained Piltrat united. This combined solution becomes excess ammonia largely untor vertingertea uruok removed, then with oleic acid acidified and undor reduced * pressure #w »a reduction to 1/3 the original volume constricted. It is then cooled. the precipitated crystals are filtered off. After drying and recrystallization from ethyl acetate, 2.95 g of o-iieroaptopropionylglyoin are obtained with a Pp ■ 94 to 96 * 0.

Ee 10.5 g of a-bromopropionylglyoin are dissolved in 30 »1 ethanol which contains 2.8 g of potassium hydroxide. 4/2 g of thioacetic acid are then added and the mixture is left to stand at room temperature for 2 days. The low "impact of potassium bromide is removed and the ijlltrat been said among verringez X * * Oraok. To remove insoluble tissue, asther is used

209817 / U84 < _C0PY

t- -> ir . ^

? -lie ^ ltharisclis I-'i ^ j & sj with • ss ^ sjri ',: ^:! ^ Iiatriuaeulfat geirocknai ULKd swecka Satfernea däe Loaua ^ EaitSola siag-aGagt. One holds 8 ο that ia refrigerator and gives siveaäa Aasäxistallisiarea Petrolätker there. Later it is filtered, the crystals are dried using a gariagen Maage ether-petroleum ether gawa ^ ciian and go. Ao 4 »2 g of a-Aoatyla ^ F-captopropioaylglyoin are obtained. After dea Uakriatallizieren aua ethyl acetate then 4ieae Ysrbindiiag sinesa Pp ■ BS-B ¹ J ⁰ Q,

Then ^ ardea 4 »2 g a-Aoetylaeroaptopropioayl ^ lyela in 30 al 2 η IlatritiiaiaydrosydlöeiaBg geiaat _s 30 Miaut © a orttnort» ait Salaaäure re-x-raliaiert and Urstar Yarriisgertea Drucä restricted to sar frookene.

Bar Ivüokatand is aakriatalliaiert aua Asthjlacstat, tvoüei one 1.9 S

receives «

10.5 g ffl-BroaproploisyX ^ lyoia id IGO al laäa ^ r galöat, naatraliaiert by Sugab © of 4 »2 g latriuabicarboaat and a & aoiiliaßesd 2ΐ3ΐ'3Γ Sigabe Ton §, 0 ι Kaliusctaathogenat sioh oaliset is filtered over Haoeaht over« lafjoeaht that the filtrate is acidified with nitric acid, usually obtained® Misfleraciilag g @ ^ af ^ @ lt & sd »^ dt Waesar ^ swasoiion · Saohä % iz Tr ^ cksan ^$ änd IJ ^ ristallieieren au® 3G ^ igaa methanol« receives aaa 10.3 ^ a-Äatisylsasathoganpropiösiylslyeia ait eiasa. Mp »112-113» 5 * 0.

L'a Ο ₃ 4 ^ is-Aeilaylsaat & ogoapropicaylslyaia ^ arslaii 80 ail Iseasaatriert «r

«, The @ $ alaoa> leaves

ait 30 al Aot & er ®atf3rat ₉ ia the rest

rL.5e Löaoa-s a ^^ cäa Satfaraaa tüs ^ rs ^ iüaal ^ ss Aaaoaisuce Stioketoff totf with Salsijänra magaoi ^ srt tmd alt ^ atriuaciilerid g · - Scdaaa übaritihrt aaa in ^ ia ^ a KÜälaöke

Sia «a-äalt-saQ-a Xriatalls ^ Qir-iioa alaiiitsi-ieTt aadl la

203317/1434.

There are 10.5 g a-Broapropioir / i ^ jl ^ oi. ^ Is PY ai. Waesar 4.2 g of sodium bicarbonate neutralized and heated on the water bath old 13, sodium bisulfate pentahydrate for 2 hours. The product is cooled, hydrochloric acid sweoka Tsrsetaen da »sodium thiosulfate is added and then filtered. The filtrate is made alkaline using sodium hydroxide and lasted 2 days for 2 days. The solution is then thinned to 100-1 with water while filling up a column of strongly acidic ionic water $ Ά das Ka ^ -'.- iaa jgiUhrt and concentrated under ringertea pressure to dryness. The crystalline RUo & itaisd is dried and uakriatalllaiert from ethyl acetate. 1.8 g of a-meroaptopropionylglyoin are obtained.

7 "6 g thiob" naoe "& ur9 ia 50 al aetäaaol .golüat, since" 3a contains xaliua hydroxide, and then 10.5 g a-broapropionylglyoiaaaid "are added. The Uaeetsgemieoa Z Sag "laag bei Haueteap ^ r" - the door is left to stand hon. The dl · JCriatalla are then separated off. Dl · K latallo are "washed with water" dried and added to methanol uakriatalliaiart " UBn " - ^: 8.6 g of a-Bsneoylmeroaptopropioaylglyolaamiil with a? Sp "149" 5-

£ a 8 are "0 g a-Benaoylaaroaptop ^ nylglyoiaaoid in 40 al aamoniakaHsohea Hethaaol gsiuet and check itself Haoht Ansehließ ammonia and methanol by Eiaaas" n nat "r gortem Draok is" ad removed, the HUokstaod Ia water jelö * t _f filtered üalöslioh ·· in water s * w * f> ah <». D «q Jsso.OTiae ^ r wl? D adt T« y «lmlgtf vli ear fs ^ e & aso mator
itioJwtand getrookao * ia4 aas «laem

209817 / U84 ^3AD original

COPY

ls sali4.3ii r2n .laa --- 32 ¹ M! * -io 2 ^ 2 3 s-iiaroaptopropionylait aiaoa Pp »I33 - 135 ³ U.

Example Π

3 = 3, 7t δ g of thiobonaoic acid are dissolved in 50% of ethane oil which contains 5 ₃ 1 Å potassium hydroxide. Zi'4 auagefallooe Xaliuabroaid is shut off, the filtrate is concentrated under reduced pressure and the remaining oil is dissolved in ether. ^ Finally, old water is used _for aqueous sodium bicarbonate solution and ααοβΓ. It is dried ait waoiaarireiaa l? Atrium sulfate and -lor ether is removed by steaming. Addition of Potroläthü. In the meantime, the crystals are crystallized out. «All of the water is filtered off and salt is extracted from an odor of ether and petroleum ether.

· Ao 13β 2 g of a-Bansoyliwiroaptoproplonylglycinäthyl'-rasit "iaea? P" 75 - 77 * 0 asich-d ^ a one has from öGs4igea Aathtmol.

warden 3.9 s dam ao received s-

Dissolved in 100 al liquid Acmaoniak, about 60 hours long iind aaaonlak away. The received Kriatalle white.;. ·; iiaaaer solved »αα das iialuelioho Beaao« »Äu? eataid au Commenced under 7arriag «rt4a Druck sur froölcsne ü & ecstand becomes a »« oiaea uaeiaoh from Aetnylaoetat and · 2äaa receives ao 1 «8

la Aethylaoetei; "Aieeliohoa share" holds aaaa 3.5 S

i? p »165 - 167 ⁹ O (oxide type j

5A CRlGiMAL

COPY

- 15 -

2Q9817 / U84

ial χα

As indicated in Beiepial Xj, warden 12 g ß-Bs glycinäthylester with a Pp * 69-71 ⁰ O auegsheisd of XX, 9 g ß-Broopropionylglyoinäthyleeter hergeeteilt.

Ka are 7 "4 g dieee" ß-Bensoylaeroaptopropiojaylglyoin & th.yleet3r3

^ it 8, ϋ g barium hydroxide ootahydrate, 5>; al of water and 30 ml Aethaao mixed is bouann 8 btunden long Siiokstoffetro "in a on a Waeaerbad to a temperature of 70 - 80 rwärat ^e G". Haoh dsa

When cooling down, the solution is acidified with thinner solubilized acid,

: Barium sulphate precipitates, filtered off and water is added. Dim

'iaachwaeeer T? ird with the pil stepped clean and under

Di-uck bis sur TrooXen »narrowed. The HUokatand turns into a

tor dried over phosphorus pentoxide under reduced pressure uad a

Ethyl acetate utakriatalli-siart. One "rlxält eo 1.5 3 ^ -

nylglyoin old a Fp ■ 101 - 105 ⁰ O.

Oxidation of the old air of the roiiaa product gives 1.3 S

old alcsa Pp «197 - 199 ^{Ü |} 3 received

Ka becomes an Oetoivoh aue 6.5 g 3atrius9Ulfid ° -Noa & iiydr & t and 0.9 ^ sulfur flower la Ό al Waeesr by, lirwäraea on eiaea Weeeerbad g löet. Then there is eiaa wäaarigs Löaucg dsa "atriu * aalaea de« ß-Brompropionylglyoine, since "au" 10.5 g ß-Broapropioaylglyoin, 4? S Natriuabicarbona t and 20 si Waee «r hargeatsllt ^ rord-sn let, and on the Vaaeerbad Heated for 2 hours. A lot of OnlÖalioheca aa next day is filtered off, the flltrat al Saleetture acidified and na oh the Usakrietallisleren aua T «e« er 5 ₉ J bie (ß-Meroaptopropionylglyoin) old sinem? Pa 137 - 199 * 0 received, 6.3 g dieee "BieCß-Maroaptoproplonyl ^ lyoiaeJ in 65 al ouepsndiert, old

Katria Äüiear ^ c ^ at gslöat, aod ana from β 3 Alusira3axoXi-3

203817/1434 -

BAD CniGiNAL COPY

• -.ι 14 ^ 3335

salaam isa ^^ jä-s'su ..llailhlicli 3:? * :? är sr «aad 1.5 SSuads long With all tea apparatus from 50 ° to 90 °, the temperature is cooled down the Hiederaohla ^ filtered off and ssit Wa β a ar uewaachen · That waeaer is combined with Piltrat and reduced Uruelrbia

Concentrated to dryness and dried the residue. After dea ua- ! Crystallized aue ethyl acetate contains 4 »2 g of ß-mercaptopropionyl-

Baiaoisl 16
becomes a Geiaiecli aas 6.5 g Hatriuaeulfid-Iionahydrat and 0.9 g

dissolved in 65 al 8 above ethsnol under iämäiraen. Then 11,9 & ß-üroapropioayl ^ lyoinätiiyJ.öeter au ^ egebesi and further for 2 hours on a water bath on the HUok river gaiutltsn «A geriaga ass üalöalioüsa will aa naoüetan Sag ab.flltriart, ethanol from the filtrate with reduced solidification Abeohiedsnsn OeIc ateh ^ ngelasaen "Then it is filtered, tait

and an a goriugoa volume of Ao than oil. Ha oh dem 'froolcnsa receives E & a 6.4 Jl bie ( _k S ~ M®? Oaptoproplonyl4lyeinäthyleeter) dt

"120" 121 * * C according to Doia Uskri ^ tullisieran au "Ae than Öl.

"Earth 6.4 S ble (p-Meroaptoprapi © aylslyeiaäthyl9" ter ia 100 al

aaaoaiakaliaohea methanol dissolved, kept at room temperature for 5 days and eodaaa egg-aged Hierd & roa receives aan 5.4 s borehole, which after dea Uakri «talliaieren aue wansor au 4.8 g"siiiß-iieroaptopropiQnylgXyoiaaaid; a ±% # lag ta? p «223-225 * 0 ÜUhrea ·

Bm 4.3 fl dieaee bie (^ - Meroaptopropiaaylgl7oiaaald «> ia 100 al 50 $ lgar £« «ig * ttare and 4 stuadea loads are stirred in 2.1 g sialcatanb at the Hauateaperator, Aa aäohstoa Sas becomes 3ch? Iefalwaaeuae diaae liaae «Oka Satiomea dee 2iaks siage leads,

FiI ¹ S ^ at aatiir f <$ τ? Ί * Ά $ β S ¹¹ SQa ISr ^ Ji star Ts ^ alsaiao -aia ^ asQ ^ tj jsd Ja s; L ^ 3-si jSsalferitßs · ysa ^ Qr .vhoapas ^ p ^ sjtts ^ a water

: -JJ d ι / / ι; ♦ «j« j, RAD ^ ¹ · '

COFT

14433-55

tee Druok getrocJcnet. Sack des Uaüriatslllaieren 3 ^ 3 '.-Ae ^^ r Aothanol receives aan 3 * 2 g ß-Marcaptopropionylglyolnaold tait Pp - 142 - 14? »5 ^β σ.

EAD ORiGiNAL

COPY

209817 / U34

Claims (1)

1. Process sum production of α- or ß-mercap topropionylgly and its abbreviations, characterized in that the meroapto group of β- or ß-meroapt © propionic acid with later slightly au ent * removing substituents, "ie benzyl", p-nitrobenyl -, Benaoyl-, p-Nitrobenaoylreaten gesohütst »alt an llalogenierungeuittel converted into the acid halide» then reacted with glycine and the substituent of the obtained, substituted by sulfur α * or p-Meroaptopropionylglyoin is removed. 2 · Procedure na oh claim 1, because it is known that the α- or β-halopropionyl flyoin or amide or Sater aiit a ijohwef elrerbind ujig UMge «etat is easy to convert into a TM ο 1-reet lets stir over and get the eo · link that does üchwtftl containing subatitoents in the α- or ß-position on » has «while obtaining the desired α- or ß-Mercaptopropio ^ i, -glycine and amides or esters * of the same tersetate or raduaiart will. 209817/1484