SU472501A3 - Method for producing substituted biguanide - Google Patents

Description

This invention relates to a method for the first and new replaceable biguanides of a general formula (I).

R, -NH-C-NH-C NH,

Nr.

YN

or ix salty,

where RI is a saturated or unsaturated hydrocarbon group with Ci-Ci2, unsubstituted or substituted by one or more fluorine atoms, cycloalkyl with Cz-Ce or

and n 0,1

residue - ICi-uV

or 2; X is hydrogen or halogen;

R2 is a saturated or unsaturated hydrocarbon group of normal or iso-structure with GI-Ci2, unsubstituted or substituted by one or more fluorine atoms, cycloalkyl with C3-Sb, alkoxyyalkyl, having a total of 2-12 carbon atoms, or alkoxyl s., --Seb.

The preparation of compounds of the general formula (I) was based on a known method, however, it was used in the process of the corresponding initial

Compound; e: 1I11 makes it possible to obtain new compounds, possessing biological properties that are biologically active.

The method of the novel method of substituted biguannda of the general formula (I) or their salts is as follows. that the carbodiimnd of the general formula (II) is R, C N-R2,

where R and R2 have the stated values,

interact with guanidine or its salt, followed by isolation of the cheshva product in the free base or in the form of a salt by known methods.

The method is carried out in an aqueous medium or in an organic solvent medium.

As an organic solvent, for example, methanol, ethanol, n-propanol, isolropanol, ethylene glycol, tetrahydrofuran, dioxane, nitroenzene, aiisol, dimethylformamide and dimethyl sulfoxide are used. The process can also use a mixture of solvents.

The method is expediently carried out at reduced temperatures, for example, at the boiling point of the mixture of solvents used in the solvent process.

The compounds of general formula (I) can be isolated both as free bases and as acid addition salts.

The latter, by interacting them with strong bases, could be translated into free-floating axes and translated into corresponding sources of the sun with a button, for example, such as sol. bromine, hydrogen, nitrogen, sulfuric, phosphoric, methanesulfonic acid, H-thol-olh-sulfonic acid, naphthalene-1,5-dnsulf () K11 Slots, acetic acid, milky, amber, ninn, n nicotine button.

PRI m e) 1. 1,2-day-n.-G) utlG) p wnpd iidroh. Uurnd.

0.715 g (7.5 MMO.ib) gundnnn-hydro.h.yurida, 1.54 g (10 mmol) dn-n-butnlcarbodimpympda, 5 ml of water n 15 MJ methano.la nag) evyut for 16 hours about) atio1 1 fl1mo1 1. Results: 1 slant residue ns-attract 15 M / I of water II three times ext) extract of 20 ml of ether, to give about 10 ml of 1H1Inns as the nochbog;)) duct 1, 2-day-n. -Buti.g-urea.

The aqueous phase is replaced with concentrated | nooiannon hydrochloric acid up to p11 4n and crystallized with iri yrifiiHBaHHH. Crude product with a drop-down point of 102 -105С is contaminated with ei.1, e-thanidium hydrochloride and non-volatile amounts of 1,2-II.-butylurea. His dusky comfort in dried chloroform, ipl1 / grovewax) t the remaining gundium hydrochloride, equilibrate the chloroform solution and in the extract), and solidify the solid residue from adregonitrnla.

The output of 0.42 g (23% of theoretical). Point. Philadelphia 131 13.3 ° C.

H) iiMei; eiuiH of the corresponding carbodiimides and get the following connections: ein:

1,2-d 1Izonr () inlbnguanid Gndrob c) mid, t. Nl. 247-248 ° C;

1,2-diethylbiguaimd hydrobromnd, t. Il. 204 ° C (from ethanol):

1.2-di-i.-buIi.chbiguaiid hydrokh / ju, t. Ii.i. 131 - 1324 (and; agoyiit 5nla);

1-ethnl-2- (2-methylbutnl) -biguayid nor grat, t. Nl. 133.5 --134.5 ° C;

1-me1-2- (2-me1-butbutnl) -bnguaide nitrate, t. Il. 88-90 ° C (from acetointryl);

2-methyl - 1 - l - chlorofeIlbnguanide nitrate, t. 1L. 136-137 ° C (nz water);

2-methyl-1 - // - chlorobenznlbng} anide nitrate, so nl. 152 ° C (nz anetheitrile);

2-methyl-1-p-phenethylbig acid iptrat. t.ch.ch. 117-118 Ch: (from ethanol);

1-ethyl-2-n-ironylbiguaide nitrate, t. 134 ° C (from acetoiitrile);

1-hti, h-2-1i Clofonylbnguanide nitrate, t. 118--119CH: (from adoetointril):

1-ethyl-2-n-butylbnguanide intrat, i.e. 164--165 ° C;

1-ethyl-2-vgo /;.- butylbigua: S1d nitrach-, t. And, h. 183 ° C (nz adetoniiril);

1-ethyl-2-from butnibiguanid nitrate, t. And, h. 183 ° С (lz acetonitrile);

1-eth11l-2-7reg. Butylbpguanide yttrate, t. Nl. 186 ° C (from ethanol);

1-eth2-isopentylbiguand nitrate, so nl. 120--122 ° C (acestonitrnla);

1-ethnl-2-cycloie1 tilb1Ggua11id inirpar, so pl. 157 - 158 ° С (from the Veda);

1,2-di-n.-i) 011plbiguanid nitrate, t, pl. 137 ° C (nz acechonntril);

 Bn.-iroinl - 2 - isonroylbiguanide and nitrate, t. Il. 178C (from ethanol);

2-ethnl- / 2-chlorophenylbnguanide nitrate, so pl. 148- -149 ° C (from acetonitrile);

2-ethyl-1-l-chlorobenzenebiguand nitrate, so pl. (from ethanol);

2-ethnl-1-p-fe11ethylbiguaide nitrate, t. Pl. (nz etaiola);

1-ethnl-2-and.-Butylbiguanidegndrochloride,

t.ch.ch. 132-133 ° C (nz apetoiitrnla); 2-II.-butyl-1-, chlorophenylbiguanide nis-rat, t. Il. 82-83 ° C;

1-ethyl-2-and-hexylbig anide hydrochloride; so nl 124--125 ° С (ns acetoiitrnla);

1 -methyl-2-i.-nronilbiguiid G11drokhlo) id, t. Il. 178-179 ° C (of);

1 -meas, h-2-i. -Butylbiguand hydrohydro.cho) nd, t.ch.ch. (nz nzoiroiaoio.cha);

1 - Methyl - 2-n. Hexylbnguaind hydrochloride, t. Il. 112-113 ° C (from acetonntril); 1-et11l-2-all1 lbigua 1nd hydrochloride, so pl. 155 -1564 (from izoi) oiaiol);

1 - al.ch nl-2-ts bug of the roiil biguaid gdrokhlo) n; 1 "t. Il. 164 --- 1b5 ° C (from acetoiitrile); 1 - ETN.CH - 2 - nzoiroinbiguangnd gndroyodi.d,

so nl 167168С;

1-met.h-2-ethn.chbn1uanid N1ggrach, so n.ch. 140 ° C (nz metai.cha);

1,2-dnal.1ilbngua Nd 1CH1drochloride, t. Il. 147 148 ° C (from nzonronanol); 1-ethyl - 2 - n. - gentbiguayid hydro.chloride, t. Il. 122-123 ° C (GHZ acetoiitrile);

1-mn.ch-2-H.-ixii gi.chbnguaaind gndroh.chorid, t. Il. Ill- 112 ° C (aistonptril);

1 - ethn.ch -2 - n.-ne11ti..chbig aiid gndroh.chorid, t. N, h. 120-12GS (nz acetonntrnla):

1-metn, h-2-i.-pentn.chbnguanid g11D |) ohlo) nd, t.ch.ch. 117-- 118 ° C (nz anetoiich | 1i.cha: ethanol 5: 1);

1-methyl-2-di-cloyroyyl-uaiid hydrochloride, i.d., sludge. 183-184 ° C (from adetonitrile);

1-methyl-2-a. H.chbiguanid gndroh.chorn, t. N.ch. 172--173 ° C (from nzopronanol);

 - allylbnguaiid hydro.chlornd, t. CH1L. 164 (from Acech-Oiitrnla):

1 - ethyl - 2 - n.-ok1CH1. | Bigu1D1d gidroh.chorid, t. And.ch. 115-116 ° C (from adetonitrile);

1-11.-ironi.ch-2-n., Chigu-ainde, t. Il. 122 - 123С (out of; now | oiit) nla); 1-meth.ch-2- (zo11ropnlbituaind N1grat, t. Ill. 137- --138 ° C (nz adetonent.ryl: nzonronanol 70:30):

1-ETN.CH-2- (2-methoxyethyl) -biguanide gndroch. Choride, t. Pl. 124-125 ° C (from acetopitrinla); 1-ethyl-2- (3-methoxynpropyl) -biguanide hydrochloride, t, pl. 119--120 ° C (from acetontdril);

1-methyl-2- (3-butaksipron) -biguanide nitrate, t. Dl. 116-117 ° C (from acetodtril);

1-ethnyl-2- (2-ethoxyethyl) -biguaiaid hydrochloride, t. N.ch. 84 ° C (from addetonitron-ether);

1-eth1 l-2- (6-msoxyhex) 1l) -b gua11pd hydrochloride;

1-ethyl-2-p. Butoxybiguaind nitrate, t. Il. 174-176 ° C (from aqueous solution);

1-eptl-2-tr11fluoroethylbigua 111D g; 1drs). Xlo)) id, t. Pl. 184-185 ° C (from acetonne trans);

1-butyl-2-trifluoroethylbiguand hydrochloride, t.nl. 144-146 ° C (from acetoiitrile);

1-methyl-2-ge11tafluorobutylbngua P1D nitrate, t. Pl. 78-80 ° C (from chloroform).

P) e d eme n z o brete e and u

Method for producing substituted biguaindas of general formula (1)

g, the sum of 2 to 12 parts of a carbon atom, pln alkox) l with C-C, characterized in that the carbodin-imide (1) of the formula (II)

R, -X C, N -R2,

where RI II R: is as defined above, is reacted with guanidine or its salt in a solvent, followed by isolation of the pellet product as free base (1b) 1ip or as a salt by known methods.

P nn o rn et e and pnn 3 n aka m 02.04.71 but to the principle: Ri-saturated or non-saturated hydrocarbon-subnuly norm. Plume is built with Ci-Co. picoolv-mn- -NH:

NVi,

Nl., Mi

OR their soley,

tl RI is iascheal or unsaturated1 a hydrocarbon group of normal or isostroy with unsubstituted substituted by one NLP with several atoms of fluorine, cycloalkyl with C3-Senyl residue

-U-H, n 0.1 ilp 2; X is hydrogen or halogen,

R2 is saturated or unsaturated} 1a hydrocarbon group of normal or nzostroy1. CH1I with C | -Ci2, unsubstituted pln replaced) with one or more fluorine atoms, cycloalkl with CG, alkoxcryl,

n, P1 residue

where / g 0.1 and tn 2; X is hydrogen, n is halogen; R2 is a saturated nln neeeei1, en11a hydrocarbon chain, but iso nly iso isostrate with incloalkyl with C; g-Co.

03/31/72 but for the following: Ri is a saturated or non-saturated aromatic hydrocarbon group of Pormalto nnln 13ost)) e11 and s (--- Ci2 nli saturated nln unsaturated hydrocarbon group of tiogo or is built with Ci-Ci2, substituted by one or several fluorine atoms; R2 is an unsaturated hydrocarbon subsoil Iorma. Tyugo or Msc) is built with C – C; nmeyushny in the sum of 2 - 12 angular. atom atoms or alkoxyl with Wed C.