SU644383A3 - Method of obtaining thionyl chlorides - Google Patents

Description

(54) METHOD OF OBTAINING SUIFFILUSTERS

 - - -one, - , .

This invention relates to a process for the preparation of non-standardized sulphyl chloride sulphides of the general formula

H, .SOCl

TJ er

Q "1

about coolg

.

where 4f is an imido group of the formula R

ABOUT

where Bj is alyuvglen 1,2-fenshlen or a group of the formula, where R is hydrogen, alkyl, phenoxymethyl, thienylmethyl, benzyl, benzyl oxane, 4-nitrobenzyloxn ,. toxibenoploxy, o {.- (gret butyloxancarbonylamino) - "benznl nli vmidazolv dinyl group of the formula O

RS

Yb1 -} - C%

SNS

where phenyl, unsubstituted or aa-compound .1y one or two halo atoms of reHa, Rg - a nigroso or acetyl group on the basis of the formula

about

but.

Hi

in, with about

 alkyl, haloalkyl С С, alcohols Q-С) 2,2,2. trichloro egoxygroup, d - has the above meaning, Hg - ankyl, bei "zil, nd-nitrobenzyl, benzhydryn, 2,2,2trnchloretil, KOTojaie can find Privevenne as intermediates in the synthesis of biologically active compounds / synergies.

Claims (3)

There is a known method for the preparation of methyl 4St chlorine 1, where 1 phthalimido group is concluded that the penicillin sulfoxide of the formula CH3 00COOR is reacted with sulfuryl chloride in carbon tetrachloride De 1. However, this nb method is applicable to the synthesis of sulfinyl chlorides in a formula I, and you can apply for you. other than phthalimide. The purpose of the invention is a process for the preparation of sulfinyl chlorides of the general formula I, possessing valuable properties; It. This is achieved by the proposed method for the preparation of sulfinyl chlorides of the general formula 1, STO5PTsIM in that penicillin sulfoxide of the general formula D. / 0 GOOB. 2 where (and have the above meaning, they are reacted with M-halogenate agent in an anhydrous inert solvent at a temperature of 75-135 C. As N-halogenating agent, preferably N-chlorosuccinimide, N-3SL phthalimide or N-chloro-N-methyl -C-toluenesulfamide. An aromatic hydrocarbon or a halogenated hydrocarbon is preferably used as a solvent. Example: Methyl-3-methyl 2- (2-glorosulfinyl-4-oxo-3-phthalimium to -2-azetidinyl) "- 3- butenoate. A solution consisting of 18.8 g (50 mmol) methyl-6-1 (-phthalimide- 2, 2-Dimethylpenam-3-carboxylate of 1-oxide and 6.7 g {5O mmol) N-chlorine of ciniimide in 1000 ml of dry carbon tetrachloride, boil for 70 minutes, then cooled, washed with water and brine, dried with magnesium sulfate, then the solution is evaporated and 19.5 g (95%) of the desired product is obtained, which is a colorless solid substance. PMR (CDCe,); 1.97 (broad C, h 3.86 (C, 3 ) j 5.05 (broad C, 2); 5.2 (d, 1; 02 Hz): 5.77 (, 1, L 4 Hz, 5.9 (d, 1, 04 rii) and 7.83 (n, 4 PRI mme R 2. I, Yitrobenzyl-3methyl-2- (2-chlorosulfinyl-4-oxo-3ftame limit-1-azeton dn) -3-butenoate. A solution consisting of 49.7 g of p, 1 mol) P-nitrobenyl-6-N-phthaimido-2, 2-dimethylpenes-3-carboxylate l-oxides and 13.4 g (O, 1 mol) of N Lorsuktinimid in 1.5 liters of 1.2 × 1-chlorotane are boiled for 7 затем minutes, then the mixture is cooled, washed with iodine, and dried with saline acTBopoMj magnesium sulfate. The solution is then evaporated, the residue is dried in vacuo for 3 hours, 52 g of the product are obtained. PMR (013Sece, s): 1.97 (C, 3); 5.05 (C, 1) 5.4 (C, 2); .5.76 (d, l, Ob Hz); 5.91 (d, 1, 3 5 Hz); 7.83 (t, 8), EXAMPLE 3. h Nitrobenzyl-Zmethyl- 2- (2-lorsulfinkl-4-oxo-. 3phenoxyacetamido-1 azetidinyl) -3 butenoate. . A solution consisting of 500 mg (l mmol) P-nitrobenzyl-6-N-phenoxyacetates to 2,2-dimethylpen.m-3 carboxypag -1-oxy and 134 g (l mmol) of N-chlorosuccinimide in 4O ml of dry 1 , 1,2-trichloroethane, boiled for 9O minutes, then the mixture is cooled, washed with water and brine, and then the solution is evaporated in vacuo to give the product c. the output of the most theoretical. PMR (CDCe3, cf): 1.9.1 (wide C, h), 4.53 (s, 2) 5, O5 (wide C, l); 5.23 (m, 2) 5.33 (s, 2) 5.57 (d, 1, D 4.5 Hz) 6.18 (d, 1, 3 4.5 Hz) and 6.9 - 8 r (m, 9). EXAMPLE 4 P-Nitrobenzyl-3-methyl-2- (2-chlorosulfinyl-4-oxo-3-phenoxyaceg to do-1-nitro-dinyl) -3-bougainate. A mixture consisting of 6 g (12 mmol) of N -nitrobenzyl-6-phenoxy-acetamido-2, 2-dimethylpenam-3-carboxypag-1-. o-oxide in 50 ml of dry toluene was boiled for 10 minutes using a Dean-Stark trap to remove traces of water. After distilling off all the water, 1.8 g of N-chlorosukinimide are added and boiled for 90 minutes. This mixture is cooled to 50 ° C and evaporated ..,. EXAMPLE 5 P-Nitrobenzyl-3-methyl-2- (2-chlorosulfinyl 4-6 x co-3-forms up to 1-aa dyn; br) -3-butenoate. A solution consisting of 1.43 g of pnitrobenzyl-6-formamiao-2, 2-dimethylpenam-3 carbaum: silate-1-oxide and 5OO mg N-chlorosuccinimide in 4 ml of 1,1,2trichloroethane is boiled for 90 min, cooled down , washed with water and brine with a solution, dried with magnesium sulfate and then the solvent is evaporated. PMR (): 1.91 (broad C, 5.03 (broad C, l); 5.20 (m, 2); 5.34 (s, 2); 5.62 (d, 1, 4.5 Hz ); 6.12 and 6.3 (KB, 1, 3, 4.5 Hz) and 7.4--8.4 (m, 4). EXAMPLE 6; 2,2,2-trichloroethyl-. 3-methyl-2 -. (2-chlorosulfinyl 4-oxc-3-phenylacetamido 1-acetide 1) 3 butenoate. A solution consisting of 500 mg of 2,2,2-trihloregil-6-phenylaceta to -2, 2-dimethylpenam -3-carboxylate-1-.ox si and 134 mg of N-chlorosuccinium-imide In 40 ml of toluene is boiled. 90 Mmi, then the mixture is cooled, washed with water and brine, dried with magnesium sulfate and the solvent is evaporated, the desired product is obtained in the form colorless foam PMR (cf): 1.90 (s, a); 3.55 (C, 2); 4.8 (Gy, 2); 4.95 (d 1, 5 4.5 Hz); 5.03 - 5.21 (t, W), 5.65 and 5.70 (KB, 1, 34.5 Hz); 7.3 (C, 5) and 7.5 (cl, NH, L. 10 Hz). EXAMPLE 7. Methyl-3-methyl-2 - {2 chlorosulfinyl-4-oxo-3- (2,2-di "methyl 3 nitroso-5. oxy 4 phenylimidazolidine 1-yl) -l-azethinyl-3-3-butene, To 55 ml of dry benzene, which was further dried using azeogropic removal of moisture, was added 0.896 g (2) methyl 6 -. (2.2) -.Dymethyl-3-nitroso-5-oxo-4-phenylimidazolidine-yl) -2,2-dimethylpenam-3-car boxyl-1-oxide and 0.536 g (4 mmol N-chlorosuccinimide, boil for one hour in nitrogen atmosphere. After distilling off the solvent, I get the target product. Example 8. Metnl 3.methyl 2- (2 Chlorosulfinyl 4-oxo-3-phthalimido -1-azetidinyl) -3-butenoate. To 300 ml of carbon tetrachloride are added; - 3.7 g (U mmol) methyl 6-phthalimide O 2,2-dimethylpenam-3-carboxylate-1-oxide and 2.2 g (U mmol) N-chloro-N -methyl- and toluenesulfbnamide, boiled for 9O minutes, cooled to room temperature, washed with water and brine, dried with magnesium sulfate, evaporated in vacuo, the desired product was obtained. PMR (CDCEj cf): 2.0 (s, 3, allklivy SC) 3.84 (Ci 3, C-ether); 5.1 (s, 2 vinyl CHg); 5.2 (C, 1, C4-H) and 5.6-6.0 (t, 2, C – H and C – H). Example 9. P-Nitrobenzyl-3 I TSH1-2- (2-chl orsulfinyl-4 oxo-3 phenoxy-iamido-1-azetidish1l) -3-butenoate. . To 15O ml of toluene distilled and passed through a molecular sieve (zeolite), 3 g (b mmol) of P-nitrobenzyl-6-phenoxy-acetamido-2, 2-dimethylphenam-3-carboxylate-1-oxide and 1.3 (b mmol ) N-chloro-M-methyl-p-toluenesulfonamide, boil for 60 minutes, cool to room temperature, wash with water and brine, dry with magnesium sulfate and evaporate to dryness in vacuum. PMR (C1) Sec,): 1.88 (C, 3 allyl CHji); 5.0 (s, 2 vinyl CH) and 5.12 (s, 1 allyl H). Example 1O. p-Nitrobenzyl-3-methyl-2- (2-chlorosulfinip-4-oxo-3-phenoxyacetamido-1-azetidinyl) -3-butenoate. 425 ml of toluene are heated with a Dean-Stark trap to azeotropically remove moisture that may be present in toluene, a total of 25 ml of toluene are distilled off. To the remaining part of toluene, 1O g (20 mmol) of h-nitrobenzyl-6-phenoxyacetamido-2, 2-dimethylpenam-3 carboxylate-1-oxide was added, and the temperature of the reaction mixture was kept slightly lower than the temperature of 1000%, and 2OO ml of toluene was distilled and 4 g (22 mmol) of N-chlorophthalimide was added, the resulting solution was added to the penicillin sulfoxide ether solution for 30 min, 55 MiiHj was boiled and the desired product was isolated; yut as usual. Example 11-Benzhydryl-3-methyl-2- (2-chlorosulfinyl-4-oxo-3-phenoxyacetamido-1 azetidinyl) -3-butenoate. To 80 o ml of toluene, 20 g of benzgi-dril-6-phenoxy-acetamido-2,2-dimethylphenam-3-carboxylate-1-oxide was added, boiled with a Dean-stark nozzle, 10O ml of toluene was distilled off. To the mixture thus obtained was added 13.2 g of M-chlorosuccinimide, boiled for 1.5 hours, obtaining the desired product. PMR (CDCe, c): 1.88 (C, h); 4.53 (C, 2); 4.90 (C, l) 5.14 (C, 2); 5.54 (s, l); 6.24 (d, 1, J 4 Hz); 6.95 (C, l); 7.15-7.4 (m, IS) and 8.0 (d, 1, 3 8 ha). Example 12. n) bnnzyl 3 "m br-2. (2..shorsu / shfynil-4 oxo. 3" -adbgoamndo-1 "azetidynal) -3. Outlet Toluene (SOO ml) is boiled with a nozzle of Dean Sgarka for the azeotropic separation of moisture from toluene, 1 g (2.4 mmol) of P-ntrobenzyl-6 acegamide-2,2-S1metwine 3-carbox lat-1-oxide, JKHHHtsf with a Dean-Stark nozzle is added to the toluene-dehydrated toluene, to bdeyd moisture present in this mixture. The mixture is cooled and 400 mg (2.9 mmol) of sukainimide, KHRHTsiT is added to it for 1 hour, then the solvent is evaporated. PMR (CDCgj c): 1.86 (broad. C, h) 2, O4; 2.09 (C, s); 4.80 (No. D 5.2 (t; 2); 5.28 (C, 2) 5.63 (p.1) 6.05 (d. 3 4 HZ and 7.4-7.8 (JCB., 4) .- .. -: V- EXAMPLE 13. 252.2 p1alor9Tyl 3 mety 2- - 31 "yorsulfne; -4-), 3 (4.H; B robenyloxycarbamido) -1. Azetidynp - Z-Yoat. A mixture consisting of 300 ml of 1.1.2 pounds of Oryotan and 10.26 g of 2.2.2 tr of AHp. (4 Nitro6enzyloxy-Urea) .2,2 Dymetish1enam 3 karbokstat 1bKySy, KyNyt T to remove approximately 75 ml of solvent for the purpose of dewatering the reaction medium. Dyeb L mixture, add 4 g of N of HyorsuchIe and propylene OXIDE. The temperature of the mixture is increased to 102 ° C and the resulting mixture RmtHTsjT 2.5 hours they yut as.: PMR (CUCej tJ): 1.94 (shi {yukai s, h) 4.83 (p. 2); 5.25 (s, 2), 5.0.5,4 (m, h) ; 6.20 (d. 1, 3 4 Hz), - 7.55 (a, 2, 1 8 Hz) and 6.24 (a 2, 3 9 Hz) And p and measures 14. P. 3 "methium-2 2" 4 4-oxo.3-. -SM-4 inoxiaethenl) M -. (2.2.2 trusylorg ethoxycarbonyl amnno) 1 "azeti datyl - 3 buteabat. A mixture consisting of 4.885 g (U mmol) h-neutr6benzyl-5-phenoC Siatsvtamy Do-2,2-dvmetilpenenam 3 carborksilata, 16.94 (8O mmol) 2,2,2i ". - trvichloroethyl chloroformate, 18 mlM, 0- (bass trimethylsilide) - trifluoromethylai-amide n 20 ml of methylene chloride, left at an acid temperature for a note, the mixture is boiled for 7 hours, then left at coagate temperature S overnight, heated then for 6 hours. The mixture is evaporated to dryness, the residue is dissolved in benzene and the solution is added to an excess of heptane. The undissolved residue is filtered off, dissolved in benzene and chromatographed on silica gel using a benzene methyl peptide to elongate, to obtain 4.76 g of P-nitrobenzyl-6-N (phenoxyacetyl) -N - (2,2,2-trichloroetho-sycarbonyl) - amyne -2,2-dimethylpenam-3-carboxylate, yield 72% of the theoretical. PMR (cf): 1.41 (s, h) 1.62 (s, h); 4.61 (s, 1) 4.84 (d, 1, 3 12 Hz); 4.99 (d, 1, 3 12 Hz); 5.20 (C, 2) 5.30 (s, 2) 5.56 (C, 2); 6.8-7.4 (W, 5) j 7.53 (d, 2, 3 9 Hz) and 8.22 (d, 2.39 Hz). ; 2.54 g (3.84 mmol) and -nitrobenzyl 6-H-. (Phenoxya-yethyl) -M - (2,2,2-trchisloxglysarbonyl) & aMnHcj - 2,2-dimetiLpenam 3- the carboxylate, the mixture is cooled to -70 ° C and the excess amount of Ozoa is fed into the reaction mixture for 9 minutes at a feed rate of 1.17 mol / min. This mixture is cured for 35 minutes at 7 ° C, after which it is heated to room temperature and the solvent is distilled off in vacuum, to obtain 2.76 g ft of nitro-benzyl-6-H h- (phenrcci-cetyl) (2.2, 2-trichloroethoxycarbryl) g mino} - 2.2 "-dimethylpenes-.3" carboxylate-1KNSI ... - .- in PMR (5): 1.22 (s, h); 1.62 (C, s); 4.60 (C, 1); 4.78 (d, 1, 3 5 Hz); 4.93 (s, 2); 5.26 (C, 2); 5, ZO (C, 2) f 593 (a, 1. 5 1 Hz); E.8-7.4 (Itt, 5); 7.51 (d, 2. 3 9 Hz) and 8.20 (d, 2, 3 9. ha). 792 mg of obtained iieiaecTBa and 155 mg (piKono 1.2 mmol) of N-chloroskshmvda are added to 40 ml of benzene, the mixture is boiled in the usual product. PMR (): 1.92 (C, C ); 4.87 (C, l); 4.96 (C, 2) 5.05 (s, 2); 5.23 (C, 2) j 5.26 (s, l) {5.34 (s, 2); 5.64 (d, 1, a 5 Hz) 5.95 (d, 1, 3 5 Hz); 6.10 (d, 1, 3 5 Hz) 6.8-75 (t, 5); 7.56 (d. 2, 3 9 Hz) and 8.23 (d, 2, 3 9 Hz). Prnm in p 15. 2,2,2-Trichloroethyp-3 methyl 2 C2-chlorosulfinI№-4-oxo-3- (ot-tert, butyl oxlcarbonylmimnophenylacetamido- (1-azeTydynil)} - 3-buteHoat. Solution 2.85 g (5 mmol) 2,2,2-trichloroethyl-6- (oC-tert.butyloxycarbonylaminophenylacetamido) -2,2-dimethylpen-3-darboxylag-1-hydroxya in 175 m of toluene is dried with azeotropic distillation of about 50 ml toluene. To the dehydrated solution, 0.685 g (5.5 mmol) H-chlorosuccinimide is added, boiled for 7 O min., cooled to room temperature, filtered, the solvent is evaporated in a vacuum to dryness and get the left product. (): 1.4O (p. 9, tert, butyl), 1.95 (s, 3 CH (CH) 4.82 (broad C, 2, -compound ether, CH)} 5.20 (W, 3, СН (СН СН СООСН СВВЗ); 5.38 (s, 1.3 g of azetidine Cg H), 5.80 (W, 1, azetidinone Cz, -N) and 7.34 (s, 5 Agn.) Example 6, 2,2,2 Trichloroethyl-3-methyl-2- 2-chlorosulfinyl-4-oxo-3- (2-thienylacetamido) -1- "5%; and -3-butenoate. Solution 3, 5 g of 2,2,2-trichloroethium-6 (2-trienylethamido) -. 2,2-dimethylpenam-3-carboxylate-1-oxide in 350m of toluene is dried by azeotropic distillation of 10O ml of toluene from the mixture, then cooled and added 1 g N-chlorosuccinimide, boiled for 5 ° min, cooled and filtered, the desired product is isolated. usually. PMR (CDCEg, d); 1.87 (s, 3, CH (CU-CT, 3.82 C, -2 side chain CHj); 4.80 (d, 2, 3 13 HZ - 5.18 (t , 3, -.CH (CHj) CH2; 5.50 (d, 1, 3 4.5 Hz, azetidinone Cg-H) and 6.05 (I1, Ij azetidinone C, - H). Formula 1. The method of obtaining sulfinylchlorides of the general formula B.SOC1 0 / -sne CHg I, COORgО where K. is an imido group of formula B. N where Rj is alkylene C ,, is C or 1,2-4 enile or a group of the formula where R 4 is hydrogen, alkyl C-C phonox methyl, thienylmethyl, benzyl, benzyloxy 4-nitrobenzyloxy, 4-methoxybenzyloxy, ° C (tert-butyloxycarbonylaminphenyl, or a kmidazolidinyl group of the formula where Rj is phenyl, unsubstituted or substituted with one or two halogen atoms, a TRg-nitroso or acetyl group, or a group of the formula where RY is t 3 haloalkyl, alkoxy Cj-Cg and 2,2,2-trickle-loroethoxy, R is as defined above, and alkyl C. -C ™, f, e, benzyl, P-neybönzyl, benzhydryl, 2,2,2-trI7sorethyl, I differ from the fact that penicillin sulfoxide is a sheer formula of the% -H-NFR, o- Y 1, SOOVz where R and Rg have the above meaning, interacting with the N-halo eneruccin agent in an anhydrous inert solvent at a temperature of 75-135 s. 2. The method according to claim 1, about g and h and yu and the fact that as N-halogenating agent use N lorsuccinimide, N-chlorophthalimide or N-chloro-N-methi-n-toluenesulfamide. 3. The method according to years. 1, that is, with the use of aromatic hydrogen or halogenated hydrocarbon as a solution. 12/24/74 at T1., - imidrgroup forums In N where fJj-alkylene with C or 1,2-} 1lenylene, or a group of the formula H4C: ONH. hydrogen, alkyl, phenox, kyutyl. benzyl, benzylox, 4-nitrobenzoxyl, 4-methoxybenzyloxy, thienyl metvl, oL- - (tert, butyloxy carbonylamido) benzyl or imioazolidinyl group of formula R € i- | -CHN, CHj gae -efile, unsubstituted or substituted by one or two halo & aethe, R -nitroso or acetyl group 6 312 pa, -anan. benzyl, P-nitrobenzyl, benzhydryl, 2,2,2-trichloro9til. 11.11.75 with R-group where R has the above meaning, R.J-all C, -C ,, haloalkyl, ashssky C-C or 2,2,2-trichloratoxy group.