SU535303A1

SU535303A1 - The method of obtaining derivatives of 1,4thiazine

Info

Publication number: SU535303A1
Application number: SU2124743A
Authority: SU
Inventors: Нина Кузьминична Гусарова; Галина Григорьевна Ефремова; Светлана Викторовна Амосова; Борис Александрович Трофимов; Михаил Григорьевич Воронков
Original assignee: Иркутский институт органической химии СО АН СССР
Priority date: 1975-04-02
Filing date: 1975-04-02
Publication date: 1976-11-15

Description

1one

Изобретение отпоситс к улучшенному способу получеиь производных 1,4-т :аз1Н1а, которые могут найти применение в качестве биологически активиых веществ.The invention is in favor of an improved method for preparing 1,4-t: az1H1a derivatives, which can be used as biologically active substances.

Известен сиособ иолучеии 4-оргаиилтетрагидротиазин-1-оксидов , в частности 4-циклогексаитетрагидротиазии-1-оксида взаимодействием эквимол рных количеств дивинилсульфокс да с циклогексиламином в этаноле при кип чении.4-orgaiyl tetrahydrothiazin-1-oxides, in particular 4-cyclohexitra-tetrahydrothiazium-1-oxide, are known to interact with equimolar amounts of divinylsulfox and cyclohexylamine in ethanol at boiling.

Недостатком известиого сиособа вл етс иевысокий выход целевого продукта (не выше 50%) 1.The disadvantage of a lime sieve is the high yield of the target product (not higher than 50%) 1.

Целью изобретени вл етс повышение выхода целевого продукта и расширение ассортимента получаемых продуктов. Поставлениа цель достигаетс описываемым способом получени производных 1,4-тиазина общей формулы IThe aim of the invention is to increase the yield of the target product and expand the range of products obtained. The objective is achieved by the described method for the preparation of 1,4-thiazine derivatives of general formula I

ItIt

ОABOUT

где R-бутил, циклогексил или беизил, взаимодействием дивипилсульфокспда, вз того в избытке, с соответствующими аминами.where R is butyl, cyclohexyl or beisyl, by the interaction of dipipelsulfoxpd, taken in excess, with the corresponding amines.

Отличительными признаками способа вл етс нроведение нроцесса с пспользованпем избытка дивинилсульфоксида по отношению к амину и расширение ассортимента получаемых производных 1,4-тиазииа.Distinctive features of the process are the reduction of the process with the use of an excess of divinyl sulfoxide with respect to the amine and the expansion of the range of the obtained derivatives of 1,4-thiazia.

Предпочтителен двукратный избыто;-; дивпиплсульфокснда но отношению к .Twofold excess is preferred; -; Dips pills sulfoxs but with respect to.

Прои,есс провод т в отсутстви растпорит,:-л , нрн медленном добавлении nr.niiia к .)нилсульфоксиду , ирн 65-75°С.The proi, ess is carried out in the absence of rasporit,: - l, nrn slow addition of nr.niiia to.) Nilsulfoxide, irn 65-75 ° C.

Пример 1. К 20,4 г ,И ЛСуЛЬ(;ОКС:1ДЛExample 1. To 20.4 g, and LSUL (; OKS: 1DL

медленно (1 моль/ч) ирг; 35--40 С иппбппл ют по капл м 7,5 г бутила.м1;1;а. Рсзкгмси иую смесь нагревают при 70°С и течение 5 ч и фракционируют. Перегонкой выдел ют 5,5 гslowly (1 mol / h) irg; 35--40 C hippleblut dropwise 7.5 g butyl.M1; 1; The mixture is heated at 70 ° C for 5 hours and fractionated. 5.5 g is recovered by distillation.

неирореагировавшего дивинилсульфоксида и 16,8 г (выход 95%) 4-бут1 Лтетраг1;дротиазии 1-окснда, т. кнп. 106-10-8°С (5-1П-з рт. ст.). Найдено, %: Н 9,65; С 54,68; N 7,64; S 18,27.non-reacted divinyl sulfoxide and 16.8 g (95% yield) 4-but1 Ltetrag1; drotyasia 1-oxnda, t. knp. 106-10-8 ° С (5-1П-з рт. Ст.). Found,%: H 9.65; C, 54.68; N 7.64; S 18.27.

CsHuNSO.CsHuNSO.

Claims

Vychnsliso,%: C 54.76; P 9.77: l 7.99; S 18.02. The PMR spectrum of the compound contains a complex multiplet of the methylene protons of the CHa – CHj tHr – S CHg – CH / fragment in the region of 2.25–3.1 ppm, the methylene proton multi-flight of the CH3 CH2 – CH2 radical in the region of b 1.15–1.62 ppm and a triplet of methyl protons with a center b of 0.94 ppm The ratio of the integral intensities confirms the structure of the obtained cyclic aminosulfoxide. Example 2. To 10.2 g of divinyl sulphoxide, 3.7 g of secondary butylamine was slowly added. The reaction mixture is heated at 65-70 ° C for 4 h and fractionated. 3.8 g of divinylsulfoxide and 8.1 g (92%) of 4-sec-butyl tetrahydrothiazine-1-oxide, t. Bale, are isolated by distillation. 125-126 ° (1 mm of mercury), 1.5400; df 1.0618. Found,%: C 54.77; H 9.95; N 8.41. CsHirNOS. Calculated,%: C 54.76; H 9.77; N 7.99. The PMR spectrum confirms the structure of the compound obtained. Example 3. To 10.2 g of divinylsulfoxide, slowly at 50 ° C, 5.9 g of cyclohexylamine are added dropwise. The mixture is heated at 65-70 ° C for 4 hours. 3.7 g of unreacted divinyl sulfoxide is isolated from the reaction mixture by distillation. The residue is recrystallized from heptane to obtain 10.9 g (90%) of 4-cyclohexyltetrahydrothiazine-1-oxide, which is a light yellow needle-shaped crystals, m.p. 68-68.5 ° C. According to literary data, m. Pl. 4-cyclexyltetrahydrothiazin-1-oxide 68 ° C. Found,%: C 59.87; H 9.54; S 15.72; N 6.91. CioHigNSO. Calculated,%: C 59.61; H 9.51; S 15.92; N 6.95. Example 4. To 10.2 g of divinyl sulfoxide heated to 40 ° C, 5.4 g of beisylamine was slowly added dropwise. The reaction mixture is heated at 70-75 ° C for 3 h and fractionated. By distillation, 3.4 g of divinyl sulfoxide and 9.4 g (90%) of 4-benzyltetrahydrothiazine-1-oxide, which is a viscous ruby-colored liquid, m.p. b.p. 154-155 ° (6-10-3 mm Hg. Art.). Found,%: C 64.89; H 7.03; N 6.43; S 16.30. CnHisNSO. Calculated,%: C 63.12; H 7.02; N 6.68; S 15.31. The PMR spectrum of the compound contains a complex multiplet of the methylene protons of the tetrahydrothiazine ring with a center at b 2.71 MD, the singlet of the methylene protons of the benzyl radical is 3.47 ppm. and multiplet feiil protons (b 7.47 ppm) The ratio of the integral intensities affects the structure of the obtained tetrahydrothiazinoxide. The invention provides a method for producing 1,4-thiazine derivatives of the general formula I, where R is butyl, cyclohexyl or benzyl by reacting divinyl sulfoxide with the corresponding amines when heated, which means that in order to increase the yield of the target product and to expand the range of products obtained, in relation to the amine.

2. A method according to claim 1, wherein, a twofold excess of divinyl sulfoxide is used with respect to the amine.

3. The method according to claim 1, wherein the process is carried out at 65-75 ° C. The source of information taken into consideration during the examination: 1. B. A. Arbuzov et al. 4-Organyltetrahydothiazin-1-oxides, CHC, 1972, (3), 410.