GB2122629A

GB2122629A - Novel silyl derivatives

Info

Publication number: GB2122629A
Application number: GB08316273A
Authority: GB
Inventors: Roger Crossley; Robin Gerald Shepherd
Original assignee: John Wyeth and Brother Ltd
Current assignee: John Wyeth and Brother Ltd
Priority date: 1982-06-25
Filing date: 1983-06-15
Publication date: 1984-01-18
Also published as: GB8316273D0; GB2122629B

Abstract

New silyl derivatives of 5,6,7,8- tetrahydroquinolines are substituted at the 8-position by the group SiR3 where R may be one of various hydrocarbon groups or an electron donating substituent. The 8-position may also carry a lithium, sodium or potassium atom. The new silyl derivatives may be prepared by treating a corresponding 8- lithio, sodio or potassio tetrahydroquinoline with a silyl halide R3SiHal followed by a metal compound R*M where M is sodium, potassium or lithium and R* is alkyl, cycloalkyl, aralkyl or aryl or an amine residue. The new silyl derivatives are useful intermediates for the preparation of known 5,6,7,8-tetrahydroquinoline-8-nitriles, amides and thioamides employing an alkyl silyl isothiocyanate or cyanate. The nitriles and thioamides are anti- ulcer agents. The Related compounds may be made by analogous methods, and are also new.

Description

SPECIFICATION Novel silyl compounds The invention relates to novel silyl derivatives of fused carboxyclic ring derivatives of pyridine and processes using the novel derivatives.

In our United Kingdom Patent Specification No. 1463666 we described a process for preparing tetrahydroquinoline-8-thiocarboxamides, nitriles and carboxyamides and related compounds by treating a corresponding sodio, lithio, potassio or magnesium halide derivative with a silyl compound of formula RxSi(NCY)4-x wherein R is alkyl, aryl or aralkyl, Y is oxygen or sulphur and x has a value from 0 to 3 and subjecting the product to hydrolysis or alcoholysis. The reaction is conducted under anhydrous conditions preferably in an inert solvent for example a hydrocarbon solvent such as benzene, toluene or n-hexane. This is very short route for preparing tetrahydroquinoline 8-thiocarboxamides directly from the above mentioned metal derivatives of the corresponding tetrahydroquinolines. However we have found that the overall yields are usually lower than 50%.After extensive research and investigation of this reaction we have discovered that better yields can usually be obtained by using a novel silyl derivative of the tetrahydroquinoline or related compound and novel metallated derivatives thereof.

Accordingly this invention provides in one aspect, new silyl compound offormula I.

wherein R1, R2, R3, R4 and R5 are the same or different and represent hydrogen or alkyl, cycloalkyl, aralkyl, or aryl radicals, any of which radicals may be substituted, or R1 and R2 taken together, or R2 and R3 taken together, form a 5, 6, or 7 membered ring which may be saturated or unsaturated and substituted or unsubstituted, and when R1 and R4 form a ring, the ring has the same number of carbon atoms as the ring carrying R4,R4 and R5 may also represent alkoxy, n is 1,2 or 3 and Xis hydrogen or lithium, sodium or potassium and R is alkyl, cycloalkyl, aralkyl or aryl or R is selected from electron donation substituents including alkoxy, cycloalkoxy, aralkoxy, aryloxy, alkylthio, cycloalkylthio, aralkylthio, or arylthio of the group RbRCN- wherein Rb and Rc are selected from alkyl, cycloalkyl, aryl and aralkyl or Rb and RC may be joined to form a heterocyclic ring with the nitrogen atom (eg., a piperidinyl or pyrrolidinyl ring, which may be substituted eg., by alkyl).

The groups R are not necessarily all the same but it is preferred that SiR3 is tri-loweralkyl silyl or more preferably trimethyl silyl.

When any of R1, R2, R3, R4, R5 or R is an alkyl radical it is preferred that this is a lower alkyl radical of 1 to 6 carbon atoms which may have a straight or branched chain eg., methyl, ethyl, n-and iso-propyl and n-, s- and t- butyl. When R, R4 or R5 is an alkoxy radical it is preferred that the radical is lower alkoxy in which the alkyl portion has 1 to 6 carbon atoms and is as defined above, from an alkyl radical.

When any of R', R2, R3, R4, R5 or R is a cycloalkyl radical such radicals having from 4 to 6 arbon atoms are preferred ie. cyclobutyl, cyclopentyl or cyclohexyl.

An aralkyl group may be an arylalkyl group in which the alkyl portion is as described herein for an alkyl group. Preferred aralkyl groups are those having from 7-12 carbon atoms.

When any of R1, R2, R3, R4, R5 or R is an aryl group it is preferably phenyl or substituted phenyl (substituted by eg., alkyl, alkoxy, ortrifluoromethyl.

Preferably the compound of formula lisa tetrahydroquinoline derivative ie n is 2.

The compound of formula I may be prepared by treating a compound of formula II

wherein M is sodium, potassium or lithium, and R1, R2, R3, R4, R5 and n are as defined in connection with formula I with a silylating agent of formula R3SiHal where R is as defined previously and Hal is chlorine, bromine or iodine to obtain a compound I, wherein Xis hydrogen, and if desired treating this with a metal compound R*M where M is sodium, potassium or lithium and R* is alkyl, cycloalky, aralkyl or aryl or an amine residue, to obtain a compound of formula I where M is sodium potassium or lithium.

The above reactions may be carried out any suitable reaction medium solvent. Thus the first stage is conveniently carried out in a reaction medium comprising an ether solvent, preferablytetrahydrofuran but other cyclic ethers eg., dioxan, may be used or dialkyl ethers, wherein the alkyl group has from 1 to 6 carbon atoms eg., diethyl ether. Other reaction media which may be used are hydrocarbon solvents such as benzene, toluene or n-hexane. The reaction medium may comprise two or more of the above solvents.

Conveniently the starting material of formula 11may be prepared in situ by reaction of a compound of formula II, wherein M is hydrogen with a suitable organometalic compound such as an alkyl, aryl or aralkyl lithium, sodium or potassium compound as described in UK Patent Specification 1432378 or using the modification described in UK Patent Specification 1463666, wherein a metal amide is reacted with a compound of formula II wherein M is hydrogen.The metal amide may be formed in situ and may be any of those described in UK Patent Specification 1463666 viz. an amide derived from a secondary amine such as a dialkylamine eg., diethylamine, di-isopropylamine, ditertiary butylamine, di-n-decylamine, dicyclohexylamine, N-t-amyl-N-t-butyl-am ine, N-isopropyl-N-cyclohexylamine, or N-(1 -ethyicyclohexyl)-1 1,3,3,- tetramethylbutylamine or a cyclic compound eg., piperidine, or 2,2,6,6-tetramethylpiperidine. Alternatively any of the metal amides described in our co-pending UK Application 8306456 filed 9th March 1983 may be used.These metal amides have the formula Ill

wherein R14 is a straight or branched chain alkyl group of 1 to 6 carbon atoms or an aryl group, R11 is hydrogen, aryl or a tertiary alkyl group of 4-6 carbon atoms, R12 is aryl or a tertiary alkyl group of 4-6 carbon atoms, R13 is a branched chain alkyl of 3 to 6 carbon atoms; X' is lithium, sodium or potassium. These metal amides are conveniently prepared by a novel process describes in UK Application 8306456 namely reacting a compound of formula IV.

wherein R11, R12 and R13 are as defined above with a metal alkyl MR14 where R74 is as defined above and M is lithium, sodium or potassium, in an inert non-polar solvent to obtain a compound of formula Ill.

Since the starting compound of formula II is conveniently prepared in situ using the metal alkyl in a hydrocarbon solvent and the silylation reaction is conveniently carried out in an ether, the reaction medium will often comprise a hydrocarbon/ether solvent. Furthermore when a compound of formula I wherein Xis sodium, potassium or lithium is desired the reaction with the metal compound RM may be carried out by adding the metal compound in a hydrocarbon solvent, e.g., n-hexane, to a solution of compound I where Xis hydrogen, prepared in situ. As will be apparent a metal amide, such as one discussed above, may be used as the RM in the preparation of a compound of formula I where Xis sodium, potassium or lithium. However, there will not normally be any advantage in using a metal amide and it is preferable to use a metal alkyl, aryl or aralkyl in both the preparation of the starting compound of formula Il and the end product of formula I where Xis sodium potassium or lithium.

The new chemical intermediates of formula I may be used in various chemical processes which are all included in the invention.

Accordingly this invention provides in one aspect, a process for preparing compounds of formula V

or acid addition salts thereof, wherein R1, R2, R3, R4, R5 and n are as defined in connection with formula I and Z Z CN, CONH2 or CSNH2 which process comprises treating a compound of formula I as defined above, wherein Xis sodium, potassium or lithium with a silyl compound of formula VI RXSi(NCY)4-x wherein Ra is selected from electron donating substituents, [including alkoxy, cycloalkoxy, aralkoxy, aryloxy, alkylthio, cycloalkylthio, aralkylthio, arylthio] or the group RbRCN-wherein Rb and Rc are selected from alkyl, cycloalkyl, aryl and aralkyl or Rb and Rc may be joined to form a heterocyclic ring with the nitrogen atom (eg., a piperidinyl or pyrrolidinyl ring, which may be substituted eg., by alkyl), and hydrocarbon substituents selected from alkyl, cycloalkyl, aralkyl or aryl, Y is oxygen or sulphur, x has a value from 0 - 3, then subjecting the product to hydrolysis or alcoholysis with the proviso that when a compound of formula V in which Z is CN is desired the molar ratio of compound RaSi(NCY)4~xto compound I is at least 2:1 and xis 3 and Y is S and if desired isolating the product as an acid addition salt.

The compounds of formula V are known compounds which are described in UK Patent Specifications 1463666,1432378,1463668,1465651 and 1495993. The compounds of formula V in which X is CSNH2 are anti-ulcer agents which display anti-ulcer and/or anti-secretory activity in standard test procedures. The nitriles of formula V where Xis CN are intermediates for the corresponding thioamides and usually also display anti-ulcer and/or anti-secretory activity. The amides of formula V in which X is CON H2 are intermediates for the corresponding nitriles and thioamides.

The preferred reaction medium for the above process is an ether solvent eg., a dialkyl ether, wherein the alkyl group has from 1 to 6 carbon atoms, eg., diethyl ether, or a cyclic ether such as tetrahydrofuran or dioxan. Other reaction media which may be used are hydrocarbon solvents such as benzene, toluene or n-hexane. Mixtures of two or more of the above mentioned solvents may be used.

In a preferred aspect of this process a compound R3SiNCY is used in which one group Ra is an electron donating substituent or a branched chain alkyl (eg C3-C10), branched aralkyl, cycloalkyl (eg C4-C8), or aryl and the other two groups Ra are alkyl, eg., t-butyldimethylsilyl isothiocyanate.

When Ra, Rb or RC is an alkyl radical, an aryl radical, an aralkyl radical or a cycloalkyl radical the radical may be as defined for Rs, R2, R3, R4 and R5. When Ra is an alkoxy radical, the radical may be C1-C10 but is preferably as defined for R4 and R5. When R or Ra is an alkylthio group the alkyl portion is as defined for an alkyl group and Ra may be C1-C10. If R or Ra is cycloalkoxy or cycloalkylthio the cycloalkyl portion of this group may be as described for a cycloalkyl group and Ra may be C4to C8.

An aralkyloxy or aralkylthio group may be such a group in which the aralkyl portion is as described for an aralkyl group. The aryl portion is preferably phenyl. An aryloxy or arylthio group may be such a group in which the aryl portion is as defined for an aryl group, 2,6-disubstituted phenyl being a preferred aryl portion.

When it is desired to prepare nitriles of formula V by the above reaction instead of using 2 or more moles of compound RXSi(NCY)4~X to compound i the reaction may be carried out by reacting 1 mol of compound RXSi(NCY)4-x with compound I wherein X is Na, K or Li followed by addition of 1 or more mols of RxSiHal4~x wherein Ra and X are as defined previously and Hal is chlorine or bromine, Ra and x in this compound need not be the same as in the reagent RXSi(NCY)4~xB This process for preparing nitriles is also included in the invention.

The new chemical intermediates of formula I may also be used in a variety of reactions in addition to those already discussed. Examples of reactions are given below: 1) To prepare substituted thioamides corresponding to those of formula V where Z is CSNHRd and Rd is alkyl instead of Z is CSNH2. These substituted thioamides may be obtained by treating a compound of formula I, wherein Xis Na, K or Li with a compound of formula RdNCS followed by treating the product with hydrogen ions. The source of hydrogen ions may be water, an alcohol eg., a lower alkanol of 1-6 carbon atoms or an aqueous mineral acid eg., a hydrohalic acid, preferably hydrochloric acid, or an organic acid such as acetic acid.

2) To prepare substituted amides corresponding to those of formula V where Z CONHRd and Rd is alkyl, instead of X is CONH2. These substituted amides may be obtained by treating a compound of formula I wherein Xis Na, K or Li with a compound of formula RdNCO, eg methyl isocyanate followed by treating the product with hydrogen ions as discussed in paragraph (1) above.

3) To prepare carboxylic acids, there salts and esters of formula V wherein Z is CO2H,CO2M where M is sodium potassium or lithium or CO2Ra and Re is alky, aralkyl or aryl. The esters may be prepared by treating a compound of formula I wherein Xis Na, Kor Li with a haloformate HalCO2Rewhere Hal is chlorine, bromine or iodine and Re is as defined previously followed by treating the product with hydrogen ions eg as discussed in paragraph (1) above. The carboxylic acid salts may be obtained by treating a compound of formula I wherein X is Na, K or Li with carbon dioxide. These salts may be converted to the free acid by treatment with acid eg., mineral acids, eg., of the type discussed in (1) above.

The three processes described above are all included in the invention.

One advantage of the new silyl compounds of formula I when used to prepare compounds of formula V is that there is a reduction in the tendency for side reactions to occur. For example, in the process of UK Patent Specification 1463666 it has been found that with certain alkyl substituted tetrahydroquinolines (eg., 4-methyl compounds) the yields of final product are less than expected. This is due, at least in part, to the tetrahydro-8-lithio-4-methyl-quinoline being converted to a 4-lithiomethyl-tetrahydroquinoline. It has been found that the novel tetrahydro-8-lithio-4-methyl-8-silyl-quinoline does not undergo a similar reaction so that the 4-methyl group is not lithiated.

THE FOLLOWING EXAMPLES ILLUSTRATE THE INVENTION EXAMPLE 1 5,6, 7,8-Tetrahydro-8-trimethylsilyl-3-methylquinoline A mixture of 5,6,7,8-tetrahydro-3-methylquinoline (29.4g,0.2M) and tetrahydrofuran (THF) (50ml) was added to a mixture of a 1.55 molar solution of butyl lithium in hexane (129m1,0.2M) and THF (50ml), maintained below 10 . After 0.5 hour the mixture was blown over by inert gas onto a mixture of trimethylsilyl chloride (50ml, 0.4M) in the THF (100ml), maintained below 10 . After 0.5 hour, the mixture was evaporated and the residue extracted with hexane.The hexane extracts were evaporated with the residue distilled to give the title compound (40g, 91%) b.p. 118-1 240/Smbar. (Found: C70.9; H,9.65; N,6.4% C,3 H21 NSi requires: C, 71.2; H,9.6; N6.4%).

EXAMPLE 2 5,6,7,8-Tetrahydro-8-trimethylsilyl-4methylquinoline The title compound was prepared in a similar manner two that described in Example 1 using 5,6,7,84etrahydro-4-methylquinoline (0.1 M), butyl lithium (0.11 M) and trimethylsilyl chloride (0.2M) in 95% yieldb.p.800/0.lmm(Found: C71.1; H,9.3; N,6.0C13N21 NSirequires: C71.2; H,9.6;N,6.4%) EXAMPLE 3 5,6,7,8- Tetrahydro-3-methylquinollne-8-thiocarboxamide A mixture of a 1.55 molar solution of butyl lithium in hexane (6.45ml,1 OmM) and THF (1 Oml) maintained below 10 was treated with a solution of 5,6,7,8-tetrahydro-8-trimethylsilyl-3-methylquinoline (2.2g, 10mM) in THF (1 Oml) to obtain 5,6,7,8-tetrahydro-8-l ithio-8-trimethylsilyl-3-methylquinol ine. After 0.5 hour a 22% solution of t-butyldimethylsilyl isothiocyanate in benzene (6.9g, 10mM) was added dropwise.After 0.5 hour the reaction mixture was quenched with 2N hydrochloric acid (25ml) and after 1 hour the aqueous layer was separated, basified (to pH9) and extracted with dichloromethane (2 x 50ml). The organic extracts were dried and evaporated to give the title thioamide (2.1g, C 100%). Recrystallisation from benzene gave analytically pure material (1.9g, 88%) m.p. 1530, identical to authentic material (Found: C63.7; H,6.9; N,13.4% C,, H,4 N2S requires: C64.0; H,6.8; N,13.6%).

EXAMPLE 4 5,6,7,8- Tetrahydro-4-methylquinollne-8-thiocarboxamide A mixture of a 1.55 molar solution of n-butyl lithium in hexane (14.2ml, 22mM) and THF (25ml), maintained below 5 was treated with a solution of 5,6,7,8-tetrahydro-8-trimethylsilyl-4-methylquinoline (4.4g, 20mM) in THF (10ml) to give 5,6,7,8-tetrahydro-8-lithio-8-trimethylsilyl-4-methylquinoline. After 0.5 hour a solution of t-butyldimethylsilyl isothiocyanate (22mM) in benzene (15my) was added; after a further 0.5 hour the mixture was quenched with 0.5N hydrochloric acid (60ml). After 1 hourtoluene (50ml) was added, the aqueous layer was separated, adjusted to pH10 and extracted with dichloromethane.The organic extract was evaporated and chromatographed on silica using ether as eluant. The title thioamide was obtained in 60% yield (identical to authentic material) together with the corresponding nitrile (20%) and 5,6,7,8-tetrahydro-4-methylquinoline (20%).

EXAMPLE 5 5,6,7,8- Tetrah ydro-4-m eth ylquin oline-8- (N-meth yithiocarboxamide A mixture of a 1.55 molar solution of n-butyl lithium in hexane (12.9ml,20mM) and THF (10ml), maintained at 5 was treated with a solution of 5,6,7,8-tetahydro-8-trimethylsilyl-4-methylquinoline (4.34g, 20mM) to obtain 5,6,7,8-tetrahydro-8-lithio-8-trimethylsilyl-4-methyl-quinoline. After 0.5 hour a solution of methyl isothiocyanate (1.46g, 20mM) in THF (1 Oml) was added and after a further 0.5 hour the mixture was quenched with N hydrochloric acid (50ml).Ether was added and the aqueous layer was separated, adjusted to pH10 and extracted with dichloromethane (2 x 50ml). The organic extract was dried, evaporated, dissolved in ethyl acetate and passed through a short pad of silica. Evaporation of the eluate followed by recrystallisation from ethyl acetate gate the title compound (2.49) m.p. 1 52-3". The hydrochloride (from propan-2-ol) had m.p. 240-5"(d) (Found:C,56.5; H,6.6; N,10.6% C2Ha6N2SHCI requires C,56.1; H,6.7; N,10.9%) EXAMPLE 6 8-Cyano-5,6, 7,8-tetrahydro-3-methylquinoline A mixture of a solution of 1.5 molar n-butyl lithium in hexane (12.9ml, 20mM) and THF (1 Oml), maintained at 5 was treated with a solution of 5,6,7,8-tetrahydro-8-trimethylsilyl-3-methylquinoline (4.349 20mM) to obtain 5,6,7,8-tetrahydro-8-lithio-8-trimethylsilyl-3-methylquinoline. After 0.5 hour a solution oft- butyldimethylsilyl isothiocyanate (7.0g 40mM) was added and the mixture allowed to warm to 20 over 12 hours. The reaction was quenched with 2N hydrochloric acid and stirred 1 hour. The mixture was extracted with ether, the aqueous phase adjusted to pH10 and extracted with ether. The organic extracts were dried and evaporated to give the title compound (39,85%) identical with authentic material.

EXAMPLE 7 5, 6, 7,8- Tetrah ydro-8-dim ethoxym eth ylsllyl-3-meth ylquinollne The title compound was prepared in a similar manner to that described in Example 1 using 5,6,7,8-tetrahydro-3-methylquinoline (0.01 M), butyl lithium (0.01 M) and dimethoxymethylsilyl chloride (0.015 M). The sample was distilled twice using a kugelrohr apparatus to give the title compound (0.25 g) bp 110-1200C/0.5 mm.

EXAMPLE 8 5,6,7,8- Tetrahydro-3-methylquinoline-8-(N-methyl)carboxamide 8-Lithio-5,6,7,8-tetrahydro-3-methyl-8-trimethylsilylquinoline, prepared as in Example 3, is treated at-200C. under nitrogen with a solution of 1 equivalent of methyl isocyanate in tetrahydrofuran. After this addition the mixture is allowed to warm to ambient temperature and the solvent removed by evaporation.

The residue is dissolved in 2NHCl and washed with ether, basified with Na2CO3 and extracted with chloroform. The extracts are dried and evaporated and the residue purified by chromatography to give the title compound.

EXAMPLE 9 Methyl-5,6, 7,8-tetrahydro-3-methylquinoline-8-carboxylate 8-Lithio-5,6,7,8-tetrahydro-3-methyl-8-trimethylsilylquinoline, prepared as in Example 3, is treated with 1 equivalent of methyl chloroformate in THF at-200C. under, nitrogen. After the addition the mixture is allowed to warm to ambient temperature and the solvent removed by evaporation. The residue is dissolved in 2NHCl and washed with ether basified with Na2CO3 and extracted with chloroform. The extracts are dried and evaporated. Distillation of the residue gives the title compound as a pale yellow oil bp 1200/0.25mm.

EXAMPLE 10 Methyl-5,6, 6,7, 8-tetrah ydro-3-m eth ylquin oline-8-carboxylate 8-Lithio-5,6,7,8-tetrahydro-3-methyl-8-trimethylsilylquinoline, prepared as in Example 3, is blown over onto ether at o C. through which a vigorous stream of CO2 gas is being passed. After the addition the resulting solid, lithium 5,6,7,8-tetrahydro-3-methyl-8-trimethylsilylquinoline-8-carboxylate, is removed by filtration. This is then dissolved in methanol (200 ml) and the solution treated with HCI gas to excess and heated at reflux for 4 hours. The solvent is removed in vacuo and the residue dissolved in water (50 ml), made alkaline with 2N NaOH and extracted with chloroform. The extracts are dried, evaporated and the residue distilled to give the title compound as a pale yellow oil bp 120V0.25 mm.

Claims

1. A silyl compound of formula I

wherein R', R2, R3, R4 and R5 are the same or different and represent hydrogen or alkyl, cycloalkyl, aralkyl, or aryl radicals, any of which radicals may be substituted, or R1 and R2 taken together, or R2 and R3 taken together, form a 5,6, or 7 membered ring which may be saturated or unsaturated and substituted or unsubstituted, and when R1 and R2 form a ring, the ring has the same number of carbon atoms as the ring carrying X, R4 and R5 may also represent alkoxy, n is 1,2 or 3 and Xis hydrogen or lithium, sodium or potassium and R is alkyl, cycloalkyl, aralkyl or aryl or R is selected from electron donating substituents including alkoxy, cycloalkoxy, aralkoxy, aryloxy, alkylthio, cycloalkylthio, aralkylthio, or arylthio, or the group RbRCN- wherein Rb and R6 are selected from alkyl, cycloalkyl, aryl and aralkyl or Rb and R6 may be joined to form a heterocyclic ring and the nitrogen atom, which ring may be substituted.

2. A compound as claimed in Claim 1, wherein when any of R, R1, R2, R3, R4 and R5 is an alkyl radical, the alkyl radical has from 1 to 6 carbon atoms.

3. A compound as claimed in Claim 1, wherein when either R4 or R5 is an alkoxy radical, the alkoxy radical has from 1 to 6 carbon atoms.

4. A compound as claimed in Claim 1, wherein when any of R, R', R2, R3, R4 or R5 is a cycloalkyl radical, the cycloalkyl radical has from 4 to 6 carbon atoms.

5. A compound as claimed in Claim 1, wherein when any of R R1, R2, R3, R4 or R5 is an aralkyl radical, the aralkyl radical has from 7 to 12 carbon atoms.

6. A compound as claimed in Claim 1, wherein when any of R, R1, R2, R3, R4 or R5 is an aryl radical, the aryl radical is phenyl or substituted phenyl.

7. A compound as claimed in Claim 1, or Claim 2, wherein SiR3 is triloweralkylsilyl.

8. A compound as claimed in Claim 7, wherein SiR3 is trimethylsilyl.

9. A compound as claimed in Claim 1, wherein R, R1, R2, R3, R4 or R5 are selected from the radicals defined in any one of claims 2, or 4-6.

10. A compound as claimed in any one of claims 1-9, wherein the compound is a tetrahydroquinoline derivative.

11. 5,6,7,8-Tetrahydro-8-trimethylsilyl-3-methylquinoline.

12. 5,6,7,8-Tetrahydro-8-trimethylsilyl-4-methylquinoline.

13. 5,6,7,8-Tetrahydro-8-dimethoxymethylsilyl-3-methylquinoline.

14. A compound as claimed in claim 1, substantially as hereinbefore described in any one of Examples 1, 2, or7.

15. A process for preparing a compound as claimed in any one of claims 1 to 13, which process comprises treating a compound of formula II

wherein M is sodium, potassium or lithium, and R1, R2, R3, R4, R5 and n are as defined in connection with formula I with a silylating agent of formula R3SiHal where R is as defined previously and Hal is chlorine, bromine or iodine to obtain a compound I, wherein X is hydrogen, and if desired treating this with a metal compound R*M where M is sodium, potassium or lithium and R* is alkyl, cycloalkyl, aralkyl or aryl or an amine residue, to obtain a compound of formula I wherein M is sodium potassium or lithium.

16. A process as claimed in Claim 15, when carried out in a reaction medium comprising an ether solvent.

17. A process as claimed in Claim 16, wherein the reaction medium comprises an ether and a hydrocarbon solvent.

18. A process as claimed in Claim 15, substantially as described in any one of Examples 1,2 or 7.

19. A compound of formula I, whenever prepared by a process as claimed in any one of claims 15, 16, 17 or 18.

20. A process for preparing compounds of formula V

or acid addition salts thereof, wherein R1, R2, R3, R4, R5 and n are as defined in any one of claims 1 to 6 and Z is CN, CONH2 or CSN H2 which process comprises treating a compound of formula las claimed in any one of claims 1 to 14, wherein X is sodium, potassium or lithium with a silyl compound of formula VI RXSi(NCY)4~x wherein Ra is selected from electron donating substituents(including alkoxy, cycloalkoxy, aralkoxy, aryloxy, the group RbRCN wherein Rb and RC are selected from alkyl, cycloalkyl, aryl and aralkyl or Rb and R6 may be joined to form a heterocyclic ring with the nitrogen atom, alkylthio, cycloalkylthio, aralkylthio, arylthio) and hydrocarbon substituents selected from alkyl, cycloalkyl, aralkyl or aryl, Y is oxygen or sulphur, x has a value from 0-3, then subjecting the product to hydrolysis or alcoholysis with the proviso that when a compound of formula V in which Z is CN is desired the molar ratio of compound RXSi(NCY)4-x to compound I is at least 2:1 and xis 3 and Y is S and if desired isolating the product as an acid addition salt.

21. A process as claimed in Claim 20, when carried out in a reaction medium comprising an ether solvent.

22. A process as claimed in Claim 21, when carried out in a reaction medium comprising an ether and a hydrocarbon solvent.

23. A process as claimed in Claim 20 or 21 wherein the compound of formula VI is R3SiNCY, wherein one group Ra is an electron donating substituent or a branched chain alkyl, branched aralkyl, cycloalkyl, or aryl and the other two groups Ra are alkyl.

24. A process as claimed in Claim 23, wherein the compound of formula VI is tbutyldimethylsilylisothiocyanate.

25. A process as claimed in Claim 20 substantially as hereinbefore described in Example 3 or 4.

26. A compound of formula V, whenever prepared by a process as claimed in any one of claims 20 to 25.

27. A process for preparing compounds of formula V as defined in Claim 20, except that Z is CSNHRd where Rd is alkyl, R1, R2, R3, R4, R5 and n being as defined in Claim 20, which process comprises treating a compound of formula las defined in any one of claims 1 to 13, and wherein X is sodium, lithium or potassium with a compound of formula RdNCS followed by treating the product with hydrogen ions.

28. A process as claimed in Claim 27, wherein the compound RdNCS is methylisothiocyanate.

29. A process as claimed in Claim 27, substantially as described in Example 5.

30. A compound of formula V as defined in Claim 20, except that Z is CSNHRd where Rd is alkyl, whenever prepared by a process as claimed in any one of claims 27 to 29.

31. A process for preparing compounds of formula V as defined in Claim 20, except that Z is CONHRd, where Rd is alkyl, R', R2, R3, R4, R5 and n being as defined in Claim 20, which process comprises treating a compound of formula las defined in any one of claims 1 to 13, and Xis sodium, lithium or potassium, with a compound of formula RdNCO, wherein Rd is alkyl, followed by treating the product with hydrogen ions.

32. A process as claimed in Claim 31,,wherein the compound RdNCO is methyl isocyanate.

33. A compound of formula V, as defined in Claim 20, except that Z is CONHRd, where Rd is alkyl, whenever prepared by a process as claimed in Claim 31 or Claim 32.

34. A process for preparing carboxylic acids and their salts of formula V, as defined in Claim 20 except that Z is COOH or CO2M where M is lithium, sodium or potassium which process comprises treating a compound of formula I, as claimed in Claim 1, wherein X is lithium, sodium, or potassium with carbon dioxide, and where a compound in which Z is COOH is desired treating the product with an acid.

35. A process for preparing carboxylic esters of formula V, as defined in Claim 20, except that 2 is CO2Re, wherein Re is alkyl, aralkyl, or aryl, which process comprises treating a compound of formula I as claimed in Claim 1, wherein X is lithium, sodium or potassium, with a haloformate Hal CO2Re, where Hal is chlorine, bromine or iodine and Re is as defined above, followed by treating the product with hydrogen ions.

36. A carboxylic acid, salt, or ester whenever prepared by a process as claimed in Claim 34 or 35.