The invention relates to a process for the preparation of 2-N-acylaminopyridines.

There is a great need for simple, cheap preparation methods for 2-N-acylaminopyridines, which compounds can be used as raw materials for pharmaceutical and agrochemical intermediates and end products.

The known preparation methods for 2-N-acylaminopyridines are based on the acylation of the ^' - corresponding 2-aminopyridines. The 2-aminopyridineε required for this synthesis are prepared in the manner described in for example DE-C-374291. In this process a pyridine is aminated with a sodium amide of the general formula NaNHR, where R is hydrogen, aryl, alkyl or a heterocyclic group such as pyridyl or guinolyl, or with a mixture of metallic sodium and a primary amine. On the whole, the reaction takes more than 5 hours. The known methods for preparing 2-N-acylaminopyridines present the disadvantage that they all proceed via a 2-aminopyridine, which is obtained through amination of the corresponding pyridine. The pyridines used as raw materials in the preparation of •these 2-aminopyridines are often not accessible or

accessible with difficulty only and the amination reaction takes a long time.

- Moreover, large material streams are required in these preparation methods, which is not attractive from an economic point of view.

The process according to the invention aims to avoid these disadvantages and limitations.

To this effect a 2-N-acylaminopyridine of formula 1 is prepared,

formula 1

where H

R, and r- = an alkyl group, a cycloalkyl group, an aryl group or a heteroaryl group, R-, - ₃ and R, = hydrogen, an alkoxy group, an aryl group, a heteroaryl or alkyl group or a cycloalkyl group and R, and R~ can together form a cycloalkyl group, by treating a 5-oxoalkanenitrile oxime of formula 2,

R- I ² i 4

R, - C - C C - C - N formula 2 P I I f

N H H H

I

OH

where R, through R. have the above meanings, in the presence of a strong acid, with an acylating agent that contains at least one R _ς group with the above meaning.

Moreover, the invention relates to a process for the preparation of 2-aminopyridineε from the 2-N-acylaminopyridines thus obtained.

A large number of 2-aminopyridines are raw materials for pharmaceutical and agrochemical intermediates and end products. For example, 2-amino-6-methylpyridine is used in the preparation of nalidixic acid. Nalidixic acid is a chemotherapeutic agent.

An important known method for the preparation of 2-aminopyridines and the ^' disadvantages involved are described above.

As the deacylation reaction in the preparation via the 2-N-acylaminopyridines is very simple, these disadvantages are avoided when a 2-N-acylaminopyridine of formula 1 obtained according to the process of the invention is converted into a 2=-aminopyridine of formula 3,

formula 3

where R, through R, have the meanings given above.

Groups R, through Rr- in formulas 1-3 and in formulas 4 and 5 to be discussed below may have the meanings given above. R, , R- , R ₃ , R ₄ and R ₅ may be substituted. As substituents in groups R ₁ through R ₅ use may be made, of all substituents that are inert under the reaction conditions, such as halogenides, alkoxy groups, alkyl groups and aryl groups. For a good development of the process R, through _ς may not be too large. Therefore, the size of each of R. through R _ς will usually be limited to 15 carbon atoms. Examples of R.-Rr are: methyl, ethyl, propyl, decyl, isobutyl, phenyl, chlorophenyl, methylcyclohexyl, benzyl, trifluoromethyl, methoxyphenyl and pyridyl. Examples of R ₂ ~R ₄ are moreover: methoxy, ethoxy, butoxy, phenoxy and chloromethoxy.

The 5-oxoalkanenitrile oximes used as starting

compounds in the process according, to the invention are the oximes of formula 2,

C = N formula 2

where R- through R. have the meanings given above.

Examples of such 5-oxoalkanenitrile oximes are:

5-oxohexanenitrile oxime,

4-methyl-5-oxohexanenitrile oxime, 2-methyl-5-oxoheptanenitrile oxime,

2,4-dimethyl-5-oxohexanenitrile oxime,

3-methyl-5-oxohexanenitrile oxime,

4-methoxy-5-oxohexanenitrile oxime,

2-(2-cyanoethyl)-cyclohexanone oxime, 2-(2-cyanopropyl)-cyclohexanone oxime,

2-(2-cyanoethyl)-4-methylcyclohexanone oxime,

2-(2-cyanoethyl)-4-methoxycyclohexanone oxime,

2-(l-methyl-2-cyanoethyl)-6-methylcyclohexanone oxime,

2-(2-cyanoethyl)cyclopentanone oxime, 2-(l-methyl-2-cyanoethyl)cyclopentanone oxime and

2-(2-cyanoethyl)-5-methyl-cyclopentanone oxime.

The oximeε can be prepared in any suitable manner.

For example, it is possible to prepare the

5-oxoalkanenitrile oximes by reacting a 5-oxoalkanenitrile with hydroxyl ammonium sulphate and treating this mixture with an alkaline solution. This method can also be used to prepare 5-oxoalkanenitrile oximeε where R ₂ is an acyl group, whether or not subεtituted, or R, is H.

Examples of this are 5-oxopentanenitrile oxime, 4-methyl-5-oxopentanenitrile oxime,

2-methyl-5-oxσpentanenitrile oxime and

3-methoxy-4-methyl-5-oxopentanenitrile oxime.

The invention also relates to the 5-oxoalkanenitrile oximeε of formula 2 where R, = hydrogen, an alkyl group, a cycloalkyl group,

R_ = hydrogen, an alkoxy group, an acyl group, an alkyl group or a cycloalkyl group, and R» and R_ can together form a cylcoalkyl group, R, and R, = hydrogen, an alkoxy group, an alkyl group or a cycloalkyl group with the exception of the compound in which

^R l ^{= H} 3 ^{or H} 2 ^CH 3 ^{and R} 2 ^tnrou 9 ^{n R} 4 ^{= H*}

The process according to the invention can alεo be uεed to prepare

2-N-acylaminopyridineε. Exampleε are: 2-N-acetylamino-6-methylpyridine,

2-N-chloroacetylamino-6-meth.ylpyridine,

2-N-benzoylamino-6-methylpyridine,

2-N-acetylamino-5,6-dimethylpyridine,

2-N-acetylamino-3,5,6-trimethylpyridine, 2-N-chloroacetylamino-3,5,6-trimethylpyridine,

2-N-acetylamino-3-methyl-6-ethylpyridine,

2-N-(2-chlorobenzoylamino)-4,6-dimethylpyridine,

2-N-acetylamino-5-methoxy-6-methylpyridine,

2-N-acetylamino-5,6,7,8-tetrahydroquinoline, 2-N-(p-methoxybenzoylamino)-3-methyl-5,6,7,8-tetrahydroquino line,

2-N-acetylamino-6-methyl-5,6,7,8-tetrahydroquinoline,

2-N-chloroacetylamino-6-methoxy-5,6,7,8-tetrahydroquinoli ne,

2-N-acetylamino-4,8-dimethyl-5,6,7,8-tetrahydroquinoline, 2-N-acetylamino-5,6-cyclopentenopyridine and

2-N-acetylamino-3-methyl-5,6-cyclopentenopyridine.

It can alεo be uεed to prepare 2-aminopyridineε such aε:

2-amino-6-methylpyridine, 2-amino-5,6-dimethylpyridine,

2-amino-3,5,6-trimethylpyridine,

2-amino-6-ethylpyridine,

2-amino-3-methyl-6-ethylpyridine, 2-amino-3-tr±fluoromethyl-6-ethylpyridine, 2-amino-4,6-dimethylpyridine,

2-amino-4,5,6-trimethylpyridine, 2-amino-6-isopropylpyridine, 2-amino-5-methoxy-6-methylpyridine, 2-amino-5,6,7,8-tetrahydroquinoline , 2-amino-4-methyl-5,6,7,8-tetrahydroquinoline,

2-amino-4,6-dimethyl-5,6,7,8-tetrahydroquinoline, 2-amino-5-methoxy-5,6,7,8-tetrahydroquinoline, 2-amino-5,6-cyclopentenopyridine and 2-amino-3-methyl-5,6-cyclopentenopyridine. The invention alεo relates to 2-N-acylamino¬ pyridines of the general formula 1, where R, and Rj- = an alkyl group or a cycloalkyl group, ^R ₂ ' ^R ₃ ^{anc R} ₄ ⁼ hydrogen, an alkoxy group, an alkyl group or a cylcoalkyl group and R- and R ₂ can together form a cycloalkyl group, with the exception of the compoundε where R- through R^ at the same time have the following meanings:

Rl = CH3, R2 through R4 = H and R5 = H, CH3 or CH.--COOET.

Moreover, the invention relates to 2-aminopyridines of the general formula 3, where

R, = an alkyl group or a cylcoalkyl group,

R ₂ , R- ₃ and R. = hydrogen, an alkoxy group, an alkyl group or a cycloalkyl group and R ₁ and R ₂ can together form a cycloalkyl group, with the exception of the compound where, at the same time, R. = CH, and R ₂ through R, = H and the compound where, at the same . time, R-, R- and R, = CH, and R, = H, the compound where, at the same time, R ₁ and ₂ = CH, and R, and R. = H, the compound where R, and R, = CH, and R~ and R, = H, the compound where R, and R, = CH,, and R ₂ and R, = H, the compound where R, = CH, and R ₂ and R, = H and , = CH-CH, and also the compound where R- = ^CH ₃ > ^{R = CH} ~^ ^CH ₃ ^2 ^an< ^ ^R ₂ and R. = H.

- 1 -

In the proceεε according to the invention the 5-oxoalkanenitrile oximes are treated, in the presence of a strong acid, with an acylating agent that contains at least one Rς group with the meaning given above. The εtrong acid that is to be present may be formed in situ or may be added as such to the reaction mixture. As acylating agent uεe may be made of an agent that is an acid halogenide according to formula 4,

0.

I

^5 ~ - X formula 4

where Rr has the meaning given above and X is a halogen atom, or use iε made of a combination of an acid halogenide of formula 4 and a carboxylic anhydride of formula 5,

0

I

R' ₅ - C 0 - C - R", formula 5

where R' ₅ and R' are the εame groupε as mentioned for Rr and R' _c and R"-. can together form a ring. When use is made of an acid halogenide and also when use is made of an acid halogenide together with an acid anhydride a strong acid is formed in situ. It is also possible to use a carboxylic anhydride according to formula 5 as an acylating agent and to add a strong acid as such to the reaction mixture, preferably a halogenous acid, hydrochloric acid being particularly preferable.

Preferably, the combination of an acid chloride and an anhydride as mentioned above is used as an acylating agent. Particularly preferable is the combination of acetylchloride and acetic anhydride. If the εole aim iε the preparation of a 2-aminopyridine, R' _■ and R"-- do not have to be the same because in that case the acyl radical is removed anyway.

When a 2-N-acylaminopyridine iε prepared, R' ₅ and R" _ς will preferably be chosen the same becauεe otherwiεe a mixture of two 2-N-acylaminopyridineε is obtained.

There are a large number of posεible embodiments of the process. Examples of suitable embodiments are as follows:

Synthesis of 2-N-acylaminopyridineε

The oxime is disεolved in a carboxylic anhydride. Preferably, uεe iε made of 2-6 molar equivalents of carboxylic anhydride relative to the amount of oxime, more in particular 2-3 molar equivalents. The temperature maintained during dissolution may vary within wide limits. However, it is preferably kept between -10°C and 20°C. Particularly preferable iε a temperature of between 0 and 5°C.

Then the εolution iε heated while HCl gaε iε passed through it.

The temperature of the reaction mixture is finally kept between 80 and 135°C, preferably between 95 and 105°C. The flow rate of the HCl gas may vary within wide limits. Often, the gas flow iε chosen so that complete converεion of the oxime takeε place in 3-4 hours.

The 2-N-acylaminopyridine formed can now be recovered through, for example, cryεtalliεation.

In a different method the oxime is disεolved in 1-4 molar equivalentε of carboxylic anhydride relative to the oxime. Preferably, uεe iε made of 1-2 molar equivalentε of carboxylic anhydride. The temperature during diεεolution may vary within wide limits. However, it is preferably kept between -10°C and 20°C. Particularly preferable is a temperature of 0-5°C. Then carboxylic chloride is supplied in an amount of at least 1 molar equivalent relative to the oxime. Preferably use is made of 1-4 molar equivalentε, 1-2 molar equivalentε being -particularly preferable.

•The solution is then heated to a temperature of over 40°C, preferably of over 80°C. Particularly preferable is a temperature of 90-110°C. The duration of the heating depends on a number of factors, including the temperature, but usually it lies between 3 and 4 hourε.

The 2-N-acylaminopyridine can be recovered through diεtillation or cryεtall ^' iεation.

Syntheεiε of 2-aminopyridine

If so desired, the 2-N-acylaminopyridines obtained with the procesε according to the invention can be converted into the correεponding 2-aminopyridineε in a manner known per εe.

To thiε effect the reaction mixture can, for example, be treated with a εtrong baεe εuch aε an alkaline εolution. The 2-aminopyridine formed can then be recovered through diεtillation or cryεtalliεation.

Example 1

Preparation of 5-oxohexanenitrile oxime

37.0 gramε (0.45 mol) of hydroxyl ammonium sulphate waε diεεolved in 75 ml of water. 50.2 gramε (0.45 mol) of 5-oxohexanenitrile waε εupplied to thiε εolution. The mixture obtained waε then cooled to about 10°C, after which 18.0 gramε of NaOH (0.45 mol) in 35 ml of water waε added (duration of the addition: 25 minutes), with stirring and ^' cooling. It was ensured that the temperature of the reaction J ⁽ mixture did not rise above 20°C during thiε addition. After the addition, the reaction mixture was stirred for 2 hours at room temperature. After the mixture had εeparated, the organic phaεe waε εeparated from the aqueouε phaεe. The aqueouε phaεe was then extracted with the aid of diethyl ether. Then the combined organic phaseε were dried over

MgSO,. After the MgSO _* had been removed via filtration, the filtrate waε evaporated uεing a rotavapor. In thiε manner

48.1 grams was obtained of 5-oxohexanenitrile oxime with a purity of 99% (yield: 84%).

The following values were meaεured with the aid of 1H-NMR:

CH ₃ - C - CH ₂ - CH ₂ - CH ₂ - Cs N

N b \ OH

¹ H-NMR (CDC1 ₃ /TMS) :

6 = 1.5-2.1; m; 6p;- H ^a + H ^d + H ^b δ = 2.1-2.6; m; 4p; H ^c + H ^e .

The εymbolε used in the representation of the H-NMR results have the following meanings:

Preparation of 2-methyl-5-oxoheptanenitrile oxime

The preparation waε effected in the same manner as in example 1, except that 2-methyl-5-oxoheptanenitrile was used as a starting material. Purity: 94%. Yield: 97%.

a d e c f

_CH CH- - CH - N

¹ H-NMR (CDC1 ₃ /TMS): δ = 0.90-1.33; m; 6p; H ^a + H ^b δ = 1.79; m; 2p; H ^c δ = 2.08-2.68; ; 5p; H ^d + H ^e + H ^f δ = 4.90; ε (w); lp; H ^h

Example 3 Preparation of 2,4-dimethyl-5-oxohexanenitrile oxime

The preparation was effected in the same way as in example 1, except that 2,4-dimethyl-5-oxohexanenitrile was uεed as a starting material.

Yield: 93%. Purity: 95%.

Example 4

Preparation of 2-(2-cyanoethyl)-cyclopentanone oxime

25.8 grams (0.31 mol) of hydroxyl ammonium εulphate waε dissolved in 50 ml of water. 27.3 grams (0.2 mol) of 2-(2-cyanoethyl)-cyclopentanone dissolved in 50 ml of diethyl ether was added to thiε εolution. The mixture obtained was then cooled to 10°C, after which 12.0 g (0.3 mol) of NaOH in 40 ml of H-0 was added, with stirring and cooling (duration of the addition: 20 minutes). It was ensured that the temperature of the reaction mixture did not rise above 20°C during the addition.

After this addition, the reaction mixture was stirred for 16 hourε at room temperature. After the mixture had εeparated, the ether phase waε separated from the aqueous phase. The aqueous phase was then extracted with the aid of diethyl ether. Then the combined ether phaεeε were dried over MgSO- .

After the MgSO. had been removed via filtration the filtrate was evaporated using a rotavapor.

In this manner 26.2 grams of 99% pure 2-(2-cyanoethyl)-cyclopentanone oxime waε obtained. Yield:

86%.

- 12 -

Example 5

Preparation of 2-(2-cyanoethyl)-cyclohexanone oxime

The preparation was effected in the same manner aε in example 4, except that 2-(2-cyanoethyl)cyclohexanone waε used as a starting material. Yield: 59%. Purity: 75%.

H-NMR (CDG1 ₃ /TMS) δ = 1.5-2.0; m; 9p; H ^c δ = 2.15-2.69; m; 4p; H + H δ = 6.68-8.34; s (w) ; Ip; H ^d

Example 6

Preparation of 4-acetyl-5-oxohexanenitrile oxime

The preparation waε effected in the εame manner aε in example 4, except that 4-acetyl-5-oxohexanenitrile waε used as a starting material. Yield: 86%. Purity: 84%.

Example 7

Preparation of 5-oxopentanenitrile oxime The preparation waε effected in the same manner as in example 4, except that 5-oxopentanenitrile was used as a starting material. Yield: 81%. Purity: 93%.

e H C - CH- - CH. CH ₂ - C __ N

N

\> H ^{^}

H-NMR (CDClg/TMS) : δ = 1.60 - 2.09; m; 2p; H ^c δ = 2.10 - 2.68; m(w) ; 4p; H ^b + H ^C δ = 6.63 and 7.31; t ;; ilpp; H

(E + Z isomers)

Example 8

Preparation of 2-N-acetylamino-6-methylpyridine

10.2 gramε. of acetic anhydride (0.1 mol) was added to 12.6 grams of 5-oxohexanenitrile oxime (0.1 mol), with cooling in a water/ice bath and stirring. At a temperature of approx. 5°C 10.2 g of acetyl chloride (0.13 mol) was supplied in 15 minutes, with continued cooling in the water/ice bath. Then the reaction mixture was heated to reflux temperature. Once a reflux temperature of about 100°C waε reached the reaction mixture waε maintained at thiε temperature. The total reaction time after the reflux temperature was reached was four hours. Then the reaction - mixture was- cooled to room temperature and poured into 100 ml of water. The aqueouε solution was neutralized with a 33 wt.% NaOH εolution and then extracted 4x, each time using 50 ml of CH-C1-. After drying and evaporation of the organic phase 10.3 g of 2-N-acetylamino-6-methylpyridine was obtained in a yield of 69% relative to the oxime. Melting point 84.5-86°C.

- 14 -

"H-NMR (CDC1 ₃ /TMS)

IT

H ^l H ^C H ⁶ H ^{^} δ = 8.90; s( ) ; lp; H

Example 9

Preparation of ^' 2-N-acetylamino-5,6-cyclopentenopyridine

25.0 g (0.25 mol) of acetic anhydride waε added to 8.0 gramε (0.05 mol) of 2-(2-cyanoethyl)cyclopentanone oxime. HCl gaε with a temperature of 18-22°C waε pasεed through the εolution for 5 hours, with cooling in a water/ice bath. The reaction mixture was stirred for 16 hours at room temperature. 75 ml of water was added to the reaction mixture, after which it was extracted 4 times, each time using 35 ml of dichloromethane. Yield: 5%. Melting point: 117.5-118°C.

H-NMR (CHC1 ₃ /TMS) δ = 2.08; s; 3p; H ^e δ = 2.78; m(w) ; 8p; H ^c" δ = 8.75; ε(w); lp; H* δ = 7.37; d; lp; H ^C δ = 7.82; d; lp; H ^d

- 15 -

Example 10

Preparation of 2-amino-6-methylpyridine 23.5 grams (0.23 mol) of acetic anhydride was added to 12.6 grams (0.1 mol) of 5-oxohexanenitrile oxime, with stirring and cooling in a water/ice bath. Then the reaction mixture was heated to reflux temperature for 4 hours, while at the same time HCl gas ^' was passed through it, said reflux temperature riεing to about 100°C.

Then' the reaction mixture waε cooled to about 50°C, after which a εolution of 26.4 g (0.66 mol) of NaOH in 75 ml of water waε added and then the mixture was stirred for 1 hour at 70°C. After this the reaction mixture was cooled to room temperature and extracted 4x, each time using 50 ml of dichloromethane. After drying and evaporation 5.9 g of 2-amino-6-methylpyridine was obtained in .a yield of 55% relative to the oxime.

Example 11

Preparation of 2-amino-6-methylpyridine

10.2 grams (0.1 mol) of acetic anhydride was added to 12.6 grams (0.1 mol) of 5-oxohexanenitrile oxime, with stirring and cooling in a water/ice bath. At a temperature of about 5°C 10.2 g (0.13 mol) of acetyl chloride was supplied in 20 minutes, with cooling in a water/ice bath and stirring. Then the reaction mixture was heated to reflux temperature for 4 hours, said reflux temperature rising from 80°C to about 130°C. Then the reaction mixture was cooled to 50°C, after which a solution of 26.4 g (0.66 mol) of NaOH in 75 ml of water waε added and the mixture was stirred for 1 hour at 70°C. Then the reaction mixture was cooled to room temperature and extracted 4x, each time using 50 ml of dichloromethane. After drying and evaporation of the organic phase 6.3 g of 2-amino-6-methylpyridine was obtained in a yield of 58% relative to the oxime. Melting point: 41.2-42.4°C.

16

H-NMR (CDC1 ₃ /TMS) : δ = 2.35; s; 3p; H ^a δ = 4.80; s(w) ; 2p; H ^b δ = 6.17; d; and 6.34; d; 2p; H ^c + H ^d δ = 7.15; t; lp; H ^e

Example 12

Preparation of 2-amino-6-methylpyridine

40.5 g of chloroacetic anhydride (0.24 mol) was added to 12.6 g of 5-oxohexanenitrile oxime (0.10 mol). Then HCl gas waε pasεed through the εolution, with εimultaneouε heating to 85°C. For the first 45 in. the temperature was kept between 80 and 95°C by means of slight cooling. Then the temperature waε kept at 95°C for 3.5 hourε. HCl waε paεsed through throughout the whole experiment. Then the reaction mixture was cooled to room temperature, after which a solution of 14 g of NaOH (0.35 mol) in 75 ml of water was added. After this 40 ml of ethanol was added (the addition - of ethanol ensureε a homogeneous reaction mixture during the hydrolysis). The reaction mixture waε then heated to reflux temperature for 2 hourε. This was followed by cooling to room temperature, after which the reaction mixture waε extracted uεing 4x 50 ml of dichloromethane. After drying and evaporation of the organic phase the yield of 2-amino-6-methylpyridine waε 15% relative to the oxime.

Example 13

Preparation of 2-amino-6-methylpyridine 32.5 g of benzoic anhydride (0.14 mol) was added to

18.0 g of 5-oxohexanenitrile oxime (0.14 mol). This mixture waε heated to 100°C. At 100°C 26.8 g of benzoyl chloride (0.19 mol) was added within 14 minutes. During the addition, brief cooling in a water bath ensured that the temperature did not rise above 115°C.

After all of the benzoyl chloride had been added the temperature was maintained at about 100 ^Q C for another 4 hours. This was followed by cooling to room temperature. A εolution of 15 g of NaOH (0.38 mol) in 50 ml of water and ^' 50 ml of ethanol waε added to the reaction mixture.

The reaction mixture waε kept at reflux temperature for 2 hourε. Then it waε cooled to room temperature and extracted 4x, each time uεing 50 ml of dichloromethane. After drying and evaporation of the organic phase the yield of 2-amino-6-methylpyridine was 7% relative to the oxime.

Example 14

Preparation of 2-amino-6-methylpyridine

52.0 g of benzoic anhydride (0.23 mol) was added to 12.6 g of 5-oxohexanenitrile oxime (0.10 mol). At the same time HCl gaε waε εupplied and the mixture waε heated to 100°C. HCl gaε waε paεεed through for 4 hours at 100°C. This was followed by cooling to 50"C (the reaction mixture would solidify at a lower temperature). A solution of 30 g of NaOH (0.75 mol) in 100 ml of water and 50 ml of ethanol was added to the reaction mixture. The reaction mixture waε kept at reflux temperature for 2 hourε. Then 50 ml of water waε added otherwise an inhomogeneouε mixture would be obtained on cooling. After this the mixture was cooled to room temperature and extracted 4x, each time using 50 ml of dichloromethane. After drying and evaporation of the organic phaεe the yield of 2-amino-6-methylpyridine was 28.1%.

- 18 -

The following products were synthesized in a manner similar to that of example 11:

Example 15

2-amino-3,5,6-trimethylpyridine

Boiling point 110°C (14.5 mm Hg); melting point 99-102°C. Yield: 63%.

H-NMR (CDC1 ₃ /TMS) δ - 2.02; ε; 2.11; εε;; 2.28; ε; 9p; H ^a + H ^b + H ^c δ - 4.25; s(w) ; 2p; H -d - 6.90; s; lp; H ^e

Example 16

2-amino-5,6,7,8-tetrahydroquinoline

Melting point: 60.5-62.5°C; yield: approx. 43%

H-NMR (CDC1 ₃ /TMS) δ = 1.78; m(w); 2.66 m(w) ; 8p; H δ = 4.33; S(w); 2p; H ^b δ = 6.22; d; lp; H ^c δ = 7.05; d; lp; H ^d .

- 19 -

Example 17

2-amino-3-methyl-6-ethylpyridine

Boiling point: 68-70°C (0.55 mm Hg); yield: approx. 43%

^• " ^" H-NMR (CDC1 ₃ /TMS) : δ = 1.24; t; 3p; H ^a δ - 2.03; s; 3p; H ^b δ = 2.60; q; 2p; H ^C δ = 4.60; ε(w); 2p; H ^C δ = 6.38; d; lp; H ^e δ = 7.08; d; lp; H ^f