Synthesis of hydrazine and chlorinated derivatives of bicyclic pyridazines

1. A method of preparing hydralazine hydrochloride, comprising the steps of:

a. heating a first mixture of 1-phthalazinone with phosphorous oxychloride thereby providing 1-chlorophthalazine;

b. contacting said 1-chlorophthalazine with an alkane comprised of from about 5 to about 7 carbon atoms;

c. removing said alkane from said 1-chlorophthalazine;

d. contacting said 1-chlorophthalazine obtained in step c with tetrahydrofuran;

e. removing said tetrahydrofuran from said 1-chlorophthalzine;

f. heating a second mixture containing 1-chlorophthalazine from step e and hydrazine hydrate thereby providing hydralazine;

g. separating said hydralazine from said second mixture;

h. contacting said hydralazine from step g with hydrochloric acid thereby providing hydralazine hydrochloride.

2. The method of claim 1 wherein said alkane is hexane.

3. The method of claim 1 wherein steps f through h are performed in vessels having a non-metallic contact surface.

4. The method of claim 1 wherein said first mixture is heated to a temperature from about 70° to about 85° C. for a time sufficient to convert 1-phthalazine to 1-chlorophthalazine.

5. The method of claim 1 wherein said 1-chlorophthalazine obtained from step e is a powder.

6. The method of one of claim 1 or 3 wherein the second mixture is prepared by adding 1-chlorophthalazine to said hydrazine prior to heating.

7. The method of one of claim 1 or 3 wherein said second mixture is heated to a temperature from about 60° to about 70° C. for a time sufficient to convert 1-chlorophthalazine to hydralazine.

8. The method of claim 1 wherein said alkane is hexane, said first mixture is heated to a temperature from about 70° to about 85° C. for a time sufficient to convert 1-phthalazine to 1-chlorophthalazine, said 1-chlorophthalazine obtained from step e is precipitated, the second mixture is prepared by adding 1-chlorophthalazine to said hydrazine prior to heating and said second mixture is heated to a temperature from about 60° to about 70° C. for a time sufficient to convert 1-chlorophthalazine to hydralazine.

9. A method of preparing hydralazine hydrochloride, comprising the steps of:

a. heating a first mixture of 1-phthalazinone with phosphorous oxychloride thereby providing 1-chlorophthalazine;

b. separating said 1-chlorophthalazine from said first mixture as a solid free flowing powder;

c. heating a second mixture containing 1-chlorophthalazine from step b and hydrazine hydrate thereby providing hydralazine;

d. separating said hydralazine from said second mixture; and

e. contacting said hydralazine from step d with hydrochloric acid thereby providing hydralazine hydrochloride.

10. The method of claim 9 , wherein said 1-chlorophthalazine is separated in step b by precipitation.

11. A method of preparing a chlorinated heterocyclic compound having the formula:

where X and Y are independently carbon or nitrogen, and R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl(C 1 –C 6 ), alkoxy, aryl heteroaryl;

comprising the steps of:

heating a first mixture of a compound having the formula:

where X and Y are independently carbon or nitrogen, and R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl (C 1 –C 6 ), alkoxy, aryl, and heteroaryl, with phosphorous oxychloride thereby providing an admixture containing said chlorinated heterocyclic compound;

contacting said mixture with an alkane comprised of from about 5 to about 7 carbon atoms; and

removing said alkane from said chlorinated heterocyclic compound.

12. A method of preparing a chlorinated heterocyclic compound having the formula:

where R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl (C 1 –C 6 ), alkoxy, aryl, heteroaryl; alkylaryl, aryloxy, and alkylaryloxy;

comprising the steps of:

heating a first mixture of a compound having the formula:

where R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl (C 1 –C 6 ), alkoxy, aryl, and heteroaryl, alkylaryl, aryloxy, and alkylaryloxy, with phosphorous oxychloride thereby providing an admixture containing said chlorinated heterocyclic compound;

contacting said mixture with an alkane comprised of from about 5 to about 7 carbon atoms; and

removing said alkane from said chlorinated heterocyclic compound.

13. The method of claim 12 where R 1 and R 2 are hydrogen.

14. The method of one of claims 11 , 12 , or 13 wherein said chlorinated heterocyclic compound is powder.