# US 5,349,095 A · Process for preparing hydroxyalkylbenzocyclobutenes

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- Number: US 5,349,095 A
- Document ID: US5349095A
- Status: Granted
- Kind: A
- Application number: 07/982,213
- Filed: 1992-11-25
- Granted: 1994-09-20
- Earliest claimed: 1992-04-01
- Assignees: The Dow Chemical Company
- Inventors: P. J. Thomas; R. Garth Pews
- Web page: https://patentgrep.com/patent/US5349095A

## CPC

- C07C 49/792: containing rings other than six-membered aromatic rings
- C07C 29/14: of a —CHO group
- C07C 33/34: Monohydroxylic alcohols containing six-membered aromatic rings and other rings
- C07C 45/004: {by reaction with organometalhalides}
- C07C 45/513: {the singly bound functional group being an etherified hydroxyl group}
- C07C 2601/06: with a five-membered ring
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

A process for preparing a substituted or unsubstituted 3- or 4-hydroxyalkylbenzocyclobutene compound comprises reducing a corresponding 3- or 4-formyl or ketobenzocyclobutene compound with a hydride at a temperature below that at which dimerization or oligomerization of the formyl- or ketobenzocycloutene compound or the thus-produced hydroxyalkylbenzocyclobutene compound is a significant side reaction, for a time sufficient to convert the formyl- or ketobenzocyclobutene compound to the hydroxyalkylbenzocyclobutene compound. In a two-step process, formylbenzocyclobutenes are prepared from bromobenzocyclobutenes in 90% yield or from benzocyclobutenes in a 70% yield, and then converted to hydroxymethylbenzocyclobutenes for an overall yield of about 85% from a bromobenzocyclobutene or of about 65% from a benzocyclobutene. In a two-step process, ketobenzocyclobutenes from bromobenzocyclobutene Grignard reagents and an N-alkanoyl- or N-aroyl-2-methylaziridine are converted to hydroxyalkylbenzocyclobutenes in high yields.

## Claims

### Claim 1

A process for preparing a substituted or unsubstituted 3- or 4-hydroxymethylbenzocyclobutene compound, comprising reducing a corresponding 3-or 4-formylbenzocyclobutene compound with a hydride selected from the group consisting of lithium aluminum hydride, sodium borohydride and NaBH.sub.3 CN at a temperature below that at which dimerization or oligomerization of the formylbenzocyclobutene compound or the thus-produced hydroxymethylbenzocyclobutene compound is a significant side reaction, for a time sufficient to convert the formylbenzocyclobutene compound to the hydroxymethylbenzocyclobutene compound, including the prior step of preparing a 3- or 4-formylbenzocyclobutene by reacting a substituted or unsubstituted 3- or 4-bromobenzocyclobutene compound with magnesium to produce a corresponding 3- or 4-benzocyclobutenyl magnesium bromide and treating the thus-formed 3- or 4-benzocyclobutenyl magnesium bromide with dimethylformamide to produce a corresponding 3- or 4-formylbenzocyclobutene compound.

### Claim 2 (depends on 1)

The process of claim 1, wherein the formylbenzocyclobutene compound is 4-formylbenzocyclobutene.

### Claim 3 (depends on 1)

The process of claim 1, wherein the hydride is sodium borohydride and reduction is carried out in an alcoholic solvent.

### Claim 4 (depends on 3)

The process of claim 3, carried out in ethanol.

### Claim 5 (depends on 1)

The process of claim 1, carried out at a temperature near ambient.

### Claim 6 (depends on 1)

The process of claim 1, wherein the formylbenzocyclobutene compound is 4-formylbenzocyclobutene, the hydride is sodium borohydride and the process is carried out in ethanol at a temperature near ambient.

### Claim 7 (depends on 1)

The process of claim 1, wherein hydride is lithium aluminum hydride and the solvent is diethyl ether or tetrahydrofuran.

### Claim 8 (depends on 1)

The process of claim 1, wherein the formylbenzocyclobutene compound is 4-formylbenzocyclobutene, the hydride is lithium aluminum hydride and the process is carried out in diethyl ether at a temperature near ambient.

### Claim 9 (depends on 1)

The process of claim 1, wherein the bromobenzocyclobutene compound is 4-bromobenzocyclobutene.

### Claim 10 (depends on 9)

The process of claim 9, wherein 4-benzocyclobutenyl magnesium bromide is prepared from 4-bromobenzocyclobutene in tetrahydrofuran.

### Claim 11

A process for preparing a substituted or unsubstituted 3- or 4-hydroxymethylbenzocyclobutene compound, comprising reducing a corresponding 3-or 4-formylbenzocyclobutene compound with a hydride selected from the group consisting of lithium aluminum hydride, sodium boro-hydride and NaBH.sub.3 CN at a temperature below that at which dimerization or oligomerization of the formylbenzocyclobutene compound or the thus-produced hydroxymethylbenzocyclobutene compound is a significant side reaction, for a time sufficient to convert the formylbenzocyclobutene compound to the hydroxymethylbenzocyclobutene compound, including the prior step of preparing a 3- or 4-formylbenzocyclobutene by reacting a benzocyclobutene compound and dichloromethyl methyl ether in the presence of titanium tetrachloride to produce the 3- or 4-formylbenzocyclobutene compound.